Title of Invention

4-PHENYL-5-OXO-1,4,5,6,7,8-HEXAHYDROQUINOLINE DERIVATIVES FOR THE TREATMENT OF INFERTILITY

Abstract

4-PHENYL-5-OXO-l,4,5,6,7,8-HEXAHYDROQUINOLINE DERIVATIVES THE TREATMENT OF INFERTILITY The present invention relates to 4-phenyl-5-oxo-1,4)5,6,7,8-hexahydroquinoline derivatives according to Formula I, Formula I or a pharmaceutically acceptable salt thereof, wherein R^ is (l-6C)alkyl, (2-6C)alkenyl or (2-6C)aDcynyl; R^ R^ are independently halogen, (l-4C)allcyl, (2-4C)alkenyl, (2-4C)-alkynyl, (l-4C)aBcoxy, (3-4C)alkenyloxy or (3-4C)alkynyloxy; R^ is phenyl or (2-5C)-heteroaryl, both substituted with R^ and optionally substituted on the (hetero)aromatic ring with one or more substituents selected from hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, (l-4C)alkyl, (l-4C)alkoxy, (1-4C_alkylthio and (di)(l-4C)-alkyIamino. The invention also relates to pharmaceutical compositions comprising said derivatives, as well as to the use of these 4-phenyl-5-oxo-l,4,5,6,7,8-hexahydro- quinoline derivatives in therapy, more specifically for the treatment of infertility.

Full Text

4-PHEl!IYL-5-OX0-l,4,5,6,7,8-HEXAHYDR0QUINOLINE DERIVATIVES AS MEDICAMENTS FOR THE TREATMENT OF INFERTILITY The present invention relates to 4-phenyl-5-oxo-l,4,5,6,7,8-hexahydroquinoline derivatives, to phannaceutical conjpositions comprising the same and to the use of said derivatives for the nMnufecture of medicaments for the treatment of infertility. Gonadotropins serve important functions in a variety of bodily functions including metabolism, temperature regulation and the reproductive process. Gonadotropins act on specific gonadal cell types to initiate ovarian and testicular differentiation and steroidogenesis. The pituitary gonadotropin FSH (follicle stimulating hormone) for example plays a pivotal role in the stimulation of follicle development and maturation whereas LH (luteinizing hormone) induces ovulation (Sharp, R.M. Clin Endocrinol. 33:787-807, 1990; Dorrington and Armstrong, Recent Prog. Horm. Res. 35:301-342,1979). Currently, FSH is applied clinically for ovarian stimulation i.e. ovarian hyperstimulation for in vitro fertilisation (IVF) and induction of ovulation in infertile anovulatory women (Insler, V., Int. J. Fertility 33:85-97,1988, Navot and Rosenwaks, J. Vitro Fert, Embryo Transfer 5:3-13, 1988), as well as for male hypogonadism and male infertility. The gonadotropin FSH is released fix)m the anterior pituitary under the influence of gonadotropin-releasing hormone and estrogens, and from the placenta during pregnancy. In the female, FSH acts on the ovaries promoting development of follicles and is the major hormone regulating secretion of estrogens. In the male, FSH is responsible for the integrity of the seminiferous tubules and acts on Sertoli cells to support gametogenesis. Purified FSH is used clinically to treat infertility in females and for some types of feilure of spermatogenesis in males. Gonadotropins destined for therapeutic purposes can be isolated fix)m human urine soim:es and are of low purity (Morse et al, Amer. J. Reproduct. Immunol, and Microbiology 17:143, 1988). Altematively, they can be prepared as recombinant gonadotropins. Recombinant human FSH is available commercially and is being used in assisted reproduction (Ohjve et al. Mol. Hum Reprod, 2:371,1996; Devroey et al. Lancet 339:1170,1992). The actions of the FSH hormone are mediated by a specific plasma membrane receptor that is a member of the large femily of G-protein coi^led receptors. These receptors consist of a single polypeptide with seven transmembrane domains and are able to interact with the Gs protein, leading to the activation of adenylate cyclase. The FSH receptor is a highly specific target in the ovarian follicle growth process and is exclusively expressed in the ovary. Blocking of the receptor or inhibiting the signalling which is normally induced after FSH-mediated receptor activation will disturb follicle development and thus ovulation and fertility. Low molecular weight FSH antagonists could form the basis for new contraceptives, while low molecular weight FSH agonists can be used for the same clinical purposes as native FSH, i.e. for the treatment of infertility and for ovarian hyperstimulation on behalf of in vitro fertilisation. Low molecular weight FSH mimetics with agonistic properties were disclosed in the International Application WO 2000/08015 (Applied Research Systems ARS Holding N.V.) and in WO 2002/09706 (Affymax Research Institute). Certain tetrahydroquinoline derivatives have recently been disclosed in the International Application WO 2003/004028 (AKZO NOBEL N.V.) as FSH modulating substances, either having agonistic or antagonistic properties. There remains a need for low molecular weight hormone mimetics that selectively activate the FSH receptor. To that aim the present invention provides 4-phenyl-5-oxo-l,455,6,7,8-hexahydroquinoline derivatives of general formula I or a phannaceutically acceptable salt thereof wherein R^ is (l'6C)aSkyX (2-6C)alkenyl or (2-6C)alkynyl; R^ R^ are independently halogen, (l-4C)alkyl, (2-4C)aIkenyl, (2-4C)alkynyl, (1-4C)- aDcoxy, (3-4C)alkenyloxy or (3-4C)alkynyloxy; R^ is phenyl or (2-5C)heteroaryl, both substituted with R^ and optionally substituted on the (hetero)aromatic ring with one or more substituents selected from hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, (l-4C)alkyl, (l-4C)alkoxy, (l-4C)a]kylthio and (di)(l-4C)alkylamino; R^ is H, (l-4C)aIkylthio, (l-4C)alkylsulfonyl, (di)(l-4C)alkylamino, R^R^-amino, R^^^^-aminocarbonyl, R^^R^^-atnino(l-4C)alkylcarbonylamino, R^ V^-amino-(l-4C)- alkyl, R^^-oxy, R^^R^^-aininocaibonyl(l-4C)alkoxy, R^^-oxy(l-4C)alkyl, R^^-oxy- carbonyl(l-4C)alkyl, R^^^^^-aminosulfonyl, R^**-oxysulfonyl, aminoiminomethyl, (di)(l-4C)alkylaminoiminomethyl or (2-6C)heterocycloaIkyliminomethyl, trifluoro- methylsulfonyl; R^-oxycarbonyl, R^^-carbonyl or R^^R^^-aminocarbonyl; R^ is H or (MC)alkyl; R^ is (l-4C)aIkylsulfonyl, (l-6C)aIkylcarbonyl, (2-6C)alkenylcarbonyl, (2-6C)- alkynylcarbonyl, (3-6C)cycloalkylcarbonyl, (3-6C)cycloalkyl(l-4C)alkylcarbonyl, (l-4C)alkoxycarbonyl, (3-4C)a]kenyloxycarbonyl, (3-4C)alkynyloxycarbonyl, (di)(l-4C)alkylaminocarbonyl, (2-6C)heterocycloalkylcafbonyl, (5-8C)alkyl, (3-6C)- cycloalkyl, (3-6C)cycloalkyl(l-4C)alkyl, (di)(l-4C)alkylammo(2-4C)alkyl, (2-6C)- heterocycloalkyl(2-4C)alkyl or phenylcarbonyl, phenylsulfonyl, phenyl(l-4C)- alkoxy(l-4C)aIkylcarbonyl, phenyl(l-4C)alkyl, (2-5C)heteroarylcafbonyl, (2-5C)- heteroarylsulfonyl, (2-5C)heteroaryl(l-4C)aIkyl, optionally substituted on the (hetero)aromatic ring with one or more substituents selected from hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, (l-4C)alkyl, (l-4C)alkoxy or (di)(l-4C)- alkylamino; R^°isHor(MC)alkyl; R^^ is hydroxy(2-4C)alkyl, ammo(2-4C)alkyl, (MC)alkoxy(2^C)a]kyl or (di)-(l-4C> aIkylamino(2-4C)a]kyl; or R^^^^ inR^^^^-aminocarbonyl may be joined in a (4-6C)heteTOcycloa]kenyl ring or a (2-6C)heterocycloaIkyl ring substituted with one or more substituents selected from (1 - 4C)alkyl, (l-4C)aIkoxy(l-4C)alkyl and hydroxy(l-4C)aIkyl; R^^ R^^ are independently H, (l-6C)alkyl, (2-6C)alkenyl, (2"6C)alkynyl, (3-6C)-cycloalkyl, hydroxy(2-4C)alkyl, (l-4C)a]koxy(2-4C)a]kyl, (3-6C)cycloaBcyl-(l-4C)-alkyl, (2-6C)heterocycloallcyl(l-4C)alkyl, amino(2-4C)a]kyl, (di)(l-4C)a]kylamino-(2-4C)a]kyl orphenyl(l-4C)alkyl, (2-5C)heteroaryl(l-4C)alkyl, optionally substituted on the (hetero)aiomatic ring with one or more substituents selected fiom hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, (MQaDcyl, (MQalkoxy and (di)(l-4C)alkylamino; or R^^R^^ in R^^R^^-aniino(l-4C)alkylcarbonylaniino may be joined in a (4-6C)hetero-cycloalkenyl ring or a (2-6C)heterocycloalkyl ring, optionally substituted with one or more substituents selected from (l-4C)alkyl, (l-4C)alkoxy(l-4C)aIkyl and hydroxy-(l^C)alkyl; R^^R^^ are independently H, (l-6C)alkyl, (2-6C)heterocycloalkyl(l-4C)alkyl, (3-6C)-cycloalkyl(l-4C)alkyl, (l-4C)a]koxy(2-4C)alkyl, hydroxy(2-4C)alkyl, (di)(l-4C)-alkylamino(2-4C)alkyl, amino(2-4C)a]kyl, (l-4C)alkoxycarbonyl-(l-4C)a]kyl, (1-6C)-alkylcarbonyl, (3-6C)cycloa]kylcarbonyl, (l-4C)alkoxycarbonyl, (3-4C)alkenyloxy-carbonyl, (di)(l-4C)alkylaminocarbonyl, (2-6C)heterocycloalkylcarbonyl or (2-5C)-heteroaryl(l-4C)alkyl, phenyl(l-4C)alkyl,(2-5C)heteroarylcarbonyl, phenylcarbonyl, optionally substituted on the (hetero)aromatic ring with one or more substituents selected from hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, (l-4C)alkyl or (l-4C)alkoxy, (di)(l-4C)alkylamiQo; or R^^^^ in R^^^^-amino(l-4C)a]kyl may be joined in a (4-6C)heterocycloalkenyl ring or a (2-6C)heterocycloalkyl ring, optionally substituted with one or more substituents selected from (l-4C)alkyl, (l-4C)alkoxy(l-4C)alkyl and hydroxy(l-4C)aIlcyl; R^^ is (2.6C)heterocycloalkyl(l-4C)alkyl, (di)(l-4C)alkylamino(2-4C)a]kyl, (2-4C)-alkoxy(l-4C)alkyl, hydroxy(2-4C)alkyl, amino(2-4C)alkyl, hydroxycarbonyl(l-4C)-alkyl, (l-4C)a]koxycarbonyl(l-4C)alkyl, (l-4C)alkoxycarbonyl, (3-4C)a]kenyloxy-carbonyl, (3-4C)alkynyloxycarbonyl, (di)(l-4C)alkylaminocarbonyl, (2-6C)hetero-cycloaDcylcarbonyl, or phenyl(l-4C)alkyl, (2-5C)heteroaryl(l-4C)alkyl, optionally substituted on the (hetero)aromatic ring with one or more substituents selected from I hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, (l-4C)alkyl, (l-4C)alkoxy and (di)(l-4C)aIkylamino; R^^R^^ are independently H, (l-6C)alkyl, (3-6C)cycloalkyl(MC)a]kyl, (1-4C)- a]koxy(2-4C)a]kyl, hydroxy(2-4C)alkyl, amino(2-4C)a]kyl, (di)(l-4C)aIkylammo- (2-4C)a]kyl, (2-6C)heterocycloalkyl(2-4C)alkyl, orphenyl(l-4C)alkyl, (2-5C)- heteroaiyl(l-4C)alkyl, optionally substituted on the (hetero)aiomatic ring with one or more substituents selected from hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, (l-4C)alkyl, (l-4C)aIkoxy and (di)(l-4C)alkylamino; or R^'R^^ in R"R^*-aminocaibonyl(l-4C)alk:oxy may be joined in a (4-6C)heteTO- cycloalkenyl ring or a (2-6C)heterocycloalkyl ring, optionally substituted with one or more substituents selected from (l-4C)alkyl, (l-4C)alkoxy(l-4C)aIkyl and hydroxy- (MQalkyl; R^^'isHorO-eQalkyl; R^°,R^^ are independently H, (l-6C)a]kyl, (l-6C)alkenyl, (l-6C)alkynyl or (1-4C)- alkoxy(l-4C)a]kyl; or R^°R^^ in R^°R^^-aininosulfonyl may be joined in a (4-6C)heterocycloalkenyl ring or a (2-6C)heterocycloa]kyl ring, optionally substituted with one or more substituents selected from (1 -4C)alkyl, (1 -4C)a]koxy(l -4C)alkyl and hydroxy- (1 -4C)aIkyl; XisOorN-R^; Y is CH2, C(0) or SO2; ZisCNorN02; R^ is H, (l-4C)alkyl; R^^ R^ are independently H, (l-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (3-6C)cyclo- alkyl, (3-6C)cycloalkyl(l-4C)alkyl, (2-6C)heterocycloalkyl, (2-6C)heterocycloalkyl- (l-4C)alkyl, (l-4C)a]koxycaxbonyl(l-4C)alkyl, (di)(l-4C)a]kylaminocarbonyl(l-4C)- alkyl or phenylamiiiocarbonyl(l-4C)alkyl, (2-5C)heteroarylaminocarbonyl(l-4C)aIlcyl, phenyl, (2-5C)heteroaryl,phenyl(l-4C)a]l£yl, (2-5C)heteroaryl(l-4C)alkyl, optionally substituted at the (hetero)atom with one or more substituents selected from hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, (l-4C)alkyl, (2-4C)aIkenyl, (2-4C)- alkynyl, (1 -4C)alkoxy and (di)(l -4C)aIkylamino; or R^^R^^ in R^R^^-aminocarbonyl may be joined in a (4-6C)heterocycloalkenyl ring or a (2-6C)heterocycloalkyl ring, optionally substituted with one or more substituents selected from (l-4C)alkyl, (l-4C)alkoxy(l-4C)alkyl and hydroxy- (l-4C)alkyl; with the proviso that the compounds of formula I wherein X is O, R* is phenyl and R^ is selected from H, (l-4C)aliylthio, (l-4C)alkylsulfonyl, di(l-4C)alkylamino, R^^- oxycafbonyl, R^^-carbonyl and R^^R^'^-aminocarbonyl, and the compounds of formula I wherein X is O, R'* is (2-5C)heteroaryl and R^ is H or (di)(l-4C)a]kylamino3 are excluded The 4-phenyl-5-oxo-l,4,5,6,7,8-hexahydroquinoline derivatives according to the present invention are potent FSH receptor activators and can be used for the same clinical purposes as native FSH since they behave like agonists, with the advantage that they may be prepared synthetically, may display altered stability properties and may be administered differently. Thus, the FSH-receptor agonists of the present invention may be used for the treatment of fertility disorders e,g. controlled ovarian hyperstimulation and IVF procedures. The term (l-4C)alkyl as used in the definition means a branched or unbranched alkyl group having 1-4 carbon atoms, being methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and tert-butyl. The term (l-6C)alkyl means a branched or unbranched alkyl group having 1-6 carbon atoms, for example methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, n-pentyl and n-hexyl. (l-5C)Alkyl groups are preferred, (l-4C)a]kyl being the most preferred. The term (5-8C)a]kyl as used in the definition means a branched or unbranched alkyl group having 5-8 carbon atoms. The term (2-6C)alkenyl means a branched or imbranched alkenyl group having 2-6 carbon atoms, such as ethenyl, 2-butenyl, and n-pentenyl. The term (2-4C)alkenyl means a branched or unbranched alkenyl group having 2-4 carbon atoms, such as ethenyl, n-propenyl and 2-butenyl. The term (2-6C)alkynyl means a branched or unbranched alkynyl growp having 2-6 carbon atoms, such as ethynyl, propynyl and n-pentynyl. The term (2-4C)alkynyl means an alkynyl group having 2-4 carbon atoms, such as ethynyl and propynyl. The term (3-6C)cycloalkyl means a cycloalkyl group having 3-6 carbon atoms, being cycloprppyl, cyclobutyl, cyclopentyl and cyclohexyl. The tenn (3-6C)cycloalkyl(l-4C)alkyl means a cycloalkylalkyl group, the cycloalkyl group of which has 3-6 carbon atoxns with the same meaning as previously defined and the alkyl group having 1-4 carbon atoms with the same meaning as previously defined. The term (3-6C)cycloa]kyl(l-4C)alkylcarbonyl means a cycloalkyl moiety having 3-6 carbon atoms as previously defined, attached to the alkyl moiety, having 1-4 carbon atoms, of an alkylcarbonyl groxip. The term (3-6C)cycloalkylcarbonyl means a cycloalkyl gcoxxp having 3-6 carbon atoms as previously defined, attached to a carbonyl group. The term (2-6C)heterocycloalkyl means a heterocycloalkyl group having 2-6 carbon atoms, preferably 3-5 carbon atoms, and at least including one heteroatom selected from N, O and/or S, which may be attached via a heteroatom if feasible, or a carbon atom. Prefened heteroatoms are N or O. Most preferred are piperidin-1-yl, morpholin-4-yl, pyrrolidin-l-yl andpiperazin-1-yl. The term (4-6C)heterocycloalkenyl means a heterocycloalkenyl group having 4-6 carbon atoms, preferably 3-5 carbon atoms, and at least including one heteroatom selected from N, O and/or S, which may be attached via a heteroatom if feasible, or a carbon atom. Preferred heteroatoms are N or O. The term (2-6C)heterocycloalkyl(l-4C)aIkyl means a heterocycloalkylalkyl group, the heterocycloalkyl group of which has 2-6 carbon atoms, preferably 3-5 carbon atoms, with the same meaning as previously defined and the alkyl group having 1-4 carbon atoms with the same meaning as previously defined. The term (2-6C)heterocycloalkyl(2-4C)a]kyl means a heterocycloalkylalkyl group, the heterocycloalkyl group of which has 2-6 carbon atoms, preferably 3-5 carbon atoms, with the same meaning as previously defined and the alkyl grovsp having 2-4 carbon atoms. The term (2-6C)heterocycloalkylcarbonyl means a heterocycloalkylcarbonyl group, the heterocycloalkyl group of which has 2-6 carbon atoms, preferably 3-5 carbon atoms, with the same meaning as defined previously. The term (2-5C)heteroaryl means a substituted or unsubstituted aromatic group having 2-5 carbon atoms and at least including one heteroatom selected fix>m N, O and S, like imidazolyl, thiadiazolyl, pyridinyl, thienyl or fiaryl. Preferred heteroaryl groups are thienyl, ftiiyl and pyridinyl. The (2-5C)heteroaryl group roay be attached via a carbon atom or a heteroatom, if feasible. The term (2-5C)heteroaryl(l-4C)aIkyl means a heteroarylalkyl group, the heteroaryl group of which contains 2-5 carbon atoms with the same meaning and preferences as previously defined and the alkyl group contains 1-4 carbon atoms with the same meaning as previously defined. The term (2-5C)heteroarylaminocarbonyl(l-4C)alkyl means a heteroaxylaminocarbonyl groiq), the heteroaryl group of which contains 2-5 carbon atoms with the same meaning and preferences as previously defined attached to an alkyl group containing 1-4 carbon atoms with the same meaning as previously defined. The term (2-5C)heteroarylcarbonyl means a heteroarylcarbonyl group, the heteroaryl group of which contains 2-5 carbon atoms with the same meaning and preferences as previously defined. The term (2-5C)heteroaiylsulfonyl means a heteroarylsulfonyl group, the heteroaryl group of which contains 2-5 carbon atoms with the same meaning and preferences as previously defined. The term (l-6C)alkylcaibonyl means an alkylcaibonyl group, the alkyl group of which contains 1-6 carbon atoms with the same meaning as previously defined. The term (2-6C)alkenylcarbonyl means an alkenylcafbonyl group, the alkenyl group of which contains 2-6 carbon atoms with the same meaning as previously defined. The term (2-6C)alkynylcarbonyl means an alkynylcarbonyl group, the alkyl group of which contains 2-6 carbon atoms with the same meaning as previously defined The term (l-4C)alkylsulfonyl means an alkylsulfonyl group, the alkyl group of which contains 1-4 carbon atoms with the same meaning as previously defined. The term (l-4C)alkylthio means an alkylthio group having 1-4 carbon atoms, the alkyl moiety having the same meaning as previously defined. The tenn (l-4C)alkoxy means an alkoxy group having 1-4 carbon atoms, the alkyl moiety having tiie same meaning as previously defined. (l-2C)Alkoxy groups are preferred The term (3-4C)aIkenyloxy means an alkenyloxy group having 3-4 carbon atoms, the aDcenyl moiety having the same meaning as previously defined The term (3-4C)aIkynyloxy means an alkynyloxy group having 3-4 carbon atoms, the alkynyl moiety having the same meaning as previously defined The terai (l-4C)a]koxycarbonyl means an alkoxycarbonyl group, the alkoxy group of which contains 1-4 carbon atoms with the same meaning as previously defined (1-2C)Alkoxycarbonyl groups are preferred The term (3-4C)alkenyloxycarbonyl means an alkenyloxycarbonyl grovq), the alkenyl group of which contains 3-4 carbon atoms. The term (3-4C)a]kynyloxycarbonyl means an alkynyloxycarbonyl group, the alkynyl groiip of which contains 3-4 carbon atoms. The term (l-4C)aIkoxy(l-4C)alkyl means an alkoxy group, the aDcyl group of which contains 1-4 carbon atoms which is attached to an alkyl group having 1-4 carbon atoms. The term (l-4C)aIkoxy(2-4C)aIkyl means an alkoxy group, the aDcyl group of which contains 1-4 carbon atoms which is attached to an alkyl group having 2-4 carbon atoms. The term (l-4C)a]koxycarbonyl(l-4C)alkyl means an alkoxycarbonylalkyl group, the alkyl groups of which contain 1-4 carbon atoms with the same meaning as previously defined The tenn phenyl(l-4C)alkyl means a phenyl group attached to an alkyl group having 1-4 carbon atoms as defined previously. The term phenyl(l-4C)alkoxy(l-4C)a]kylcarbonyl means a phenylalkoxy moiety, the alkyl groiip of which contains 1-4 carbon atoms attached to the alkyl group of a alkylcarbonyl moiety, the alkyl group also containing 1-4 carbon atoms. The term phenylairiinocarbonyl(l-4C)alkyl means a phenylaminocarbonyl group attached to an alkyl groiq> having 1-4 carbon atoms as defined previously. The term hydroxy(2-4C)alkyl as used herein means an hydroxyalkyl group having 2-4 carbon atoms, the alkyl moiety having the same meaning as previously defined The term hydroxycarbonyl(l-4C)a]kyl means a hydroxycarbonylalkyl group, the alkyl group of which contains 1-4 carbon atoms with the same meaning as previously defined. The term (di)(l-4C)aIkylamino as used herein means an amino groxip, monosubstituted or disubstituted with alkyl groups, each of which contains 1-4 carbon atoms and has the same meaning as previously defined. The tenn (di)(l-4C)alkylaniinocarbonyl means a (di)alkylaminocarbonyl group, the (di)a]kylamino group of which is as defined previously. The tenn (di)(l-4C)a]kylaminocarbonyl(l-4C)alkyl means a (di)allcylaminocarbonyl-alkyl group, the alkyl groups of which contain 1-4 carbon atoms with the same meaning as previously defined. The tenn aminocarbonyl(l-4C)alkoxy means an aminocarbonylalkoxy group, the alkyl group of which contains 1-4 carbon atoms with the same meaning as previously defined. The term (di)(l-4C)aIkylamino(2-4C)aIkyl as used herein means an (di)alkylamino group having 1-4 carbon atoms, connected via the amino group to an alkyl group having 2-4 carbon atoms, the alkyl moieties having the same meaning as previously defined. The term amino(l-4C)alkylcarbonylamino means an aminoalkylcarbonylamino group, the alkyl groi^ of which contains 1-4 carbon atoms with the same meaning as previously defined. The term amino(2-4C)alkyl as used herein means an aminoalkyl group having 2-4 carbon atoms, the alkyl moiety having the same meaning as previously defined. The term (di)(l -4C)a]kylaminoiminomethyl as used herein means an alkylaminonninomethyl group, the amino group of which is monosubstituted or disubstituted with allcyl groups having 1-4 carbon atoms and having the same meaning as previously defined. The term (2-6C)heterocycloalkyHminomethyl as used herein means a heterocycloalkyliminomethyl group, the heterocycloalkyl moiety of which is as previously defined. The term halogen means fluorine, chlorine, bromine or iodine; chlorine, bromine or iodine being preferred. The term pharmaceutically acceptable salt represents those salts which are, within the scope of medical judgement, suitable for use in contact for the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, and are commensurate with a reasonable benefit/risk ratio. Pharmaceutically acceptable salts are well known in the art. They may be obtained during the final isolation and purification of the compounds of the invention, or separately by reacting the fi'ee base function with a suitable mineral acid such as hydrochloric acid, phosphoric acid, or sulfiiric acid, or with an organic acid such as for example ascorbic acid, citric acid, tartaric acid, lactic acid, maleic acid, malonic acid, fumaric acid, glycolic acid, succinic acid, propionic acid, acetic acid, methanesulfonic acid, and the like. The acid function can be reacted with an organic or a mineral base, like sodium hydroxide, potassium hydroxide or lithium hydroxide. The invention also relates to con:qK)unds of formula I, wherein R^ is (l-6C)alkyl. More in particular, the invention relates to compounds wherein R^ is (l-4C)alkyL Another aspect of the invention are compounds according to formula I wherein R , R is halogen and/or (l-4C)alkoxy. In yet another aspect, the invention concerns compounds of formula I, wherein Y is CH2. Another aspect of the invention is a compound wherein Z is CN. In another aspect the invention concerns compounds wherein X = O. The invention also relates to compounds according to general Formula I wherein R^ is R^R^-amino, R^V^-aminocafbonyl, R^^R^^-amino(l-4C)alkylcafbonylamino, R^^^^--amino(l -4C)alkyl or R^^R^^-aminocarbonyl(l -4C)a]koxy, In another aspect the invention concerns compounds wherein R^isH, R^ is (l-4C)a]kylsulfonyl, (1.6C)alkylcarbonyl, (3-6C)cycloalkylcarbonyl, (1-4C)-alkoxycarbonyl, (3-4C)a]kenyloxycarbonyl, (di)(l-4C)alkylaininocarbonyl5 (2-6C)-heterocycloalkylcarbonyl, or phenylcarbonyl, phenyl(l-4C)a]koxy(l-4C)alkylcarbonyl, (2-5C)heteroaiylcarbonyl, (2-5C)heteroarylsulfonyl or (2-5C)heteroaryl(l-4C)a]kyl, optionally substituted on the (hetero)aromatic ring with one or more substituents selected ftom, halogen or (l-4C)alkoxy; R^^isHor(l-4C)alkyl; R" is hydroxy(2^C)aIkyl, amino(2-4C)alkyl, (l-4C)a]koxy(2^C)alkyl or (di)(l-4C)-a]kylamino(2-4C)alkyl; or R^° and R^^ form together with the N to which they are bonded a (4-6C)heterocyclo-aDcenyl ring or a (2-6C)heterocycloal]cyl ring, optionally substituted with one or more substituents selected from (l-4C)alkyl; R^^ R^^ are independently H, (l-6C)alkyl, (3-6C)cycloalkyl, hydroxy(2-4C)alkyl, (l-4C)a]koxy(2-4C)alkyl, (2-6C)heterocycloallcyl(l-4C)alkyl or (di)(l-4C)-alkylamino(2-4C)alkyl or phenyl(l-4C)all£yl, (2-5C)heteroaryl(l-4C)alkyl, optionally substituted on the (hetero)aromatic ring with one or more substituents selected from halogen; or R^^ and R^^ form together with the N to which they are bonded a (4-6C)heterocyclo-alkenyl ring or a (2-6C)heterocycloalkyl ring, both optionally substituted with one or more substituents selected from (l-4C)alkyl or hydroxy(l-4C)alkyl; R^'^^R^^ are independently H, (l-6C)a]kyl, hydroxy(2-4C)alkyl, (l-4C)a]koxycaxbonyl-(l-4C)aIkyl, (l-6C)alkylcarbonyl, (3-6C)cycloa]kylcarbonyl, (l-4C)alkoxycarbonyl or (2-5C)heteroaryl(l-4C)alkyl or (2"5C)heteroarylcarbonyl3 phenylcarbonyl; R^^ is (2-6C)heterocycloalkyl(l-4C)a]kyl, (di)(l-4C)alkylamino(2-4C)a]kyl, (2-4C)-alkoxy(l-4C)alkyl, hydroxycarbonyl(l-4C)alkyl, (l-4C)alkoxycarbonyl(l-4C)alkyl; or phenyl(l-4C)alkyl or (2-5C)heteroaryl(l-4C)alkyl, optionally substituted on the (hetero)aromatic ring with one or more substituents selected from halogen or (1-4C)-I aDcoxy; R^^,R^^ are independently H, (l-6C)alkyl, (3-6C)cycloalkyl(l-4C)alkyl, (l-4C)alkoxy-(2-4C)allcyl, (2-6C)heterocycloalkyl(2-4C)alkyl; or phenyl(l-4C)alkyl or (2-5C)hetero- aryl(lAC)z\ky\ optionally substituted on the (hetero)aromatic ring with one or more substituents selected from halogen; or R" and R^^ fonn together with the N to which they are bonded a (4-6C)heterocyclo- alkenyl ring or a (2-6C)heterocycloalkyl ring, optionally substituted with one or more substituents selected from (l-4C)a]kyl or hydroxy(l-4C)alkyL The invention also relates to con5)ounds according to Formula I wherein R^ is R^ - amino. Another aspect of the invention concerns con5)ounds wherein R^ is H and R^ is (1- 4C)a]kylsulfonyl. Still another aspect of the invention concerns compounds wherein one or more of the specific definitions of the groups R^ through R^^ and X, Y and Z as defined here above are combined in the definition of the 4-phenyl-5-oxo-l,4,5,6,7,8-hexahydroquinoline derivatives of formula I. The invention also concerns corc5)ounds selected from the group of iV-{3-[2-Bromo-4- (3-cyano-2-methyl-5-oxo-7-propyl-l,4,5,6,73-hexahydro-quinolin-4-yl)-6-ethoxy- phenoxymethyl]-phenyl}-3,4,5-trimethoxy-benzamide; iV-{3-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-l54,5,6,73-hexahydTo-quinolin- 4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-2-[(pyridin-4-yhnethyl)-amino]-acetamide; iV-{3-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-pTOpyl-l54,5,6,7,8-hexahydro-qx3inolin- 4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-2-[4-(2-hydroxy"ethyl)-piperazin-l-yl]- acetamide; 4-{3-Bromo-4-[3-(3,6-dihydro-2ff-pyridine-l-carbQnyl)-benzyloxy]-5-etiioxy-phenyl}- 2-methyl-5-oxo-7-propyl-l,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile; 3-[Bis-(2-methoxy-ethyl)-aniino]-iV-{3-[2-bromo-4-(3-cyano-2-methyl-5-oxo-7- propyl-l,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}- propionamide; 2-{3-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-l,4,5,6,7,8-hexahydro-quinolin- 4-yl)-6-ethoxy-phenoxymethyl]-phenoxy}-i\r^-dimethyl-acetamide; 4- {3-Bromo-5-ethoxy-4-[3-(2-morpholin-4-yl-2-oxo-ethoxy)-benzyloxy]-phenyl} -2- methyl-5-oxo-7-propyl-l,4,5,6,7,8-hexahydro-qu]noline-3-carbonitrile; Furan-2-carboxylic acid {2-[2-bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-l,4,5,6,7,8- hexahydro-qumolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-aimde; 7V-{2-[2-Bromo-4 4-yl)-6-ethoxy-phenoxymethyl]-phenyl} -acrylamide; Cyclopropanecarboxylic acid {2-[2-bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl- l,4,5,6,73-hexahydro-qumolm-4-yl)-6-e1hoxy-phenoxyme%l]-p^ 2-[2-Bromo-4-(3'-cyano-2-me1hyl-5-oxO"7-propyl-l,4,5,6,73-hexahydro-qumolm yl)"6-ethoxy-phenoxymethyl] -phenyl} -cafbamic acid methyl ester; l-{2-[2-Bromo-4-(3-cyano-2-meihyl-5-oxo-7-propyl4A5,6J,8-hexahydro-quinol^^ 4-yl)-6-ethoxy-phenoxyinethyl]-phenyl}-3-inethyl-urea {3-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-l,4,5,6,7,8-hexahydxo-qidnolin-4- yl)-6-elhoxy-pheiioxyine1hyl]-pyridin-2-yl}-carbamic acid methyl ester 4-(3-Bromo-5-e1hoxy-4-{3-[(lf^imidazol-4-ybnethyl)-amino]-ben2yloxy}-phenyl)-^ methyl-5-oxo-7-propyl-l54,5,6,7,8-hexahydro-quinoline-3-carbonitrile; 7V-{3-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-lA5v6,7,8-hexahydro-quinolin- 4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-methaiiesulfonamide; {4-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-l,4,556,7,8-hexahydro-quinolin-4- yl)-6-ethoxy-phenoxymethyl]-phenyl} -carbamic acid allyl ester; 4-[3-Bromo-5-ethoxy"4-(l-methaBesulfonyl-li?"pyrrol-2-yhnethoxy)-phenyl]"2" methyl-5-oxo-7-propyl-l54,5,6,7,8-hexahydro-quinoline-3-carboiiitrile; 4-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4- yl)-6-ethoxy-phenoxymethyl]-N-methyl-benzamidine; 4-{3-Bromo-5-ethoxy-4-[(pyridin-3-ylmethyl)-amino]-phenyl}-2-methyl-5-oxo-7- propyl-l,4,5,6,758-hexahydro-quinoliiie-3-carboiiitrile; iV-(2-{[2-Bromo4-(3-cyano-2-methyl-5-oxo-7-propyl-l,4,5,6,758-hexahydro-quinolin- 4-yl)-6-ethoxy-phenylamino]-methyl}-phenyl)-methaiiesulfonamide; 4- {3-Bromo-4-[2-(cyclopropylmethyl-amino)-ben2yloxy]-5-ethoxy-phenyl} -2-methyl- 5-oxo-7-propyl-l,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile; or 7^-{2-[2-Bromo-4-((4R,7S)-3-cyano-2-methyl-5-oxo-7-propyl-lA5,6,7,8-hexahydro quinolin-4-yl)-6-ethoxy-phenoxymethyl]-4,5-difluoro-phenyl}-methanesulfoiianud Suitable methods for the preparation of the 4-phenyl-5-oxo-l,4,5,6,7,8-hexahydroquinoline derivatives of the invention are outlined below. The 4-phenyl-5-oxo-l,4,5,6,7,8-hexahydroquinoline derivatives I of the present invention can be prepared starting from appropriately functionalised I54-dihydropyridine derivatives of general stmcture H, wherein R\ R^, R^, X, Y and Z are as previously defined and A is a phenyl or a heteroaryl ring. For example, acylation or sulfonylation of compounds of general formula Il-b yields con:5)ounds of general formula I-a, wherein R , R , R% X^Y and Z are as previously defined, R^ is H, R^ is an acyl or sulfonyl group and A is a (substituted) phenyl or a (substituted) heteroaryl ring. In a typical experiment, compounds Il-b are reacted in a solvent, such as dichlorometiiane, JV;7V-dimethylfonnamide, dimethyl sulfoxide, ethanol, tetrahydrofuran, 1,4-dioxane, toluene, l-methyl-pyTrolidin-2-one or pyridine with an E^ropriately substituted acyl halide, acid anhydride or sulfonyl halide in the presence of a base such as triethylamine, iVIA'^-diisopropylethylamine (DiPEA) or pyridine, to give iV-acylated or iV^sulfonylated derivatives of formula I-a, respectively. Alternatively, iV^acylated compounds of general formula I-a can be obtained by reaction of a (hetero)aromatic carboxylic acid in the presence of a coupling reagent such as diisopropyl carbodiimide (DIC), (3-dimethylaminopropyl)-ethyl-carbodiimide (EDCI), 0-(benzotriazol-1 -yl)-iV;iV; JV',iV*'-tetramefliyluronium tetrafluoroborate (TBTU) or 0-(7-azabenzotriazol-1 -yl)-7V;JV;jV;iV"-tetramethyluronium hexafluoro-phosphate (HATU) and a tertiary amine base (e,g, DiPEA) in a solvent such as N,N'-dimethylformamide or dichloromethane at ambient or elevated temperature. Compounds of general formula I-b, wherem R^, R^, R^, X, Y and Z are as previously defined, R^ is a (substituted) alkyl group Md A is a (substituted) phenyl or a (substituted) heteroaryl ring, can be prepared by reductive alkylation of the amino group with appropriately substituted aldehydes of general formula E-C(0)H (E = alkyl, cycloalkyl, cycloalkylalkyl, (di)alkylaininoalkyl, heterocycloalkylalkyl, (hetero)aryl, (hetero)arylalkyl) and a suitable reducing agent such as sodium cyanoborohydride or sodium triacetoxyborohydride. Likewise, appropriately substituted ketones can be used in this procedure. Alternatively, compounds of general formula Il-b can be converted to the corresponding (hetero)arylimine II-c upon reaction with appropriately substituted aldehydes of general formula E-C(0)H (see above) by methods known to those skilled in the art, followed by reduction with a reducing agent such as sodium borohydride to give compounds of general formula I-b. In this case, appropriately substituted ketones can be used as well. Alternatively, compounds of general formula Il-b can be converted to 2,4-dinitrobenzenesulfonamide derivatives Il-d by sulfonylation with 2,4-dinitrobenzenesulfonyl chloride. The sulfonamide can be alkylated to give compoimds of general formula Il-e by using art known Mitsunobu reactions with appropriately substituted primary or secondary alcohols of formula R^-OH (R^ = alkyl, cycloalkyl, cycloalkylalkyl, (di)alkylaminoalkyl, heterocycloalkylallg^l or (hetero)arylalkyl), triphenylphosphine (optionally resin bound) and a dialkyl azodicarboxylate in appropriate solvents such as 1,4-dioxane, tetrahydrofuran or dichloromethane at elevated or ambient temperature. Alt^natively, the sulfonamide can be alkylated using alkyl halides of formula R^-Hal (Hal = CI, Br, I) and a suitable base such as K2CO3 in a solvent such as JV^JV-dimethylfonnamide, tetrahydrofiaran or 154-dioxane. Cleavage of the N-S sulfonamide bond with a primary amine such as propylamine in a suitable solvent such as dichloromethane then gives conqjounds of fonnula I-b. Alternatively, the N-S sulfonamide bond can be cleaved using merc^toacetic acid and a tertiary amine base in a solvent such as dichloromethane. Precedence for these types of reactions can be found in Uterature. For example, see: Tetrahedron Lett. 38 (1997) 5831-5834, Bioorg. Med, Chem. Lett. 10 (2000) 835-838. Compounds of general formula I-c, wherein R\ R^, R^, R^, X,Y and Z are as previously defined, R is (l-4C)aIkyl and A is a (substituted) (hetero)aryl group, can be prepared from compounds I-a, I-b or Il-f Alkylation of compounds I-a with R -Hal (Hal = CI, Br, I) or R*^-OH by the same methods described for the alkylations of con5)ounds Il-d yields the desired JNT^-disubstituted aniline derivatives I-c. Additionally, alkylation of compounds of fonnula I-b by the same metiiods described for the reductive alkylation of compounds of formula H-b also yields i\yV-disubstituted aniline derivatives of formula I-c. Con:5)ounds of general formula 11-:^ prepared by the same methods described for the synthesis of con^wunds of formula I-b, can be acylated, sulfonylated or reductively alkylated as described for the preparation of I-a and I-b, respectively, to give compounds of general formxila I-c. The nitro group in compounds of general formula Il-a can be reduced to the corresponding amino groiip to give compounds of general formula Il-b. Typically, con^)ounds Il-a are treated with zinc and acetic acid in a suitable solvent such as THF or dioxane at ten5)eratures between 0 ^'C and reflux temperature. Alternative methods include treatment with iron, SnCla or hydrogen in the presence of a transition metal catalyst such palladium or platinum on charcoal, using methods and reagents well known to those skilled in tiie art Alternatively, compounds of general formula Il-b can be obtained by cleavage of known JV-protecting groups such as an Allyloxycarbonyl (Alloc), Fluoren-9-yl-methoxycarbonyl (Fmoc) or ^ert-butoxycafbonyl (Boc) group in compounds of general formula Il-g to give the corresponding derivatives Il-b. Related protective group manipulations can be found in Protective groups in Organic Synthesis, T.W, Greene and P.G.M. Wuts, John Wiley & sons, Inc., New York, 1999 , Carboxylic acid derivatives of general formula Il-i, accessible by saponification of corresponding alkyl esters Il-h, can be condensed with amines of general structure using a coupling reagent as described before for the preparation of derivatives I-a to give compounds of formula I-d, wherein R\ R^, R^, R^^, R^\ X, Y and Z are as previously defined and A is a (substituted) phenyl or a (substituted) heteroaryl ring, A similar coupling method has been described before for the preparation of derivatives I-a, Alternatively, coirpounds of general formula Il-i can be converted to the corresponding acid chlorides II-j by art known methods. Treatment of carboxylic acids of general formula Il-i with thionyl chloride or oxalyl chloride and DMF in a suitable solvent such as dichloromethane or toluene gives the corresponding acid chlorides II-j. Subsequent reaction with amines of general structure R^^^^NH, optionally in the presence of a suitable tertiary amine base yields compounds of general formula I-d. Compounds of general formula I-e, wherein R\ R^, R^, R^^ R^^, X,Y and Z are as previously defined and A is a (substituted) phenyl or a (substituted) heteroaryl ring, can be obtained by acylation of compounds of general formula E-b with appropriate acyl halides to give compounds Il-k, followed by standard substitution of the chloride or bromide with amines of general formula R^^R^^NH. Additionally, compounds of general formula I-e with a two-carbon spacer between the carbonyl and the NR^^R^^ group can be obtained by acylation of conipoimds of general formula E-b with a,p-unsaturated acyl chlorides to give compounds of general formula II-l, folbwed by art known Michael addition reactions with appropriately substituted amines of general formula R^^R^^NH. Con:5)ounds of general formula I-:^ wherein R\ R^, R^, R^^, R^^, X,Y and Z are as previously defined and A is a (substituted) phenyl or a (substituted) heteroaryl ring, can be prepared by alkylation of amines of general formula R^'^^^NH with halides of general formula Il-m, under the agency of a tertiary base such as JVjiV-diisoprppyl ethylamine or triethylamine in an appropriate solvent such as iy^JV-dimethylformamide, tetrahydrofiiran or dichloromethane. Derivatives of general formula I-g, wherein R\ R^ R^, R^^, X,Y and Z are as previously defined and A is a (substituted) phenyl or a (substituted) heteroaryl ring, can be prepared by alkylation of the hydroxyl grovtp in compounds of general formula II-o with an alkyl halide of general formula R^^-Hal, in which Hal may be Br, CI or I. Typically, such a reaction is carried out in an aprotic solvent such as NJ^-dimethylformamide, 1,4-dioxane or tetrahydrofbian in the presence of a base, such as sodium hydride, potassium carbonate, cesium carbonate or trietyl amine at ambient or elevated tenperature. Alternatively, conversion of conrpounds of general formula II-o into aryl ethers of general formula I-g may be accomplished under Mitsunobu-type alkylation conditions. In such a transformation, alkylation of the hydroxyl group in conipounds of formula II-o is effected with alcohols of general formula R^^-OH under the agency of (resm bound) triphenyl phosphine and diethyl azodicarboxylate or its derivatives in a suitable ^rotic solvent such as tetrahydrofuran or dichloromethane. Derivatives of general formula II-o can be obtained by cleavage of the hydroxyl-protecting group in compounds of general formula Il-n, Suitable protective groups, well-known to those skilled in the art, are the tetrahydropyranyl (THP) or ^ert-butyl dimethylsilyl (TBS) protective groups. Cleavage of the THP and TBS groups is generally acconaplished by treatment with acids, such as hydrochloric acid, trifluoromethanesulfonic acid or trifluoroacetic acid in a suitable solvent, such as tetrahydrofuran or methanol. Alternatively, the TBS group can be removed by treatment with tetra-n-butylammonium fluoride in tetrahydrofuran. Related protective group manipulations can be found in Protective groups in Organic Synthesis, T.W. Greene and P.G.M, Wuts, John Wiley & sons, Inc, New York, 1999. Corcpounds of the present invention with general formula I-h can be prepared by condensation of derivatives Il-q with amines of general formula R R NH under the agency of a coupling agent and a tertiary amine base, as described e.g for the preparation of derivatives of general formula I-d The requisite derivatives of formula I-q are accessible in a two-step synthetic protocol fix)m compounds of general formula n-o, i.e, alkylation of the phenolic moiety with an appropriate halogenated alkyl ester to obtain derivatives of formula II-p, followed by acid or base-mediated cleavage of the ester function, well known to those skilled in the art. Derivative of general formula I-i are accessible fromnitriles of general formula Il-rby the art known Pinner amidine synthesis. This synthetic procedure comprises the selective conversion of the nitrile function on the (hetero)aTyl ring of derivatives Il-r I . — ^ - - _ ^—^. into imidates II-s by treatment with an qypropriate acid such as hydrochloric acid, using a suitable alcohol as a solvent, optionally in the presence of cosolvents such as 1,4-dioxane or diefliyl efeer, at ambient or elevated ten:5)erature. Reaction with the appropriate acyclic or cyclic amine yields the amidine derivatives I-i. Related anddine foimations are well known to those skilled in the art. For example, see: J. Med- Chem. 42 (1999) 5415-5425, Bioorg, Med. Chem. Lett 13 (2003) 697^700, J. Org. Chem. 62 (1997), 8449-8454. Con5>ounds of general formula Ill-a whra^in X is O can be used to prepare compounds I-j, wherein R\ R^ R^, R'*, Y and Z are as previously defined and X is O, by 0-alkylation, 0-acylation or 0-sulfonylation using standard conditions, well known to those skilled in the art. The substitution pattern of the (hetero)aryl ring in R"* is as previously defined. In a typical e:?5)eriment, compounds IH-a axe reacted in a solvent, such as dichloromethane, jy;iV-dimethylfoxmainide, dimethyl sulfoxide, ethanol, tetrahydro&ran, l,4'-dioxane, toluene, l'methyl-pyrrolidin-2-one ot pyridine with an appropriately substituted (hetero)aromatic alkyl haEde of formula IV, acyl chloride of formula V, or sulfonyl chloride of formula VH in the presence of a base such as triethylamine, iVr^'diisopropylethylamine (DiPEA), potassium carbonate, cesium carbonate or sodium hydride, optionally in the presence of a catalytic amount of potassium iodide or tetrabutylammonium iodide, to give O-aDcylated, O-acylated or O-sulfonylated derivatives of formula I-j, respectively. Alternatively, O-alkylated con^^ounds of general formula I-j in which Y is CH2 can be obtained by using art known Mitsunobu reactions with alcohols of formula Vin, triphenylphosphine (optionally resin bound) and a dialkyl azodicarboxylate (e.g. diethyl azodicarboxylate) in appropriate solvrats such as 1,4-dioxane, tetrahydro&ran or dichloromethane at elevated or ambient temperature. Additionally, 0-acylated confounds of general fonnula I-j, wherein Y is C(0) can be obtained by reaction of a (hetero)aromatic carboxylic acid of formula VT in &e presence of a coupling reagent such as diisopropyl carbodiimide (DIG), (3-dimethylaminopropyl)-ethyl-raibodiimide (EDCI), C?-(benzotriazoM-yl)-iV',iV,iV',iV-tetramethyluronimn tetrafluoroborate (TBTU) or 0-(7-azaben2:otria2:ol-1 -yl)-A^,iV,iV',A'"'-tetrametbyluronium hexafluorophosphate (HATU) and a tertiary amine base (€.g. D3*EA) in a solvent such as TViTs^-dimethylfcamamide or dichloromethane at ambient or elevated temperature. Likewise, conpounds of general formula I-k can be prepared from compounds IH-b by iV^alkylation, JV-acylation or i\r-sulfonylation using the same methods described for the II: A = (substituted) phenyl or (substituted) heteroaryi synthesis of compounds I-j using the reagents of formula IV-X. Additionally, con5)ounds of general formula I-k in which Y is CH2 can be prepared by reductive amination of (hetero)aromatic aldehydes of formula IX with compounds Hl-b and a suitable reducing agent such as sodium cyanoborohydride or sodium triacetoxyborohydride. Alternatively, compounds of general formula m-b can be converted to the corresponding benzimine xipon reaction with (hetero)aromatic aldehydes IX by methods known to those skilled in the art, followed by reduction with a reducing agent such as sodium borohydride to give compounds I-k in which Y = CH2. Con5)ounds of general formula I-k wherein R\ R^, R^, R"^ and Z are as previously defined and X is NH can be iV^alkylated by the same methods as described for the preparation of derivatives I-b to afford conpounds of general formula I-l, wherein R^ is a (l-4C)a]kyl group. Con:5)ounds of general formula H are also accessible from derivatives of general formula Ill-a and Ill-b using the same methods as described for the preparation of compounds of general formula I-j and I-k using reagents of formula X-XV. Similar to the iV-alkylations of compounds of general formula I-k to give I-l, con5)ounds of general formula Il-t, wherein R^ R^, R^ and Z are as previously defined and A is a (substituted) phenyl or a (substituted) heteroaryl can be JV-alkylated to give compounds of general formula II-u, wherein R is a (MC)alkyl group. Con:5)Ounds of general formula I, wherein R\ R^, R^, R^, X, Y and Z are as previously defined, can also be prepared starting from cyclohexane-l,3-diones of general formula XVI, enamines of general formula XVII and benzaldehydes of general formula XVIQ- a-b, by the well-documented three con5)onent Hantzsch-type cyclo-condensation reaction. Related Hantzsch-type cyclo-condensation reactions can be found in: Bioorg. Med. Cheia Lett. 12 (2002) 1481-1484, J. Chem. Soc, Perldn Trans. 1 (2002) 114M156, Synlett (2002) 89-92, Drug Dev. Res. 51 (2000) 225-232, Drag Dev. Res. 51 (2000) 233-243, J. Med. Chem. 42 (1999) 1422-1427, ibid. 5266-5271, ibid. 41 (1998) 2643-2650, WO 9408966, Arzneim.-Forsch./Drug Res. 45 (1995) 1054-1056, J. Med. Chem. 34 (1991) 2248-2260, ibid, 17 (1974) 956-65, Indian J. Chem., Sect B (1994) 526-531, Chenx Rev. 72 (1972), 1-42. The above mentioned reaction is typically conducted at elevated tenperature in suitable solvents such as acetic acid, (iso)propanol, ethanol, methanol or mixtures thereof. Compounds of general formula n and IH-a-b are also prepared by the previously mentioned Hantzsch-type cyclo-condensation, by using substituted benzaldehydes of general fonnula XEX or XX, respectively. Compounds of general formula Ill-c-d in which R is Br can also be obtained by ortho-bromination of phenols or anilines, which are well known to those skilled in the art Thus, compounds of fonnula Ill-e-f afford compounds of formula m-c-d i5)on treatment with bromine in a suitable solvent such as acetic acid, ethanol or dichloromethane or mixtures thereof, optionally in the presence of sodium acetate. Alternatively, iV^bromosuccinimide in T^^iV-dimethylformamide or acetonitrile can be used to achieve tbis conversion. For example, see: J. Chenx Soc. Perkin Trans.2 6 (2000) 1113-1118, J. Org. Chem. 44 (1979), 4733-4735. Con5)ounds of general formula Ill-e-f are prepared by the aforementioned Hantzsch reaction using benzaldehydes of general formula XXI-a-b. Coiqpounds of general formula IV to XV are either commercially available, documented in literature or readily synthesized by those skilled in the art. The substituted cyclohexane-l,3-diones of general formula XVI are commercially available or can be prepBxed by literature procedures. Relevant examples are found in: J. Med. Chem. 43 (2000) 4678-4693, Tetrahedron 56 (2000) 4753-4758, J. Med. Chem. 35 (1992) 3429-3447, ibid. 24 (1981) 1026-1034, Org. Synt Coll. Vol. V (1973) 400, Chem- Ber. 88 (1955) 316-327, Justus Liebig Ann. Chem. 570 (1950) 15-31, The compound of formula XVII-a is commercially available and compound XVII-b can be prepared by art-known methods, see for exarcple: Drug Dev. Res. 51 (2000) 225-232. Benzaldehydes of general formula XVni-a, wherein R , R , R and Y are as previously defined and X = O, are readily prepared from benzaldehydes of general formula XX-a using the same methods as described for the conversion of compounds of formula Dl-a to I-j. Likewise conpounds of general formula XVQI-b are prepared from XX-b using the same methods as described for the conversion of compounds of formula ni-b to I-k Benzaldehydes of general formula XX-a and XX-b are commercially available or can be prepared according to literature procedures: J. Chem. Soc, Perkin Trans. 2 (2000) 1119-1124, J. Chem. Soc, Chem. Common. 4 (1993) 419-420, Synth. Commun, 20 (1990) 2659-2666, Chem. Phaim. Bull. 34 (1986) 121-129, Indian J, Chem, Sect. B 20 (1981) 1010-1013, Monatsh. Chem. 106 (1975) 1191-1201, DE 1070162, J. Org. Chem. 23 (1958) 120, Tetrahedron Lett. 25 (1984), 2901-2904, J. Org. Chem. 25 (1960), 2053-2055, J. Chem. Soc., Perkm Trans. 2 (1992), 2235-2242. Additionally, benzaldehydes of general formula XX-c wherein R^ is bromide and X is N-H can be obtained by bromination of coii5)ounds of general formula XXI using the same procedures described for the conversion of compounds of general formula ni-f to Ill-d Con^jounds of general formula XXI are easily prepared ftom compounds of general formula XXn using the same reduction methods that were described for the preparation of compounds of general formula Il-b from Il-a. Con5)ounds of general formula XXII are coirunercially available, reported in literature or can be readily be prepared by those skilled in the art. Similarly, derivatives of general formula XDC-a-b are accessible from compounds XX-a-b upon reaction with compounds X to XV, as previously described for the preparation of derivatives XVDI-a-b. The compounds of the present invention possess at least two chiral carbon atoms and may therefore be obtained as pure enantiomers, or as a mixture of enantiomers, or as a mixture of diastereomers. Methods for obtaining the pure enantiomers are well known in the art, e.g. crystallization of salts which are obtained from optically active acids and the racemic nmrture, or chromatography using chiral columns. For separation of diastereomers, straight phase or reversed phase columns may be used. Additionally, enantiomerically pure hexahydroquinoline derivatives of general formula XXTTT may be obtained in enantiomerically pure form by dehydration of enantiomerically pure amides XXIV with trifluoroacetic anhydride and a suitable base such as triethylamine or pyridine in a suitable solvent such as dichloromethane, 1,4-dioxane or tetrahydrofinran at 0 ^C or ambient tenperature. Related dehydrations of amides to give nitriles can be found in literature, for exanqjle, see: Org. Prep. Proced. Int. 26 (1994) 429-438, Acta Chem. Scand. 53 (1999) 714-720, J. Org, Chem 57 (1992) 2700-2705- Con5)ounds of general formula XXIII may then be converted - if necessary - to con^jounds of general formula I by the syntheses outlined above. Amides of general formula XXIV can be prepared by cleavage of the chiral benzyl group of amides of genera] fomiula XXV (mdicated for XXV-a). This reaction can be effected by stirring with an acid such as trifluoroacetic acid in dichloromethane. Coirpoimds of general formula XXV are obtained by a Hantzsch-type cyclo-condensation as described previously, starting from XVI, enamine XXVI and an appropriately substituted benzaldehyde. This reaction gives a mixture of 4 stereoisomers of general formulas XXVa-d which may be separated by chromatographic techniques, such as flash column chromatography using silica gel and/or HPLC, Enamine XXVI can be prepared by methods known to those of skill in the art in two steps from the commercially available (S)-l-(4-Methoxy-phenyl)-ethylamine and diketene or 2,2,6-trimethyl-l,3-dioxin-4-one. The compounds of the invention may form hydrates or solvates. It is known to those of skill in the art that charged compounds form hydrated species when lyophilized with water, or form solvated species when concentrated in a solution with an appropriate organic solvent The compounds of this invention include the hydrates or solvates of the con5)oimds hsted. The 4-phenyl-5-oxo-l,4,5,6,7,8-hexahydroquinoline derivatives of the invention were found to agonists of the FSH receptor. Methods to determine receptor binding, as well as in vitro and in vivo assays to determine biological activity, of gonadotropins are well known. In general, expressed receptor is contacted with the compoimd to be tested and binding or stimulation or inhibition of a fimctional response is measured. To measure a ftmctional response, isolated DNA encoding the FSH receptor gene, preferably the human receptor, is expressed in suitable host cells. Such a cell might be the Chinese Hamster Ovary cell, but other cells are also suitable. Preferably the cells are of mammalian ori^ (Jia et al, MoLEndocrin., 5:759-776,1991). Methods to construct recombinant FSH expressing cell lines are well known in the art (Sambrook et al., Molecular Cloning: a Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, latest edition). Expression of receptor is attained by expression of the DNA encoding the desired protein. Techniques for site directed mutagenesis, ligation of additional sequences, PCR, and construction of suitable e3q)ression systems are all, by now, well known in the art. Portions, or all, of the DNA encoding Ihe desired protein can be constructed synthetically using standard solid phase techniques, preferably to include restriction sites for ease of ligation. Suitable control elements for transcription and translation of the included coding sequence can be provided to the DNA coding sequences. As is well known, expression systems are now available which are compatible with a wide variety of hosts, including prokaryotic hosts such as bacteria and eukaryotic hosts such as yeast, plant cells, insect cells, mammalian cells, avian cells and the like. Cells expressing the receptor are tiien contacted with the test compound to observe binding, or stimulation or inhibition of a functional response. Alternatively, isolated cell membranes containing the expressed receptor may be used to measure bmding of the test compound. For measurem^it of binding, radioactive or fluorescent compounds may be used. As reference compound human recombinant FSH can be used. In the alternative also competition binding assays may be performed. Another assay involves screening for FSH receptor agonist compounds by determining stimulation of receptor mediated cAMP accumulation. Thus, such a method involves e^qxression of the receptor on the cell surfece of a host cell and exposing the cell to the test compound. The amount of cAMP is then measured. The level of cAMP will be increased, by the stimulating effect of the test compound iipon binding to the receptor. In addition to direct measurement of e.g. cAMP levels in the exposed cell, cells lines can be used which in addition to transfection with receptor encoding DNA are also transfected with a second DNA encoding a reporter gene the expression of which responds to the level of cAMP. Such reporter genes might be cAMP inducible or might be constructed in such a way that they are connected to novel cAMP responsive elements. In general, reporter gene expression might be controlled by any response element reacting to changing levels of cAMP. Suitable reporter genes are e.g. LacZ, alkaline phosphatase, firefly luciferase and green fluorescence protein. The principles of such traosactivation assays are well known in the art and are described e.g. in Stratowa, Ch., Himmler, A. and Czemilofsky, A.P., (1995) Curr. Opin, Biotechnol. 6:574. The present invention also relates to a pharmaceutical coinposition comprising a 4-phenyl-5-oxo-l,4,5,6,7,8-hexahydroqiiinoline derivative or pharmaceutically acceptable salts thereof having the general formula I in admixture with pharmaceutically acceptable auxiliaries and optionally other therapeutic agents. The auxiliaries must be "acceptable" in the sense of being compatible with the other ingredients of the composition and not deleterious to the recipients thereof Conpositions include e.g. Ifaose suitable for oral, sublingual, subcutaneous, intravenous, intramuscular, nasal, local, or rectal administration, and the like, all in unit dosage forms for administration. For oral administration, the active ingredient may be presented as discrete units, such as tablets, capsules, powders, granulates, solutions, suspensions, and the like. For parenteral administration, the pharmaceutical composition of the invention may be presented in unit-dose or multi-dose containers, e,g. injection liquids in predetermined amounts, for example in sealed vials and ampoules, and may also be stored in a freeze dried (lyophilized) condition requiring only tiie addition of sterile liquid carrier, e.g. water, prior to use. Mixed with such pharmaceutically acceptable auxiliaries, e.g. as described in the standard reference, Genoaro, A.R. et al., Remington: The Science and Practice of Pharmacy (20th Edition-, Lqjpincott Williams & Wilkins, 2000, see especially Part 5: Phannaceutical Manufecturing), flie active agent may be compressed into solid dosage units, such as pills, tablets, or be processed into capsules or suppositories. By means of phaimaceutically acceptable liquids the active agent can be applied as a fluid composition, e.g. as an injection preparation, in the form of a solution, suspension, emulsion, or as a spray, e.g. a nasal spray. For making solid dosage units, the use of conventional additives such as fillers, colorants, polymeric binders and the like is contemplated In general any pharma-ceutically acceptable additive which does not interfere with the function of the active compounds can be used. Suitable carriers with which the active agent of the invention can be administered as solid compositions include lactose, starch, cellulose derivatives and the like, or mixtures thereof, used in suitable amounts. For parenteral administration, aqueous suspensions, isotonic saline solutions and sterile injectable solutions may be used, containing pharmaceutically acceptable dispersing agents and/or wetting agents, such as propylene glycol or butylene glycol. The invention further includes a pharmaceutical coroposition, as hereinbefore described, in combmation with packaging material suitable for said composition, said packaging material including instructions for the use of Ihe confiposition for the use as hereinbefore described. The exact dose and regimen of administration of the active ingredient, or a pharmaceutical con5>osition thereof, may vary with the particular compound, the route of administration, and the age aod condition of the individual subject to whom the medicament is to be administered. In general parenteral administration requires lower dosages than other methods of administration which are more dependent iipon absorption. However, a suitable dosage for humans may be 0.05-25 mg per kg body weight. The desired dose may be presented as one dose or as multiple subdoses administered at appropriate intervals throughout the day, or, in case of female recipients, as doses to be administered at appropriate daily intervals throughout the menstrual cycle. The dosage as well as the regimen of administration may differ between a female and a male recipient. Thus, the conipounds according to the invention can be used in therapy. A further aspect of the invention resides m the use of a 4-phenyl-5-oxo-l,4,5,6,7,8-hexahydroquinoline derivative having the general formula I for the naanufecture of a medicament to be used for the treatment of disorders responsive to FSH receptor mediated pathways, preferably for the treatment of fertility disorders. Thus, patients in need thereof can be administered with suitable amounts of the compounds according to the invention. In yet another aspect tiie invention resides in the use of a 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivative having the general formula I for the manufacture of a medicament to be used for the treatment of infertility. The invention is illustrated by the following examples. General Comments: The foHowmg abbreviations are used in the examples: DMA = JV^JV-dimethylaniline, DIPEA == i\r,Ar.diisopropylethylamine, TFA = trifluoroacetic add, HATU = 0-(7-azabenzotriazole-l-yl)-jy;iy;iV',iV^'-tetramethyluronium hexafluorophosphate, Fmoc = 9-fluorenylmethoxycarbonyl, Fmoc-Cl = 9-fluorenylmethoxycarbonylchloride, Alloc = allyloxycaibonyl, DMF = JV;7\r.dimethylformamide, THF = tetrahydrofiuran. Unless stated otherwise, all final products of the examples below were lyophUized from water/1,4-dioxane mixtures, water/^^-butanol or water/acetonitrile mixtures. If the con5)ound was prepared as a TFA salt, the acid was added in an appropriate amount to the solvent mixture before lyophilization. The names of the final products described in the examples were generated using the Beilstein Autonom program (version: 2.02.304). The following analytical HPLC methods were used for determination of retention times: Method 1: Colimm: 5 pm Luna C-18(2) 150x4.6 mm; flow: 1 ml/min; detection: 210 nm; column teii5)erature: 40 ""C; solvent A: CH3CN/H2O = 1/9 (v/v); solvent B: CH3CN; solvent C: 0.1 M aqueous trifluoroacetic acid; gradient: solvent A/B/C = 65/30/5 to 10/85/5 (v/v/v) in 30.00 min, then constant for an additional 10.00 min at A/B/C = 10/85/5 (v/v/v). Method 2: Identical to method 1, except for the gradient used: Gradi^t: solvent A/B/C = 75/20/5 to 15/80/5 (v/v/v) in 30-00 min, then constant for an additional 10.00 min at A/B/C-15/80/5 (v/v/v). Method 3: Identical to method 1, except for the gradient used: Gradient: solvent A/B/C = 35/60/5 to 10/85/5 (v/v/v) in 30.00 min, then constant for an additional 10.00 min at A/B/C = 10/85/5 (v/v/v). Method 4: Identical to method 1, except for the gradient use± Gradient: solvent A/B/C = 95/0/5 to 15/80/5 (v/v/v) in 30.00 min, then constant for an additional 10.00 min at A/B/C =15/80/5 (v/v/v). Method 5: Identical to method 1, except for the gradient used: Gradient: solvent A/B/C = 75/25/0 to 0/100/0 (v/v/v) in 20,00 min, then constant for an additional 10.00 min at A/B/C = 0/100/0 (v/v/v). Method 6: Identical to method 1, except for the gradient used: Gradient: solvent A/B/C == 60/40/0 to O/IOO/O (v/v/v) in 20.00 min, then constant for an additional 10.00 min at A/B/C = 0/100/0 (v/v/v). Method 7: Identical to method 1, except for the gradient used: Gradient: solvent A/B/C = 70/30/3 to 40/60/3 (v/v/v) in 30.00 min, then constant for an additional 10.00 min at A/B/C = 0/100/3 (v/v/v). Mefliod 8: Column: 3 pm Luna C-18(2) 100x2 mm (Phenomenex); flow: 0.25 ml/min; detection: 210 nm; column temperature: 40 ""C; solvent A: CHsCN/HsO =1/9 (v/v); solvent B: CH3CN; gradient solvent A/B ^ 65/35 to 10/90 (v/v) in 30.00 min, in 2.00 minutes to A/B = 0/100 (v/v), then constant for an additional 8,00 min at A/B = 0/100 (v/v), then in 1.00 minute to A/B = 65/35 (v/v) and finally constant for an additional 15.00 min at A/B - 65/35 (v/v). Method 9: Column: Chiralpak AD-H 25 x 0.46 cm; detection: Chirality (+/-) and 210 nm; Conditions : isocratic heptane/isopropylalcohol 80/20 (v/v). The dkstereomeric ratio (Diast. ratio:) was determined if baseline separation of the individual diastereomers was observed using the appropriate analytical HPLC method. Alternatively, the diastereomeric ratio was determined by ^H NMR analysis when distinct signals coiresponding to the diastereomers were identified. Preparative HPLC-purifications were performed on a Luna C"18(2) column (5 pm) (150 X 21.2 mm) with water/acetonitrile mixtures, optionally in the presence of 0.1% aqueous TFA, using the indicated gradient: Flow: 20 ml/min: Detection: 210 nm: Example 1 ?^-{3-r2-Bromo-4-f3 (a). 3"Bromo-5-eflioxv-4-f3-mtro-benzvloxv)-ben2aldehvde A mixtuie of 3-nitrobenzylhromide (2 g), 3-bromo-5-ethoxy-4-hydroxy benzaldehyde (2.06 g), K2CO3 (2.55 g) and BU4NI (186 mg) in DMF (50 ml) was stirred at 60^C for 2 h. The reaction mixture was diluted with ethyl acetate and washed with water and brine. The organic layer was dried (MgS04), filtered and concentrated in vacuo. The residue was recrystallized from heptane. Yield: 2.98 g. MS-ESI: [M+H]^ = 380/382 (b). 4-[4-f3-Nitro-benzvloxv)-3-brotDO-5-ethoxv-phenvn-2-methvl-5-oxo-7-propvl-L4.5,6,7,8-hexahydro-quinoline"3-carbonitrile A mixture of the product of example la (2g), 3-aminocrotonitrile (431 mg) and 5-propylcyclohexane-l,3-dione (810 mg) in ethanol (20 ml) was stirred at 80^C for 4 h. The reaction mixture was concentrated in vacuo and the residue was chromatographed on silica gel in heptane/ethyl acetate = 1/1 (v/v) as eluent Yield: 2.7 g. MS-ESI: [M+H]^ = 580/582 (c). 4-r4-f3-Amino-benzvloxv)-3-bromo-5-ethoxv-phenvlV2-methvl-5-oxo-7-propvl-1,4,5.6J,8-hexahvdro-quinoline-3-carboni1rile SnCla (1.62 g) was added to a solution of the product of exantple lb (500 mg) in ethanol (10 ml). After stirring for 18 h, the reaction mixture was poured in water and extracted with ethyl acetate. The organic layer was separated and washed with 0.5N NaOH and water, dried (MgS04)5 filtered and concentrated in vacuo. Yield: 440 mg. MS-ESI: [M+H]^ = 550/552 (d). JV^{3-[2-Bromo-4-f3-cvano-2-mgthvl-5-oxo-7-propvl-l,4,5,6,7,8--hexahvdro-quin-olin-4-vlV6-ethoxv-phenoxvme1hvl1-phenvU-3,4,5-trimethoxV"benzamide A mixture of the product of example Ic (44 mg), 3,4,5-trimelhoxybenzoylchloride (39 mg) and DEPEA (70 yH) in dichloromethane (10 ml) was stirred for 18 h. The reaction mixture was diluted with dichloromethane and washed with water and brine. The organic layer was sq)arated, dried (MgS04), filtered and concentrated in vacuo. The residue was purified by preparative HPLC (0 —> 90% acetonitrile). Yield: 39 mg. MS-ESI: [M+H]^ = 744.4/746.4; anal. HPLC: Rt = 20.73 min 1 (method 1) Example 2 A^-(3-r2-Bromo-4-f3-cvano-2-methvl-5-oxO"7-propvl-L4,5,6J.8-hexahvdTo-qianQlm^ 4-vlV6-ethoxv-i3henoxvmethvl1-phenvU-33-dime1favl-butvr^^ Acylation of the product described in example Ic (44 mg) with 3,3-dimethyl-bvrtyryl chloride(16 mg) was perfoimed according to the method described in example Id. Yield: 36 mg. MS-ESI: [M+H]^ = 648/650; anal, HPLC: Rt = 22.58 min (method 1) Example 3 iV^I3"r2-Bromo-4-f3-cvano-2-methvl-5-oxo-7-pmpvl-L4,5.6J,8-hexahvdio-quinolin-4"VlV6-ethoxv-phenoxymethvl]-phenvll-2-[fpvridin-4-vlmethvl>"amino]-aceta^ (a). 2-Bromo-jy-(3-[2-bromo-4-f3-cvano-2-methyl-5-oxo-7-propvl-l,4,S,6J,8-hexa-hvdro-quinolin-4-vlV6-ethoxv-pheDOXvmethvl] -phenvU -acetamide Bromoacetyl chloride (600^1) in dichloromethane (5 ml) was added dropwise to a solution of the product of example Ic (1,32 g) andDIPEA (2.1 ml) in dichloromethane (25 ml). After stirring for 4 h, the reaction mixture was washed with water. The organic layer was separated, dried (MgS04)5 filtered and concentrated in vacuo. Yield: 900 mg. MS-ESI: [M+m^ = 670/672/674 (b). A^-l3-r2-Bromo-4-r3-cvano-2-methvl-5-oxo-7-propvl-L4.5,6J.8-hexahvdro-quin-olin-4-vl)-6-ethoxv-phenoxvmethvl1-phenvU-2-r(pvridin-4-vlmethvlVamino1-acetamide A mixture of the product of exaxaple 3a (50 mg) and 4-picolylamine (81 mg) in dichloromeihane/THF = 4:1 (v/v) (2.5 ml) was stirred for 18 h. The reaction mixture was diluted with dichloromethane and washed with water and brine. The organic layer was separated, dried (MgS04), filtered and concentrated in vacuo. The residue was purified by preparative HPLC (0 -^ 90% acetonitrile, 0.1% TFA). Yield: 17.9 mg (as TTA salt). MS-ESI: [M+H]"' = 698.4/700.4; anal. HPLC: Rt = 8.85 min (diastl), Rt = 9.07 mm (diast2) (mefliod 2) Example 4 7^-0-r2-Bromo-4-r3-cvano-2-methvl-5-oxo-7-T)ropvl"1.4.5,6J,8-hexahvdro-quinolin-4-vlV6-ethoxv-phenoxvmethvl1-phenvU-2-fcvclopentvl-me1favl-amino)-acetamide Reaction of the product described in example 3a (50mg) with cyclopentyl-methyl-amine (74 mg) was performed according to the method described in exan5)le 3b. Yield: 53 mg (as TFA salt). MS-ESL [M+H]^ = 689/691; anal. HPLC: Rt = 13.45 min (diastl), Rt = 13.72 min (diast2) (method 2). Example 5 Ar-|3-r2-Bromo-4-r3-cvano-2-methvl-5-oxo-7-propvl-1.4,5,6J.8-hexahvdro-qu^ 4-vlV6-ethoxv-phenoxvmethvn-T>henvU -2-r4-f 2-hvdroxv-ethvlVpiperazm-l -vll-acetamide RediCtion of the product described in example 3a (50mg) with 2-piperazin-l-yl-ethanol (98mg) was performed according to the metiiod described in example 3b. Yield: 41 mg (as TFA salt). MS-ESI: [M+H]^ = 720/721; anal. HPLC: Rt - 10.40 min (diastl) Rt = 10.67 min (diast2) (method 2). Example 6 3-[2-BromO"4-(3-cvano-2-methyl-5-oxo-7-propvl-l,4,5,6J,8-hexahvdrO"quinolin-4-vlV6-ethoxv-phenoxvmethyl]-.^-ethvl-JV'-f2-hvdroxy-ethyl)-benzamide fa\ 3-f2-Bromo-6-ethoxv-4-formvl-phenoxvmeflivl)-benzoic acid methyl ester Alkylation of 3-bromo-5-ethoxy-4-hydroxy benzaldehyde (2 g) with 3-bromomethyl-benzoic add methyl ester (2.06 g) was performed according to the method described in example la. The residue was chromatographed on silica gel in heptane/ethyl acetate = 7/3 (v/v) as eluent Yield: 2.42 g. MS-ESI: [M+Hf = 393/395 (b). 3-r2-Bromo-4-f3-cvano-2-methvl-5-oxo-7-propvl-l,4J,6J,8-hexahvdro-quipolin-4-vl)-6"ethoxv-phenoxvmethvll-benzoic acid methyl ester The title con5)Ound was prepared according to the method described in example lb starting firom the product of example 6a (2.4 g), 3-aminocrotonitrile (504 mg) and 5-propylcyclohexane-l,3-dione (947 mg). Yield: 2.96 g. MS-ESI: [M+H]^ = 593/595 (c). 3-r2-Bromo-4-f3-cvano-2-methvl-5-oxo-7-propvl-lA5.6.7,8-hexahvdro-quipolin-4-vl)-6-ethoxv-phenoxvmethvl1-benzoic acid A mixture of the product of example 6b (2.96 g) and 2N NaOH (5 ml) in dioxane (100 ml) was stirred for 3 days. The reaction mixture was poured in water followed by addition of 4N HCl until pH 2 and extraction with ethyl acetate. The organic layer was washed with brine, dried (MgS04), filtered and concentrated in vacuo. Yield: 3.0 g. MS-ESI: [M+H]^-579/581 (d). 3-r2-Bromo-4-r3-cvano-2-methvl-5-oxo-7-propvl-l,4,5,6,7.8-hexahvdro-quipolin-4-ylV6-ethoxv-phenoxvmethvll-iV"-ethvl-A^-f2-hvdrQXv-ethvlVbenzamide A mixture of the product of example 6c (90 mg), 2-ethylamino-ethanol (49 pi) and TBTU (82 mg) in dichloromethane (5 ml) was stirred for 4h. The reaction mixture was washed with sat. NaHCOs, dried (MgS04) and concentrated in vacuo. The residue was purified by preparative HPLC (0 -^ 90% acetonitrile, 0.1% TFA). Yield: 43 mg. MS-ESI: [M+H]^ = 650/652; anal. HPLC: Rt = 19.96 min (diast 1), Rt = 20.22 min (diast 2) (method 2). Diast. ratio: 3:1 Example 7 4-{3-BTomo-4-r3-f3.6-dihvdTO-2iJ-pvridine-l-carbonvlVbeDzvloxv1-5-etfaoxv-ph 2-methvl-5"Oxo-7-prot>vl-l,4.5,6J,8-hexahvdro-quinoline-3-c^boDitrile Coupling of the compound described in exaniple 6c witii 1,2,3,6-tetrahydro-pyridine (47 pi) and TBTU (82 mg) was performed according to the method described in example 6d. Yield: 61 mg, MS-ESI: [M+H]^ = 644/646; anal. HPLC: Rt - 23.48 min (diast 1), Rt = 23.75 min (diast 2) (method 2) Diast ratio: 3:1 Example 8 l3-r2"Bromo-4-f3-cvano-2-methvl-5-oxo-7-propvl-L4.5,6J,8-hexahvdrD-quinolin-4-vl)-6-ethoxv-phenoxvmethvl'|-phenoxv)-acetic acid tert-hntvl ester (a). 3-Bromomethvl-phenol At 0 ^C and under a nitrogen atmosphere catbontetrabromide (28.05 g) was added over a period of 20 min to a suspension of 3-hydroxybenzylalcohol (7 g) and ""triphenylphosphine (22.18 g) in dichloromethane (250 ml). After stirring for 1 h at O^^C, the reaction mixture was concentrated in vacuo. The residue was chromatographed on silica gel in heptane/ethyl acetate == 2/1 (v/v) as eluent. Yield: 10 g. MS-ESI: [M-H]' = 184.8/186.8 (b\ 2-(3-Bromomethvl-t>henoxvVtetrahvdro-pvran At 0*^C 3,4-dihydro-2H-pyraii (9.8 ml) and a catalytic amount of pyridinium-/>-toluenesulfonate were added to a solution of the product of example 8a (10 g) in dichloromethane (300 ml). After stirring for 1.5 h at room temperature, the reaction mixture was diluted with dichloromethane and washed with sat. NaHCOs and brine. The organic layer was separated, dried (MgS04), filtered and concentrated in vacuo. The residue was chromatographed on silica gel in heptane/ethyl acetate = 4/1 (v/v). Yield: 13.6 g. (c\ 3-Bromo-5-ethoxv-4-r3-ftetrahvdro-pvran-2-vloxvVbenzvloxv1-benzaldehvde Alkylation of 3-ethoxy-4-hydroxy-5-bromo-benzaldehyde (11.19 g) with the product of example 8b (13.6 g) was performed according to the method described in example la. The residue was chromatographed on silica gel in heptane/ethyl acetate - 3/1 (v/v) as eluent. Yield: 17.8 g. MS-ESI: [M+H]^ = 435/437 (d). 4- l3-Bromo-5-ethoxv-4-r3-ftetrahvdro-pvran-2-vlQXvVbeiizvloxv -2- meihvl-S-oxo-7-propvl-lA5,6J,8-hexahvdro-Qiikolme-3"Carbcmtrile The title compound was prepared according to the method described in example lb, using the product of example 8c (5.5 g), 3-aminocrotonitrile (1 g) and 5-propylcyclohexane-l,3-dione (1.95 g). Yield: 6.4 g. MS-ESI: [M+H]^ = 635.4/637.4 (e). 4-r3-Bromo-5-ethoxv-4-f3-hvdroxv-benzvloxvVphenvl1-2-methvl-5-oxo-7"propvl-L4,5.6,7,8"hexahvdro-QuiDoliDe-3-carbonitrile Oxalic acid was added to a solution of the product of example 8d (6.4 g) in methanol (135 ml) and water (15 ml) to pH 2. After stirring at 55^C for 2 h, the reaction mixture was concentrated in vacuo. The residue was dissolved in ethyl acetate and washed with water, sat. NaHCOs and brine. The organic layer was separated, dried (MgS04), filtered and concentrated in vacuo. Yield: 5.5 g. MS-ESI: [M+H]"" = 551.2/553.2 (f). (3-r2-Bromo-4-r3-cyano-2-methvl-5-oxo-7-propvl-l,4,5,6.7,8-hexahvdro-quinolin-4-vlV6-ethoxv-i>henoxvmethvll-phenoxvl-acetic acid ^er^-butyl ester A mixture of the product of example 8e (100 mg), tert-butyl bromoacetate (105 mg) and CSCO3 (355 mg) in dioxane (7 ml) was stirred at 80**C under a nitrogen atmosphere for 18 h. The reaction mixture was diluted with ethyl acetate and washed with water, sat. NaHCOa and brine. The organic layer was separated, dried (MgS04), filtered and concentrated in vacuo. The residue was purified by preparative HPLC (50 -^ 100% acetonitrUe). Yield: 34.5 mg. MS-ESI: [M+H]'" = 665.4/667.4; anal. HPLC: Rt= 10.16 min (diastl), 10.55 min (diast2) (method 3) Diast, ratio: 5:1 Example 9 JV^{3-r2-Bromo-4-(3-cvano-2-methvl-5-oxo-7-T)ropvl-lA5,6J,8-hexahvdrD-quiDolin^ 4-vl)-6-ethoxv-phenoxvmethvl1-phenvU-2-(3-Pvrrn1idtn-1-Yl-propvlaminQ)-acetemid Reaction of the product described in example 3a (lOOmg) with 3-pyrrolidin-l-yl-propylamine (191 mg) was performed according to the method described in example 3b. Yield: 32 mg (as TFA salt). MS-ESI: [M+H]^ = 718.6/720.6; anal. HPLC: Rt = 7,24 min (method 2). Example 10 {3-fBenzyl-methy1-aiTiiTio)TJy-{3-r2--bromo-4-f3--cvano-2-me1hvl-5-oxo-7-propvl-1.4,5.6J,8-hexahvdro-quinolin-4-vlV6-ethoxv-phenoxvmethvl]-phenvU-propionaTTiide (a). iV-(3-r2"Bromo-4-f3-cvano-2-methvl-5-oxo-7-propvl-1.4.5,6,7,8-hexahvdro- quinolin-4"VlV6-ethoxv-phenoxvmethvn"phenvl}-acrylaTnide To a solution of the product of example Ic (1.5 g) in dichloromethane was added acryloylchloride (222 pi) and DIPEA (2.38 ml). After stiiring for 18 h, the reaction mixture was washed with water. The organic layer was separated, dried (MgS04), filtered and concentrated in vacuo. Yield: 1.65 g. ESI-MS: [M+H]"^ = 604.2/606.2 (b). (3-ffienzvl-methvl-aminoVAr-|3-r2-bromo-4-('3-cvaDO-2--methvl-5-oxo-7-propvl-L4J.6J.8-hexahvdro-qiiinolin-4"VlV6-ethoxv-phenoxvmeihvll-DhenvU-OTOpionatDide A mixture of the product of exaniple 10a (150 mg) and N-methyl-benzylamine (300 mg) in TEIF (2.5 ml) was sthred for 18 h. The reaction mixture was concentrated in vacuo. The residue was dissolved in ethyl acetate and washed with water. The organic layer was separated, dried (MgS04), filtered and concentrated in vacuo. The residue was purified by preparative HPLC (10 -^ 90% acetonitrile, 0.1% TFA). Yield: 34 mg (as TFA salt). MS-ESI: [M+H]^ = 725,4/727.4; anal. HPLC: Rt = 14.32 min (diastl), Rt = 14.58 min (diast2) (melhod 2) Example 11 3-rBis-f2-methoxv-ethvlVamino1-Ar-(3-r2-bromo-4-f3-cvano-2-methvl-5-oxo-7-propvl-1.4.5,6,7,8-hexahvdro-auinolin-4-vl)-6-ethoxv-T)henoxvmethvn-phenvl}-oropionamide The title compound was obtained according to the method described for example 10b, startmg from Bis-(2-methoxy-ethyl)-amine (319 mg) and the product of example 10a (150 mg). Yield: 30 mg (as TFA salt), MS-ESI: [M+H]^ = 737.4/739.4; anal. HPLC: Rt = 13.24 min (method 2). Example 12 4-l3-Bromo-5-ethoxv-4-r3-fpvridin-2-vlmethoxvVbenzvloxv1-phenvU-2-metbvl-5-oxo-7-propvl-1.4.5,6J,8-hexahvdro-quinoline-3-carbonitrile A mixture of the product of exanrple 8e (100 mg), 2-picolylchloride hydrochloride (31.2 mg) and CsCOs (124 mg) in DMF (7 ml) was stirred at 60'C under a nitrogen atmosphere for 18 h. The reaction mixture was diluted with ethyl acetate and washed with water, sat. NaHCOs and brine. The organic layer was separated, dried (MgS04), filtered and concentrated in vacuo. The residue was purified by preparative HPLC (0 -^ 100% acetonitrile, 0.1% TFA). Yield: 19.6 mg (as TFA salt). MS-ESI: [M+H]^ = 642.1/644.1; anal. HPLC: Rt = 17.24 min (method 2). Example 13 4- (3-Bromo-5-etiioxv-4-r3-f4-fluoro-benzvloxvVbenzvloxv1-phenvU -2-methvl-5-oxo-7-propvl-L4,5,6,7,8-hexahvdro-quinoline-3-carbonitrile The title compound was obtained according to the method described for example 12, starting firom 4-fluoro-benzylbromide (23,7 |j]) and the product of example 8e (100 mg). The residue was purified by preparative HPLC (50 -> 100% acetonitrile). Yield: 58.9 mg, MS-ESI: [M+H]^ - 659.2/661.2; anal. HPLC: Rt = 14.38 min (diastl), Rt = 14.90 min (diastZ) (method 3). Diast ratio: 5:1 Example 14 4-l3-Bromo-443-f2-diethvlamino-ethoxvVbenzvloxv1"5-ethoxv-phenvU-"2-methvl-5-oxo-7-T>ropvl-1.4,5.6,7.8-hexahvdro-qianoline-3-carbonitrile The title compound was obtained according to the method described for exaniple 12, starting from 2-diethylaminoethylchlQride hydrochloride (32,7 mg) and the product of example 8e (100 mg). The residue was purified by preparative HPLC (0 —> 100% acetonitrile, 0.1% TFA). Yield: 62.9 mg (as TFA salt). MS-ESL [M4-H]^= 650,4/652,4; anal. HPLC: Rt = 13.35 min (diast 1), Rt = 13,70 (diast 2) (method 2), Example 15 2- {3-r2-Bromo-4-r3-cvano-2-methvl-5-oxo*7-propvl-l ,4,5,6,7,8-hexahvdro-quinolin> 4-vl)-6-ethoxv-phenoxvmethvn -nhenoxv) -JVL/V-dimethvl-acetamide The title compound was obtained according to the method described for example 12, starting from 2-chlorO"iV;7^-dimethylacetamide (19.6 pJ) and the product of example 8e (100 mg). The residue was purified by preparative HPLC (0 —> 100% acetonitrile). Yield: 53.8 mg. MS-ESI: [M+H]^ = 636.4/638.4; anal. HPLC: Rt - 20.44 min (diastl), Rt = 20.77 min (diast2) (method 2), Diast, ratio: 5:1 Example 16 4-(3-Bromo-5-ethoxv-4-['3-f2-methoxv--ethoxvVbenzvloxvl-phenvl)-2-methvl-5-oxo- 7-proT?vl'L4.5,6,7.8-hexahvdro-qumoline-3-carbonitrile A mixture of the product of example 8e (100 mg), 2-methoxyethanol (29 pJ), diefhylazodicarboxylate (57 pi) and tr^jhenylphosphine polymer bound (122 mg) in dichloromethane (6 ml) was stirred under a nitrogen atmosphere for 54 h. The reaction mixture was filtered and concentrated in vacuo. The residue was purified by preparative HPLC (50 -> 100% acetonitrile). Yield: 15 mg. MS-ESI: [M+H]^ = 609.2/611.2; anal. HPLC: Rt = 7.66 min (method 3). Example 17 4-(3-BTomo-5-ethoxv-4-r3-r2-inorpholin-4-vl-2-oxo--ethoxv)-ben2vloxv1"Phenvll-2-methvl-5-oxo-7-propvl-L4,5.6J,8-hexahvdTO-quinoline-3-carbonitrile (a). {3-r2-Bromo-4-r3-cvano-2-methvl-5-oxo-7-propvl-L4,S,6J,8-hexahvdro-aum-oliD-4-vl)"6-ethoxv-phenoxvme1favl1-phenoxv) -acetic acid A mixture of the coir5)Ound of example 8f (620 mg) in dichloromethane (45 ml) and trifluoracetic acid (5 ml) was stirred for 4 h. The reaction mixture was diluted with dichloromediane, washed with water and brine. The organic layer was separated, dried (MgS04), filtered and concentrated in vacuo. Yield: 553 mg. MS-ESI: [M+H]"" = 609,2/611.2 (b). 4-(3-Bromo-5-ethoxv-4-r3-r2-morDholin-4-vl-2"Oxo-ethoxv>-benzvloxvl-phenvl>-2-methvl-5-oxO"7-propvl-1.4,5,6J,8-hexahvdro-qirinoline-3-carbonitrile Coi5)ling of the compound described in example 17a (79 mg) with morpholine (34 jil) and TBTU (62 mg) was performed according to the method described in example 6d. Yield: 50,5 mg. MS-ESI: [M+H]^ = 678.4/680.4; anal, HPLC: Rt = 16.29 mm (diastl), Rt = 16.65 (diast2) (method 1), Diast ratio: 5:1 Example 18 2-(3-r2-Bromo-4-r3-cvano-2-methvl-5-oxo-7-propvl-L4,5,6.7,8-hexahvdro-quinolin-4-vl)-6-ethoxv-nhenoxvmethvll-T)henoxv>-JSr-thiophen-2-vlmethvl-acetamide Coi5)ling of the compound described in example 17a (75 mg) with 2-thiophenemethylamine (38 |il) and TBTU (59 mg) was performed according to the method described in example 6d. The residue was purified by preparative HPLC (40 -^ 100% acetonitrile). Yield: 45.7 mg. MS-ESI: [M+H]"" = 704.4/706.4; anal. HPLC: Rt = 6.96 min (method 3). Example 19 J\r-|2-r2-Bromo-4-(3-cvano-2-methvl-5-oxo-7-pronvl-1.4.5,6J,8-hexahvdro-quinolin-4-vl)-6-ethQxv-phenQxvmethvn-phenvI} -2-pvrrolidin-1 - vl-acetamide fay 3-Bromo-5-ethoxv-4-f2-nitro-benzvloxvVbenzaldehvde Alkylation of 3-bromo-5-ethoxy-4-hydroxybenzaldehyde (5 g) with 2-nitrobenzylbromide (4.85 g) was performed according to the method described in example la. Yield: 7.88 g. MS-ESL- [M+H]^ - 380/382 (b). 4-r3-Bromo-5-ethoxv-4-f2-nitro-benzvloxvVphenvlV2-methvl-5-oxo-7-propvl-1.4,5,6,7,8-hexahvdro-quinoline-3-carbonitrile The title compound was prepared according to the method described in example lb starting fi-om the product of example 19a (7.88 g), 3-aminocrotonitrile (1.7 g) and 5-propylcyclohexane-l,3-dione (3.2 g).Yield: 8.54 g. MS-ESL [M+H]^ = 580.2/582.2 (c), 4-r4-(2-Ammo-beDzvloxvV3-bromo-S-ethoxv-phenvl1-2"methvl-5-oxo-7-pr^^ 1,4,5,6,7,8-hexahvdro-Qiunoline-3-cafboDitrile At 0**C Zinc dust (9.01 g) was added portion wise to a solution of the product of example 19c (6,9 g) and acetic acid (5.9 ml) in THF (150 ml). After stirring at O^^C for 1 h and at room temperature for 2 h, the reaction mixture was filtered, diluted with dichloromethane and washed with sat NaHCOa and brine. The organic layer was separated, dried (MgS04), filtered and concentrated in vacuo. Yield: 3.66 g. MS-ESI: [M+H]^ = 550.2/552.2 (d). 2"Bromo-JV-(2-r2-bromo-4-r3-cvano-2"methvl-5-oxo-7-propvl-L4,5,6,7,8"hexa-hvdro-quinolin-4-vlV6-ethoxy-pheDOXvmethvl1-phenyl}-acetamide Reaction of bromoacetyl chloride (0.546 ml) with tiie product of example 19c (1.2 g) was preformed according to the method described for example 3a. Yield: 1.36 g. MS-ESI: [M+H]^ = 626.2/628.2 (e). JV^|2-r2-Bromo-4-f3-cvano-2-methvl-5-oxO"7-propvl-1.4,5,6J,8"hexahvdro-quin-olin-4-vl)-6-ethoxv-phenoxvmethvl1 -phenyl) -2-pvrrolidin-1 -vl-acetamide A mixture of the product of example 19d (136 mg) and pyrrolidiae (181 \}1) in THF (5 ml) was stirred for 54 h. The reaction mixture was diluted with ethyl acetate and washed with water, sat. NaHCOs and brine. The organic layer was dried (MgS04), filtered and concentrated in vacuo. The residue was purified by preparative HPLC (10 -> 100% acetonitrile, 0.1% TFA). Yield: 51.8 mg (as TFA salt). MS-ESI: [M+H]^ = 661.4/663.4; anal. HPLC: Rt = 13.58 (method 2) Example 20 N' (2-r2-Bromo-4-f 3-cvano-2-methvl-5-oxo-7-propvl-1,4,5,6,7,8-hexahvdro-quinoliD- 4-vlV6-ethoxv-nhenoxvmethvl1-phenvU-2-rr2-dimethvlamino-ethvl)-methvl-amino1- acetamide The title compound was prepared according to the method described in example 19e starting fi-om the product of example 19d (136 mg) and Ar^^-trimethyl-ethane-1,2" diamine (277 pi). Yield: 41 mg (as TFA salt). MS-ESI: [M+H]^ = 690.4/692.4 ; anal HPLC: Rt = 12.14 min (diast 1), Rt - 12.46 (diast 2) (method 2). Diast. ratio: 7:1 Example 21 4-r3-Bromo-5-ethoxv-4-f2-methvlsulfanvl-pvrtmidin-4-vlmethoxvVphenvl1-2-methyl-5-oxo-7-propvl-1.4.5,6,7.8-hexahvdro-quinoline-3-carbomtrile U\ 5-Bromo-2-methvlsulfanvl-pvrimidine-4-carboxvlic acid At 5^C triethylamine (16.9 ml) was added dropwise to a solution of mucobromic acid (10.31 g) and 2-niethyl-isothiourea (11.13 g) in water (200 ml). After stiiring at 5^C for 3 h, the reaction mixture was allowed to warm up (room temperature) and stirring was continued for another 54 h. The reaction mixture was acidified with cone. HQ (33%). The title product was obtained by filtration. Yield: 4.1 g. MS-ESI: [M+H]^ = 249/251 (h\ 2-Methvlsulfanvl-Pvrimidine-4-carboxvlic acid The product of example 21a (517 mg) in methanol (25 ml) was hydrogenated in a PARR ^jparatus in the presence of KOH (260 mg) and 10% Pd on BaS04 (260 mg) for 4 h. The reaction noixture was filtered over decalite and washed with methanol (warm). The filtrate was concentrated to 50% of its volume followed by addition of cone. HCl (33%) to pH 1. The precipitate (KBr) was filtered off and the mother liquor was concentrated in vacuo. The residue was recrystallized from dioxane. Yield: 200 mg. MS-ESI: [M+H]^ = 170 (c). 2-Methvlsulfanvl-T)VPTnidiTi-4-vlVinethanol At O^'C oxalyl chloride (295 pi) was added to a solution of DMF (91.2 pi) in dichloromethane (2 ml). After stirring at 0*^C for 1 h, the reaction mixture was concentrated in vacuo. The residue was dissolved in acetonitrile (2 ml) and THF (3 ml), followed by portion wise addition of the product of example 21b (200 mg) at O^C in a nitrogen atmosphere. After stirring at 0*^C for 15 min, the reaction mixture was cooled (-78^C) and 2M NaBH4 in DMF (590 pi) was added. After stirring at -20*^0 for 3 h, the reaction mixture was quenched with 2N HCl and concentrated in vacuo. The residue was dissolved in water and the remaining solution was adjusted to pH 11 with 2N NaOH, followed by extraction with dichloromethane. The organic layer was separated, dried (MgS04), filtered and concentrated in vacuo. Yield: 180 mg. MS-ESI: [M+H]'^ = 156 (d\ 3-Bromo-S-ethoxv-4-r2-methvlsulfanvl-pvrtniidin-4-vlmethoxvVbenzaldehvde A mixture of the product of example 21c (180 mg), 3"bronx)-5-ethoxy-4-hydroxy benzaldehyde (289 mg), triphenylphosphine polymer bound (393 mg) and diethylazodicarboxylate (186pl) in dichloromethane (25 ml) was stirred for 18 h. The reaction mixture was filtered off and the filtrate concentrated in vacuo. The residue was chromatographed on silica gel in heptane/ethyl acetate = 3/2 (v/v) as eluent. Yield: 98 mg. MS-ESI: [M+H]"' = 383/385 (e). 4-r3-Bromo-5-ethoxv-4-('2-methvlsulfanvl-pvrimidin-4-vhnethoxvVphenvl]-2-methvl-5-oxo-7-T>ropvl-L4,5,6,7,8-hexahvdro-quinoline-3-carbonitrile The title compoimd was prepared according to the method described in example lb starting from the product of example 22d (49 mg), S-aminocrotonitrile (11 mg) and 5-propylcyclohexane-l,3-dione (20 mg). The residue was purified by preparative HPLC (0 -> 100% acetonitrile, 0.1% TFA). Yield: 24 mg (as TFA salt). MS-ESI: [M+H]^ = 583.2/585.2; anal. HPLC: Rt = 25.06 min (diastl), Rt = 25.51 min (diast2) (method 2). Diast. ratio: 4:1 Example 22 Furan-2-carboxvlic acid l2-r2"bromo-4-f3-cvanO"2-methvl-5-oxo-7-propvl"l,4.5,6,7,8- hexahydro-quinoIin-4-yl)-6-ethoxy-phenoxvmethvl]-phenvl}-amide A mixture of the product of example 19c (100 mg), 2-furoylchloride (36 isl) and DIPEA (159 fil) in dichloromethane (5 ml) was stirred for 16 h. The reaction mixtare was diluted with dichloromethane and washed with sat. NaHCOs. The organic layer was separated, dried (MgS04), filtered and concentrated in vacuo. The residue was purified by preparative HPLC (20 -> 100% acetonitrile). Yield: 67 mg. MS-ESI: [M+H]^ = 644.4/646.4; anal. HPLC: Rt = 20.19 min (method 1), Example 23 jy-|2-r2-Bromo-4-f3-cvano-2-methvl-5-oxo-7-propvl-L4,5,6,7,8-hexahvdro-qxmiolin-4-vlV6-ethoxv-phenoxvmethvl]-phenvl} -acrylamide Reaction of the product of example 19c (100 mg) with acryloylchloride (29 pi) in the presence of DIPEA (159 pi) was performed according to the method described in example 22. Yield: 51.1 mg, MS-ESI: [M-fH]^ = 604.4/606.4; anal. HPLC: Rt = 19.01 min (diastl), Rt = 19.42 mm (diast2) (method 1). Diast. ratio: 9:1 Example 24 Cvclopropanecarboxvlic acid {2-r2-bromo-4-f3-cvano-2-methvl-5-oxo-7-propvl-L4.5.6J,8-hexahvdro-quinolin-4-vl)-6-ethoxv-pheDoxvmethvn-phenvU-amide Reaction of Ihe product of example 19c (100 mg) with cycloprqpanecarbonylchloride (33 pi) in the presence of DIPEA (159 pi) was performed according to the method described m example 22. Yield: 52.1 mg. MS-ESI: [M+H]^ = 618.2/620.2; anal. HPLC: Rt = 20.30 min (diastl), Rt = 20.71 min (diast2) (method 1). Diast ratio: 7:1 Example 25 2-r2-Bromo-4-(3-cvano-2-methvl-5-oxo-7-propy]-L4,5,6,7,8-hexahydro-quinolin-4-vlV6-ethoxv-phenoxvmethvll"phenvU-carbamic acid methvl ester Reaction of the product of example 19c (100 mg) with methylchlorofonnate (28 jU) in the presence of DEPEA (159 pi) was performed according to the method described in example 22. Yield: 65.9 mg. MS-ESI: [M+H]^ = 608.2/610.2; anal. HPLC: Rt = 21.37 min (diastl), Rt = 21.87 min (diast2) (method 1). Diast. ratio: 11:1 Example 26 2-r2-Bromo-4-f3"CvanO"2-methvl-5-oxo-7-propvl-l,4,5,6.7.8-hexahvdro-quinolin-4-vD-6-ethoxv-t)henoxvmethvn-T)henvll-carbamic acid isobutvl ester Reaction of the product of example 19c (100 mg) with isobutyl chloroformate (47 pi) in the presence of DIPEA (159 pi) was performed according to the method described in example 22. Yield: 70 mg. MS-ESI: [M+H]^ = 650.4/652.4; anal. HPLC: Rt= 26.84 min (diast), Rt = 27.26 mm (diast2) (method 1), Diast. ratio: 7:1 Example 27 2-r2-Bromo-4-(3-cvano-2-methvl"5-oxo-7-propvl-1,4,5.6,7,8-hexabvdro-quinolin-4-vl)-6-ethoxv-phenoxvmethvn-fi3ran-3-caTboxvlic acid methyl ester (a). 2-(2-Bromo-6-ethoxv-4-formvl-phenoxvmethvlVfiiran-3-carboxvlic acid methyl ester Alkylation of 3-bTomo-5-ethoxy-4-hydroxy benzaldehyde (123 mg) with 2-bTomomefliyl-furan-3-carboxylic acid methyl ester (109 mg) was performed according to the method described in example la. Yield: 191 mg. MS-ESI: [M+H]^ = 383/385 (b). 2-r2-Bromo-4-f3-cyano-2-methyl-5-oxo-7-propyl-1 A5.6.7,8-hexahvdro-quinolin-4-yl)-6-ethoxv-phenoxvmethyl1-fi3ran-3-carboxylic acidmethvl ester The title compound was prepared according to the method described in example lb starting from the product of example 27a (191 mg), 3-aminocrotonitrile (41 mg) and 5-propylcyclohexane-l,3-dione (77 mg). The residue was purified by preparative HPLC (10 -> 90% acetonitrile). Yield: 168 mg. MS-ESI: [M+H]"" = 583/585; anal. HPLC: Rt = 23.06 min (diastl), Rt = 23.43 min (diast2) (method 2). Diast. ratio: 4:1 Example 28 Propane-1-sulfonic acid l2-r2-bromo-4-r3-cvano-2-methvl-5-oxO"7-propyl-l,4.5.6,7.8-hexahvdro-quinolin-4-ylV6-ethoxv-phenoxymethyll-phenyU-amide Propane-1-sulfonyl chloride (31 pi) and pyridine (44 pi) were added to a solution of the product of example 19c (100 mg) in dichloromethane (3 ml). After stirring for 18 h, the reaction mixture was diluted with dichloromethane and washed with sat. NaHCOa. The organic layer was separated, dried (MgS04)5 filtered and concentrated in vacuo. The residue was purified by preparative HPLC (20 -> 100% acetonitrile). Yield: 52.7 mg. MS-ESI: [M+m^ = 656.4/658.4; anal. HPLC: Rt = 22.36 min (diastl), Rt = 22.72 min (diast2) (method 1). Diast. ratio: 7:1 Example 29 4-[2-Bromo-4-f 3-cvaDo-2-methvl-5-oxo-7"propvl-1,4,5,6,7,8-hexahvdrD-qumolip-4-vlV6-e1hoxv-pheaioxvmethvll-JV-f2-melhoxv-ethvl)"benzainide f aV 4-r2-Bromo-6-ethoxv-4-fonnvl-phenoxvmethvl)-beDzoic acid methyl ester Alkylation of 3-bromo-5-ethoxy-4-hydroxy benzaldehyde (4 g) with 4-bromomethyl-benzoic acid methyl ester (3.73 g) was performed according to the method described in example la. Yield: 6.4 g. MS-ESI: [M+H]^ = 393/395 (b). 4-f2-Bromo-4-r3-cyano-2-methvl-5-oxo-7-propyl-lA5,6,7,8-hexahydro-quiDolin-4-ylV6-ethoxy-phenoxymethvl1 "benzoic acid methyl ester The title compound was prepared according to the method described in example lb starting from the product of example 29a (6.4 g), 3-aminocrotonitrile (1.34 g) and 5-propylcyclohexane-l,3-dione (2.51 g). Yield: 6.74 g. MS-ESI: [M+H]^ = 593/595 (c). 4-[2"Bromo-4-r3-cvano-2"methvl-S-oxo-7-proT>vl-L4,5,6J.8-hexahydro-quinolin-4-ylV6-ethoxv-phenoxvmetfayl')-benzoic acid A mixture of the product of example 29b (6.5 g) and 2N NaOH (1L3 ml) in dioxane (400 ml) was stirred at 50^C for 18 h. The reaction mixture was poured in water and in addition 4N HCa was added until pH 2, followed by extraction with ethyl acetate. The organic layer was washed with brine, dried (MgS04)3 filtered and concentrated in vacuo. Yield: 6.4 g. MS-ESI: [M+H]^= 579/581 (d). 4-r2-Bn)mo-4-f3-cyano-2-metbvl-5-oxo-7-propv]-1.4,5,6J,8-hexahydro-quinolin-4-ylV6-ethoxv-phenoxvmethyn^iV"-r2-methoxv-ethyl')-benzamide Coupling of the compound described in example 29c (100 mg) with 2-meihoxy-ethylamine (44pl) and TBTU (82 mg) was performed according to the method described m example 6d. Yield: 70 mg. MS-ESI: [M+H]^ = 636.4/638.4; anal. HPLC: Rt = 19.25 min (diastl), 19.55 min (diast2) (method 2). Diast ratio: 4:1 (HPLC) Example 30 4-{3-Bromo-5-ethoxv-4-('3-fisobutylamino-methyl)-beDzvloxv1-phenyl>-2-methyl-5-oxo-7-propyl-l,4.5,6,7.8-hexahydro-quinoline-3-carbQnitrile (a). 4-r3-Bromo-5-ethoxy-4-hydroxv-phenyl)-2-melhyl-5-oxo-7-propyl-l,4.5.6,7,8-hexahydro-quinoline-3-carbonitrile The title compound was prepared according to the method described in example lb starting from 3-bromo-5-ethoxy-4-hydroxy-benzaldehyde (6 g), 3-aminocrotonitrile (2.01 g) and 5-propylcyclohexane-l,3-dione (3.8 g). The reaction mixture was cooled (O'^C) and liie title compound was filtered off and washed with ethanol (cold). Yield: 6.3 g. MS-ESI: [M+H]^ = 445/447 (b), 4-r3-Bromo-4-f3-bromomethvl-benzvloxvV5-ethoxv-phenvn-2-methvl-S-oxo-7-propvl-1.4,5,6,7.8-hexahvdro-quinoline-3-carbonitrile A mixture of the product of example 30a (L96 g), a,a,-dibromo-m-xylene (9.31 g) and K2CO3 (1.22 g) in DMF (100 ml) was stirred at 60^C under a nitrogen atmosphere for 2 h. The reaction mixture was diluted with ethyl acetate and washed with water , sat. NaHCOa and brine. The organic layer was dried (MgS04), filtered and concentrated in vacuo. The residue was chromatographed on silica gel in heptane/ethyl acetate = 1/2 (v/v). Yield: 2.52 g MS-ESI: [M+H]^ = 627.4/629.4/631.4; anal, HPLC: Rt = 17.71 min (diastl), 18.07 min (diast2) (method 6). Diast ratio: 4:1 (c). 4-13-Bromo-S-ethoxv-4-r3-fisobutvlaanino-methvlVbenzvloxvl-phenvU-2-methvl-5-oxo-7-propvl-l,4,5.6,7,8-hexahvdro-quinoline-3-carbonitrile A mixture of the product of example 30b (100 mg) and iso-butylamine (79pl) in acetonitrile (5 ml) was stirred for 18 h. The reaction mixture was concentrated in vacuo; the residue was dissolved in dichloromethane and washed with sat. NaHCOs. The organic layer was separated, dried (MgS04)5 filtered and concentrated in vacuo. The residue was purified by preparative HPLC (0 -^ 100% acetonitrile, 0.1% TFA). Yield: 76 mg (as TFA salt). MS-ESI: [M+H]^ = 620.4/622.4; anal. HPLC: Rt - 13.56 min (diastl), Rt = 13.85 min (diast2) (method 2), Diast. ratio: 3:1 Example 31 4-r3-Bromo-5-ethoxv-4-r3-irfpvridin-4-vlme&y1)-aTniTio]-methvn-beDzvloxvV phenvn-2-methvl'5-oxo-7-propvl-L4.5,6J,8-hexahvdro-quinoline-3-carbonitrile The title compound was prepared according to the method described in example 30c starting firom the product of example 30b (100 mg) and 4-(aminomethyl)pyridine (Slpl) in acetonitrile (5 ml). Yield: 41 mg (as TFA salt). MS-ESI: [M+H]"" = 655.2/657.2; anal, HPLC: Rt = 8.08 min (method 2). Diast. ratio: 3:1 Example 32 4-r4-f3-Aminomethvl-benzvloxvV3-bromo-5-ethoxv-phenvll-2"methvl-5-oxo-7-pronvl-l,4,5,6,7.8-hexahvdrO'quinoline-3-carbonitrile (a). 4-r4"f3-A2idome1favl"beDzvloxvV3-broiDO-5-ethoxv-phenvl1-2>-inethvl-5"OXO-7-proi)vl-l,4.5,6,7.8-hexahvdro-qumolme-3-caAomtrile A mixture of the product of example 30b (250 mg) and NaNs (78 mg) in DMF (10 ml) was stirred for 2 h. The reaction mixture was poured in water and the precipitate was filtered off, washed with water and dried in vacuo (50*^0). Yield: 197 mg. MS-ESI: [M+H]"" = 590.4/592.4; anal. HPLC: Rt = 23.72 min (diastl), Ry = 24.12 min (diast2) (method 1). Diast. ratio: 3.5:1 (b). 4-r4-f3-Aminomethvl-benzvloxv)-3-bromo-5-e1faoxv-phenvll-2-methvl-5-oxo-7-propvl-l,4,5,6J.8-hexahvdro-qiiinoline-3-carbonitrile A mixture of the product of example 32a (133 mg), triphenylphosphine polymer bound (150 mg) and 10 drops of water in THF/dichloromethane = 2:1 (v/v) was stirred at 40°C for 18 h. The reaction mixture was filtered and concentrated in vacuo. The residue was purified by preparative HPLC (0 -^ 100% acetonitrile, 0.1% TFA). Yield: 197 mg (as TFA salt). MS-ESI: [M+H]^ = 564.2/566.2; anal. HPLC: Rt = 10.31 min (diastl), Rt = 10.58 min (diast2) (method 2), Diast. ratio: 3:1 Example 33 4-r3-Bromo-5-ethoxv-4-r3-hvdroxvmethvl-benzvloxv)-phenvll-2"methvl-5-oxo-7-propvl-L4,5,6,7,8-hexahvdro-quinoline-3-carbonitrile A mixture of the product of example 30b (100 mg) and CaCOa (80 mg) in dioxane/water = 1/1 (v/v) was stirred at lOO^C for 18 h. The reaction mixture was diluted with dichloromethane followed by addition of 2N HCl. The organic layer was separated, washed with sat. NaHCOs, dried (MgS04), filtered and concentrated in vacuo. The residue was purified by preparative HPLC (20 —> 100% acetonitrile). Yield: 44 mg. MS-ESI: [M+H]"" = 565.2/567.2; anal. HPLC: Rt = 15.96 min (diastl), Rt = 16.33 min (diast2) (method 1). Diast ratio: 4:1 Example 34 1 - l2-r2-Bromo-4-f 3-cvano--2-methvl-5-oxo-7-propvl-1,4,5,6,7,8-hexahydrn-qninnliTi-4-vn-6-ethoxv-phenQxvmethvl]-phenvn-3-metfavl-urea A mixture of the compound of example 19c and 4-nitrophenyl chloroformate (55 mg) in dichloromethane (4 ml) was stirred for 2 h. Meihylamine (2.7 ml, 2M in THF) was added and stirring was continued for another 3 h. The reaction mixture was diluted with dichloromethane and washed with sat. NaHCOs. The organic layer was separated, dried (MgS04), filtered and concentrated in vacuo. The residue was purified by preparative HPLC (20 -^ 100% acetonitrile). Yield: 54 mg. MS-ESI: [M+H]^ = 607.2/609.2; anal. HPLC: Rt = 15.88 min (diastl), Rt = 16.18 min (diast2) (method 1). Diast. ratio: 8:1 Example 35 Piperazine-1 -carboxvlic acid {2-r2-bromo-4-f 3-cvaiio-2-methvl-5-oxo-7-propvl-1,43,6 J.8-hexahvdro-QumoliD-4-vlV6-ethoxv-phenoxvmethvll-phenvll-am The title compound was prepared according to the method described in example 34 starting from the product of example 19c (150 mg), 4-nitrophenyl chlorofoimate (55 mg) and piperazine (469 mg). The residue was purified by preparative HPLC (0 —> 100% acetonitrile, 0.1% TFA). Yield: 69 mg (as TFA salt). MS-ESI: [M+H]^ = 662.2/664,2; anal, HPLC: Rt = 11,70 min (diastl), Rt = 12.04 min (diast2) (method 1). Diast. ratio: 5:1 Example 36 JV'-l3-|"2-BTomo-4-f3-cvano-2-methvl-5-oxO'7-propvl-L4,5,6.7,8"hexahvdro-quinolin-4-vn-6-ethQxv-phenoxvmethvl1-benzvll-3,3-dimetbvl-butvTamide Acylation of the product of example 32b (100 mg) with terr-bulylacetyl chloride (27|il) was performed according to the method described in example Id. Yield: 33,5 mg. MS-ESI: [M+H]^ = 662.4/664.4; anal, HPLC: Rt = 21.26 min (diastl), Rt = 21,54 min (diast2) (method 1). Example 37 {3-r2-Bromo-4-(3-cvaDo-2-methvl-5-oxo-7-propvl-L4,5,6J,8-hexahvdro-quinolin-4" vl)-6-ethoxy-phenoxvme1favll-benzvn-carbamic acid ethyl ester Reaction of the product of example 32b (100 mg) with ethylchloroformate (19 jil) in the presence of DIPEA (93 [il) was performed according to the method described in example 22. Yield: 37 mg. MS-ESL [M+H]^ = 636.2/638.2; anal. HPLC: Rt = 19.81 mm (diastl), Rt = 20.14 min (diast2) (method 1). Diast, ratio: 4.5:1 Example 38 l3-r2-BronK>-4-(3-cvano-2-methvl-5-oxo-7-propvl-L4,5,6,7,8-hexahvdrO"qiiinolin-4-vl)-6-ethoxy-phenoxvmethvn-pvridin-2-vU-carbamic acid methyl ester (a). 4-f2-Ainino-pvridin-3"Vlmethoxv)-3-bromo-5-ethoxv-benzaldehvde Mitsunobu reaction of 3-bromo-5"ethoxy-4-hydroxy benzaldehyde (490 mg) with (2-amino-pyridin-3-yl)-methanol ( 250 mg) was preformed according to the method described for example 2Id. The residue was chromatographed on silica gel in dichloromethane/methanol = 99/1 (v/v) as eluent. Yield: 500 mg. MS-ESI: [M+H]^ = 351/353. (b). 4-r4-f2-Ainino-pvridiD-3"Vlmethoxv)-3-bromo-5-ethoxv-phenvl1-2"^ 7-pTopvl-L4,5.6J,8-hexahv Tte title compound was prepared according to the method described in example lb starting from the product of example 38a (500 mg), 3-aminocrotonitrile (116mg) and 5-propylcyclohexane-l,3-dione (218 mg). Yield: 290 mg. MS-ESI: [M+H]^ = 551/553 (c). {3-r2-BTomo-4-f3-cvano-2"methvl-5-oxo-7-propvl-L4,5.6J,8-hexahvdro-Qum-olin-4-vlV6-ethoxv-phenoxvme1favl1-pvridin-2-vl}-carbamic acid methyl ester Reaction of the product of example 38b (50 mg) with methylchloroformate (8 pi) in die presence of DIPEA (47 pi) was performed according to the method described in example 22. The residue was purified by preparative HPLC (10 —► 90% acetonitrfle). Yield: 17 mg MS-ESI: [M+H]^ = 609/611; anal. HPLC: Rt = 13.82 min (diastl), Rt = 14.08 min (diast2) (method 5). Diast ratio: 7:2 Example 39 4-(3-Bromo-5-ethoxv-4- B-Ff 1 J/-imidazol-4-vhnethvl)-aminol-benzvloxv> -phenvlV2-metfavl-5-oxo-7-propvl-L4,5,6,7,8-hexahvdro-quinoline-3-carbQnitrile A mixture of the product of example Ic (100 mg), liy-imidazol-4-carbaldehyde (21 ^g)^ NaCNBRj (25 mg) and acetic acid (114|il) in methanol (3 ml) was stirred for 18 h. The reaction mixture was diluted with ethyl acetate, washed with sat. NaHCOs and brine. The organic layer was separated, dried (MgS04), filtered and concentrated in vacuo. The residue was purified by preparative HPLC (40 —> 100% acetonitrile). Yield: 13 mg. MS-ESI: [M+H]^ - 550.2/552.2; anal. HPLC: Rt = 7.27 min (method 1). Diast. ratio: 4:1. Example 40 4-r2-Bromo-4-f 3-cvano-2-methvl-5-oxo-7-propvl-1,4,5,6 J,8-hexahvdro-quinolin-4-vl)-6-ethoxV"phenoxvmetbvll-JV-f2-methoxv-ethvl)-benzenesulfonamide fa). 4 - bromomethvl-benzenesulfonvl chloride At 20 °C benzoyl peroxide (600 mg) was added to a suspension of 4-methyl-benzenesulfonyl chloride (9.5 g) and 7V-bromosuccinimide (8.9 g) in 1,2-dichloropropane (60 M), The reaction mixture was stirred at 80 'C for 2 h. The reaction mixture was concentrated and the title compound was obtained as a white solid aflier recrystallization flx)m heptane. Yield: 2.26 g. (1)14-BTomomel3ivl-iV'-r2-me1hoxv-etfavlVben2enesulfonam At 20 ^'C triethylamine (61 mg) was added to a solution of the product of example 40a (135 mg) in diethyl ether (2 ml). After 5 minutes, 2-methoxy-ethylamine (37 mg) was added. The reaction mixture was stirred at 20 ^'C for 3h and concentrated in vacuo. The residue was dissolved in dichloromethane (20 ml) and washed several times with sat. NaHCOs- The organic phasewas separated, dried (MgS04) and concentrated in vacuo. The title product was obtained as brown oil. Yield: 120 mg. MS-ESI: [M+H]"^ = 308/310. (c\ 4-[2-Bromo-4-f3-cvano-2-methvl-S-oxo-7-propvl-l,4,5.6,7,8"hexahvdro-quinolin" 4-vl),6-ethoxv-phenoxvmethvlVJV-f2-methoxv-ethvlVbenzenesulfonamide At 20 °C a solution of the product of example 40b (120 mg) in DMF (3 ml) was added to a suspension of the product of 30a (222 mg), K2CO3 (200 mg) and KI (10 mg) in DMF (7 ml). The reaction mixture was stirred at 20 °C for 16 h and poured into 10 ml sat. NaHCOa and extracted with ethyl acetate. The organic layer was concentrated, dissolved in dichloromethane and washed with water, dried (MgS04) and concentrated in vacuo. The title product was obtained via preparative HPLC (0-^90% CH3CN, 0.1% TFA). Yield: 22 mg. MS-ESI: [M+H]^ = 672/674; anal. HPLC: Rt - 21.31 min (method 2). Diast. ratio: 4:1 Example 41 4-r2-Bromo-4-(3-cvano-2-methvl-5-oxo-7-propvl-L4.5,6,7,8-hexahvdro-quinolin-4-vl)-6-eihoxv-phenoxvme1hvll-JVJV"-diethvl-benzenesulfonamide fa). 4-Bromomethvl-^^-diethyl-benzenesulfonamide The title compound was obtained analogously to example 40 b, starting firom diethylamine (37 mg) and the product of example 40a (135 mg). Yield: 122 mg, Rf (heptane/ethyl acetate (1/1, v/v)) = 0.45. MS-ESI: [M+H]^ = 306/308. (b). 4-r2-Bromo-4-r3-cvano-2-methvl-5-oxo-7-propvl-1.4,5,6,7,8-hexahvdro-qxiinolin-4-vlV6-ethoxv-phenoxvmethvl1-A^JV-diethvl-benzenesulfonamide The title compound was obtained analogously to example 40 c, starting from product of example 41a (122 mg) and the product of example 30a (222mg). Yield: 79 mg, MS-ESI: [M+m^ = 670/672; aoal. HPLC: Rt= 26,63 min (diastl), 26.93 min (diast2) (method 2). Diast. ratio: 4:1 Example 42 JV^{3-r2-Bromo-4-f3-cvano-2-methvl-5-oxo-7-T3ropvl-1.4.5.6J,8-hexahvdro-4-vlV6"eihoxv-phenoxvmethvl1-phenvU-me1iianesulfonam Sulfonylation of the product of example Ic (100 mg) with methanesulfonyl chloride (15 \d) was prefonned according to the method described in example 28. Yield: 46 mg. MS-ESI: [M+m*" = 628/630; anal. HPLC: Rt == 20.76 min (diastl), Rt - 21.01 min (diast2) (method 2). Diast. ratio: 4:1 Example 43 Thiophene-2-sulfonic acid l3-f2-bromo-4-f3-cyano-2-methvl-5"OXO-7-propvl- 1,4 J,6 J,8-hexahvdro-qumolin-4-vlV6-ethoxy-phenoxvmeflivll-phenvl} -amide Sulfonylation of the product of exan:q)le Ic (100 mg) with thiophene-2-sulfonyl chloride (36 ^1) was prefomied according to the method described in example 28. Yield: 70 mg. MS-ESI: [M+H]^ = 696.2/698.2; anal. HPLC: Rt = 23.75 min (method 2). Diast. ratio: 4:1 Example 44 4-r2-Bromo-4-(3-cvano-2-methvl-5-oxo"7-propvl-1.4,5,6J,8-hexahvdTO-quiaolin-4-vl)-6-ethoxv-phenoxvmethvn-ben2enesulfonic acid isot?ropvl ester (aV Toluene-4-sulfonic acid isopropvl ester At 0 **C, 4-methyl-benzenesulfonyl chloride (3.8 g) was added to a solution of 2-propanol (6.12 ml) in pyridine (6.6 ml). The reaction mixture was stirred at 0 °C for 2 h and then at 20 ^^C for 16 h. The reaction mixture was poured into water (150 ml) and extracted with dichloromethane. The combined organic phases were washed with 3M aqueous HCl and sat. NaHCOs. After drying (MgS04) and concentrating in vacuo, the title product was obtained as a pale yellow oil. Yield: 2.89 g. MS-ESI: [M+H]'^ = 215. fb). 4-Bromomethvl-beixzenesulfonic acid isopropvl ester At 20 °C benzoyl peroxide (48 mg) was added to a solution of the product of example 44a (956 mg) and iV-bromosuccinimide (712 mg) in deuterochloroform (5 ml). The reaction mixture was stirred at 80 °C for 3 h. The reaction mixture was poured into 20 ml of sat. NaHCOs and extracted several times with dichloromethane. The combined organic layers were dried (MgS04) and concentrated in vacuo. The title product was obtained as pale yellow oil. Yield: 1.06 g. (c). 4-r2-Bromo-4-f3-cvano-2-methvl-S-oxo-7-piopvl-l,4,5,6,7,8-hexahvdro-quinolin-4-vlV6-etiioxv-phenoxvmethvn-benzenesulfonic acid isopropvl ester The title compound was obtained analogously to example 40c, starting from the product of example 44b (293 mg) and product of example 30a (400 mg). Yield: 38 mg. MS-ESI: [M+m^ = 657/659; anal. HPLC: Rt = 22.64 min (diastl), Rt = 22.64 min (diast 2) (method 2), Diast. ratio: 10:1 Example 45 3-r2-Bromo-4-f3-cvaDO-2-methvl-5-oxo-7-proT)vl-L4.5,6,7.8-hexahvdro-Quinolin-4-vl)-6-ethoxv-T)henoxvmethvn-JV"methvl-benzenesulfonamide faV 3 - bromomethvl-benzenesulfonvl chloride The title compound was obtained analogously to example 40a5 starting from 3-methyl-benzenesulfonyl chloride (8.5 g), JV-bromosuccinmide (8.9 g) and benzoylperoxide (600 mg) in deuterochloroform (20 ml) as solvent. Yield: 3.1 g. (b\ 3-BTomomethvl-JV-methyl-benzenesulfonamide The title compound was obtained analogously to example 40b, starting from methylamine (105 mg) and the product of example 45a (269 mg) and the product of example 30a (200 mg). Yield: 220 mg. MS-ESI: [M-Me]" = 250/252 fc). 3-r2-Bromo-4-f3-cvano-2-methvl-5-oxo-7-propvl-L4,5,6,7,8-hexahvdro-quinolin-4-vlV6-ethoxv-phenoxvmethvn-JV-methvl-benzenesulfonamide The title compound was obtained analogously to example 40 c, starting from the product of example 45b (220 mg) and the product of example 30a (200 mg). Yield: 17 mg. MS-ESI: [M+H]^ = 628/630; anal. HPLC: Rt = 20.7 min (diastl), Rt = 20.7 min (diast2) (method 2). Diast. ratio: 10:1 Example 46 4- (3-Bromo-5-ethoxv-4"r3-(mon)holine-4-sulfonvl)-ben2vloxv1-phenvU -2-methvl-5-oxo-7-pTopvl-l,4,5,6,7,8-hexahvdro-quiDoline-3-carbomtrile (a). 4-f3-Bromomethvl-benzenesulfonvlVmorpholiDe The title compound was obtained analogously to example 40 b, starting from morpholine (137 |il), and the product of example 45a (269 mg). Yield: 280 mg. (b), 4- (3-Bromo-5-ethoxv-4-r3-rmorDholine-4-sulfonvlVbenzvloxv1-phenvU -2- methvl-5-oxo-7-propvl-L4,5,6,7.8-hexahvdro-quinoline-3-carbonitrile The title compound was obtained analogously to example 40c, starting from the product of example 46a (280 mg) and the product of example 30a (200 mg). Yield: 63 mg. MS-ESI: [M+H]^ = 684/686; anal. HPLC: Rt = 22.84 min (method 2). Diast. ratio: 10:1 Example 47 4-r2-Bromo-4-f 3-cvano-2-methvl-5-oxo-7-propvl-1,4,5,6,7,8-hexahvdro-quiDolm-4-vlV6-ethoxv-T)heDOxvmethvn-beiizenesulfomc acid At 20 °C a solution of KI (91 mg) in water (0.5 ml) was added to a solution of the product of example 44c (37 mg) in acetone (0.5 ml). The reaction mixture was stirred at 60 °C for 16 h and poured into water (15 ml). After evaporation of acetone, the reaction mixture was extracted several times with dichloromethane. The organic phases were combined dried (MgS04) and concentrated. The title product was obtained via preparative HPLC (0->90% CH3CN, 1% TFA). Yield: 7 mg. MS-ESI: [M+H]^ = 617/615; anal. HPLC: Rt = 14,31 min (diastl), Rt = 14,65 min (diast2) (method 2). Diast. ratio: 6:4 (HPLC) Example 48 N' l4-r2-BTomo-4-f 3-cvano-2-methvl-5-oxo-7-propvl-l ,4.5.6,7.8-hexahvdro-qiiinolin-4-vlV6-ethoxv-phenoxvmethvn-phenvll-methanesulfonamide fa). r4-Hvdroxvmethvl--phenvl)-carbamic acid 9ff-fluoren-9-vlmethvl ester A mixture of (4-amino-phenyl)-methanol (500 mg), Fmoc-Cl (1.2 g) and pyridine (1 ml) in THF (15 ml) was stirred for 1 h. The reaction mixture was diluted with ethyl acetate and washed with water. The organic layer was separated, dried (MgS04), filtered and concentrated in vacuo. The residue was recrystallized fi-om dichloromethane. Yield: 470 mg. MS-ESI: [M+Hf = 346. fbY f4-Chloromethvl-phenvlVcarbamic acid 9i?-fluoren-9-yhnethvl ester Thionyl chloride (1.03 ml) in dichloromethane (5 ml) was added dropwise to a solution of the product of example 48a (460 mg) in dichloromethane (10 inl). After stirring for 2 h, the reaction mixture was concentrated in vacuo. Yield: 476 mg. Rf = 0.75 (heptane/ethyl acetate = 1/2 (v/v) (c). {4-r2-Bromo-4-f3-cvano-2-methvl-5-oxo-7-propvl-l,4,5,6,7,8-hexahvdro-quin-olin-4-vl)-6-etfaoxv-phenoxvmethvl1 -phenvU -carbamic acid 9//-fluoren-9-vlmetbvl ester A mixture of the product of example 48b (100 mg), the product of example 30a (122 mg) and K2CO3 (114 mg) in DMF (5 ml) was stirred for 4 h. The reaction mixture was diluted with ethyl acetate and washed with water and brine. The organic layer was separated, dried (MgS04), filtered and concentrated in vacuo. Yield: 233 mg MS-ESI: [M-fH]^ = 772,4 7774.4 (d). 4-r4-r4-Amino-benzvloxv)0-bronK)-5-ethoxv-phenvl1-2-methvl-5-oxo-7-pTopvl-1,4.5,6,7,8-hexahvdro-Qumoline-3-caTbonitiile Piperidine (335 pi) in dichlcoromethane (5 nil) was added dropwise to a solution of the product of example 48c (223 mg) in dichloromethane (5 ml). After stirring for 2 h, the reaction mixture was concentrated in vacuo. The residue was chxomatographed on silica gel in heptane/ethyl acetate = 1/4 (v/v) as eluent. Yield: 55 mg, MS-ESI: [M-fH]'^ = 550.2/552,2 (e). iV-J4-[2-Bromo-4-f3-cvano-2-methyl-5-oxo-7-propvl-L4.5,6.7,8-hexahvdrO"qiiin-olin-4-vlV6-ethoxy-phenoxvmethvl]-phenvU-methanesulfonamide Methanesulfonyl chloride (8 p.1) and pyridine (21 pi) were added to a solution of the product of example 48d (50 mg) in dichloromethane (2 ml). After stirring for 2 h, the reaction mixture was diluted with ethyl acetate and washed with water. The organic layer was separated, dried (MgS04), filtered and concentrated in vacuo. The residue was purified by preparative HPLC (10 -^ 100% acetonitrile). Yield: 11 mg, MS-ESI: [M+H]^ = 628/630; anal, HPLC: Rt = 19,78 min, Diast. ratio: 8:1 Example 49 JV-f2-r2-Bromo-4-(3-cvano-2-methvl-5-oxo-7-propvl-l,4,5,6J,8-hexahvdro-quinolin-4-vl)-6-methoxv-phenoxvmethvn-phenvU-methanesulfonamide (a). 4-(3-Bromo-4-hvdroxv-5-metfaoxv-phenvlV2-methvl-5-oxo-7"propvl-1.4,S,6,7,8-hexahvdro-quinoline-3-carbonitrile The title compoimd was obtained analogously to example lb, starting fi-om 3-Bromo-4-hydroxy-5-methoxy-benzaldehyde (3,0 g). 3-aminocrotonitrile (1.08 g) and 5-propylcyclohexane-l,3-dione (1.98 g). Yield: 4.8 g. MS-ESI: [M-hH]"" = 431/433. (b), 4-r3-Bromo-5-methoxv-4-f2-nitro-benzvloxv)-phenvll-2-methvl-5-oxo-7-propvl-1.4,5,6.7,8-hexahvdro-Quinoline-3-carbonitrile The title con:5)ound was obtained analogously to example 30b5 starting firom 1-bromomethyl-2-nitro-benzene (200 mg) and the product of example 49a (400 mg). Yield: 384 mg, MS-ESI: [M+H]^ = 566/568; anal, HPLC: Rt = 24.50 min (diastl), Rt = 24.95 min (diast2) (method 2). Diast. ratio: 10:1 (c). 4-[4-f7-AmiTio-benzvloxvV3-bromo-5-methoxv-phenvll-2-methvl-5-oxo-7-propvl-1,4.5,6,7.8-hexahvdro-quinoline-3-carbonitrile The title conpoimd was obtained analogously to exairple 19c, starting from the product of example 49b (300 mg). Yield: 289 mg. MS-ESI: [M+H]^ = 536/538; anal. HPLC: Rt = 17.45 min (diastl), Rt = 17.91 min (diast2) (method 2). Diast ratio: 10:1 (d). JV-|2-r2-Bromo-4-f3-cvanO"2-methvl-S-oxo-7-propvl"l,4,5.6J,8-hexahvdrO"quin-olin-4-vl)-6-methoxv-T)henoxvmethvl1-T)henvU-methanesulfonamide The title compound was obtained analogously to example 28, starting from the product of example 49c (100 mg) and methanesulfonyl chloride (20 jxl). Yiel± 61 mg. MS-ESI: [M+H]^ = 614/616; anal. HPLC: Rt = 22.20 min (meihod 2). Diast. ratio: 15:1 Example 50 (4-r2-Bromo-4-r3-cvano-2-methvl-5-oxo-7"propvl-l,4,S,6J.8-hexahvdro-quinoIin-4-vl)-6-ethoxv-phenoxvmethvl1-phenvn-carbamic acid allvl ester U\ r4-Hvdroxvmethvl-phenvlVcarbamic acid allvl ester Alloc-Cl (537 g) in dichloromethane (5 ml) was added dropwise to a solution of (4-amino-phenyl)-methanol (500 mg) and pyridine (5 ml) in dichloromethane (5 ml). After stirring for 2 h, the reaction mixture was diluted with dichloromethane and washed with water. The organic layer was separated, dried (MgS04), filtered and concentrated in vacuo. The title compound (243 mg) was obtained by rectystallization from dichloromethane. The mother liquor was chromatogr^hed on silica gel in heptane/ethyl acetate =1/1 (v/v) as eluent which yielded another 245 mg of the title con^jound Yield: 488 mg. fb). f4-CMoromethvl-phenvlVcarbamic acid allvl ester The title compound was prepared analogously to example 48b starting from the product of example 50a (480 mg) and thionyl chloride (1.7 ml). The residue was chro-matographed on silica gel in heptane/ethyl acetate == 1/1 (v/v) as eluent Yield: 310 mg. (c). {4-r2-Bromo-4-f3-cvano-2-methvl-5-oxo-7-propvl-L4,5,6,7.8-hexahvdro-quin-olin-4-vl)-6-ethoxv-phenoxvmethvll-phenyl)-carbamic acid allvl ester The title compoxmd was prepared analogously to example 48c starting from the product of example 50b (300 mg) and the product of example 30a (593 mg). Yield: 333 mg. MS-ESI: [M+m^ = 634.4/636.4; anal. HPLC: Rt == 24.99 min (method 2). Example 51 4-r3 -Bromo-5-ethoxv-4-(' 1 -methanesulfonvl-1 J/-pvrrol-2-vlmethoxvVphenvn -2-methvl-5-oxo-7-propvl-L4,5,6J,8-hexahvdro-quinoline-3-carbonitrile (aY 1-Methanesulfonyl-lJ/-T)vrrole-2-carbaldehvde A solution of pyrrole-2-carboxyaldehyde (500 mg) in TEIF (5 ml) was added to a suspension of NaH (252 mg, 60% dispersion on oD) in THF (15 ml). After stirring for 15 min, a solution of methanesulfonyl chloride (570 pi) in THF (5 ml) was added dropwise. After stirring for 1 h, water (25 ml) was added and the THF was evaporated The residue was diluted with dichloromethane and washed with water, sat. NaHCOs and brine. The organic layer was separated, dried (MgS04), filtered and concentrated in vacuo. The residue was chromatographed on silica gel in heptane/ethyl acetate = 1/1 (v/v) as eluent Yield: 265 mg. (h\ (1 -Methanes^^lfonvl-lJg-pvrrol-2-vlVmethanol At O^^C LiBH4 (1.15 ml, 2.0M in THF) was added dropwise to a solution of the product of example 51a (265 mg) in diethylether (10 ml). After stirring at 0*^C for 30 min, water (2 ml) and acetic acid (2 ml, 10% in water) were added. The water layer was separated and extracted with dichloromethane. The organic layer was washed with water and brine, separated, dried (MgS04), filtered and concentrated in vacuo. Yield: 205 mg. (c). 2"Chloromethvl-1 -methanesulfonyl-1 jy-pvrrole At 0*^C methanesulfonyl chloride (136 [il) was added dropwise to a solution of the product of example 51b (205 mg) and DIPEA (307 p.1) in dichloromethane (6 ml). After stirring for 30 min, the reaction mixture was diluted with dichloromethane (30 ml) and washed with ice water (30 ml), 10% HCl (30 ml) and sat, NaHCOs- The organic layer was separated, dried (MgS04), filtered and concentrated in vacuo. Yield: 252 mg. (d). 4-r3-Bromo-5-ethoxv-4-fl-methanesulfonvl-l.H-pvrrol-2"VlmethoxvVphenvl1-2-methvl-5-oxo-7-propvl-L4,5.6,7,8-hexahvdro-quinoline-3-carbonitrile Alkylation of the product of example 30a (539 mg) with the product of example 51c (252 mg) was performed according to tiae method described in example la. The residue was purified by preparative HPLC (40 -> 100% acetonitrile). Yield: 363 mg, MS-ESI: [M+H]^ = 602.4/604.4; anal. HPLC: Rt = 15.53 min (diastl), Rt = 15.99 min (diast2) (method 1). Diast. ratio: 11:1 Example 52 JV-r2-Bromo-4-r3-cvano-2-methvl-5-oxo-7-propvl-l,4,5,6,7,8-hexahvdro-quinolin-4-vlV6-ethoxv-phenvn-2-nitro-ben2amide U). 3-Ethoxv-4-nitro-benzaldehvde At 20 °C iodoethane (3.78 g) was added to a suspension of K2CO3 (1.09 g) and 3-hydroxy-4-nitro-benzaldehyde (1.0 g) in DMF (5 ml). The reaction mixture was stirred at 70 °C for 18 h, poured into water and then extracted with ethyl acetate. The organic phases were combined, dried (MgS04) and concentrated in vacuo. The title product was obtained as a yellow solid Yield: 1.17 g. MS-ESI: \M-¥Hf = 196. (b). 4-f3-Ethoxv-4"nitro-phenvlV2-methvl-5-oxo-7-propvl-1.4,5,6,7.8-hexahvdro-aum oline-3-carbomtrile The title compound was obtained analogously to exan^le lb, starting ftom the product of example 52a (1.16 g), 3-aminocrotonitrile (502 mg) and 5-propylcyclohexane-l,3-dione (920mg). Yield: L24 g. MS-ESI: [M+H]^ = 396. (c), 4-r4-Aniino-3-ethoxv-phenvD-2-methvl-5-oxo-7-propvl-L4,5,6,7,8-hexahvdro-quinoline-3-carbonitrile The title compound was obtained analogously to example 19c starting from the product of exan^jle 52b (1.2 g). Yield: 1.1 g. MS-ESI: [M+H]^ = 366. (d). 4-r4-Amino-3-bromo-5-ethoxv-phenvl)-2-methvl-5-oxo-7-propvl-1.4,5,6,7,8-hexa-hvdro-qiiiTin1iTie-3 -carbonitrile At 0 °C a solution of bromine (56 |il) in dichloromethane (5 ml) was added slowly to a mixture of the product example 52c (365 mg) and sodium acetate (89 mg) in acetic acid (10 ml) and dichloromethane (5 ml). The reaction mixture was stirred at 0 **C for 1 h, poured into water and then extracted with dichloromethane. The organic phases were combined, dried (MgS04) and concentrated in vacuo. The title compound was obtained after flash column chromatography (sihca gel, heptane/ethyl acetate (1/4, v/v), Rf = 0.55). Yield: 1.17 g. MS-ESI: [M-hH]^ = 444/446. (e). JV-r2-Bromo-4-r3-cvano-2-methvl-5-oxo-7-propyl-l,4.5.6.7,8-hexahvdro-quinolin-4-vlV6-eflioxv-phenvl1-2-nitro-benzamide At 20 °C, 2-nitro-benzoyl chloride (125 mg) was slowly added to a solution of the product of example 52d (200 mg) and iV;iV-dimethylaniline ( 172 \il) in THE (5 ml). The reaction mixture was stirred at 20 °C until total conversion and then poured in sat. NaHCOa and extracted with ethyl acetate. The organic phases were combined, dried (MgS04) and concentrated in a vacuo. The title compound was obtained by recrystallization from acetonitrile. Yield: 37 mg, MS-ESI: [M+H]'^ = 593/595; anal. HPLC: Rt = 17.98 min (method 2). Example 53 4- [3 -Bromo-5-ethoxv-4-r 1 -trifluoromethanesulfonvl- liy-pvrrol-2-vlmethoxvVphenvn -2-metfavl-5-oxo-7-propvl"l,4.5,6.7.8-hexahvdro-quinoline-3-carbonitrile f aV 1 -Trifluoromethanesulfonvl-lJy-pvrrole-2-carbaldeihvde At -78*^C and under a nitrogen atmosphere, trifluoromelhanesulfonic anhydride (3.2 ml) was added dropwise to a solution of pyrrole-2-carboxyaldehyde (1 g) and DIPEA (3.67 ml) in dichloromethane (100 ml). After stirring for 5 min at -78^C, the reaction mixture was poured into sat NaHCOs (200 ml) and extracted with dichloromethane. The organic layer was separated, washed with water, dried (MgS04), filtered and concentrated in vacuo. The residue was chromatographed on silica gel in heptane/ethyl acetate = 2/1 (vA^) as eluent Yield: 675 mg, (h\ (1 -Trifluoromethanesulfonvl- li/'-pvrrol-2-vl)-methanol The title compound was obtained analogously to example 51b starting fix)m the product of exan5)le 53a (300 mg). Yield: 361 mg (c). 2-Chloromethvl-1 -trifluoromethanesulfonvl-1 ff-pvrrole The title compound was obtained analogously to example 51c starting jfrom the product of exan5)le 53b (361 mg). Yield: 391 mg (d). 3-Bromo-5-ethoxv-4-ri-trifluoromethaDesulfonvl-li?-pvTrol-2-vlmethoxvVbenzal-dehvde Alkylation of 3-bromo-5-ethoxy-4-hydroxy benzaldehyde (387 mg) with the product of example 53c (391 mg) was performed according to the method described in example la. The residue was chromatographed on silica gel in heptane/ethyl acetate = 3/1 (v/v) as eluent. Yield: 208 mg. MS-ESI: [M+H]^ = 456.2/458.2 (e). 4-r3-Bromo-5-ethoxv-4-fl-trifluoromethanesulfonvl-lJy-pvrrol-2-vlmethoxvV phenvll-2-methvl-5-oxo-7-propvl-1.4,5,6J,8-hexahvdro-quinoline-3-carbonitrile The title compound was obtained analogously to example lb starting fi-om the product of example 53d (208 mg). The residue was purified by preparative HPLC (20 —> 100% acetonitrile). Yield: 166 mg. MS-ESI: [M+H]^ = 656.2/658.2; anal, HPLC: Rt = 23.99 min (diastl), Rt = 24.47 (diast.2) (method 1). Diast. ratio: 5:1. Example 54 4-r2-Bromo-4-f3-cvano-2-methvl-5-oxo-7-propvl-L4,5,6,7,8-hexahvdro-quinolin-4-vlV6-ethoxv-nhenoxvmethvll-iV-methvl-benzamidine (a), 4-r3-Bromo-4-f4-cvano-benzvloxv)-5-ethoxv-phenvn-2-mefhvl-5-oxo-7-propvl-L4,5,6J,8-hexahvdro-quinoline-3-carbonitrile Alkylation of the product of example 30a (2,5 g) with a-bromo-j7-tolunitrile (1.21 g) was performed according to the method described in example 30b. The reaction mixture was poured in water and filtered over decalite. The residue was washed with water en dichloromethane. The organic layer was separated, washed with water and brine, dried (MgS04), filtered and concentrated in vacuo. The residue was chromatographed on silica gel in heptane/ethyl acetate = 3/1 (v/v) as eluent Yield: 2.6 g. MS-ESI: [M+H]^ = 560 7562 (b). 4-r2-Bromo-4-(3-cvano-2-naethvl-5-oxo-7"propvl-1.4,S,6J,8-hexahvdro-quinolin-4'Vl)-6-ethoxv-phenoxvmethvn-benziniidic acid ethyl ester HCl (g) was bubbled through a solution of the product of example 54a (1.5 g) in ethanol (10 ml) for 2 h. After additional stirring for 2 h, the reaction mixture was concentrated in vacuo. Yield: 1.62 g. (c). 4-r2-Bromo-4-f3-cvano-2-methyl-5-oxo-7*propvl-l,4.5,6,7,8-hexahvdro-quiDolin-4-vn-6-ethoxv-phenoxvmethvl1-JV-metbvl-benzamidine A mixture of the product of example 54b (180 mg), methylamine (126 jJ, 8 M in EtOH) and triethylamine (126 /il) in ethanol (1 ml) was stkred for 54 h. The reaction mixture was concentrated in vacuo. The residue was purified by preparative HPLC (10 -^ 90% acetonitrile. 0.1% TEA). Yield: 56.5 mg (as TFA salt). MS-ESI: [M+H]^ = 591/593; anaL HPLC: Rt = 17.8 min (method 4). Example 55 2-r2-Bromo-4-f3"Cvano-2-methvl-5-oxo-7-propvM.4,5,67,8"hexahvdro-quiDolin-4-vlV6-eflioxv-phenoxvmethvn-pyrrole-1-carboxvlic acid ^er^-butvl ester (a). 2-Formvl-pvrrole-l-carboxvlic acid tert-hutvl ester Bocylation of pyTrole-2-carboxyaldehyde (750 mg) in the presence of NaH (410 mg, 60% dispersion on oil) and Boc-On (2.72 g) was performed according to the method described in example 51a. The residue was chromatographed on silica gel in heptane/ethyl acetate = 2/1 (v/v) as eluent. Yield: 196.2 mg. fbV 2-Hvdroxvmethvl-pvTrole-l-carboxvlic acid tert-hxxtvl ester Reduction of the product of example 55a (500 mg) with LiBEU was performed according to the method described in example 51b. The residue was chromatographed on silica gel in hq)tane/ethyl acetate = 2/1 (v/v) as eluent Yield: 350 mg. (c\ 2-Methanesulfonvloxvmethvl-pvrrole-l-carboxvlic acid tert-hutvl ester Sulfonylation of the product of example 55b (350 mg) with methanesulfonyl chloride (210 pi) was performed according to the method described in example 51c. The reaction mixture was washed with water, sat. NaHCOs and brine. The organic layer was separated, dried (MgS04), filtered and concentrated in vacuo. Yield: 487 mg. (d). 2-r2-Bromo-4'r3-cvano-2-me1hvl-5-oxo-7-propvl-l,4,5.6J,8"hexahvdro-quinolto-4-vlV6-ethoxv-phenoxvmeflivn-pvTrole"l-carboxvlic acid ^er^-butvl ester Alkylation of the product of example 30a (787 mg) with the product of example 55c (487 mg) was performed according to the method described in example la. The residue was purified by preparative HPLC (20 -^ 100% acetonitrile). Yield: 61 mg. MS-ESI: [M+H]^ = 624.2/626.2; anal. HPLC: Rt = 29.35 min (diastl), Rt = 29,70 min (diast2) (method 2). Diast, ratio: 4:1. Example 56 4--{3-Bromo-S-ethoxv-4-rrpvridin-3--vlmethvl)-flTninn]-phenvU-2-metbyl-5-Qxo-7-propvl-1,4,5,6 J,8"hexahydro-quinoline-3-carbomtrile At 20 **C pyridine-3-carbaldehyde (210 iu,l) was added to a solution of the product of example 52d (100 mg) and acetic acid (127 |xl) in methanol (4 ml). The reaction mixture was stirred at 20 °C for 16 h and then NaCNBHt (142 mg) was added. The reaction was stirred at 20 °C for 24 h, poured in water and extracted with ethyl acetate. The title product was obtained via preparative HPLC (0->90% CH3CN, 0.1% TFA). Yield: 27 mg (as TFA salt). MS-ESI: [M+H]^ = 535/537; anal. HPLC: Rt = 8,56 min (mefliod 2). Example 57 4"f3-Bromo-5-ethoxv-4-r2-nitro-benzvlamino)-phenvll-2-methvl-5-oxO"7-propvl-l,4,5,6,7.8-hexahvdro-quinoline-3'-carbonitrile The title compound was obtained analogously to example 56, starting from 2-nitro-benzaldehyde (1.93 g) and the product of example 52d (570 mg). The residue was purified by preparative HPLC (0-^90% CH3CN). Yield: 610 mg. MS-ESI: [M+H]^ = 579/581: HPLC: Rt = 24.35 min (diastl), Rt = 24.85 min (diast2) (method 2), Diast. ratio: 9:1 (HPLC) Example 58 JV-f2-fr2-Bromo-4-f3"Cvano-2-methvl'5-oxo-7-propvl-1.4.5.6,7,8-hexahvdro-quinolin-4-vl)'6-ethoxv-phenvlamino'|-methvl)-phenvl)-methanesvdfonamide (a). 4-r4-f2-Amino-benzvlamino)-3-bromo-5-ethoxv--phenvll-2-methvl-5-oxo-7-pro-pvl-l,4,5,6J,8-hexahvdro-quinoline-3-carbonitrile The title compound was obtained analogously to example 19c, starting from the product of example 57 (550 mg). Yield: 510 mg. [M+H]'^ = 549/551. (b). JV-f2-ir2-Bromo-4-r3-cvano-2-me1hvl-5'Oxo-7-CTOpvl-l,4,5,6J,8-hexahv The title compoimd was obtained analogously to example 28, starting fix)m the product of example 58a (130 mg) and methanesulfonyl chloride (20 ^il). Yield: 31 mg. MS-ESI: [M+H]^ = 627/629; anal. HPLC: Rt = 20,82 min (diastl), Rt = 21.35 min (diast2) (method 2). Diast. ratio: 4:1 (HPLC) Example 59 (3'i r2-Bromo-4-r3-cvano-2-methvl-5-oxo-7-propvl-1,4,5,6,7.8-hexahvdro-quinoliD-4-vl)"6"ethoxv-pheDvlamino1"methvl}-phenvl)-carbamic acid methyl ester (a). 4-r3"Bromo-5-ethoxv-4-r3-nitTo-beDzvlaminoVphenvll-2-methvl-5-oxo-7-propvl-L4,5,6,7,8-hexahvdrO"quinoIme-3-carbonitrile The title compound was obtained analogously to example 56, starting from 3-nitro-benzaldehyde (1.93 g) and the product of example 52d (570 mg). Yield: 630 mg. MS-ESI: [M+H]^ = 579/581; anal. HPLC: Rt = 23.91 min (diastl), Rt = 24.32 min (diast2) (method 2). Diast. ratio: 6:1 (HPLC) (b). 4-r4-r3-Amino-benzvlaminoV3-bromo-5-ethoxv-phenvll-2-methvl-5-oxo-7-pro-pvl-L4,5,6,7,8-hexahvdTo-quinoline-3-carbQnitrile The title compound was obtained analogously to example 19c, starting from the product of example 59a (570 mg). Yield: 510 mg. [M+H]^ = 549/55L (c). (3-{[2-Bromo-4-r3-cyano-2-methyl-5-oxo-7-propvl-L4,5,6,7,8-hexahvdro-quin-olin-4-ylV6-ethoxy-phenylaminol-methvl}-phenvl)-carbamic acid methyl ester The title compound was obtained analogously to example 25, starting from the product of example 59b (130 mg) and methylchloroformate (24 pi). Yield: 29 mg. MS-ESL [M+H]^ = 607/609; anal. HPLC: Rt = 17.89 min (method 2). Example 60 2-r2-Bromo-4-f 3-cvano-2-methvl-5-oxo-7-propvl" 1,4,5,6,7.8-hexahvdro-quinolin-4-vlV6-etfaoxv-phenoxvmethvll-benzamidine: compound with hydrochloric acid (a). 4-r3-Bromo-4-(2"Cvano-benzvloxvV5--ethoxv-phenvlV2-methvl-5-oxo-7-propvl-L4,S,6J,8-hexahvdro-quinoline-3-carbonitrile Alkylation of the product of example 30a (2,5 g) with a-bromo-o-tobnitrile (1.21 g) was performed according to the method described in example 54a. Yield: 2.44 g, MS-ESI: pvl+H]^ = 560/562 (b.) 2"r2"BTomo-4-f3-cvaco-2-me1favl-5-oxo-7-OTOPVl'1.4.5,6J,8-hexahv HCl (g) was bubbled through a solution of the product of example 60a (200 mg) in ethanol (1 ml) for 1 h. After additional stirring for 2 weeks, the reaction mixture was concentrated in vacuo. The residue was dissolved in ethanol and NH4OAC (83 mg) was added After stirring for 18 h, the reaction mixture was concentrated in vacuo. The residue was chromatographed on silica gel in heptane/ethyl acetate = 1/1 (v/v) as eluent. Yield: 17.4 mg (HCl-salt), MS-ESI: [M+H]^ = 577/579; anal. HPLC: Rt = 16.8 min (diastl) (method 4). Example 61 4-(3"Bromo-5-ethoxv-4-r3-riiDino-morpholin-4-vl-methvlVbenzvloxvl-phenvll-2-methvl-5-oxo-7-propvl-1.4,5.6J,8-hexahvdro-qiimoline-3-<:arbonitrile> (a). 4-["3-Bromo-4-r3--cvano-benzvloxv)-5-ethoxv-phenvll-2-methvl'5-oxo-7-propvl-l,4,5,6J,8-hexahvdro-quinoline-3-caTbonitrile Alkylation of the product of exan^le 30a (2.5 g) with a-bromo-m-tokmitrile (1.21 g) was performed according to the metiiod described in example 54a. Yield: 2.6 g. MS-ESI: [M+H]^ == 560 /562 (b). 3-r2-Bromo-4-r3-cvano-2-methvl-5-oxo-7-propvl-L4,5,6J.8-hexahvdro-quinolin-4-vlV6-ethoxv-phenoxvmethvn-benzimidic acid ethyl ester The title confound was prepared analogously to example 54b, starting fi-om the product of example 61a (1.5 g). Yield: 1.62 g. (c), 4-(3-Bromo-5-ethoxV"4-r3-rimino-morpholin-4-vl-methvl)-benzvloxv1-phenvU-2" methvl-5"OXO'7-propvl-1.4,5,6,7,8-hexahvdro-quinoline-3-carbonitrile The title compound was prepared analogously to example 54c, starting from the product of example 61b (180 mg) and morpholine (77.8 mg). Yield: 86.7 mg (as TFA salt). MS-ESI: [M+H]^ = 647/649; anal. HPLC: Rt = 17.7 min (method 4). Example 62 4-f3-Bromo-4-r2-(cvclopropvlmethvl-ainino)-benzvloxvl-5-ethoxv-phenvn-2-methvl-5-oxO'7-proT)vl-l,4,5.6J,8-hexahvdro-qumoline-3-carbonitrile (a). JV-{2-[2-Bromo-4-r3-cvano-2-methvl-5-oxo-7-propvl-l,4,5.6,7.8-hexahvdro-quin-olin-4-vl)-6-ethoxy-phenoxvmethvl1 -phenyl) -2,4-dmitro-benzenesulfonamide 2,4-Dinitro-benzenesulfonyl chloride (3.2 g) and pyridine (3.8 ml) were added to a solution of the product of exaii5)le 19c (5 g) in dichloromethane (30 ml). After stirring for 3 h, the reaction mixture was poured in water and acidified with 2N H(JL I'He organic layer was separated and washed with sat NaHCOs and brine. The organic layer was separated, dried (MgS04), filtered and concentrated in vacuo. The residue was chromatographed on silica gel in heptane/ethyl acetate = 1/2 (v/v) as eluent. Yield: 5 g. MS-ESI: [M+H]^ = 780.2/782.2 (b). JV^{2-r2-Bronio-4-f3>cvano-2"niethvl-5-oxo-7-prot)vl-l,4,5,6,7,8-hexahvdro-quin- olin-4-vlV6-ethoxv-nhenoxvmethvll-phenvl>-iV-cvclopropvlmethvl-2,4-dim benzenesulfonamide Diisopropylazodicaiboxylate (102 jil) was added dropwise to a solution of the product of example 62a (200 mg), cycloprqpanemethanol (38.2 mg) and triphenylphosphine (134 mg) in THF (6 ml). After stirring for 10 min, the reaction mixture was concentrated in vacuo. The residue was chromatographed on silica gel in heptane/ethyl acetate = 1/2 (v/v) as eluent Yield: 158 mg. ESI-MS: [M+H]^ = 834.4/836.4 (c). 4- (3-Bromo-4-r2-f cvclopropvlmethvl-amino)-benzvloxv1-5-ethoxv-phenvll -2-methvl-5-oxo-7-propvl-l,4,5.6,7.8-hexahvdrO"quinoline-3-carbonitrile A mixture of the product of example 62b (158 mg) and propylamine (200 p.1) in dichloromethane (10 ml) was stirred for 1 h. The reaction noixture was concentrated in vacuo and the residue was purified by preparative HPLC (10-^90% CH3CN). Yield: 72 mg. MS-ESI: [M+H]"" = 604.4/606.4; anal. HPLC: Rt = 21.8 min (diastl), Rt = 22.39 min (diast2) (method 1). Diast ratio: 6:1 Example 63 4- {3-Bromo-5-ethoxv-4-r2-(3-methyl-butylamino)-ben2yloxy1-phenvl) ■2-methvl-5-oxo-7-propyl-K4,5,6,7,8-hexahvdro-quinohne-3-carbonitrile (a). JV-{2-[2-Bromo-4-(3-cvano-2"methyI-5-oxo-7-propvl-L4,5,6.7,8-hexahvdro-quin-olin-4-vlV6"ethoxv-phenoxymethvll-phenvll-^-r3-methvl-butvl)-2.,4-dinitro- benzenesulfonamide The title compound was obtained analogously to example 62b, starting fi-om the product of example 62a (200 mg) and isoamylalcohol (56 jil). Yield: 205 mg. MS-ESI: [M+H]^ = 850.4/852.4 (b). 4-(3-Bromo-5-ethoxv-4-r2-r3-methvl-butvlamino>-benzvloxvl-phenvU-2-methyl-5-oxo-7-propvl-L4.5,6J,8-hexahvdro-quinoline-3'Carbonitrile The title compoxmd was prepared analogously to example 620, starting fi-om the product of compound 63a (205 mg). Yield: 66.7 mg. MS-ESI: [M-fH]^ = 620.4/622.4; anal. HPLC: Rt = 23.61 min (diastl), Rt = 24.05 min (diast2) (method 5). Diast ratio: 5:1 Example 64 (2-r2-Bromo-6-etfaoxv-4-r2-methvl-3-ffltro-5-oxo-7-propvl-l,4,5,6,7,8-hexahvdro-quinoliB-4-vlVphenoxvmethvll-phenvU-carbamic acid methyl ester fal. l-Nitro-propaD-2-one At 0 °C sodium hydride (60 % dispersion on oil) (1.28 g) was added to a solution of nitromethane (1.95 g) in THF (25 ml). The reaction mixture was stirred at 20**C for 30 minutes and then added to a solution of 1-pyrazol-l-yl-ethanone (2.72 g) in THF (25 ml). The reaction mixture was stirred at 60 ^C for 18 h. The solid formed was fiQtered, dissolved in water (50 ml), acidified to pH==3 with 1 M HCl and then extracted several times with ethyl acetate. The organic phases were combined dried (MgS04) and concentrated The title product was obtained as a yellow oil. Yield: 2.47 g. (h\ l-MethvI-2-nitro-vinvlamine A mixture of the product of example 64a (1.6 g) and NEUOAc (1.3 g) in toluene (25 ml) was heated under reflux for 18 h with azeotropic removal of water using a Dean-Stark apparatus. The reaction mixture was concentrated in vacuo and chromatographed on silica gel in heptane/ethyl acetate = 2/1 as ehient. Yield: 10.7 g (c\ (2"Hvdroxvmethvl-phenvl)-carbamic acid methyl ester Reaction of aminobenzylalcohol (3 g) with methylchloroformate (1.9 ml) in the presence of DIPEA (12.8 ml) was performed according to the method described in example 22. The residue was chromatogmphed on silica gel in dichloromethane/ethyl acetate == 25/1 as eluent Yield: 4.19 g. f dV ('2-Chloromethvl-phenvl)-carbamic acid methyl ester The title compound was prepared analogously to example 48b starting from the product of exanple 64c (4.19 g) and thionyl chloride (10 ml). Yield: 1.98 g. (e). r2-f2-Bromo*6-ethoxy-4-foimvl-phenoxymethyl)-phenyll-carbamic acid melhvl ester Alkylation of 3-bromo-5-ethoxy-4-hydroxy benzaldehyde (614 mg) with the product of example 64d (500 mg) was preformed according to the method described in example lb. Yield: 845 mg. (f). ^2-r2-Bromo-6-ethoxv-4-f2"methvl-3-nitro-5-oxo-7-propvl-l,4,5,6.7,8-hexahydro-quinolin-4-vlVphenoxvmethvn-phenvU-carbamic acid methyl ester Reaction of the product of example 64e (100 mg) with the product of example 64b (28 mg) and 5-propylcyclohexane-l,3-dione (41 g) was performed according to the method described in example lb. The residue was purified by preparative HPLC (10 -> 90% acetonitrile). Yield: 75 mg, MS-ESI: [M+H]^ = 628/630; anal. HPLC: Rt = 26.22 min (diastl), Rt = 26.67 min (diast2) (method 2), Diast. ratio: 4:1 Example 65 4-r3-Bromo-5-elhoxv-4-r3-methoxv-benzvloxv)-phenvn-2"methvl-3-nitro-7-propvl-4,6 J,8-tetrahvdr0" Iff-quinolin-S-one (a). 4-r3-Bromo-5-ethoxv-4-hvdroxv-phenvlV2-metbvl-3-nitro-7-propyl-4,6,7,8-tetra-hydro- lff-qumoIm-5-one Reaction of the product of example 64b (1 g) with 3-bromo-5-eihoxy-4-hydroxy benzaldehyde (2.57 g) and 5-propylcyclohexane-l,3-dione (1.61 g) was performed according to the method described in example lb. The residue was recristallized fi-om dichloromethane. Yield: 2.8 g. MS-ESI: [M+H]^ = 465/467 (b). 4-r3-Bromo-S-ethoxv-4-r3-methoxv-benzvloxvVphenvn-2-methvl-3'nitrO'7-pro-pvl-4,6J,8-tetrahvdro-l//-qiiinolin-5-one The title compound was obtained analogously to example 30b, starting from the product of example 65a (100 mg) and l-bromomethyl-3-methoxy-benzene (50 mg). Yield: 36 mg. MS-ESI: [M+H]^ = 554/556; anal. HPLC: Rt = 27.18 min (diastl), Rt = 27.61 min (diast2) (method 2). Diast ratio: 1:1 Example 66 4-[3-Bromo-5-etfaoxv-4-r2-methvl"tMazol-4-vhnethoxv)-phenvl1"2-me1hvl-3-nitro-7 propvl-4,6,7,8-tetrahvdro-l.g-quinolin-5-one The title compound was obtained analogously to example 30b, starting from 4-chloromethyl-2-methyl-thiazole (37 mg) and the product of example 65a (100 mg). Yield: 27 mg. MS-ESI: [M+H]^ = 574/576; anal. HPLC: Rt = 22.01 min (diast), Rt = 22.50 min (diast2) (method 2). Diast ratio: 1:1 Example 67 (4-r2--Bromo-4-f3-cvano-2-methvl-5-oxo-7-propvl-l,4,5,6,7,8-hexahvdro-quiaolin-4-vl)-6-ethoxv-phenoxymethyl]-phenvll-acetic acid methyl ester Alkylation of tiie product of example 30a (196 mg) with (4-bromomethyl-phenyl)-acetic add methyl ester (107 mg) was performed according to the method described in example 30b. The residue was purified by preparative HPLC (10->90% acetonitrile). Yield: 116mg,MS-ESr. [M+H]^ = 607/609;anal,HPLC:Rt = 28.41 niin(method4). Example 68 (4-f2-Bromo-4-r3-cvano-2-methvl-5-oxo-7-propvl-l,4.5.6J,8-hexahvdrD-quinolin-^^ vlV6-ethoxv-pheDoxvmethvn-phenoxvl-acetic acid (a). M-r2-Bromo-4-f3-cvano-2-methvl-5-oxo-7-propvl-lA5,6J,8-hexahvdro-qidD-olip-4-vlV6-ethoxv-phenoxvmethvn-phenoxvl-acetic acid methyl ester AUylation of the product of example 30a (445 mg) with (4-bromomethyl-phenoxy)-acetic acid methyl ester (259 mg) was performed according to the method described in example 67. Yield: 308 mg. MS-ESI: [M+H]^ = 623/625; anal. HPLC: Rt = 23.67 min (method 2). (b). {4-r2-Bromo-4-f3-cvano-2-methvl-5-oxo-7-propvl-U4,5.6J.8-hexahvdro-quin-olin-4-vl)-6-ethoxv-phenoxvmethvn-phenoxv) -acetic acid Saponification of the product of example 68a (230 mg) was performed according to the method described in example 6c. Yield: 166 mg. MS-ESI: [M+H]^ = 609/611; anal. HPLC: Rt= 19.32 min. Example 69 JV-(3-ir2-BrQmo-4-(3-cvano-2-methvl-5-oxo-7-propvl"L4,5.6J.8-hexahvdro-quinolin-4-vl)-6-ethoxv-phenvlamino1-methvll-pvridin-2-vl)-methanesulfonamide (a). ^-f3-Cyano-p'vridin-2-vlVmethanesulfonamide A mixture of 2-chloro-nicotinonitrile (2 g), HaNSO^Me (1.73 g) and K2CO3 (4.44 g) in DMF (100 ml) was stirred at 100*^C for 18 h. The reaction mixture was concentrated in vacuo. The residue was dissolved in ethyl acetate and washed with water and brine. The organic layer was separated, dried (MgS04), filtered and concentrated in vacuo. The residue was chromatographed on silica gel in dichloromethane/melhanol = 98/2 (v/v) as eluent Yield: 1.32 g. MS-ESI: [M+H]^ = 198.2 fb). JV-r3-Formvl-nvridin-2-vl)-methanesulfonamide Raney nickel (2.64 ml, 50% suspension in water) was added to a solution of the product of example 69a (1.32 g) in formic acid (55 ml). After stirring at 100**C for 3 h, the reaction mixture was filtered over decalite and washed with formic acid. After concentration of the filtrate, the residue was dissolved in ethyl acetate and washed with sat NaHCOs and brine. The organic layer was separated, dried (MgS04), filtered and concentrated in vacuo. The residue was chromatographed on silica gel in heptane/ethyl acetate = 2/1 (v/v) as eluent. Yield: 461 mg, MS-ESI: [M+H]^ = 201.2 (c). JV^f3-(r2-BromO"4-r3-cvano-2-methvl-5>oxo-7-propvl-lA5,6.7,8-hexahvdro-quin-olin-4-vlV6-ethoxv-phenvlamino1-methvU-pvridin-2-vl)"methanesul^^ A mixture of the product of example 52d (200 mg), the product of example 69b (99 mg) and acetic acid (129 jil) in methanol (8 ml) was stirred for 18 h followed by addition of NaCNBHa (141 mg). Stirrmg was continued for another 4 h. The reaction mixture was diluted with ethyl acetate and washed with water, sat. NaHCOs and brine. The organic layer was separated, dried (MgS04), filtered and concentrated in vacuo. The residue was purified by preparative HPLC (10-»90% CH3CN). Yield: 145 mg. MS-ESI: [M+H]^ = 628/630; anal. HPLC: Rt = 10.77 min (diastl ), Rt = 11.17 min (diast2) (method 2). Diast. ratio: 9:1 Example 70 4-r3-Bromo-4-(2,5-dimethvl-2H-pvrazol-3-vlmethoxvV5-ethoxv-phenvl1-2-methvl-^ nitro-7-propvl-4,6,7.8-tetrahvdro-liy-quinolin-5-one (a). 5-Chloromethvl-l 3-dimethvMg-pvrazole The title compound was prepared analogously to example 48b starting from (2,5-dimethyl-2J?-pyrazol-3-yl)-methanol (778 mg) and thionyl chloride (2.35 ml). Yield: 900 mg. fbV4-r3-Bromo-4-r2,5-dimethvl-2iy-p\Tazol-3-vhnethoxv)-5-ethoxv-phenvll-2-methvl^ 3-nitro-7-propvl-4,6.7,8-tetrahvdro-l.H"qu3nol]n-5-one Alkylation of the product of example 65a (100 mg) with the product of example 70a (48 nag) was performed according to the method described in example 30b. The residue was purified by preparative HPLC (10 -^ 90% acetonitrile). Yield: 77.3 mg. MS-ESI: [M+H]^ = 573/575; anal. HPLC: Rt = 20.14 min (diastl), Rt = 20.64 min (diast2) (method 2). Diast. ratio: 4:1 Example 71 JV'-(2-r2-Bromo-4-r3-cvaDo-2-methvl>5-oxo-7-propvl-l,4,5,6J,8-hexahvdro--quinolin-4-vlV6-ethoxv-T)henoxvmethvn-5-trifluorometfavl-phenvl)-methanesulfonamide (a). 4-r3-Bromo-5-ethoxv-4-(2-nitro-4-trifluoromethvl-benzvloxvVphenvn-2-methvl-5-oxo-7-propvl-L4.5,6,7,8-hexahvdro-quiDoline-3-carbonitrile Angulation of the product of example 30a (778 mg) with l-chloromethyl-2-nitro-4-trifluoromethyl-benzene (419 mg) was performed according to the method described in example 30b. The residue was chromatographed on silica gel in heptane/ethyl acetate = 2/1 (v/v) as eluent. Yield: 493.9 mg. MS-ESI: [M+H]^ = 648/650 (b). 4-r4-f2-Ainitin-4-iTifluoromethvl-benzvloxvV3"bromo-5-ethoxv--phenvl1-2-meflivl-5-oxo-7-proT)vl-l,4,S.6.7.8-hexahvdro-quinoliDe-3-carboDitrile Reduction of the product of example 71a (431 mg) with zinc dust (1.08 g) was performed according to the method described in example 19c. Yield: 400 mg. MS-ESI: [M+H]^ = 618/620 (c). JV^I2-r2-Bromo4-f3-cvano-2-methvl-5-oxo-7-propvl-l,4,5,6J,8-hexahvdro-qiun- olin-4-vD-6-ethoxv-phenoxvmetbvl1-5-trifluoromethvl-phenvU- dirmethanesulfon)amide A mixture of the product of exan^le 71c (120 mg), methanesulfonyl chloride (23 pi) and triethylamine (81 pJ) in dichloromethane (2 ml) was stirred at 40^C for 54 h. The reaction mixture was concentrated in vacuo. Yield: 150 mg (crude), ESI-MS: [M+H]^ = 774/776 (d). iV-f2-r2"Bromo-4-f3-cvano-2-methvl-S-oxo-7-propvl-L4.5,6J,8-hexahvdro-quin-olin-4-vl)-6-ethoxV"pbenoxvmethvll-S-trifluoromethvl-T3henvl}-methanesulfonamide A mixture of the cmde product of example 71c (150 mg) and 2M NaOH (1 nil) in dioxane (2 ml) was stirred for 18 h. The reaction mixture was acidified with 0.5N HCl, diluted with ethyl acetate and washed with sat. NaHCOs and brine. The organic layer was separated, dried (MgS04)5 filtered and concentrated in vacuo. The residue was purified by preparative HPLC (10->90% CH3CN). Yield: 32.4 mg. MS-ESI: [M+H]^ = 696/698; anal. HPLC: Rt = 26.7 min (diastl), Rt = 27.0 min (diast2) (method 2). Diast. ratio: 1:1 Example 72 Ar-(2-r2-Bromo-4-ff4R,7SV3-cvano-2-methvl-5-oxo-7-propvl4,4,5,6,7,8-hexahvdro-Quinolin-4-vlV6-eflioxv-T>henoxvmethvn-4,5-difluoro-phenvU-methanesulfonamide fa). (1SVJV-r 1 -f4-Methoxv-phenvlVethvn -3 -oxo-butvramide To a solution of (S)-l-(4-methoxy-phenyl)-ethylamine (25 g) in dichloromethane (60 mL) was added TEA (20 g) and DMPA (200 mg). Then a solution of 4-methylene-oxetan-2-one (16.7 g) in dichloromethane (60 ml) was added over a period of 30 minutes and then stirred at 20 °C for 18 h. The mixture was washed with IM HCl, aq. NaHCOa and aq. NaCl. The organic layer was dried (MgS04), filtered and concentrated in vacuo. Yield: 39.8 g. MS-ESI: [M+H]' = 236 (h\ (IS)- 3-Amino-but-2-enoic acid ri-f4-methoxV"phenvlVelfavn-aiDide To a suspension of (S)TA^-[l-(4-metiioxy-phenyl)-elhyl]-3-oxo-birtyramide (10 g) in toluene (800 ml) was added at 20 *'C ammonium acetate (10 g) and the reaction was heated for 20 h at 100 °C in a Dean Stark system. The mixture was concentrated in vacuo and the product obtained was used without further purification in the following reaction step. fcY 4-(3-Bromo-5-ethoxv-4-hvdroxv-phenvl)-2-methvl-5-oxo-7-propvl-L4,5,6J,8-hexahvdro-quinoline-3-carboxvlic acid flS)-ri"f4-methoxv-phenvD-ethyl'|-amide A mixture of (S)- 3-amino-but-2-enoic acid [l-(4-methoxy-phenyl)-ethyl]-amide (10 g), 3-bromo-5-ethoxy-4-hydroxy-benzaldehyde (10.4 g) and 5-propylcyclohexane-l,3-dione (6.5 g) in ethanol (150 ml) was stirred at 80^ for 18 hr. The mixture was concentrated in vacuo. The residue was dissolved in toluene (100 ml) and dichloromethane (50 ml) and evaporated until a precipitated formed The solid obtained was then crystallized in EtOAc. Yield: 12.9 g. MS-ESI: [M+H]^ = 597.4/599.4; anal. HPLC Rt = 16.70 (diast.l) Rt = 17.55 (diast.2) Rt = 18.81 (diast.3) Rt = 19.74 (diast,4) (method 7). Diast. ratio diast.l:diast2:diast3:diast4= 10:1:10:1, (d). r4S, 7S)-4-r3-Bromo-5-ethoxv-4-hvdroxv-phenvlV2-methvl-5-oxo-7-propvl- 1 A5,6,7,8-hexahvdro-auinoline-3-carboxvlic acid flSVri-r4-methoxv-phenvlVethvn- amide The mixture of stereoisomers obtained in Example 72c was then separated by chromatogr^hy on silicagel in heptane/ethyl acetate 2/8 -> 0/1 (v/v) as eluent. Yield: 2.6 g MS-ESI: [M+H]^ = 597.4/599.4; anal. HPLC Rt = 18,81 (diast.3) (method 7). Diast. ratio: 0:0:1:0 (e). f4R.7S)-4-r3-Bromo-5-ethoxv-4-hvdroxv-phenvlV2-methvl-5-oxo-7-T)ropvl-L4.5,6,7,8-hexahvdro-quinoline-3-carbomtrile A solution of (4S,7S)-4-(3-Bromo-5-ethoxy-4-hydroxy-phenyl)*2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinoIine-3-carboxylic acid [1 -(4-methoxy-phenyl)-efliyl]-amide (Example 72d, 1.43 g) was dissolved in TEA (30 mL) and stirred at 75°C for 1 hr. The TEA was evaporated in vacuo and the residue was then dissolved in dichloromethane (30 ml). Triethylamine (1.04 g) and trifuoroacetic acid anhydride (0,95 g) were added dropwise at 0°C for 15 minutes. The reaction was stirred for 1 hr and the reaction mixture was washed with water (20 ml). The organic layer was dried (MgS04), filtered, concentrated in vacuo and concentrated. The residue was purified by chromatography on silicagel in heptane/ethyl acetate 1/0 -> 0/1 (v/v) as ehient Yield: 777 mg. MS-ESI: [M+H]' = 445.4.4/447.4 (f). r4.5-Difluoro-2-nitro-phenvlVmethanol To a solution of to 4,5-difluoro-2-nitrobeirzoic acid (25.9 g) in THF (90 ml), cooled to 0 °C, was carefully added borane-tetrahydrofiiran con:5)lex (319 ml, IM in THF). After the addition was con:q)lete, the mixture was stirred at 60'^C for 3 h. Methanol (150 ml) was added to the mixture at 0°C and after 10 minutes the mixture was concentrated in vacuo. The residue was poured into water and extracted wilh ethyl acetate. The organic layer was washed with sat. aq. NaCl, dried (MgS04), filtered and concentrated in vacuo. Yield: 24.1 g fgl f4IL7S)-4-r3-Bromo-4-r4,5-difluoro-2-nitro-benzvloxvV5-ethoxv-T)henvn-2- methvl-5-oxo-7-propvl-L4,5,6,7,8-hexahvdro-quinoline-3-carbonitrile To a mixture of (4,5-difluoro-2-nitro-phenyl)-methanol (Example 72f, 5.1 g), (4R, 7S)-4-(3-Bromo-5-ethoxy-4-hydroxy-phenyl)-2-methyl-5-oxo-7-propyI-1,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile (Example 72e5 10.0 g) and polymer-supported triphenylphosphine (13.5 g, 3 mmol/g loading) in THF (500 ml), cooled to O'^C, was added diisopropyl azodicarboxylate (DIAD) (5.3 ml). After 1.5 h, the mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silicagel in heptane/ethyl acetate 4/1 -> 2/3 (v/v) as eluent. Yield: 13.5 g, MS-ESI: [M+H]^ = 616.10/618.10 (h\ f4R.7SM-r4-(2-Amino-4,5-difluoro-benzvloxv)-3-bromo-5-ethoxv-phenvn-2-methvl-5-oxo-7-propvl-L4,5,6,7.8-hexahvdro-quinoline-3-carbonitrile A solution of (4R,7S)-4-[3-Bromo-4-(4,5-difluoro-2-nitro-benzyloxy)-5-ethoxy-phenyl]-2-methyl-5-oxo-7-propyl-l,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile (Exaxaple 72 g, 10.6 g) and acetic acid (19.6 ml) in THF (400 ml) was cooled to 0°C. Zinc dust (27.6 g) was added in portions under vigorous stirring. The mixture was stirred for 2 h at 0*^C and then filtered. The solids were washed with dichloromethane and the combined filtrates were washed with sat aq. NaHCOa- The organic layer was dried (MgS04), filtered and concentrated in vacuo. Yield: 10.9 g. MS-ESI: [M+H]^ - 586.05/588,05 fiyjV:^^-a-r2-BTomo-4-fr4R.7SV3-cvano-2-methvl-5-oxo-7-piopvl-^ hexahvdro-quiDolin-4-vl)-6-etfaoxv-phenoxvmetfavl1-4,5-(Hfluoro-ph bismeihanesulfonamide A solution of (4R,7S)-4-[4-(2-Ammo-4,5-difluoro-beaizyloxy)-3-bromO"5-ethoxy-phenyl]-2-methyl-5-oxo-7-propyl-l,4,5,6,73-hexahy(fro-qiunolme-3-carbom (Example 72 h, 10.9 g) and triefliylamine (11.9 ml) in dichloromefliane (140 wS), cooled to O^C, was treated with methanesulfonyl chloride (3.3 ml). After stirring for 2 h at 0°C, the mixture was diluted with 0.2N hydrochloric acid and extracted with dichloromethane. The organic layer was washed with sat aq. NH4CI, dried (MgS04), filtered and concentrated in vacuo. The residue was purified by chromatogr^hy on silicagel in heptane/ethyl acetate 7/3 -^ 2/5 (v/v) as eluent Yield: 11.Og. MS-ESI: [M+H]"" = 742,08/744.08 G). iy-l2-r2-Bromo-4-ff4R.7SV3-cvano-2-methvl-5-oxo-7-T)ropvl-lA5,6,7,8- hexahvdro-quinolin-4-vl)-6-ethoxv-phenoxvmethvn-4,5-difluoro-phenvU" metiianesulfonamide A';Ar.{2-[2-Bromo-4-((4R,7S)-3-cyano-2-methyl-5-oxo-7-propyl-l,4,5,6,7,8-hexahydro-qumolin-4-yl)-6-ethoxy-phenoxymethyl]-4,5-difluoro-phenyI}-bismethanesulfonamide (Exanple 72 i, 11.0 g) was dissolved in dioxane (190 ml) and treated with 2N NaOH (80 ml). After 2 h the mixture was quenched with 2N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with sat aq. NH4CI, dried (MgS04), filtered and concentrated in vacuo. The residue was purified by chromatography on silicagel in toluene/acetone 1/0 -> 3/1 (v/v) as eluent Yield: 7.98 g. MS-ESI: [M+H]^ = 664.06/666.06; anal. HPLC Rt = 17.18 min (method 8) Chiral purity: 99.2% (levorotatory or -) (method 9) Example 73 Aponistic activity of compounds at the human FSH receptor expressed in CHO cells Agonist activity of the compounds at the human FSH receptor was tested in Chinese Hamster Ovary (CHO) cells stably transfected with the human FSH receptor and cotransfected with a cAMP responsive element (CRE)/promotor directing the expression of a firefly luciferase reporter gene. Binding of the compoimd to the Gs-coupled FSH receptor will resxilt in an increase of cAMP, which in turn will induce an increased transactivation of the luciferase reporter construct. The luciferase activity was quantified using a luminescence counter. The compounds were tested in the concentration range of 0.1 nM to 10 pM. This assay was used to determine the EC50 (concentration of test con5)ound causing half-maximal (50 %) luciferase stimulation) and efScacy of the compounds compared to recombinant human FSH. For this, the software program XL^t (Excel version 2.0, built 30, ID Business Solutions Limited) was used Con5)ounds of all examples had an activity (EC50) of less than 10"^ M. Some of the con:5)Ounds, such as those of examples 1, 3, 5, 7,11, 15, 17, 22, 23, 24, 25, 34, 38, 39, 42,50,51, 54, 56, 58, 62 and 72 showed an EC50 of less than 10"^ M. Claims 1. A 4-phenyl-5-oxo-l,4,5,6,7,8-hexaliydroquinoline derivative according to Fonnula I, 5 or a pharmaceutically acceptable salt thereof, wherein R^ is (l-6C)a]kyl, (2-6C)aIkenyl or (2-6C)alkynyl; R^, R^ are independently halogen, (l-4C)alkyl, (2-4C)aIkenyl, (2-4C)alkynyl, (l-4C)aIkoxy, (3-4C)alkenyloxy or (3-4C)alkynyloxy; R is phenyl or (2-5C)heteroaryl5 both substituted with R and optionally 10 substituted on the (hetero)aromatic ring with one or more substituents selected from hydroxy, amino, hatogen, nitro, trifluoromethyl, cyano, (l-4C)alkyl, (l-4C)a]koxy, (l-4C)alkylthio and (di)(l-4C)alkylamino; R'^ is H, (l-4C)alkylthio, (l-4C)allcylsulfonyl, (di)(l-4C)alkylamino, RV-amino, R23^^-aminocarbonyl, R23R23-amino(l-4C)alkylcarbonylamino, R23^^- 15 amino(l-4C)aIkyl, R23-oxy, R"R23-aminocarbonyl(l-4C)a]koxy, R23-oxy(l- 4C)alkyl, R23-oxycarbonyl(l-4C)alkyl, R^*^^^-aminosulfonyl, R23-oxysulfonyl, aminoiminomethyl, (di)(l-4C)alkylaminoiminomethyl or (2-6C)-heterocycloalkyliminomethyl, trifluoromethylsulfonyl; R23-oxycarbonyl, R23-carbonyl or R23R23-aminocarbonyl; 20 R^isHor(l-4C)alkyl; R^ is (l-4C)alkylsulfonyl, (l-6C)a]kylcarbonyl, (2-6C)alkenylcarbonyl, (2-6C)-alkynylcarbonyl, (3-6C)cycloaBcylcarbonyl, (3-6C)cycloalkyl(l-4C)alkyl-carbonyl, (MQalkoxycafbonyl, (3-4C)alkenyloxycarbonyl, (3-4C)a]kynyloxy-carbonyl, (di)(l-4C)a]kylaniinocarbonyl, (2-6C)heterocycloalkylcarbonyl, 25 (5-8C)alkyl, (3-6C)cycloalkyl, (3-6C)cycloalkyl(l-4C)alkyl, (di)(l-4C)a]kyl- amino(2-4C)a]kyl, (2-6C)heterocycloalkyl(2-4C)alkyl or phenylcarbonyl, phenylsulfonyl, phenyl(l-4C)aIkoxy(l-4C)alkylcarboiiyl, phenyl(l-4C)alkyl, (2-5C)heteroarylcarbonyl, (2-5C)heteroarylsulfonyl, (2-5C)heteroaryl(l-4C)-alkyl, optionally substituted on the (hetero)aromatic ring with one or more substituents selected from hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, (l-4C)alkyl, (1-4alkoxy or (di^(l-4C)alkylamino; R^Ss H or (MC)alkyl; R23 is hydroxy(2^C)alkyl, amino(2-4C)alkyl, (l-4C)alkoxy(2-4C)alkyl or (di)-(l-4C)a]kylamino(2-4C)alkyl; or R23^^ m R^*^^^-aminocarbonyl may be joined in a (4-6C)heterocycloalkenyl ring or a (2-6C)heterocycloalkyl ring substituted with one or more substituents selected from (l-4C)alkyl, (l-4C)a]koxy(l-4C)alkyl and hydroxy(l-4C)alkyl; R23 R23 are independently H, (l-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (3-6C)-cycloalkyl, hydroxy(2-4C)alkyl, (l-4C)alkoxy(2-4C)alkyl, (3-6C)cycloalkyl-(l-4C)alkyl, (2-6C)heterocycloalkyl(l-4C)allcyl, amino(2-4C)aIlcyl, (di)(l-4C)-a]kylamino(2-4C)a]kyl orphenyl(l-4C)a]kyl, (2-5C)heteroaiyl(MC)alkyl, optionally substituted on the (hetero)aromatic ring with one or more substituents selected from hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, (1-4C)-aUcyl, (1-4alkoxy and (di)(l-4C)aIkylaniino; or R^ V^ in R23R"-amino(l-4C)aIkylcarbonylamino may be joined in a (4-6C)-heterocycloalkenyl ring or a (2-6C)heterocycloalkyl ring, optionally substituted with one or more substituents selected from (l-4C)alkyl, (l-4C)a]koxy(l-4C)-alkyl and hydroxy(l -4C)alkyl; R23R23 are independently H, (l-6C)alkyl, (2-6C)heterocycloalkyl(l"4C)alkyl, (3-6C)cycloallcyl(l-4C)alkyl, (l-4C)aIkoxy(2-4C)alkyl, hydroxy(2-4C)alkyl, (di)(MC)a]kylamino(2-4C)alkyl, amino(2-4C)alkyl, (l-4C)alkoxycarbonyl-(l-4C)aIkyl, (l-6C)a]kylcarbonyl, (3-6C)cycloalkylcaibonyl, (l-4C)alkoxy-carbonyl, (3-4C)alkenyloxycarbonyl, (di)(l-4C)a]kylaminocarbonyl, (2-6C)-heterocycloalkylcaxbonyl or (2-5C)heteroaryl(l-4C)a]kyl, phenyl(l-4C)aIkyl, (2-5C)heteroarylcarbonyl, phenylcarbonyl, optionally substituted on the (hetero)aiomatic ring with one or more substituents selected from hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, (l-4C)allQ^l or (1-4alkoxy, (di)(l-4C)alkylainino; or may be joined in a (4-6C)heterocycbalkenyl ring or a (2-6C)heterocycloalkyl ring, optionally substituted with one or more substituents selected from (l-4C)aIkyl, (l-4C)alkoxy(l-4C)alkyl andhydroxy(l-4C)aIkyl; R23 is (2-6C)heterocycloalkyl(l-4C)alkyl, (di)(MC)alkylamino(2-4C)alkyl, (2-4C)aIkoxy(l-4C)alkyl, hydroxy(2-4C)alkyl, amino(2-4C)alkyl, hydioxycarbonyl(l-4C)alkyl, (l-4C)a]koxycarbonyl(l-4C)aIkyl, (l-4C)aIkoxy-carbonyl, (3-4C)aIkenyloxycarbonyl, (3-4C)alkynyloxycarbonyl, (di)(l-4C)-alkylaminocarbonyl, (2-6C)lieterocycloalkylcarbonyl, orplienyl(l-4C)a]kyl, (2-5C)heteroaryl(l-4C)alkyl, optionally substituted on the (Tietero)aromatic ring with one or more substituents selected from hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, (l-4C)allcyl, (l-4C)alkoxy and (di)(l-4C)alkylamino; R23R23 are independently H, (l-6C)alkyl, (3-6C)cycloalkyl(l-4C)alkyl, (1-4C)-a]koxy(2-4C)a]kyl, hydroxy(2-4C)aIkyl, amino(2-4C)a]kyl, (di)(l-4C)alkyl-amino(2-4C)alkyl, (2-6C)heterocycloalkyl(2"4C)alkyl, orphenyl(l-4C)a]kyl, (2-5C)heteroaryl(l-4C)alkyl, optionally substituted on the (hetero)aromatic ring with one or more substituents selected from hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, (l-4C)alkyl, (l-4C)alkoxy and (di)(l-4C)aIkylamino; or R23R23 in R23R23-aminocarbonyl(l-4C)aIkoxy may be joined in a (4-6C)hetero-cycloalkenyl ring or a (2-6C)heterocycloalkyl ring, optionally substituted with one or more substituents selected from (l-4C)alkyl, (l-4C)alkoxy(l-4C)alkyl and hydroxy(l-4C)al]cyl; R^MsHor(l-6C)alkyl; R23R23 are independently H, (l-6C)alkyl, (1.6C)alkenyl, (l-6C)alkynyl or (1 -4C)aIkoxy(l -4C)alkyl; or R^V^ inR23^^^-aminosulfonyl may be joined in a (4-6C)heterocycloalkenyl ring or a (2-6C)heterocycloaIkyl ring, optionally substituted with one or more substituents selected from (l-4C)alkyl, (l-4C)a]koxy(l-4C)alkyl andhydroxy-(l-4C)aIkyl; XisOorN-R^; Y is CH2, C(0) or SO2; ZisCNorNOa; R^ is H, (l-4C)alkyl; R^\ R23 are independently H, (1.4C)a]kyl, (2-4C)alkenyl, (2-4C)aIkynyl, (3-6C)-cycloalkyl, (3-6C)cycloalkyl(l-4C)alkyl, (2-6C)lieterocycloa]kyl, (2-6C)hetero-cycloalkyl(l-4C)alkyl, (l-4C)a]koxycarbonyl(l-4C)aIkyl, (di)(l-4C)a]kylamino-carbonyl(l-4C)a]kyl or phenylaminocarbonyl(l-4C)alkyl, (2-5C)heteroaryl-aniinocarbonyl(l-4C)a]kyl, phenyl, (2-5C)heteroaryl3 phenyl(l-4C)a]kyl, (2-5C)heteroaryl(l-4C)alkyl, optionally substituted at the (hetero)atom with one or more substituents selected ftom hydroxy, amino, halogen, nitre, trifluoromethyl, cyano, (l-4C)alkyl, (2-4C)a]kenyl, (2-4C)alkynyl, (l-4C)alkoxy and (di)(1.4C)-aDcylamino; or R23R^"* in R23R23-aminocarbonyl may be joined in a (4-6C)heterocycloalkenyl ring or a (2-6C)heterocycloa]kyl ring, optionally substituted with one or more substituents selected from (l-4C)alkyl, (l-4C)aIkoxy(l-4C)alkyl and hydroxy-(1 -4C)alkyl; with the proviso that the compounds of fonnula I wherein X is O, R^ is phenyl and R is selected from H, (l-4C)alkylthio, (l-4C)allcylsulfonyl, di(l-4C)alkylamino, R -oxycarbonyl, R -cafbonyl and R R -aminocarbonyl, and the compounds of foimula I wherein X is O, R^ is (2-5C)heteroaryl and R^ is H or (di)(l-4C)alkylamino, are excluded. 2. The 4-phenyl-5-oxo-l,4,5,6,7,8-hexahydroquinoline derivative according to claim 1 wherein R^ is (l-6C)a]kyl. 3. The 4-phenyl-5-oxo-l,4,5,6,7,8-hexahydroquinoline derivative according to claims 1 -2 wherein R is halogen. 4. The 4-phenyl-5-oxo-l,4,5,6,7,8-hexahydroqmnoline derivative according to claims 1-3 wherein R^ is (l-4C)alkoxy, 5. The 4-phenyl-5-oxo-l,4,5,6,7,8-hexahydroquinoline derivative according to claims 1-4 wherein Z is CN. 6. The 4-phenyl-5-oxo-l,4,5,6,7,8-hexahydroquinoline derivative according to claims 1-5 wherein X is O. 7. The 4-phenyl-5-oxo-l,4,5,6,7,8-hexahydroquinoline derivative according to claims 1-6 wherein Y is CH2. 8. The 4-phenyl-5-oxo-l54,5,6,7,8-hexahydroqiiinoline derivative according to claims 1-7 wherein R'^ is R^R^-amino, R23^^-aminocarbonyl, R23R23-amino- (1-4C)a]kylcarbonylamino, R^'^^^-aminoC1-4alkyl or R"R23-aminocarbonyl(l-4C)aIk:oxy. 9. The 4-phenyl-5-oxo-l,4,5,6,7,8-hexahydroquinoline derivative according to claims 1-8 wherein R^isH; R^ is (l-4C)a]kylsulfonyl, (l-6C)alkylcarbonyl, (3-6C)cycloa]kylcarbonyl, (l-4QaIkoxycarbonyl, (3-4C)alkenyloxycarbonyl, (di)(l-4C)aIkylamino- carbonyl, (2-6C)heterocycloalkylcarbonyl, or phenylcarbonyl, phenyl(l-4C)- a]koxy(l-4C)aIkylcarbonyl5 (2-5C)heteroarylcarbonyl, (2-5C)heteroarylsulfonyl or (2-5C)heteroaTyl(l-4C)alkyl, optionally substituted on the (hetero)aromatic ring with one or more substituents selected from, halogen or (l-4C)a]koxy; R23isHor(l-4C)alkyl; R23 is hydroxy(2-4C)alkyl, amino(2-4C)aIkyl, (l-4C)alkoxy(2-4C)aIkyl or (di)- (l-4C)alkylamino(2-4C)alkyl; or R23^^ inR23^^-aminocarbonyl may be joined in a (4-6C)heterocycloalkenyl ring or a (2-6C)heterocycloalkyl ring, optionally substituted with one or more substituents selected from (l-4C)aIkyl; R23, R23 are independently H, (l-6C)a]kyl, (3-6C)cycloalkyl, hydroxy(2-4C)- alkyl, (l-4C)aIkoxy(2-4C)alkyl, (2.6C)heterocycloalkyl(l-4C)a]kyl or (di)- (l-4C)a]kylamino(2-4C)alkyl or phenyl(l-4C)alkyl or (2-5C)heteroaryl(l- 4C)aIkyl, optionally substituted on the (hetero)aromatic ring with one or more substituents selected from halogen; or R23R23 in R23R23-airiino(l-4C)alkylcarbonylamino may be joined in a (4-6C)- heterocycloalkenyl ring or a (2"6C)heterocycloa]kyl ring, optionally substituted with one or more substituents selected from (l-4C)aIkyl or hydroxy(l"4C)alkyl; B}\'B}^ are independently H, (l-6C)alkyl, hydroxy(2-4C)alkyl, (1.4C)a]koxy- carbonyl(l-4C)a]kyl, (l-6C)alkylcarbonyl, (3-6C)cycloalkylcarbonyl, (1-4C)- alkoxycarbonyl, (2-5C)heteroaryl(l-4C)aIkyl, (2-5C)heteroarylcarbonyl or phenylcarbonyl; R23 is (2-6C)heterocycloalkyl(l-4C)alkyl, (di)(l-4C)aIkylamino(2-4C)alkyl, (2-4C)alkoxy(l-4C)alkyl, hydroxycarboiiyl(l-4C)alkyl, (l-4C)a]koxycarbonyl-(l-4C)alkyl; orphenyl(l-4C)alkyl or (2-5C)heteroaiyl(l-4C)alkyl, optionally substituted on the (hetero)aronaatic ring with one or more substituents selected from halogen or (l-4C)alkoxy; R23R23 are independently H, (l-6C)alkyl, (3-6C)cycloalkyl(l-4C)alkyl, (1-4C)-a]koxy(2-4C)aIkyl or (2-6C)heterocycloalkyl(2-4C)a]kyl; or phenyl(l-4C)alkyl or (2-5C)heteroaryl(l-4C)allcyl, optionally substituted on the (hetero)aromatic ring with one or more substituents selected from halogen; or R^ V^ in R23R23-aminocarbonyl(l-4C)aIkoxy may be joined in a (4-6C)hetero-cycloalkenyl ring or a (2-6C)heterocycloalkyl ring, optionally substituted with one or more substituents selected from (l-4C)a]kyl or hydroxy(l-4C)aIkyl. 10. The 4-phenyl-5-oxo-l5455,6,758-hexahydroquinoline derivative according to claim 8 wherein R^ is R^R^-amino. 11. The 4-phenyl-5-oxo-l54,5,6,758-hexahydroquinoline derivative according to claim 10 wherein R is H and R is (1 -4C)alkylsulfonyL 12. A 4-phenyl-5-oxo-l,4,556,7,8-hexahydroquinoline derivative or a pharmaceutically acceptable salt thereof selected from the group of -^-{3-[2-BromO"4-(3-cyano-2-methyl-5-oxO"7-propyl-l,4,5,6,758-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-354,5-trimethoxy-benzamide; JV-{3-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-prppyl-l,4,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-2-[(pyridin-4-ylmethyl)-amino]-acetamide; iV-{3-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-l,4,5365758-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-2-[4-(2-hydroxy-ethyl)-piperazin-1 -yl]-acetamide; 4-{3-Bromo-4-[3-(3,6-dihydro-2i7-pyridine-l-carbonyl)-benzyloxy]-5-ethoxy-phenyl} -2-methyl-5-oxo-7-propyl-l ,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile; 3-IBis-(2-methoxy-ethyl)-amino]-iV-{3-[2-bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-l54,5,6,7,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-propionamide; 2-{3-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-l,4,556,7,8-hexahydro- quinolin-4-yl)-6-e1hoxy-phenoxymethyl]-phenoxy}-^^-dimelhy 4-{3-Bromo-5-ethoxy-4-[3-(2-morpholin-4-yl-2-oxo-ethoxy)-benzyloxy]-phenyl}-2-me carbonitrile; Furan-2-carboxylic acid {2-[2-broino-4-(3-cyano-2-methyl-5-oxo-7-pxopyl- 1,4,5,6,7,8-hexahydro-quinolm"4-yl)-6-elhoxy-phenoxyme1hyl]-phenyl} -amide; iV-{2-[2-Broino-4-(3-cyano-2-inethyl-5-oxo-7-propyl-l,4,5,6,7,8-liexahydro- quinolin-4-yl)-6-ethoxy-phenoxymethyl] -phenyl} -acrylamide; Cyclopropanecarboxylic acid {2-[2-bromo-4-(3-cyaiio-2-inethyl-5-oxo-7-propyl- 1,4,5,6 J,8-hexahydro-quinolin-4-yl)-6-ethoxy-phenoxyinethyl]-phenyl} -amide; 2-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro- qiiinolin-4-yl)-6-elhoxy-phenoxymethyl]-phenyl}-carbainic acid methyl ester; l-{2-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-l,4,5,6,7,8-hexahydro- qx3inolin-4-yl)-6-ethoxy-phenoxymethyl] -phenyl} -3 -methyl-urea {3-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-l,4,5,6,7,8-hexahydro- quinolin-4-yl)-6-ethoxy-phenoxymethyl]-pyridin-2-yl}-carbamic acid methyl ester 4-(3-Bromo-5-ethoxy-4-{3-[(li/-imidazol-4-ylmethyl)-amino]-benzyloxy}- phenyl)-2-methyl-5-oxo-7-propyl-l34,5,6,7,8-hexahydro-qimoline-3- carbonitrile; -W-{3-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-l,4,5,6,758-hexahydro- quinolin-4-yl)-6-ethoxy-phenoxymethyl] -phenyl} -methanesulfonamide; {4-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-l,4,5,6,7,8-hexahydro- quinolin-4-yl)-6-ethoxy-phenoxymethyl]-phenyl}-carbaroic acid allyl ester; 4-[3-Bromo-5-ethoxy-4-(l-methanesulfonyl-li?-pyrrol-2-ylmethoxy)-phenyl]-2- methyl-5-oxo-7-propyH,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile; 4-[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-propyl-l,4,5,6,7,8-hexahydro- qiunolm-4-yl)-6-ethoxy-phenoxymethyl]-iV'-methyl-benzamidine; 4-{3-Bromo-5-ethoxy-4-[(pyridin-3-ylmethyl)-aniino]-phenyiy-2-methyl-5-oxo- 7-propyl-l,4,5,6,7,8-hexahydro-qiunoline-3-carbonitrile; ^-(2-{[2-Bromo-4-(3-cyano-2-methyl-5-oxo-7-pr€>pyl-l,4,5,6,7,8-hexahydro- qumolin-4-yl)-6-ethoxy-phenylamino]-me1hyl}-phenyl)-me1iianesidfonamide; 4- {3-Bromo-4-[2-(cyclopropylme1hyl-a3iiino)-benzyloxy] -S-ethoxy-phenyl} -2- methyl-5-oxo-7-propyl-l,4,5,6,758-hexahydro-quinoline-3-carbom1iile;or iV-{2-[2-Bromo-4-((4R,7S)-3-cyano-2-me1hyl-5-oxo-7-propyl-lA5,6,7,^ hexahydro-qmolm-4-yl)-6-ethoxy-phenoxyme1iiyl]-4,5-diflu methanesulfonamide 13. A 4-phenyl-5-oxo-l,4,5,6,758-liexaliydroqimiolme derivative according to claims 1-12 for use in therapy. 14. A pharmaceutical composition comprising a 4-phenyl-5-oxo-l,4,5,6,7,8- hexahydroquinoline derivative of any one of claims 1-12, and phaimaceutically suitable auxiliaries. 15. Use of the 4-phenyl-5-oxo-l54,5,6,7,8-hexahydroquinoline derivative of any one of claims 1-12, or a phamiaceutically acceptable salt or solvate thereof for the manufacture of a medicament for the treatment of fertility disorders.

Documents:

4957-CHENP-2007 ENGLISH TRANSLATION 03-02-2012.pdf

4957-CHENP-2007 OTHER DOCUMENT 03-02-2012.pdf

4957-CHENP-2007 AMENDED CLAIMS 09-12-2014.pdf

4957-CHENP-2007 AMENDED PAGES OF SPECIFICATION 09-12-2014.pdf

4957-CHENP-2007 CORRESPONDENCE OTHERS 19-05-2014.pdf

4957-CHENP-2007 CORRESPONDENCE OTHERS 03-02-2012.pdf

4957-CHENP-2007 CORRESPONDENCE OTHERS 23-10-2014.pdf

4957-CHENP-2007 CORRESPONDENCE OTHERS 03-01-2013.pdf

4957-CHENP-2007 CORRESPONDENCE OTHERS 29-08-2013.pdf

4957-CHENP-2007 EXAMINATION REPORT REPLY RECEIVED 27-05-2014.pdf

4957-CHENP-2007 FORM-1 03-01-2013.pdf

4957-CHENP-2007 FORM-13 03-01-2013.pdf

4957-CHENP-2007 FORM-3 19-05-2014.pdf

4957-CHENP-2007 FORM-6 03-02-2012.pdf

4957-CHENP-2007 FORM-6 29-08-2013.pdf

4957-CHENP-2007 FORM-6-1 29-08-2013.pdf

4957-CHENP-2007 OTHER PATENT DOCUMENT 09-12-2014.pdf

4957-CHENP-2007 OTHERS 29-08-2013.pdf

4957-CHENP-2007 POWER OF ATTORNEY 03-02-2012.pdf

4957-CHENP-2007 POWER OF ATTORNEY 03-01-2013.pdf

4957-CHENP-2007 POWER OF ATTORNEY 29-08-2013.pdf

4957-CHENP-2007 AMENDED CLAIMS 16-05-2014.pdf

4957-CHENP-2007 AMENDED PAGES OF SPECIFICATION 16-05-2014.pdf

4957-CHENP-2007 ASSIGNMENT 09-12-2014.pdf

4957-CHENP-2007 CORRESPONDENCE OTHERS 07-11-2014..pdf

4957-CHENP-2007 CORRESPONDENCE OTHERS 14-11-2014.pdf

4957-CHENP-2007 EXAMINATION REPORT REPLY RECEIVED 09-12-2014.pdf

4957-CHENP-2007 EXAMINATION REPORT REPLY RECEIVED 16-05-2014.pdf

4957-CHENP-2007 FORM-1 09-12-2014.pdf

4957-CHENP-2007 FORM-1 16-05-2014.pdf

4957-CHENP-2007 FORM-5 09-12-2014.pdf

4957-CHENP-2007 FORM-5 16-05-2014.pdf

4957-CHENP-2007 OTHERS 16-05-2014.pdf

4957-chenp-2007-abstract.pdf

4957-chenp-2007-claims.pdf

4957-chenp-2007-correspondnece-others.pdf

4957-chenp-2007-description(complete).pdf

4957-chenp-2007-form 1.pdf

4957-chenp-2007-form 26.pdf

4957-chenp-2007-form 3.pdf

4957-chenp-2007-form 5.pdf

4957-chenp-2007-pct.pdf

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