Kowa Company Limited

The University of Edinburgh

University of Strathclyde

Toru Kanke

Hiroyuki Ishiwata

Yasushi Wada

Mototsugu Kabeya

Masahiro Tamura

Kazuhiro Onogi

Hendrik Timmerman

Jiro Matsumoto

Tsutomu Tohma

Mingqiang Zang

Koji Nakamura

Shankar Kumar

Naoya Tsurushita

Hiroyuki Yanai

Takeo Deushi

Junichi Kawagoe

Kentaro Okamura

Maki Tamura

Takashi Nakagawa

Toshiaki Takizawa

Yoshio Takahashi

Kyoko Yasuoka

Junya Tagashira

Alan Lang Harvey

Robert Ramage

Robin Plevin

Kevin Thomas Shaw

Lu Jiang

Pu Wang

Louise Claire Young

Compounds represented by the general formula (1) or salts thereof or solvates of both; PAR-2 antagonists containing the compounds; and preventive or therapeutic agents for PAR-2 related diseases containing the antagonists as the active ingredient: (1) wherein Ris hydrogen, halogeno, or a group represented by the general formula (2): (wherein Ris straight-chain or branched Calkylene or the like; and Rand Rtogether with the nitrogen atom adjacent to them form a 5- to 7-membered ring); Ris straight-chain or branched Calkyl or the like; Rand Rare each independently hydrogen, one to three halogen atoms, or the like; and A-A-Ais a tripeptide residue composed of &#x3b1;-amino acids each independently selected from the group consisting of glycine, alanine, cyclohexylalanine, and so on.

PAR-2 antagonists

The present invention relates to a pharmaceutical composition for preventing/treating conditions associated with PAR-2. The present invention also relates to a method for preventing/treating the condition using the pharmaceutical composition and use for manufacturing the pharmaceutical composition. The pharmaceutical composition comprises a compound represented by the following general formula (1), salt or solvate thereof and a pharmaceutically acceptable carrier: Ar&#x2014;CO&#x2014;AA&#x2014;AA&#x2014;AA&#x2014;AA&#x2014;NH&#x2014;X&#x2014;Y (1) wherein, Ar represents a phenyl group or an aromatic heterocyclic group optionally having substituent(s): AArepresents a hydrophobic amino acid: AArepresents an amino acid absent of substituent(s) having more than two carbon atoms: AArepresents an amino acid absent of substituent(s) having more than two carbon atoms: AArepresents a basic amino acid: X represents a straight chain or branched bivalent saturated aliphatic hydrocarbon group having 1 to 6 carbon atoms: Y represents basic substituent(s); straight chain, branched, or cyclic bivalent saturated aliphatic hydrocarbon group having 1 to 6 carbon atoms; or an aromatic hydrocarbon group having 6 to 10 carbon atoms. The compound represented by the general formula (1) has dramatically improved PAR-2 activation potency compared to peptide comprised of 6 amino acids (Tethered receptor agonist peptide: TRAP) in spite of reduction of the number of amino acid.

PAR-2 agonist

A compound, or a salt or solvate thereof having a structure of Ar&#x2014;CO-AA-AA-AA-AA-NH&#x2014;X&#x2014;NRRis disclosed. Ar represents an optionally substituted phenyl group or an aromatic heterocyclic group; AArepresents a hydrophobic amino acid; AArepresents an unsubstituted amino acid containing 2 or more carbon atoms; AArepresents an unsubstituted amino acid containing 2 or more carbon atoms; AArepresents a hydrophobic amino acid; X represents a divalent saturated aliphatic hydrocarbon group having 2-6 carbon atoms; and Rand Rrepresent a saturated or unsubstituted aliphatic hydrocarbon group having 1-8 carbon atoms, or alternatively Rand Rmay form a ring together with an adjacent nitrogen atom. A pharmaceutical composition for prevention/treatment of diseases associated with PAR-2 is also disclosed. The pharmaceutical composition includes the above compound, a salt or a solvate thereof and a pharmaceutically acceptable carrier.

The present invention relates to a peptide derivative represented by the general formula (I) or a salt thereof: Z-(CH)&#x2014;CO&#x2014;NH-Leu-Ile-Gly-AA-AA-CO&#x2014;R (I) wherein Z represents an aryl group which may or may not have a substituent or a heteroaryl group which may or may not have a substituent; n represents 0, 1 or 2: AA-AArepresents Lys-Val or Arg-Leu; and R represents &#x2014;OH or &#x2014;NH, and relates to a pharmaceutical composition comprising a peptide derivative represented by the general formula (I) or a salt thereof, and a pharmaceutically acceptable carrier thereof. The peptide derivative is useful as a prophylactic and therapeutic agent of dysfunction of masticatory, dysphagia, dysgeusia, ozostomia, intra-oral cavity dysphoria, intra-oral cavity infections, intra-oral cavity inflammations, dry eye, ectocornea detachment, keratitis, corneal ulcer, conjunctivitis, stomach ulcer, duodenal ulcer, gastritis, diarrhea, enteritis or Sjogren's syndrome.

Par-2-activating peptide derivative and pharmaceutical composition using the same

The present invention relates to a composition for prevention and treatment of kidney diseases comprising one or more effective component(s) of a PAR-2 activating agent which is able to activate PAR-2 and a pharmaceutically acceptable carrier. The present invention further relates to a method for prevention and treatment of kidney diseases comprising administration of a composition for prevention and treatment of kidney diseases containing a PAR-2 activating agent which is able to activate PAR-2 to patients suffering from kidney diseases, and also relates to the use of a PAR-2 activating agent which is able to activate PAR-2 for the manufacture of a composition for prevention and treatment of kidney diseases. The present invention furthermore relates to a method for screening an effective ingredient for prevention and treatment of kidney diseases comprising screening of the activating action of the test substance to PAR-2.

Method for treatment of kidney diseases

The present invention is directed to a tetrazole derivative represented by the following formula (1) or a salt thereof: ##STR1## wherein R.sup.1 and R.sup.2 independently represent a hydrogen atom, a hydroxyl group, a lower alkyl group, a substituted or unsubstituted alkoxy group, or a substituted or unsubstituted alkanoyloxy group; R.sup.3 represents a hydrogen atom or a substituted or unsubstituted lower alkyl group; A represents a methyleneoxy group or a vinylene group; B represents a substituted or unsubstituted quinolyl group, a substituted or unsubstituted quinazolyl group, or a substituted or unsubstituted benzimidazolyl group; and a broken line indicates that there may be a double bond; and to a medicine containing the compound as an active ingredient. The medicine according to the present invention is endowed with excellent antileukotriene activity and antihistaminic activity, and is useful for the prevention and treatment of, for example, asthma.

Tetrazole derivatives

The present invention is directed to a tetrazole derivative represented by the following formula (1) or a salt thereof: ##STR1## wherein R.sup.1 and R.sup.2 independently represent a hydrogen atom, a hydroxyl group, a lower alkyl group, a substituted or unsubstituted alkoxy group, or a substituted or unsubstituted alkanoyloxy group; R.sup.3 represents a hydrogen atom or a substituted or unsubstituted lower alkyl group; A represents a methyleneoxy group or a vinylene group; Z represents a substituted or unsubstituted benzimidazolyl group; and a broken line indicates that there may be a double bond; and to a medicine containing the compound as an active ingredient. The medicine according to the present invention is endowed with excellent antileukotriene activity and antihistaminic activity, and is useful for the prevention and treatment of, for example, asthma.

The present invention is directed to a piperidine derivative represented by the following formula (1) or a salt thereof: ##STR1## wherein R.sup.1, R.sup.2, and R.sup.3 individually represent hydrogen atoms, etc., Y represents ##STR2## B represents a single bond, an alkylene group, --S--CH.sub.2 --, or --CH.dbd.CH--, E represents a single bond or a trimethylene group, Z represents an oxygen atom, etc., and n represents a number between 2 and 5 inclusive; and to a medicine containing the compound. The medicine according to the present invention is endowed with excellent anti-histaminic activity and antileukotriene activity, and exhibits reduced side effects such as drowsiness.

Piperidine derivatives

Growing community of inventors

Tokyo, Japan

Toru Kanke