Pfizer Corporation

Astellas Pharma Gmbh

Raqualia Pharma Inc.

Takeshi Hanazawa

Hirotaka Tanaka

Yuji Shishido

Kazunari Nakao

Tadashi Inoue

Satoshi Nagayama

Misato Hirano

Hiroshi Shibata

Yuji Koga

Tsubasa Watanabe

Kazuhiko Ohne

Eisuke Nozawa

Hiroki Koike

Ippei Sato

Shunichiro Hachiya

Kyoichi Maeno

Yoshimasa Imamura

Kenichiro Imamura

Toshio Kurosaki

Ryo Mizoguchi

Maiko Iida

Hiroki Ishioka

Satoshi Nahayama

An excellent drug for treating or preventing cardiovascular diseases, based on cGMP production enhancing action due to soluble guanylate cyclase activating action, is provided. It was found that imidazopyridine compounds having a carbamoyl group at the 3-position and a substituent bonded at the 8-position via an oxygen atom in an imidazo[1,2-a]pyridine skeleton exhibits a cGMP production enhancing action by a potent soluble guanylate cyclase activating action, and is useful as a drug for treating or preventing various soluble guanylate cyclase-related cardiovascular diseases, thereby completing the present invention.

Imidazopyridine compounds

[Problem] A pharmaceutical composition for treating or preventing various cardiovascular diseases, which have sGC activities based on improvement of cGMP signals, is provided. [Means for Solution] It was found that imidazo[1,2-a]pyridine compounds having a carbamoyl group at the 3-position and a particular cyclic group at the 8-position via a methyleneoxy group, or a salt thereof have sGC activation, and are useful as active ingredients of pharmaceutical compositions for treating or preventing various sGC-related cardiovascular diseases, in particular, peripheral arterial diseases, intermittent claudication, critical limb ischemia, hypertension, and pulmonary hypertension, thereby completing the present invention.

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 relates to compounds of the formula (I): or a pharmaceutically acceptable salt thereof, wherein:A, B, X, R, R, R, R, R, R, Rand Rare each as described herein or a pharmaceutically acceptable salt, and compositions containing such compounds and the use of such compounds in the treatment of a condition mediated by acid pump antagonistic activity such as, but not limited to, as gastrointestinal disease, gastroesophageal disease, gastroesophageal reflux disease (GERD), peptic ulcer, gastric ulcer, duodenal ulcer, NSAID-induced ulcers, gastritis, infection of, dyspepsia, functional dyspepsia, Zollinger-Ellison syndrome, non-erosive reflux disease (NERD), visceral pain, heartburn, nausea, esophagitis, dysphagia, hypersalivation, airway disorders or asthma.

Chromane substituted benzimidazole derivatives

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

Growing community of inventors

Tokyo, Japan

Takeshi Hanazawa