Astellas Pharma Gmbh

Rational Drug Design Laboratories

Yamanouchi Pharmaceutical Company Ltd.

Mitobridge, Inc.

Wataru Hamaguchi

Junji Miyata

Akio Kamikawa

Hiroshi Suzuki

Nobuyuki Shiraishi

Toru Kontani

Takayuki Goto

Yuji Kondo

Hartmut Greiner

Itsuro Shimada

Takashi Sugane

Isao Kinoyama

Kyoichi Maeno

Tomofumi Takuwa

Takeshi Suzuki

Takahiko Tobe

Yohei Koganemaru

Hiroaki Hoshii

Tomoaki Kawano

Takuya Washio

Ryuichi Sekioka

Eriko Honjo

Kenji Sudo

Takehiro Miyazaki

Michael Arlt

Takuma Morita

Atsuyuki Kohara

Tetsuya Kimizuka

Takayuki Suzuki

Hiroyuki Moritomo

Noriyuki Kawano

Ryushi Seo

Kenji Negoro

Minoru Sakurai

Shunji Kageyama

Ikumi Kuriwaki

Shimpei Kawakami

Eiichi Nakai

Junko Maeda

Jeffrey Ciavarri

Yumi Yamashita

Yoji Miyazaki

Osamu Kaneko

Kai Kitamura

Kenichi Kakefuda

[Problem] A compound which is useful as a STING inhibitor is provided. [Means for Solution] The present inventors have found aryl alkynamide derivatives having an inhibitory action on STING. The aryl alkynamide derivatives of the present invention have an inhibitory action on STING and can be used as an agent for treating an autoimmune disease, a neurodegenerative disease, a type I interferonopathy and/or other STING-mediated disease.

Aryl alkynamide derivatives

A sulfur-containing bicyclic compound of the present invention has a PAM action of GABA. A composition containing the sulfur-containing bicyclic compound. And, a method for preventing and/or treating schizophrenia, CIAS, cognitive impairment, fragile X syndrome, autism spectrum disorder, spasticity, anxiety disorder, substance addiction, pain, fibromyalgia, or Charcot-Marie-Tooth disease by administering the sulfur-containing bicyclic compound.

Sulfur-containing bicyclic compound

To provide a compound useful as an active ingredient of a pharmaceutical composition for treating 11&#x3b2;-hydroxysteroid dehydrogenase type 1-related diseases such as dementia, schizophrenia, depression, pain (particularly, neuropathic pain or fibromyalgia), diabetes (particularly, type II diabetes mellitus), insulin resistance and the like. [Means for Solution] A bicyclic heterocyclic compound (the bicyclic heterocycle is formed when a cyclohexane ring is fused with a 5- to 6-membered monocyclic heterocycle that has only a nitrogen atom as a hetero atom) substituted with an acylamino group such as a (hetero)aroylamino group or the like or a pharmaceutically acceptable salt thereof was found to have an excellent selective inhibitory action against 11&#x3b2;-HSD1. Accordingly, the bicyclic heterocyclic compound of the present invention can be used for treating dementia, schizophrenia, depression, pain (particularly, neuropathic pain or fibromyalgia), diabetes (particularly, type II diabetes mellitus), insulin resistance, and the like.

Bicyclic heterocyclic compound

A sulfur-containing bicyclic compound having a PAM action of GABA, and it use for preventing and/or treating schizophrenia, CIAS, cognitive impairment, fragile X syndrome, autism spectrum disorder, spasticity, anxiety disorder, substance addiction, pain, fibromyalgia, or Charcot-Marie-Tooth disease. A pharmaceutical composition for preventing and/or treating schizophrenia, cognitive impairment associated with schizophrenia (CIAS), cognitive impairment, fragile X syndrome, autism spectrum disorder, spasticity, anxiety disorder, substance addiction, pain, fibromyalgia, Charcot-Marie-Tooth disease, or the like, which has a positive allosteric modulator (PAM action) of GABA.

To provide an excellent agent for preventing or treating dementia and schizophrenia based on serotonin 5-HTreceptor regulating action, it was found that a tetrahydroisoquinoline derivative characterized by a structure in which an acylguanidino group binds to a N atom of a tetrahydroisoquinoline ring or the like, and a cyclic group binds to an unsaturated ring has a potent 5-HTreceptor regulating action and an excellent pharmacological action based on the regulating action and also discovered that the tetrahydroisoquinoline derivative is useful as an agent for treating or preventing dementia, schizophrenia, and the like, whereby the present invention has been completed.

Tetrahydroisoquinoline derivative

[Object] An excellent agent for preventing or treating dementia, schizophrenia, and the like, based on serotonin 5-HTreceptor modulating action, is provided. [Means for Solution] It was confirmed that acylguanidine derivatives (the following formula I; any one of Z, Z, Z, Zand Zis nitrogen atom, and the others are carbon atoms) which have the characteristic structure in which the guanidine is bonded to one ring of the quinoline or isoquinoline via a carbonyl group, and a cyclic group is bonded to the other ring, exhibit potent 5-HTreceptor modulating actions and excellent pharmacological actions based on the 5-HTreceptor modulating action, and thus can be excellent agents for preventing or treating dementia, schizophrenia, bipolar disorder, or attention deficit hyperactivity disorder. Thus, the present invention has been completed. 

Nitrogenous-ring acylguanidine derivative

There is provided a pharmaceutical drug, particularly a novel compound useful for prophylaxis or a therapeutic treatment of various diseases involving infections with viruses of the herpesvirus family, specifically various herpesvirus infections such as varicella (chicken pox) via varicella zoster virus, varicella zoster via recurrent infection with latent varicella zoster virus, herpes labialis and herpes encephalitis via HSV-1 and genital herpes via HSV-2 infection. An N-{2-[(4-substituted phenyl)amino]-2-oxoethyl}tetrahydro-2H-thiopyran-4-carboxamide derivative, of which phenyl group is substituted at position 4 with a specific 5- or 6-membered heteroaryl group, and a salt thereof have an effective anti-virus activity, and the oral administration thereof at a low dose enabled the therapeutic treatment of the above diseases.

Amide derivative

The invention relates to a triazole derivative with an activity inhibiting glycine transporter and for use as a pharmaceutical drug, and a novel triazole derivative. The inventive triazole derivative has an excellent activity inhibiting glycine transporter and is useful as a therapeutic agent of dementia, schizophrenia, cognitive disorders, or cognitive disorders involved in various diseases such as Alzheimer disease, Parkinson's disease, or Huntington disease or the like, or spasm involved in diseases such as nerve degenerative diseases and cerebrovascular disorders, or the like. Particularly, the pharmaceutical drug is useful for the amelioration of learning disability of dementia and the like.

Triazole derivative

The invention relates to a novel amide derivative which is an N-({[4-(substituted thiazol-4-yl)phenyl]carbamoyl}methyl)amide derivative having a characteristic in that an aryl or heteroaryl group as an aromatic ring group is directly substituted on the N atom of amido group. Since said amide derivative has excellent anti-herpesvirus action, it is useful as medicaments and antiviral agents, particularly as preventive or therapeutic agents for various diseases accompanied by Herpesviridae virus infections, illustratively, varicella (chickenpox) accompanied by varicella zoster virus infection, shingles accompanied by the recurrent infection of latent varicella zoster virus, labial herpes and herpes encephalitis accompanied by HSV-1 infection, genital herpes accompanied by HSV-2 and the like various herpesvirus infections.

A pharmaceutical drug, particularly a novel compound useful for the prophylaxis or therapeutic treatment of various diseases involving infections with viruses of the Herpesviridae family, specifically various herpesvirus infections such as varicella (chicken pox) via varicella zoster virus, varicella zoster via recurrent infection with latent varicella zoster virus, herpes labialis and herpes encephalitis via HSV-1 and genital herpes via HSV-2 infection. N-{2-[(4-Substituted phenyl)amino]-2-oxoethyl}tetrahydro-2H-thiopyran-4-carboxamide derivative where the phenyl group is substituted at position 4 with a specific five-membered or 6-membered heteroaryl group, has such great anti-virus activity that the oral dosing thereof at a low dose enabled the therapeutic treatment of the diseases.

Tetrahydro-2H-thiopyran-4-carboxamide derivative

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Tokyo, Japan

Wataru Hamaguchi