Pfizer Corporation

Evotec Ag

Renovis, Inc.

Satoshi Nagayama

Hirotaka Tanaka

Yuji Shishido

Kazunari Nakao

Tadashi Inoue

Takeshi Hanazawa

Misato Hirano

Koji Ando

Andrew Antony Calabrese

Tadashi Kawashima

Matthew Alexander Duncton

Kentaro Futatsugi

This invention relates to novel substituted pyridylmethyl bicyclocarboxamide compounds and to their use in therapy. These compounds are particularly useful as modulators of the VR1 (Type I Vanilloid) receptor, and are thus useful for the treatment of pain, neuralgia, neuropathies, nerve injury, burns, migraine, carpal tunnel syndrome, fibromyalgia, neuritis, sciatica, pelvic hypersensitivity, bladder disease, inflammation, or the like in mammals, especially humans.

Substituted pyridylmethyl bicycliccarboxyamide compounds

This invention provides a compound of the formula (I): And their use for the treatment of disease conditions caused by overactivation of the VR1 receptor such as pain, or the like in mammal. This invention also provides a pharmaceutical composition comprising the above compound. 

Substituted N-bicyclicalkyl bicycliccarboxyamide compounds

This invention provides a compound of the formula (I): wherein A and B are independently CRor N; D and E are each independently CRor N; Rrepresents (C-C)alkyl; Rrepresents hydrogen, halogen, hydroxy, (C-C) alkyl, halo(C-C) alkyl, hydroxy(C-C) alkyl, (C-C)alkoxy or (C-C)alkoxy-(C-C)alkyl; R, R, R, R, Rand Reach independently represent hydrogen, halogen, (C-C)alkyl, halo(C-C)alkyl, (C-C)alkoxy, hydroxy(C-C)alkyl or (C-C)alkoxy-(C-C)alkyl; or Rand Rare taken together with the carbon atom to which they are attached to form a 3- to 7-membered carbocyclic ring or heterocyclic ring in which one or two non-adjacent carbon atoms are optionally replaced by an oxygen atom, a sulfur atom or NH; Rand Reach independently represent hydrogen, halogen, (C-C)alkyl, halo(C-C)alkyl, hydroxy(C-C)alkyl, (C-C)alkoxy, hydroxy(C-C)alkoxy, (C-C)alkoxy-(C-C)alkyl, (C-C)alkoxy-(C-C)alkoxy, (C-C)alkylthio, (C-C)alkylsulfinyl, (C-C)alkylsulfonyl, NH, [(C-C)alkyl]NH&#x2014;, [(C-C)alkyl]N&#x2014;, HN&#x2014;(C-C)alkoxy, (C-C)alkyl-NH&#x2014;(C-C)alkoxy, [(C-C)alkyl]N(C-C)alkoxy; HN&#x2014;(C-C)alkoxy-(C-C)alkyl, (C-C)alkyl-NH&#x2014;(C-C)alkoxy-(C-C)alkyl, [(C-C)alkyl]N(C-C)alkoxy-(C-C)alkyl or 5- or 6- membered heterocyclic ring containing at least one nitrogen atom; Rrepresents halogen, (C-C)alkyl, halo(C-C)alkyl, hydroxy(C-C)alkyl, (C-C)alkoxy, hydroxy(C-C)alkoxy, (C-C)alkoxy-(C-C)alkyl, (C-C)alkoxy-(C-C)alkoxy, halo(C-C)alkylsulfonyl, halo(C-C)alkylsulfinyl, halo(C-C)alkoxy, halo(C-C)alkylthio, [(C-C)alkyl]NH&#x2014; or [(C-C)alkyl]N&#x2014;; or Rand R, when E is CR, are taken together with the carbon atoms to which they are attached form a 5-8 membered carbocyclic or heterocyclic ring, in which one or two non-adjacent carbon atoms are optionally replaced by oxygen, sulfur, N or NH groups, wherein the carbocyclic ring or the heterocyclic ring is unsubstituted or substituted with one or more substituents each independently selected from the group consisting of hydroxy, (C-C)alkyl, (C-C)alkoxy and hydroxy(C-C)alkyl; and Rrepresents hydrogen, halogen, (C-C)alkyl or hydroxy(C-C)alkyl; or a pharmaceutically acceptable salt or solvate thereof.

Substituted sulfonylaminoarylmethyl cyclopropanecarboxamide as VR1 receptor antagonists

This invention provides a compound of the formula (I): wherein, variables A, B, D, E, and Rto Rare as defined in the specification.

This invention provides compounds of the formula (I) useful for the treatment of disease conditions caused by over activation of Vr1 receptors such as pain or the like in mammals as well as compositions comprising them.

Substituted N-sulfonylaminophenylethyl-2-phenoxyacetamide compounds as VR1 receptor antagonists

Compounds of the general formula (I): pharmaceutical compositions comprising a compound of general formula (I); and methods of treating disease conditions caused by overactivation of the VR1 receptor by administering a compound of general formula (I) to a subject.

Substituted aryloxymethyl bicyclicmethyl acetamide compounds

This invention provides a compound of the formula (I): wherein Rrepresents a (C&#x2013;C)alkyl group; Rrepresents a hydrogen atom, a halogen atom, a hydroxy group, a (C&#x2013;C)alkyl group or a (C&#x2013;C)alkoxy group; R, R, Rand Reach independently represents a hydrogen atom, a (C&#x2013;C)alkyl, or a halogen atom; Rrepresents a hydrogen atom, a halogen atom, a hydroxy group, a (C&#x2013;C)alkyl group optionally substituted with a piperidino group, a (C&#x2013;C)alkoxy group optionally substituted with a 3&#x2013;7 membered cycloalkyl ring, a hydroxy(C&#x2013;C)alkoxy group, a (C&#x2013;C)alkoxy-(C&#x2013;C)alkyl group, a (C&#x2013;C)alkoxy-(C&#x2013;C)alkoxy group, a halo (C&#x2013;C)alkyl group, a (C&#x2013;C)alkylthio group, a (C&#x2013;C)alkylsulfinyl group or a (C&#x2013;C)alkylsulfonyl group; Rrepresents a (C&#x2013;C)alkyl group, a halo(C&#x2013;C)alkyl group, a (C&#x2013;C)alkoxy group, a hydroxy(C&#x2013;C)alkoxy group, a (C&#x2013;C)alkoxy-(C&#x2013;C)alkyl group or a (C&#x2013;C)alkoxy-(C&#x2013;C)alkoxy group; or Rand R, when adjacent to each other, taken together with the carbon atoms to which they are attached form a 5&#x2013;8 membered carbocyclic or heterocyclic ring, wherein the carbocyclic ring or the heterocyclic ring is unsubstituted or substituted with one or more substituents selected from the group consisting of a hydroxy group, a (C&#x2013;C)alkyl group, a (C&#x2013;C)alkoxy group and a hydroxy(C&#x2013;C)alkyl group; and Rrepresents a hydrogen atom or a halogen atom; or a pharmaceutically acceptable salt or solvate thereof. These compounds are useful for the treatment of disease conditions caused by overactivation of VR1 receptor, such as pain or the like in mammalian. The present invention also provides a pharmaceutical composition comprising the compound of formula(I).

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Aichi-ken, Japan

Satoshi Nagayama