Title of Invention

ACETYLENE DERIVATIVES HAVING MGLUR 5 ANTAGONISTIC ACTIVITY

Abstract The invention provides compounds of formula I wherein m, n, A, R, R', R", Ro, X and Y are as defined in the description, and their preparation. The compounds of formula I are useful as pharmaceuticals.
Full Text Abstract of the disclosure
The invention provides compounds of formula I

wherein m, n, A, R, R', R", Ro, X and Y are as defined in the description, and their preparation. The compounds of formula I are useful as pharmaceuticals.




Claims
1. A compound of fomnula I

wherein
m isOorl,
n is 0 or 1 and A is liydroxy X is liydrogen and Y is hydrogen, or
A forms a single bond with X or with Y; Ro is hydrogen, (Ci)all wherein Ri is (CM)alkyl or -COR2 wherein R2 is hydrogen or (Ci)alkyl, and R is -COR3, -COOR3, -CONR4R5or-S02R6, wherein R3 is (CM)alkyl, (C3-7)cycloalkyl or
optionally substituted phenyl, 2-pyridyl or 2-thienyl, R4 and R5, independently, are
hydrogen or (Ci)alkyl and Re is (Ci)alkyl, (C3.7)cycloalkyl or optionally substituted
phenyl, R' is hydrogen or (Ci)alkyl and R" Is hydrogen, or (CM)alkyl, or R' and R" together form a group -CH2-(CH2)p-
wherein p is 0,1 or 2, in which case one of n and p Is different from 0, with the proviso that Ro is different from hydrogen, trifluoromethyl and methoxy when m is 1, n is 0, A is hydroxy, X and Y are both hydrogen, R is COOEt and R' and R" together form a group -(CH2)2-, in free base or acid addition salt form.
2. The compound of claim 1 which is (-)-(3aR, 4S, 7aR)-4-hydroxy-4-m-tolylethynyl-octahydroindole-1-carboxylic acid methyl ester in free base or acid addition salt form.

3. A process for the preparation of a compound of formula I as defined in claim 1, or a salt thereof, which comprises the step of
a) for the production of a compound of formula I wherein A is hydroxy, reacting a
compound of formula II

b) for the production of a compound of formula I wherein A fomis a single bond with X or
with Y, dehydrating a compound of formula I wherein A is hydroxy,
and recovering the resulting compound of formula I in free base or acid addition salt form.
4. A compound of claim 1 in free base or pharmaceutically acceptable acid addition salt
form, for use as a pharmaceutical.
5. A compound of claim 1 in free base or pharmaceutically acceptable acid addition salt
form, for use in the treatment of disorders associated with irregularities of the
glutamatergic signal transmission, and of nervous system disorders mediated full or in
part by mGluRS.

6. A pharmaceutical composition comprising a compound of claim 1 in free base or pharmaceutical!/ acceptable acid addition salt form, in association with a pharmaceutical carrier or diluent.
7. The use of a compound of claim 1 in free base or phamriaceutically acceptable acid addition salt form, in the treatment of disorders associated with in-egularities of the glutamatergic signal transmission, and of nervous system disorders mediated full or in part by mGluRS.
8. The use of a compound of claim 1 in free base or pharmaceutically acceptable acid addition salt form, for the manufacture of a pharmaceutical composition designed for the treatment of disorders associated with irregularities of the glutamatergic signal transmission, and of nervous system disorders mediated full or in part by mGluRS.
9. A method of treating disorders associated with irregularities of the glutamatergic signal transmission, and nervous system disorders mediated full or in part by mGluRS, which method comprises administering to a subject in need of such treatment a therapeutically effective amount of a compound of claim 1 in free base or pharmaceutically acceptable acid addition salt form.
10. A combination comprising a therapeutically effective amount of a compound of claim 1 in free base or pharmaceutically acceptable acid addition salt form and a second dmg substance, for simultaneous or sequential administration.

11. A pharmaceutical composition substantially as herein described and exemplified.


Documents:

1200-CHENP-2004 AMENDED PAGES OF SPECIFICATION 09-05-2011.pdf

1200-CHENP-2004 AMENDED CLAIMS 09-05-2011.pdf

1200-chenp-2004 description(complete).pdf

1200-chenp-2004 form-3 09-05-2011.pdf

1200-chenp-2004 abstract.pdf

1200-chenp-2004 claims.pdf

1200-CHENP-2004 CORRESPONDENCE OTHERS 27-07-2010.pdf

1200-CHENP-2004 CORRESPONDENCE PO.pdf

1200-CHENP-2004 EXAMINATION REPORT REPLY RECIEVED 09-05-2011.pdf

1200-chenp-2004 form-19.pdf

1200-chenp-2004 form-3.pdf

1200-chenp-2004 form-5.pdf

1200-CHENP-2004 OTHER PATENT DOCUMENT 09-05-2011.pdf

1200-chenp-2004 pct.pdf

1200-chenp-2004 power of attorney.pdf

1200-chenp-2004 correspondence others.pdf

1200-chenp-2004 correspondence po.pdf

1200-chenp-2004 form-1.pdf

1200-chenp-2004 others.pdf

abs 1200-chenp-2004 abstract.jpg


Patent Number 248218
Indian Patent Application Number 1200/CHENP/2004
PG Journal Number 26/2011
Publication Date 01-Jul-2011
Grant Date 28-Jun-2011
Date of Filing 01-Jun-2004
Name of Patentee NOVARTIS AG
Applicant Address LICHTSTRASSE 35, CH-4056 BASEL
Inventors:
# Inventor's Name Inventor's Address
1 GASPARINI, FABRIZIO WEIHERHOFSTRASSE 10, CH-4415 LAUSEN
2 AUBERSON, YVES MAIENGASSE 4, CH-4123 ALLSCHWIL
3 OFNER, SILVIO HAUPTSTRASSE 1B, CH-4142 MUNCHENSTEIN
PCT International Classification Number A61K31/4709
PCT International Application Number PCT/EP02/13670
PCT International Filing date 2002-12-03
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 0128996.6 2004-12-04 U.K.