Banyu Pharmaceutical Co. Ltd

Msd K.k.

Taisho Pharmaceutical Co., Ltd.

Nissan Chemical Industries Limited

Shigeru Tokita

Hiroaki Tanaka

Akio Kanatani

Nagaaki Sato

Norikazu Ohtake

Tsuyoshi Nagase

Ryo Yoshimoto

Makoto Jitsuoka

Takuya Suga

Yuji Haga

Akira Naya

Sayaka Mizutani

Toshiyuki Takahashi

Toshihiro Wada

Hajime Asanuma

Hirofumi Ota

Kazuhiko Takahashi

Takahiro Oi

Daisuke Tsukahara

Shoichi Kuroda

Keishi Hayashi

Takashi Mizutani

Hidekazu Takahashi

Hidehito Kotani

Yoshihisa Shirasaki

Takumi Okada

Tomomichi Chonan

Shiho Ishikawa

Noriko Saito

Yudai Imai

Shigetada Sasako

Seishi Ishiyama

Shin Itoh

Masahiro Bohno

Keiko Fusegi

Takanori Kawaguchi

Rui Jibiki

Kengo Watatani

Kanako Iwakiri

Tsuyoshi Busujima

There are provided compounds represented by the following general formula (I) or pharmaceutically acceptable salts of thereof, which have a superior monoacylglycerol acyltransferase 2 inhibitory action: wherein wherein

Nitrogen-containing condensed heterocyclic compound

A 2-pyridone compound represented by the formula [1]: {wherein in the formula [1],the ring represented by A represents a benzene ring or a pyridine ring,X represents any of the structures represented by the formulas [3] shown below: V represents a single bond or a lower alkylene group, andW represents a single bond, an ether bond or a lower alkylene group (wherein the lower alkylene group may contain an ether bond)},a tautomer or stereoisomer of the compound, a pharmaceutically acceptable salt thereof, or a solvate thereof is a compound that has an excellent GK activating effect and is useful as a pharmaceutical.

2-pyridone compounds

The present invention provides a compound represented by formula (I) below, or a pharmaceutically acceptable salt thereof, which, having histamine H3 receptor antagonist or inverse agonist activity, is useful in the prophylaxis or therapy of metabolic diseases, circulatory diseases, or nervous system diseases. [where, for example, Ar is a divalent group formed by eliminating two hydrogen atoms from benzene, Xis a nitrogen atom, sulfur atom or oxygen atom, Ris a 5- to 6-membered heteroaryl group, Ring A is a 5- to 6-membered heteroaryl ring, Rand Rare amino groups or alkylamino groups, and Xis represented by formula (II): (where Rand Rare lower alkyl groups, and n is an integer from 2 to 4).]

Fused ring 4-oxopyrimidine derivative

Compounds of a formula (I) [wherein, A represents formula (III-1) R3 is a hydrogen, lower alkyl et al; m is 0 or 1; R1 is a hydrogen atom, halogen atom et al, R2 is a hydrogen et al; p is 0 to 4; X is a carbon atom or nitrogen atom; and X1 to X4 is a lower alkyl et al], or pharmaceutical acceptable salts thereof. These have a potency antagonistic to binding to histamine H3 receptor, or have a potency inhibiting the constant activity of histamine H3 receptor, and are useful in the therapy of obesity, diabetes et al.

Substituted pyridone derivative

Disclosed is a substance having an antagonistic effect on the binding of histamine to a histamine H3 receptor or an inhibitory effect on the activity which a histamine H3 receptor constantly exhibits. A compound represented by the formula (I) or a pharmaceutically acceptable salt thereof; (I) wherein R1 represents a phenyl group which may be substituted or the like and R2 represents a cyano group which may be substituted or the like, or R1 and R2 together form an aliphatic heterocylic ring which may be substituted; R3 represents a group represented by the formula (II-1) below; and all of X1 to X4 represent a carbon atom or the like: (II-1) where R4 and R5 represent a lower alkyl group or the like; and m1 represents an integer of 2 to 4.

Piperidine derivative

Provided are compounds of a formula (I) and their pharmaceutically-acceptable salts: wherein X1, X2 and X3 each independently represent N or CH; W represents the following formula (II): or the following formula (III): Y represents a group of a formula (IV): The compounds have a histamine-H3 receptor antagonistic or inverse-agonistic activity and are useful for remedy and/or prevention of obesity, diabetes, hormone secretion disorders, sleep disorders, etc.

Heteroaryloxy nitrogenous saturated heterocyclic derivative

A compound represented by, e.g. the formula (I): [wherein X, Y, Z, and W each independently represent optionally substituted methine; A, B, and D each independently represent &#x2014;C(O)&#x2014;, etc.; Q represents a methine or a nitrogen; and R represents the formula (II-1), optionally substituted with lower alkyl, etc.; (wherein Rrepresents a lower alkyl, etc; and Rand Reach independently represents a lower alkyl, etc.)] or a pharmaceutically acceptable salt of the compound. The compounds and salt have antagonistic activity against a histamine H3 receptor or inverse agonistic activity against a histamine H3 receptor. They are useful in the prevention or treatment of metabolic diseases, circulatory diseases, or neurotic diseases.

Carbamoyl-substituted spiro derivative

This invention provides a compound or its pharmaceutically-acceptable salt of formula (I) wherein Rrepresents a lower alkyl group et al; Rand Rare same and different and represents hydrogen atm et al; Rrepresents the substituent of the formula (II) et al; Xrepresents NH, O or S; Y represents N or C; Ar is a divalent substituent derived from aryl et al, by removing two hydrogen atoms therefrom; the ring A represents a 5- or 6-membered heteroaryl group; this compounds has a histamine-H3 receptor antagonistic effect or a histamine-H3 receptor inverse-agonistic effect and is useful for preventive or remedy of metabolic system diseases, circulatory system diseases or nervous system diseases.

Quinazoline derivative

Provided are a histamine-H3 receptor antagonist; and a preventive and/or a remedy for metabolic system diseases such as obesity, diabetes, hormone secretion disorder, hyperlipemia, gout, fatty liver, circulatory system diseases, for example, stenocardia, acute/congestive cardiac insufficiency, cardiac infarction, coronary arteriosclerosis, hypertension, nephropathy, sleep disorder and various diseases accompanied by sleep disorder such as idiopathic hypersomnia, repetitive hypersomnia, true hypersomnia, narcolepsy, sleep periodic acromotion disorder, sleep apnea syndrome, circadian rhythm disorder, chronic fatigue syndrome, REM sleep disorder, senile insomnia, night worker sleep insanitation, idiopathic insomnia, repetitive insomnia, true insomnia, electrolyte metabolism disorder; and central and peripheral nervous system diseases such as bulimia, emotional disorder, melancholia, anxiety, epilepsy, delirium, dementia, shinzophrenia, attention deficit/hyperactivity disorder, memory disorder, Alzheimer's disease, Parkinson's disease, sleep disorder, recognition disorder, motion disorder, paresthesia, dysosmia, epilepsy, morphine resistance, narcotic dependency, alcoholic dependency. The histamine-H3 receptor antagonist comprises a piperidine derivative compound of formula (I) [wherein Xand Xindependently represent a nitrogen atom or CH; Y represents a specific group; Xrepresents O&#x2014;(CH); Rand Rindependently resent a hydrogen atom, a halogen atom, a linear or branched lower alkyl group, a lower alkoxy group, or an acetyl group substituted with 2 or 3 fluorine atoms; s is 0 or 1; and m is an integer to make (m+s) 0 or from 1 to 4], or its pharmaceutically-acceptable salt. 

The present invention is directed to a form I crystal of 2-methyl 3-{4-[3-(1-pyrrolidinyl)propoxy]phenyl}-5-trifluoromethyl-4(3H)-quinazolinone that is useful for example in the treatment of sleep disorders or various sleep disorder-associated diseases.

Crystal form of 2-methyl-3-{4-[3-(1-pyrrolidinyl)propoxy]phenyl}-5-trifluoromethyl-4(3H)-quinazolinone

The invention provides a compound or its pharmaceutically-acceptable salt of formula wherein Ais a hydrogen, etc.; j and k are 0 or 1;is a double bond, etc.;is a double bond, etc.;one of Wand Wis E&#x2014;O&#x2014;W, etc., and the other is a hydrogen atom, etc.; E is a divalent group derived from a benzene ring, etc., by removing two hydrogen atoms therefrom; W is a group of formula (II-1): which has a histamine-H3 receptor antagonistic effect or a histamine-H3 receptor inverse-agonistic effect and is useful for prevention or remedy of metabolic system diseases, circulatory system diseases or nervous system diseases.

Nitrogenous fused heteroaromatic ring derivative

Compound of the formula: (I) [wherein each of X, Xand Xindependently represents N or CH, W represents the formula (II):(II) or the formula (III):(III) and Y represents a group of the formula (IV):(IV)], or a pharmacologically acceptable salt thereof. This compound exhibits histamine receptor H3 antagonist or inverse agonist activity and is useful of the treatment and/or prevention of obesity, diabetes, hormonal secretion abnormality, sleep, disorder, etc. 

Provided are a histamine-H3 receptor antagonist; and a preventive and/or a remedy for metabolic system diseases such as obesity, diabetes, hormone secretion disorder, hyperlipemia, gout, fatty liver, circulatory system diseases, for example, stenocardia, acute/congestive cardiac insufficiency, cardiac infarction, coronary arteriosclerosis, hypertension, nephropathy, sleep disorder and various diseases accompanied by sleep disorder such as idiopathic hypersomnnia, repetitive hypersomnnia, true hypersomnnia, narcolepsy, sleep periodic acromotion disorder, sleep apnea syndrome, circadian rhythm disorder, chronic fatigue syndrome, REM sleep disorder, senile insomnia, night worker sleep insanitation, idiopathic insomnia, repetitive insomnia, true insomnia, electrolyte metabolism disorder, and central and peripheral nervous system diseases such as bulimia, emotional disorder, melancholia, anxiety, epilepsy, delirium, dementia, shinzophrenia, attention deficit/hyperactivity disorder, memory disorder, Alzheimer's disease, Parkinson's disease, sleep disorder, recognition disorder, motion disorder, paresthesia, dysosmia, epilepsy, morphine resistance, narcotic dependency, alcoholic dependency. The histamine-H3 receptor antagonist comprises a piperidine derivative compound of formula (I) [wherein Xand Xindependently represent a nitrogen atom or CH; Y represents a specific group; Xrepresents O&#x2014;(CH); Rand Rindependently represent a hydrogen atom, a halogen atom, a linear or branched lower alkyl group, a lower alkoxy group, or an acetyl group substituted with 2 or 3 fluorine atoms; s is 0 or 1; and m is an integer to make (m+s) 0 or from 1 to 4], or its pharmaceutically-acceptable salt. 

Internal domain 3 of seven transmembrane G protein-coupled receptors is important for G protein binding or receptor activity, and is well conserved. In H3 receptors, which are a type of G protein-coupled receptor, this region is also conserved in the same way. Therefore, as a result of using PCR to introduce point mutations into sequences encoding the region in H3 receptor cDNA, H3 receptor mutants comprising extremely strong constitutive activity could be successfully produced. The present inventors further found that by using constitutively active H3 receptor mutants, drug candidate compounds such as H3 receptor inverse agonists can be screened more easily and efficiently.

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Tsukuba, Japan

Shigeru Tokita