Title of Invention	"AN ANTIDOTE S-(w-AMINOALKYLAMINO) ALKYL ARYL SULPHIDE DIHYDROCHLORIDES"
Abstract	This invention relates to a new antidote S-(o-Aminoalkylamino) alkyl aryl sulphide dihydrochlorides particularly S-2(2-aminoethylamino)ethyl phenyl sulphide dihydrochloride against highly toxic Sulphur Mustard, prepared by the process claimed in present application No. 547/DEL/99 dated 08 April, 99.

Full Text

FIELD OF INVENTION This invention relates to a new and effective antidote - S-(co-Aminoalkylamino) alkyl aryl sulphide dihydjochlorides particularly S-2(2-aminoethylamino) ethyl phenyl sulphide dihydrochloride, against highly toxic sulphur mustard (SM). PRIOR ART Sulphur mustard (SM) is a highly toxic chemical and a well known chemical warfare agent. This chemical attacks not only skin but all epithelial tissues with which it comes into contact including those of eyes and airways. Exposure to higher doses of sulphur mustard causes systemic toxicity with little or no involvement of the eyes, respiratory tract or skin. The signs and symptoms of systemic poisoning are similar to those caused by nuclear radiation. Two causes of antidotes have been tested against SM toxicity. The first type of antidote is called as 'SM scavenger' and comprises of compounds that prevent alkylation of critical targets. Representative members of this class that have been tested are sodium thiosulphate, N-acetyl-L-cysteine, and several other sulphur compounds such as thiophosphonates, thiophosphates and thiocarbamates. These classes of compounds have several disadvantages that would preclude their practical use as antidote for systemic toxicity of sulphur mustard. One of tne disadvantage ot the above type of compounds is that they can only be administered intravenously thereoy making them unsuitable for self— mBtration. Another disadvantage of the above ot compounds is that they are suitable only for pre-treatment. Still another disadvantage of the aoove type ot compounds tor use as antidote against SM is that these compounds are excreted rapidly by the Kidney after which their efficacy as FSM scavenger' is lost. The second type of the compounds known in the + art as 'NAD level stabilisers'. Nicotinamide and nicotinic acids have been tested as representatives of this class. Although some of these compounds under certain circumstances have been found effective in preventing bh toxjcity, these also suffer from certain drawbacks.' HOP drawback ot these compounds is that they are effective in lymphocytes but not in cultured keratinocytes. Another disadvantage of these compounds is that if these compounds are administered 24 hours after SM exposure, they fail to provide any protection against SM toxicity. Still another disadvantage of the above type of compounds is that these compounds tail to prevent SM— induced Adenosine I r i phosphate(*Vl H > loss in the cells and thus these compounds provide only short term cytoprotection. further disadvantage1 of the above type of compounds is that like tirst type of compounds, these compounds can only oe administered intravenously. Ot- FHb INVENTION i he? primary object of the present invention is to propose a new and effective antidote i3- wnother object of the present invention is to propose a new and effective antidote S- (Q) -Hmi nos] kylami no> alkyl aryl sulphide dihydrochlorides particularly b-2 compound suitable for self —administration. h>ti I. i another object of the present invention is to propose a new and effective antidote S-ito-Aminoaikylamino) alkyl aryl sulphide dihydrochlorides particularly S-2 (2-aminoethylamino) ethyl phenyl sulphide dihydrochloride which is effective as a pretreatment and also as a therapeutic agent. Further object of the present invention is to propose a new and effective antidote S— C ethyl phenyl sulphide* ai hyarochior i de which provides cyto-protect: x i in. •btill furtner object of the present invention is to propose a new and effective antidote S—— Aminoa]kylamino) alkyl aryl sulphide dihydrochlorides particularly S-2 (2-aminoethylamino) ethyl phenyl sulphide dihydrochloride whichis effective in lymphocytes as well as cultured keratinocytes. bTAThtlENT OF INVENTION According r.o this invention there is provided a new and effective antidote B-(W-Aminoalkylamino) alkyl aryl sulphide dihydrochlonde particularly S-2 (2-aminoethylamino) ethyl phenyl sulphide dihydrochlorlde, against known chemical warfare agent sulphur mustard. The process for the preparation of this compound has already been claimed in pending patent application No 547/DEL/99 dated 8th April 99. The process of the invention comprises of the condensation of S (f)-Aminoalkylamino)ethyl bromide dihydrobromide with aryl mercaptan in the presence of an organic base in an organic solvent The organic base used is primary or secondary or tertiary alkylamme or arylamine. The organic base preferably used on the present invention is tri ethylamine. The organic solvents used were chloroform, carbon tetrachloride. dimethyl sulphoxide or dimethyl formamide. The organic solvent preferred in the invention is chloroform The reaction was carried out at -15 to +15°C with efficient stirring for 2 - 5 hours. The residue comprising of the free base was converted to its hydrochlonde salt by treatment with concentrated hydrochloric acid. The antidote compound of the present invention can be administered both orally as well as intraperitoneally making it a unique compound which is suitable for self-administration. The compound is effective as a pre-treatment as well as a therapeutic agent and provides cytoprotection in cases of systemic toxicity. The process provides 60-65% yield of compound with a very high purity of more than 99%. The compound of the present invention S-(c)-Ammoalkylamino) alkyl aryl sulphide dihydrochlorides particularly S-2 (2-aminoethylammo) ethyl phenyl sulphide dihydrochlonde. has the following properties PROPERTIES Melting Point 194-195°C Thin Layer More than 99% Pure Chromatography [Methanol Chloroform Ammonia (1:3 1)] Spectral Data IR (KBr. cm'1) 1611, 1530, 1438, 737 'HNMR (CD3OD) MS (ESI) m/z197(M+H)+ Stability Stable in both Acidic and Basic Media PHARMACOLOGICAL EVALUATION OF THE COMPOUND The pharmacological evaluation of S-(r>-aminoalkylamino)alkyl aryi sulphide dihydrochlondes particularly S-2 (2-ammoethylamino) ethyl phenyl sulphide dihydrochlonde has been carried out on randomly bred adult female swiss mice weighing 25-28 gm each. For the estimation of LD50 [D1]of the compound, freshly prepared solutions of the compound were administered intraperitonially or orally The compound was administered as a single injection or as a single feeding and the animals were observed for mortality for a period of fourteen days For the protection studies sulphur mustard was applied topically on the back of mice after closely clipping the hair Freshly prepared solutions of the compound in distilled water were injected or given orally and the animals were observed for fourteen days for mortality. The results were analysed statistically and it was found that S-(w-aminoalkylammo)alkyl aryl sulphide dihydrochlorides particularly S-2 (2-ammoethylamino) ethyl phenyl sulphide dihydrochlonde provided significant protection both parenterally as well as orally. It is to be understood that the new antidote S-(o)-Aminoalkylamino) alkyl aryl sulphide dihydrochlorides particularly S-2 (2-ammoethylamino) ethyl phenyl sulphide dihydrochlonde of the present invention prepared by the said process is susceptible to modifications, adaptations and changes by those skilled in the field of art Such modifications, adaptations and changes are intended to be within the scope of the present invention which is set forth by the following claims:- WE CLAIM: 1. A new antidote S-(w-Aminoalkylamino) alkyl aryl sulphide dihydrochlorides particularly S-2(2-aminoethylamino) ethyl phenyl sulphide dihydrochloride against highly toxic Sulphur Mustard, prepared by the process claimed in present application No,547/Del/99 dated 08 April 99. 2. A new antidote S-(co-Aminoalkylamino) alkyl aryl sulphide dihydrochlorides particularly S-2(2-aminoethylamino) ethyl phenyl sulphide dihydrochloride against highly toxic Sulphur Mustard as claimed in claim 1, wherein the compund can be administered orally as well as parenterally. 3. A new antidote S-(co-Aminoalkylammo) alkyl aryl sulphide dihydrochlorides particularly S-2(2-aminoethylamino) ethyl phenyl sulphide dihydrochloride against highly toxic Sulphur Mustard as claimed in claim 1, wherein the compound is effective for pre-treatment. 4. A new antidote S-(tt)-Aminoalkylamino) alkyl aryl sulphide dihydrochlorides particularly S-2(2-aminoethylamino) ethyl phenyl sulphide dihydrochloride against highly toxic Sulphur Mustard as claimed in claim 1 wherein the compound can be used as therapeutic agent. 5. A new antidote S-((o-Aminoalkylamino) alkyl aryl sulphide dihydrochlorides particularly S-2(2-aminoethylamino) ethyl phenyl sulphide dihydrochloride against highly toxic Sulphur Mustard as claimed in claim 1 wherein the compound provides cytoprotection 6. A new antidote S-(co-Aminoalkylamino) alkyl aryl sulphide dihydrochlorides particularly S-2(2-aminoethylamino) ethyl phenyl sulphide dihydrochloride against highly toxic Sulphur Mustard as claimed in claim 1 wherein the compound is effective in lymphocytes as well as cultured keratinocytes. 7 A new antidote S-(co-Aminoalkylamino) alkyl aryl sulphide dihydrochlorides particularly S-2(2-aminoethylamino) ethyl phenyl sulphide dihydrochloride against highly toxic Sulphur Mustard as substantially described herein.

Documents:

819-del-2003-abstract.pdf

819-del-2003-claims.pdf

819-DEL-2003-Correspondence Others-(24-08-2011).pdf

819-del-2003-Correspondence-Others-(11-02-2011).pdf

819-DEL-2003-Correspondence-Others-(21-02-2011).pdf

819-del-2003-correspondence-others.pdf

819-del-2003-description (complete).pdf

819-del-2003-form-1.pdf

819-del-2003-Form-15-(11-02-2011).pdf

819-del-2003-form-18.pdf

819-del-2003-form-2.pdf

819-DEL-2003-GPA-(21-02-2011).pdf

819-DEL-2003-GPA-(24-08-2011).pdf