Eli Lilly and Company

Lilly Industries, Inc.

Merck + Co., Inc.

Colin P Dell

Colin W Smith

Peter Thaddeus Gallagher

William M Owton

Michael Brunavs

Jai P Singh

Bruce Anthony Dressman

Thomas Charles Britton

Andrew Caerwyn Williams

Terence Alan Hicks

Ana Isabel Mateo Herranz

Jason Kenneth Myers

Jean Michel Vernier

Peter Charles Astles

Jose Antonio Martinez-Perez

Rowena Villanueva Cube

Stephen Richard Baker

Martine Keenan

Veronique Dehlinger

Adam Jan Sanderson

Sonia Gutierrez

Eric Samuel Nisenbaum

Lourdes Prieto

Colin William Smith

David R Dobson

The present invention relates to compounds of the Formula (I) which are useful for treating conditions associated with mGluR3 receptors, such as depression, schizophrenia and migraine, pharmaceutical compositions thereof, and methods of using the same. 

1-(hetero)aryl-3-amino-pyrrolidine derivatives for use as mGluR3 antagonists

The present invention relates to compounds that modulate neurotransmission by promoting the release of neurotransmitters such as acetylcholine, dopamine and norepinephrine. More particularly, the present invention relates to thio-bridged aryl compounds that are capable of modulating acetylcholine receptors and pharmaceutical compositions comprising such compounds. The compounds disclosed are useful for the treatment of dysfunctions of the central and autonomic nervous systems.

Modulators of acetylcholine receptors

Pharmaceutical compounds of the formula ##STR1## in which n is 0, 1 or 2 and R.sup.1 is attached at any of the positions 7, 8, 9 or 10, and each R.sup.1 is halo, carboxy, trifluoromethyl, hydroxy, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, C.sub.1-4 alkylthio, hydroxy-C.sub.1-4 alkyl, hydroxy-C.sub.1-4 alkoxy, nitrogen-containing heterocyclyl, nitro, trifluoromethoxy, --COOR.sup.5 where R.sup.5 is an ester group, --COR.sup.6, --CONR.sup.6 R.sup.7 or --NR.sup.6 R.sup.7 where R.sup.6 and R.sup.7 are each hydrogen or C.sub.1-4 alkyl;

Pharmaceutical compounds

Pharmaceutical compounds of the formula ##STR1## in which n is 0, 1 or 2 and R.sup.1 is attached at any of the positions 7, 8, 9 or 10, and each R.sup.1 is halo, carboxy, trifluoromethyl, hydroxy, C.sub.1 -4 alkyl, C.sub.1-4 alkoxy, C.sub.1-4 alkylthio, hydroxy-C.sub.1-4 alkyl, hydroxy-C.sub.1-4 alkoxy, nitrogen-containing heterocyclyl, nitro, trifluoromethoxy, --COOR.sup.5 where R.sup.5 is an alkyl group, --COR.sup.6, --CONR.sup.6 R.sup.7 or --NR.sup.6 R.sup.7 where R.sup.6 and R.sup.7 are each hydrogen or C.sub.1-4 alkyl;

5,6-dihydronaphtho [1,2-b]pyrans and their use as pharmaceutical

Pharmaceutical compounds of the formula ##STR1## in which R.sup.1 and R.sup.2 are each hydrogen, hydroxyl, halo, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, acyloxy, --O-glucoside, optionally substituted phenyl or optionally substituted phenyl-C.sub.1-4 alkoxy;

Pharmaceutical compound of the formula ##STR1## R.sup.1 is phenyl or heteroaryl selected from thienyl, pyridyl, benzothienyl, quinolinyl, benzofuranyl or benzimidazolyl, said phenyl and heteroaryl groups being optionally substituted, or R.sup.1 is furanyl optionally substituted with C.sub.1-4 alkyl;

Pyrano[3,2-h]quinolines for treating restenosis

Methods of treating an immune disease, cell proliferation, restenosis and vascular smooth muscle cells using the pharmaceutical compounds of the formula ##STR1## in which R.sup.2 is phenyl, naphthyl or heteroaryl selected from thienyl, pyridyl, benzothienyl, quinolinyl, benzofuranyl or benzimidazolyl, said phenyl, naphthyl and heteroaryl groups being optionally substituted, or R.sup.2 is furanyl optionally substituted with C.sub.1-4 alkyl; and salts thereof.

Methods of using dihydropyrans

This invention provides a method of treating diabetic complications in mammals which comprises the administration of a compound of the Formula I: ##STR1## in which n, R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are variables.

Therapy for diabetic complications

A pharmaceutical compound of the formula ##STR1## in which n is 0, 1 or 2 and R.sup.1 is attached at any of the positions 5, 6, 7, 8, 9 or 10, and each R.sup.1 is halo, trifluoromethyl, C.sub.1-4 alkoxy, hydroxy, nitro, C.sub.1-4 alkyl, C.sub.1-4 alkylthio, hydroxy-C.sub.1-4 alkyl, hydroxy-C.sub.1-4 alkoxy, trifluoromethoxy, carboxy, --COOR.sup.5 where R.sup.5 is an ester group, --CONR.sup.6 R.sup.7 or --NR.sup.6 R.sup.7 where R.sup.6 and R.sup.7 are each hydrogen or C.sub.1-4 alkyl; R.sup.2 is phenyl, naphthyl or heteroaryl selected from thienyl, pyridyl, benzothienyl, quinolinyl, benzofuranyl or benzimidazolyl, said phenyl, naphthyl and heteroaryl groups being optionally substituted, or R.sup.2 is furanyl optionally substituted with C.sub.1-4 alkyl; R.sup.3 is nitrile, carboxy, --COOR.sup.8 where R.sup.8 is an ester group, --CONR.sup.9 R.sup.10 where R.sup.9 and R.sup.10 are each hydrogen or C.sub.1-4 alkyl, or R.sup.11 SO.sub.2 -- where R.sup.11 is C.sub.1-4 alkyl or optionally substituted phenyl; and R.sup.4 is --NR.sup.12 R.sup.13, --NHCOR.sup.12, --N(COR.sup.12).sub.2 or --N.dbd.CHOCH.sub.2 R.sup.12 where R.sup.12 and R.sup.13 are each hydrogen or C.sub.1-4 alkyl optionally substituted with carboxy, ##STR2## where X is C.sub.2-4 alkylene, or --NHSO.sub.2 R.sup.14 where R.sup.14 is C.sub.1-4 alkyl or optionally substituted phenyl; provided that when n is 0, R.sup.3 is nitrile and R.sup.4 is --NH.sub.2, R.sup.2 is not phenyl or phenyl substituted in the para-position with a single chloro, hydroxy or methoxy substituent; and salts thereof.

This invention provides a method of treating diabetic complications in mammals which comprises the administration of a compound of the Formula I: ##STR1## in which n, R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are variables.

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Dorking, United Kingdom

Colin P Dell