Mitsubishi Tanabe Pharma Corporation

Sanofi-Aventis

University College London

Mitsubishi Pharma Corporation

Sanofi-Synthelabo

Canbex Therapeutics Limited

Ucl Business Plc

Minerva Neurosciences, Inc.

Masahiro Okuyama

Kazutoshi Watanabe

Fumiaki Uehara

Yoshihiro Usui

Kenji Fukunaga

David Lawrence Selwood

David Baker

Keiichi Aritomo

Shinsuke Hiki

Mitsuru Ooizumi

Cristina Visintin

Gareth Pryce

Norimitsu Hayashi

Toshiyuki Kohara

Akira Nakao

Sandra Werner

Nadine Noel

Aya Shoda

Daisuke Iijima

Hideki Horiuchi

Kenji Usui

Tokushi Hanano

Satoshi Yokoshima

Hiroshi Iwamura

Haruko Yamabe

Nobuaki Fujimoto

Koichi Yamakoshi

Noriaki Itagaki

Ken-ichi Saito

Remy Luthringer

David Selwood

Provided are a novel compound having a superior inhibitory action on KAT-II, a production method thereof, use thereof, and a pharmaceutical composition containing the aforementioned compound and the like. A compound represented by the formula (I) or a pharmacologically acceptable salt thereof. wherein each symbol is as defined in the DESCRIPTION.

Bicyclic heterocyclic compound

The present invention provides a novel bicyclic or tricyclic heterocyclic compound represented by the formula (I) wherein ring A is an optionally substituted aromatic group,

Bicyclic or tricyclic heterocyclic compound

The present disclosure relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Z is selected from OH, NHCHCHF, NHCH(Me)CHOH and NHCHCHOH; X is an alkylene, alkenylene, or alkynylene group, each of which may be optionally substituted by one or more substituents selected from alkyl, COOH, CO-alkyl, alkenyl, CN, NH, hydroxy, halo, alkoxy, CFand nitro; Y is a polar functional group selected from OH, NO, CN, COR, COOR, NRR, CONRR, SOH, SO&#x2014;R, SONRRand CF, where each of Rand Ris independently H or a hydrocarbyl group; A is phenyl or pyridyl; and B is (CH)where n is 0; with the proviso that: (i) when A is phenyl, and Z is OH, X&#x2014;Y is other than C&#x2261;C&#x2014;(CH)COH, C&#x2261;C&#x2014;(CH)COMe, (CH)COH. Uses of such compounds as medicaments for the treatment of a muscular disorder, a gastrointestinal disorder, or for controlling spasticity or tremors are provided.

Modulator

The present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Z is ORor NRRwherein each of Rand Ris independently H, or a hydrocarbyl group; X is an alkylene, alkenylene, or alkynylene group, each of which may be optionally substituted by one or more substituents selected from alkyl, COOH, CO-alkyl, alkenyl, CN, NH, hydroxy, halo, alkoxy, CFand nitro; Y is a polar functional group selected from OH, NO, CN, COR, COOR, NRR, CONRR, SOH, SO&#x2014;R, SONRRand CF, where each of Rand Ris independently H or a hydrocarbyl group; A is an aryl or heteroaryl group, each of which may be optionally substituted; and B is (CH2)where n is 0, 1, 2, 3, 4 or 5; with the proviso that: (i) when A is phenyl, n is 0, and Z is OH, X&#x2014;Y is other than meta-C&#x2261;&#x2014;C&#x2014;(CH)COH, meta-C&#x2261;&#x2014;C&#x2014;(CH)OH, meta-C&#x2261;C&#x2014;(CH)COMe, meta-(CH)COH, ortho-CHCOH, ortho-(CH)COH and ortho-(CH)COH; and (ii) when A is phenyl, n is 0, and Z is OMe, X&#x2014;Y is other than meta-C&#x2261;C&#x2014;(CH)OH. Further aspects of the invention relate to the use of such compounds in the preparation of a medicament for the treatment of a muscular disorder, a gastrointestinal disorder, or for controlling spasticity or tremors.

Production method of an optically active morpholine compound represented by the formula 10, or a compound represented by the formula 55, which includes the following steps:  wherein each symbol is as defined in the specification. An optically active 2-aryl-substituted morpholine compound and 3-oxo-3-(pyrimidin-4-yl)propionate, which are important as starting materials for synthesizing 2-(2-arylmorpholin-4-yl)-1-methyl-1H-[4,4']bipyrimidinyl-6-one having a tau protein kinase 1 inhibitory activity and useful as a therapeutic drug for Alzheimer's disease and the like, can be produced in a high yield by an industrially advantageous method.

Intermediate compound for synthesizing pharmaceutical agent and production method thereof

A pyrimidone derivative represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof useful as a tau protein kinase 1 inhibitor: wherein X represents CH or nitrogen atom; Rrepresents a C?1#191-C?12#191 alkyl group which may be substituted; Rrepresents a C?1#191-C?8#191 alkyl group which may be substituted, a benzene ring which may be substituted, a naphthalene ring which may be substituted, an indan ring which may be substituted, a tetrahydronaphthalene ring which may be substituted, or an optionally substituted heterocyclic ring having 1 to 4 hetero atoms selected from the group consisting of oxygen atom, sulfur atom, and nitrogen atom, and having 5 to 10 ring-constituting atoms in total. 

3-substituted-4-pyrimidone derivatives

A pyrimidone derivative represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof having inhibitory activity against tau protein kinase 1: wherein Rrepresents a C-Calkyl group which may be substituted;R represents, for example, a group represented by the following formula (II): wherein Rand Rindependently represent a hydrogen atom or a C-Calkyl group;Rrepresents a benzene ring which may be substituted, a naphthalene ring which may be substituted, an indan ring which may be substituted, a tetrahydronaphthalene ring which may be substituted, or an optionally substituted heterocyclic ring having 1 to 4 hetero atoms selected from the group consisting of oxygen atom, sulfur atom and nitrogen atom, and having 5 to 10 ring-constituting atoms in total.

3-Substituted-4-pyrimidone derivatives

A pyrimidone derivative having tau protein kinase 1 inhibitory activity which is represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof; useful for prventive and/or therapeutic treatment of diseass such as neurodegenerative diseases (e.g. Alzheimer disease); wherein Q represents CH or nitrogen atom; R represents a C-Calkyl group; the ring of Formula (I): represents piperazine ring or piperidine ring; each X independently represents a C-Calkyl group, an optionally partially hydrogenated C-Caryl ring, an indan ring or the like; m represents an integer of 1 to 3; each independently represents a halogen atom, a hydroxy group, a cyano group, a C-Calkyl group or the like; n represents an integer of 0 to 8; when X and Y or two Y groups are attached on the same carbon atom, they may combine to each other to form a C-Calkylene group. 

2,3,6-Trisubstituted-4-pyrimidone derivatives

A pyrimidone derivative represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof having inhibitory activity against tau protein kinase 1: wherein Rrepresents a C-Calkyl group which may be substituted; R represents, for example, a group represented by the following formula (II): wherein Rand Rindependently represent a hydrogen atom or a C-Calkyl group; Rrepresents a benzene ring which may be substituted, a naphthalene ring which may be substituted, an indan ring which may be substituted, a tetrahydronaphthalene ring which may be substituted, or an optionally substituted heterocyclic ring having 1 to 4 hetero atoms selected from the group consisting of oxygen atom, sulfur atom and nitrogen atom, and having 5 to 10 ring-constituting atoms in total. 

Novel compounds represented by the following formula (I) that act as a ligand to sigma receptor/binding cite and a medicament comprising the same as an active ingredient: wherein X represents an alkyl group, an aryl group, a heterocyclic group or the like; Q represents a group represented by &#x2014;CH&#x2014;, &#x2014;CO&#x2014;, &#x2014;O&#x2014;, &#x2014;CH(OR)&#x2014; or the like wherein Rrepresents a hydrogen atom, an alkyl group or the like; n represents an integer of from 0 to 5; Rand Reach represent a hydrogen atom, an alkyl group or the like; B represents either of the following groups: wherein R, R, R, and Reach represent a hydrogen atom, a halogen atom, an alkoxyl group or the like; m represents 1 or 2; and the ring of: represents an aromatic heterocyclic ring.

Cyclic amide derivatives

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Osaka, Japan

Masahiro Okuyama