1. A method for determining the binding ability of a compound to a cell expressing an \u03b12\u03b42 subunit of a calcium channel comprising providing a cell line expressing an \u03b12\u03b42 sub-unit of a calcium channel, said cell line having ATCC No. PTA-1823; contacting the cells with the compound; and determining the binding ability of the compound to the cells.
2. The method of claim 1 wherein the compound is gabapentin.
3. The method of claim 1 wherein the compound is a 3-alkyl substituted gabapentin.
4. The method of claim 1 wherein the compound is pregabalin.
5. The method of claim 1 wherein the compound is a 3-alkyl derivative of y-aminobutiric acid (GABA).
6. A cell line having ATCC No. PTA-1823.
7. A method for determining the binding ability of a compound to an \u03b12\u03b42 subunit of a calcium channel comprising; providing an \u03b12\u03b42 subunit of a calcium channel encoded by the nucleotide sequence set forth in accession NO. AF 042792; contacting the \u03b12\u03b42 subunit with the compound; and determining the binding ability of the compound to the \u03b12\u03b42 subunit.
8. The method of claim 7 wherein the compound is gabapentin.
9. The method of claim 7 wherein the compound is a 3-alkyl substituted gabapentin.
10. The method of claim 7 wherein the compound is pregabalin.
11. The method of claim 7 wherein the compound is a 3-alkyl derivative of GABA.
12. The method of claim 7 wherein the \u03b12\u03b42 subunit is a purified protein.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A process for the preparation of a compound of formula (C)
12
(wherein R1 represents hydrogen or carboxy-C6-1-alkyl; and
R2 represents COOH, COOC1-6 alkyl or CN) or salt thereof comprising reacting a compound of formula (B)
13
(wherein R1 and R2 are as hereinbefore defined) or a salt thereof with a copper andor silver compound in the presence of palladium or a compound thereof:
2. prowess as claimed in claim 1 wherein R1 is hydrogen.
3. A process as claimed in claim 1 or 2 wherein R2 is CN or COOCH3.
4. A process as claimed in any one of claims 1 to 3 wherein said copper compound is copper fluoroborate, a copper halide, copper nitrate, copper sulphate, copper trifluoromethane sulphonate (copper triflate) or Nafioncopper resin.
5. A process as claimed in any one of claims 1 to 4 wherein said silver compound is silver trifluoromethane sulphonate (silver triflate), silver fluoroborate, silver hexafluorophosphate or silver nitrate.
6. A process as claimed in claim 5 wherein said silver compound is silver nitrate.
7. A process as claimed in any one of claims 1 to 6 wherein said palladium compound is tetrakis (triphenylphosphine) palladium(0), bistriphenylphosphine palladium dichloride or bis (benzonitrile) palladium dichloride.
8. A process as claimed in any one of claims 1 to 7 wherein the reaction of compounds (B) and (C) takes place in an alcohol solvent at reflux.
9. A process for the preparation of a compound of formula (F)
14
(wherein R2 represents COOH, COOC1-6 alkyl or CN; and
R3 represents hydrogen, mesylate, triflate, tosylate or carboxy-C1-6-alkyl) or a salt thereof comprising:
(I) reacting a compound of formula (B)
15
(wherein R1 represents hydrogen or carboxy-C1-6-alkyl; and
R2 is as hereinbefore defined) or a salt thereof with a copper andor silver compound in the presence of palladium or a compound thereof to yield a compound of formula (C)
16
(wherein R1 and R2 are as hereinbefore defined) as described in any one of claims 1 to 8;
(II) converting said compound of formula (C) into a compound of formula (E)
17
(Wherein R2 and R3 are as hereinbefore defined and R4 represents a halogen atom) or a salt thereof; and
(III) reacting said compound of formula (E) with azacyclonol.
10. A process as claimed in claim 9 wherein R3 is carboxy-C1-6-alkyl.
11. A process for the preparation of a compound of formula (F)
18
(Wherein R2 Represents COOH, COOC1-6 Alkyl or CN and R3 represents hydrogen, mesylate, triflate, tosylate or carboxy-C1-6-alkyl) or a salt thereof
comprising reacting a compound of formula (E)
19
(Wherein R2 and R3 are as hereinbefore defined and R4 represents a halogen atom) or a salt thereof
with azacyclonol.
12. A process as claimed in claim 11 wherein said compound of formula (E) is prepared from a compound of formula (G)
20
(wherein R2 represents COOH, COOC1-6 alkyl or CN and R3 represents hydrogen, mesylate, triflate, tosylate or carboxy-C1-6-alkyl).
13. A compound of formula (E), (G) or (F) or a salt thereof.
14. A process for the preparation of a compound of formula (H)
21
comprising reacting a compound of formula (D)
22
(wherein R4 is a halogen atom) with azacyclonol.
15. A process as claimed in claim 14 wherein R4 is an iodine atom.
16. A process as claimed in any one of claims 9 to 12, 14 and 15 further comprising converting said compound of formula (F) or (H) into fexofenadine by hydrolysis.
17. A pharmaceutical composition comprising a compound of formula (E), (G) or (F) or a salt thereof along with at least one pharmaceutical excipient or carrier.