Title of Invention	"A NOVEL CYCLIC DONOR-ACCEPTOR CONJUGATE,PROCESS AND A SUPRAMOLECULAR FLUORESCENT MARKER THEREOF"
Abstract	The present invention provides a cyclic donor-acceptor conjugate or its pharmaceutical acceptable derivatives of general formula 1. The present invention further provides a process for the preparation of cyclic donor-acceptor conjugate of formula 1. The present invention also provides a supramolecular fluorescent marker comprising a cyclic conjugate containing two aryl groups, one of which is anthracene, linked together by suitable spacer moieties, represented by Formula 1 and highly fluorescent indicator HPTS, for the detection and quantification of GTP and ATP under physiological pH conditions and in biological fluids. This supramolecular marker is highly soluble in aqueous medium, extremely stable in the dark and under irradiation conditions and exhibit favorable absorption and fluorescence emission properties. The cyclic conjugate of Formula 1 forms an effective complex with the highly fluorescent indicator; HPTS resulting in the formation of a supramolecular probe through electrostatic and hydrophobic interactions. The supramolecular marker thus formed is found to be effective in differentiating selectively GTP and ATP from other nucleotides and recognizes GTP and ATP through "turn-on" fluorescence mechanism. The supramolecular marker is extremely useful as a visual fluorescent marker for the detection and quantification of GTP and ATP under physiological pH conditions and in biological fluids.

Title of Invention

"A NOVEL CYCLIC DONOR-ACCEPTOR CONJUGATE,PROCESS AND A SUPRAMOLECULAR FLUORESCENT MARKER THEREOF"

Abstract

The present invention provides a cyclic donor-acceptor conjugate or its pharmaceutical acceptable derivatives of general formula 1. The present invention further provides a process for the preparation of cyclic donor-acceptor conjugate of formula 1. The present invention also provides a supramolecular fluorescent marker comprising a cyclic conjugate containing two aryl groups, one of which is anthracene, linked together by suitable spacer moieties, represented by Formula 1 and highly fluorescent indicator HPTS, for the detection and quantification of GTP and ATP under physiological pH conditions and in biological fluids. This supramolecular marker is highly soluble in aqueous medium, extremely stable in the dark and under irradiation conditions and exhibit favorable absorption and fluorescence emission properties. The cyclic conjugate of Formula 1 forms an effective complex with the highly fluorescent indicator; HPTS resulting in the formation of a supramolecular probe through electrostatic and hydrophobic interactions. The supramolecular marker thus formed is found to be effective in differentiating selectively GTP and ATP from other nucleotides and recognizes GTP and ATP through "turn-on" fluorescence mechanism. The supramolecular marker is extremely useful as a visual fluorescent marker for the detection and quantification of GTP and ATP under physiological pH conditions and in biological fluids.

Full Text	We Claim 1. A cyclic donor-acceptor conjugate or its pharmaceutical acceptable derivative of general formula 1 (Formula Removed) 2. The compound as claimed in claim 1, wherein the representative compounds of general formula 1 are as follows: Cyclo[bis(ethylenedipyridinium-9,10-anthracene) tetrahalide(la); Cyclo [bis (ethylenedipyridinium-9,10-anthracene) tetrakis hexafluorophos phate(1b); Cyclo[bis(dipyridinium-9,10-anthracene) tetrahalide (1c); Cyclo[bis dip yridinium-9,10-anthracene) tetrakishexafluorophosphate (1d); Cyclo[bis(pyrazinium-9,10-anthracene) tetrahalide (1e); Cyclo[bis(pyrazinium -9,10-anthracene) tetrakishexafluorophosphate (1f); Cyclo[bis(imidazolium-9,10-anthracene) dihalide (1g); Cyclo[bis(imidazolium -9,10-anthracene) tetrakishexafluorophosphate (1h); Cyclo[bis(ethylenedipyridinium-9,10-anthracene)1", 6"-pyrene tetrahalide(H); Cyclo[bis(ethylenedipyridinium-9,10-anthracene) 1", 6"-pyrenetetrakishexa fluorophosphate (1j); Cyclo[bis(dipyridinium-9,10-anthracene) 1", 6"-pyrene tetrahalide (1k); Cyclo[bis(dipyridinium-9,10-anthracene)1",6"-pyrenetetrakishexafluorophosp hates (11); Cyclo[bis(pyrazinium-9,10-anthracene) 1", 6"-pyrene tetrahalide (1m) and Cyclo[bis(pyrazinium-9,10-anthracene)1",6"-pyrenetetrakishexafluorophosph ate (1 n). 3. The compound as claimed in claim 1, wherein the cyclic donor-acceptor conjugate in combination with a highly fluorescent indicator is useful as supramolecular probe for the detection and quantification of nucleotides in buffer and biological fluids. 4. The compound as claimed in claim 3, wherein the highly fluorescent indicator used in supramolecular probe is 8-hydroxy-1, 3, 6-pyrene trisulfonate. 5. The compound as claimed in claim 3, wherein the nucleotide used is selected from the group consisting of guanosine 5'-triphosphate, adenosine 5'-triphosphate, adenosine 5'-monophosphate, adenosine 5'-diphosphate, cytidine 5'-triphosphate, uridine 5'-triphosphate and iosine 5'-triphosphate. 6. A process for the preparation of cyclic donor-acceptor conjugate, its salt or pharmaceutically acceptable derivatives of general formula 1; the said process comprising the steps of: a) reacting a molar ratio of 9, 10-bis(halo substituted methyl) anthracene to a nitrogen containing compound selected from pyrazine, ethylenedipyridine, bipyridyl, and imidazole with a molar ratio of 1:6 to 1:7, in a dry organic solvent for a period of about 30 minutes, under reflux, for about 4 hours and cooling the resultant reaction mixture to a temperature of 25-30°C, followed by filtration by known method to obtain the compound of general formula 2, (Formula Removed) b) reacting the compound of general formula 2 obtained in step(a) with 9, 10-bis(halo substituted methyl) anthracene or 9,10-bis(halo substituted methyl) phenanthracene in a dry organic solvent, under reflux, for a period of about 24 hours and cooling the resultant reaction mixture to a temperature of 25-30°C, followed by filtration by known method to obtain the desired cyclic donor-acceptor conjugate of general formula 1, 7. A process as claimed in claim 6, wherein the 9, 10-bis(halo substituted methyl) anthracene used in steps (a) & (b) is selected from 9,10-bis (chloromethyl) anthracene, and 9,10-bis(bromomethyl)anthracene. 8. A process as claimed in claim 6, wherein the 9, 10-bis(halo substituted methyl) phenanthracene used in step (b) is selected from 9,10-bis (chloromethyl)phenanthracene, and 9,10- bis(bromomethyl)phenanthracene. 9. A process as claimed in claim 6, wherein the organic solvent used in steps (a) & (b) is selected from acetonitrile, dimethyl formamide and tetrahydrofuran. 10. A supramolecular probe useful for the detection and quantification of nucleotides in biological fluids comprising a cyclic donor acceptor compound of general formula 1 or its salt or its pharmaceutically acceptable derivatives and a highly fluorescent indicator, 8-hydroxy-1,3,6-pyrene trisulfonate. 11. A cyclic donor-acceptor conjugate or its pharmaceutical acceptable derivative of general formula 1, a process substantially as herein described with reference to the examples and drawing accompanying this specification.

Full Text

We Claim
1. A cyclic donor-acceptor conjugate or its pharmaceutical acceptable
derivative of general formula 1
(Formula Removed)
2. The compound as claimed in claim 1, wherein the representative
compounds of general formula 1 are as follows:
Cyclo[bis(ethylenedipyridinium-9,10-anthracene) tetrahalide(la);
Cyclo [bis (ethylenedipyridinium-9,10-anthracene) tetrakis hexafluorophos phate(1b);
Cyclo[bis(dipyridinium-9,10-anthracene) tetrahalide (1c); Cyclo[bis dip yridinium-9,10-anthracene) tetrakishexafluorophosphate (1d); Cyclo[bis(pyrazinium-9,10-anthracene) tetrahalide (1e); Cyclo[bis(pyrazinium -9,10-anthracene) tetrakishexafluorophosphate (1f); Cyclo[bis(imidazolium-9,10-anthracene) dihalide (1g); Cyclo[bis(imidazolium -9,10-anthracene) tetrakishexafluorophosphate (1h);
Cyclo[bis(ethylenedipyridinium-9,10-anthracene)1", 6"-pyrene tetrahalide(H);
Cyclo[bis(ethylenedipyridinium-9,10-anthracene) 1", 6"-pyrenetetrakishexa fluorophosphate (1j);
Cyclo[bis(dipyridinium-9,10-anthracene) 1", 6"-pyrene tetrahalide (1k); Cyclo[bis(dipyridinium-9,10-anthracene)1",6"-pyrenetetrakishexafluorophosp hates (11);
Cyclo[bis(pyrazinium-9,10-anthracene) 1", 6"-pyrene tetrahalide (1m) and Cyclo[bis(pyrazinium-9,10-anthracene)1",6"-pyrenetetrakishexafluorophosph ate (1 n).
3. The compound as claimed in claim 1, wherein the cyclic donor-acceptor conjugate in combination with a highly fluorescent indicator is useful as supramolecular probe for the detection and quantification of nucleotides in buffer and biological fluids.
4. The compound as claimed in claim 3, wherein the highly fluorescent indicator used in supramolecular probe is 8-hydroxy-1, 3, 6-pyrene trisulfonate.
5. The compound as claimed in claim 3, wherein the nucleotide used is selected from the group consisting of guanosine 5'-triphosphate, adenosine 5'-triphosphate, adenosine 5'-monophosphate, adenosine 5'-diphosphate, cytidine 5'-triphosphate, uridine 5'-triphosphate and iosine 5'-triphosphate.
6. A process for the preparation of cyclic donor-acceptor conjugate, its salt or pharmaceutically acceptable derivatives of general formula 1; the said process comprising the steps of:
a) reacting a molar ratio of 9, 10-bis(halo substituted methyl) anthracene to a nitrogen containing compound selected from pyrazine, ethylenedipyridine, bipyridyl, and imidazole with a molar ratio of 1:6 to 1:7, in a dry organic solvent for a period of about 30 minutes, under reflux, for about 4 hours and cooling the resultant reaction mixture to a temperature of 25-30°C, followed by filtration by known method to obtain the compound of general formula 2,
(Formula Removed)
b) reacting the compound of general formula 2 obtained in step(a) with 9, 10-bis(halo substituted methyl) anthracene or 9,10-bis(halo substituted methyl) phenanthracene in a dry organic solvent, under reflux, for a period of about 24 hours and cooling the resultant reaction mixture to a temperature of 25-30°C, followed by filtration by known method to obtain the desired cyclic donor-acceptor conjugate of general formula 1,
7. A process as claimed in claim 6, wherein the 9, 10-bis(halo substituted
methyl) anthracene used in steps (a) & (b) is selected from 9,10-bis
(chloromethyl) anthracene, and 9,10-bis(bromomethyl)anthracene.
8. A process as claimed in claim 6, wherein the 9, 10-bis(halo substituted
methyl) phenanthracene used in step (b) is selected from 9,10-bis
(chloromethyl)phenanthracene, and 9,10-
bis(bromomethyl)phenanthracene.
9. A process as claimed in claim 6, wherein the organic solvent used in steps
(a) & (b) is selected from acetonitrile, dimethyl formamide and
tetrahydrofuran.
10. A supramolecular probe useful for the detection and quantification of
nucleotides in biological fluids comprising a cyclic donor acceptor
compound of general formula 1 or its salt or its pharmaceutically

acceptable derivatives and a highly fluorescent indicator, 8-hydroxy-1,3,6-pyrene trisulfonate. 11. A cyclic donor-acceptor conjugate or its pharmaceutical acceptable derivative of general formula 1, a process substantially as herein described with reference to the examples and drawing accompanying this specification.

Documents:

1892-DEL-2006-Abstract-(20-06-2012).pdf

1892-del-2006-abstract.pdf

1892-DEL-2006-Claims-(20-06-2012).pdf

1892-DEL-2006-Correspondence Others-(20-06-2012).pdf

1892-del-2006-correspondence-others.pdf

1892-del-2006-description (provisional).pdf

1892-del-2006-drawings.pdf

1892-del-2006-form-1.pdf

1892-del-2006-form-18 (14-02-2008).pdf

1892-del-2006-form-2.pdf

1892-del-2006-form-3.pdf

1892-del-2006-form-5.pdf

abstract.jpg

« Previous Patent

Next Patent »

Patent Number

253901

Indian Patent Application Number

1892/DEL/2006

PG Journal Number

36/2012

Publication Date

07-Sep-2012

Grant Date

31-Aug-2012

Date of Filing

22-Aug-2006

Name of Patentee

COUNCIL OF SCIENTIFIC & INDUSTRIAL RESEARCH

Applicant Address

ANUSANDHAN BHAWAN, RAFI MARG, NEW DELHI-110001, INDIA.

Inventors:

#	Inventor's Name	Inventor's Address
1	DANABOYINA RAMAIAH	REGIONAL RESEARCH LABORATORY,(COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH), THIRUVANANTHAPURAM-695019, KERELA, INDIA
2	PRAKASH P. NEELAKANDAN	REGIONAL RESEARCH LABORATORY, THIRUVANANTHAPURAM-695019, KERELA, INDIA.
3	MAHESH HARIHARAN	REGIONAL RESEARCH LABORATORY, THIRUVANANTHAPURAM-695019, KERELA, INDIA.

PCT International Classification Number

C07H

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA