公开(公告)号：EP0852226A4

公开(公告)日：1998-09-02

申请号：EP96929512

申请日：1996-09-04

Applicant: KOWA CO

Inventor： HIRATA MITSUTERU ,  DEUSHI TAKEO ,  TAKAHASHI YOSHIO ,  TAMURA MASAHIRO ,  OHSHIMA TAKESHI ,  ODA TOSHIAKI ,  ISHIKAWA TETSUYA ,  SONOKI HIROYUKI ,  SHIRATSUCHI MASAMI

IPC: C07D403/04 ,  A61K31/506 ,  A61P9/00 ,  A61P9/12 ,  C07D213/00 ,  C07D239/52 ,  C07D239/545 ,  C07D295/00 ,  C07D401/14 ,  C07D239/48 ,  A61K31/505

CPC classification number: C07D239/52

Abstract: Pyrimidine derivatives represented by general formula (1) or their salts and a drug comprising the same as the active ingredient, wherein R1 represents hydroxy, lower alkoxy, phenyloxy, aralkyloxy or -NR2R3 wherein R?2 and R3¿ represent each hydrogen, hydroxy, lower alkyl, phenyl, aralkyl, or a heterocyclic group; X represents oxygen or N-R4 wherein R4 represents lower alkyl, phenyl, formyl or lower alkoxycarbonyl; m is 2 or 3; and n is 1 or 2. The compounds have a potent inhibitory activity on endothelins having a potent vasoconstrictor activity and are useful in the treatment of circulatory disorders, etc.

公开(公告)号：EP1818329A4

公开(公告)日：2009-08-05

申请号：EP05811715

申请日：2005-11-29

Applicant: KOWA CO ,  WESTERN THERAPEUTICS INST INC

Inventor： OHSHIMA TAKESHI ,  HIDAKA HIROYOSHI ,  SHIRATSUCHI MASAMI ,  ONOGI KAZUHIRO ,  ODA TOSHIAKI

IPC: C07D401/12 ,  A61K31/551 ,  A61P9/10

CPC classification number: C07D401/12

Abstract: (S)-(-)-1-(4-fluoroisoquinolin-5-yl)sulfonyl-2-methyl-1,4­homopiperazine hydrochloride dihydrate; a process for producing the dihydrate; and a medicinal composition containing the dihydrate. This compound has lower hygroscopicity than anhydrous crystals of (S)-(-)-1-(4-fluoroisoquinolin-5-yl)sulfonyl-2-methyl­1,4-homopiperazine hydrochloride and is superior in chemical stability. It is hence useful as a medicine.

Abstract translation: （S） - （ - ） - 1-（4-氟异喹啉-5-基）磺酰基-2-甲基-1,4-高哌嗪盐酸盐二水合物; 生产二水合物的方法; 和含有该二水合物的医药组合物。 该化合物与（S） - （ - ） - 1-（4-氟异喹啉-5-基）磺酰基-2-甲基-1,4-高哌嗪盐酸盐的无水结晶相比吸湿性低，化学稳定性优异。 因此它是有用的药物。

公开(公告)号：EP1400513A4

公开(公告)日：2005-04-13

申请号：EP02736189

申请日：2002-06-27

Applicant: KOWA CO

Inventor： KODAMA TATSUHIKO ,  TAMURA MASAHIRO ,  ODA TOSHIAKI ,  YAMAZAKI YUKIYOSHI ,  NISHIKAWA MASAHIRO ,  DOI TAKESHI ,  KYOTANI YOSHINORI ,  TAKEMURA SHUNJI

IPC: A61P9/10 ,  A61P11/06 ,  A61P29/00 ,  A61P37/08 ,  A61P43/00 ,  C07D213/36 ,  C07D213/81 ,  C07D213/82 ,  C07D401/12 ,  A61K31/496 ,  A61K31/506 ,  A61K31/551

CPC classification number: C07D213/81 ,  C07D213/36 ,  C07D213/82 ,  C07D401/12

Abstract: A cyclic diamine compound represented by the following general formula (1): (1) [wherein A represents (CH2)n, (CH2)n-CH=CH, CO-(CH2)n, or CO-(CH2)n-CH=CH (wherein n is a number of 0 to 3); Z represents the formula (2) or (3): (2) (3) (wherein R1, R2, R3, R4, R5, and R6 are the same or different and each represents hydrogen, alkyl, etc., X and Y are the same or different and each represents CH or nitrogen); and m is 1 or 2], an acid addition salt of the compound, or a hydrate of either; and a medicine containing any of these. The compound (1) has excellent inhibitory activity against cell adhesion and cell infiltration. It is useful in the prevention of and treatments for allergy, asthma, rheumatism, arteriosclerosis, inflammation, etc.

公开(公告)号：EP1400521A4

公开(公告)日：2005-04-06

申请号：EP02736190

申请日：2002-06-27

Applicant: KOWA CO

Inventor： KODAMA TATSUHIKO ,  TAMURA MASAHIRO ,  ODA TOSHIAKI ,  YAMAZAKI YUKIYOSHI ,  NISHIKAWA MASAHIRO ,  DOI TAKESHI ,  KYOTANI YOSHINORI

IPC: A61K31/496 ,  A61P9/10 ,  A61P11/06 ,  A61P29/00 ,  A61P37/08 ,  A61P43/00 ,  C07D213/74 ,  C07D401/14

CPC classification number: C07D401/14 ,  A61K31/496 ,  C07D213/74

Abstract: Piperazine compounds represented by the general formula (1), acid-addition salts thereof, or hydrates of both: (1) [wherein X is -CH2-, -C(O)-, or -CH(CH3)-; R1 is hydrogen or alkyl; R2 is hydrogen, alkyl, hydroxyalkyl, arylalkyl, heteroarylalkyl, carboxyalkyl, carbamoylalkyl, aminoalkyl, or guanidinoalkyl]. The compounds (1) exhibit excellent inhibitory activities against cell adhesion and cell infiltration and are useful in the prevention and treatment of allergy, asthma, rheumatic diseases, arteriosclerosis, inflammation, and so on.

公开(公告)号：EP0801062A4

公开(公告)日：1998-04-29

申请号：EP95940471

申请日：1995-12-19

Applicant: KOWA CO

Inventor： HIRATA MITSUTERU ,  DEUSHI TAKEO ,  TAKAHASHI YOSHIO ,  TAMURA MASAHIRO ,  OHSHIMA TAKESHI ,  ODA TOSHIAKI ,  SONOKI HIROYUKI ,  SHIRATSUCHI MASAMI

IPC: C07D239/69 ,  C07D239/52 ,  A61K31/505

CPC classification number: C07D239/69

Abstract: A pyrimidine derivative represented by general formula (1) or a salt thereof and a medicine comprising the same as the active ingredient, wherein R1 represents lower alkyl; R?2 and R3¿ represent each hydrogen, alkyl or alkoxy; R?4 and R5¿ represent each hydrogen or alkyl; R6 represents alkyl, -OR?7 or NR8N9¿; and n represents a number of 0 to 3 (wherein R?7, R8 and R9¿ represent each hydrogen, alkyl, aryl, aralkyl, amino, heterocycle, etc.). The compound has a potent inhibitory activity on endothelin having potent vasoconstrictor and cell proliferation effects and is useful in treating circulatory disorders, etc.

公开(公告)号：AU2005308060B2

公开(公告)日：2011-02-17

申请号：AU2005308060

申请日：2005-11-29

Applicant: D WESTERN THERAPEUTICS INSTITUTE INC ,  KOWA CO LTD

Inventor： OHSHIMA TAKESHI ,  SHIRATSUCHI MASAMI ,  ONOGI KAZUHIRO ,  HIDAKA HIROYOSHI ,  ODA TOSHIAKI

Abstract: The present invention is directed to (S)-(-)-1-(4-fluoroisoquinolin-5-yl)sulfonyl-2-methyl-1,4-homopiperazine hydrochloride dihydrate, to a method producing the dihydrate, and to a drug composition containing the dihydrate. The compound of the present invention has less hygroscopicity as compared with (S)-(-)-1-(4-fluoroisoquinolin-5-yl)sulfonyl-2-methyl-1,4-homopiperazine hydrochloride anhydrous crystals and thus, exhibits excellent chemical stability.

公开(公告)号：CA2451241C

公开(公告)日：2011-01-04

申请号：CA2451241

申请日：2002-06-27

Applicant: KOWA CO

Inventor： KODAMA TATSUHIKO ,  TAMURA MASAHIRO ,  ODA TOSHIAKI ,  YAMAZAKI YUKIYOSHI ,  NISHIKAWA MASAHIRO ,  DOI TAKESHI ,  KYOTANI YOSHINORI ,  TAKEMURA SHUNJI

IPC: C07D213/72 ,  A61K31/496 ,  A61K31/506 ,  A61K31/551 ,  A61P9/10 ,  A61P11/06 ,  A61P29/00 ,  A61P37/08 ,  A61P43/00 ,  C07D213/36 ,  C07D213/81 ,  C07D213/82 ,  C07D401/06 ,  C07D401/12

Abstract: A cyclic diamine compound of formula (1): (see formula 1) wherein A is (CH2)n, (CH2)n-CH=CH, CO- (CH2)n or CO-(CH2)n-CH=CH, in which n is a number of 0 to 3; Z represents a formula (2) or (3): (see formula 2) (see formula 3) in which R1, R2, R4, R5 and R6 are individually a hydrogen atom, alkyl group, and X and Y are individually CH or a nitrogen atom; and m is 1 or 2; an acid-addition salt thereof, or a hydrate thereof, and a medicine containing such a compound, having excellent effects on both adhesion and cell infiltration, as well as being useful for the prevention and treatment of allergy, asthma, inflammation, rhumatism, and orteriosclerosis. 120

公开(公告)号：DE602005020835D1

公开(公告)日：2010-06-02

申请号：DE602005020835

申请日：2005-11-29

Applicant: WESTERN THERAPEUTICS INST INC ,  KOWA CO

Inventor： OHSHIMA TAKESHI ,  HIDAKA HIROYOSHI ,  SHIRATSUCHI MASAMI ,  ONOGI KAZUHIRO ,  ODA TOSHIAKI

IPC: C07D401/12 ,  A61K31/551 ,  A61P9/10

Abstract: The present invention is directed to (S)-(-)-1-(4-fluoroisoquinolin-5-yl)sulfonyl-2-methyl-1,4-homopiperazine hydrochloride dihydrate, to a method producing the dihydrate, and to a drug composition containing the dihydrate. The compound of the present invention has less hygroscopicity as compared with (S)-(-)-1-(4-fluoroisoquinolin-5-yl)sulfonyl-2-methyl-1,4-homopiperazine hydrochloride anhydrous crystals and thus, exhibits excellent chemical stability.

公开(公告)号：MY134200A

公开(公告)日：2007-11-30

申请号：MYPI20031300

申请日：2003-04-08

Applicant: KOWA CO

Inventor： MATAKI CHIKAGE ,  KODAMA TATSUHIKO ,  DOI TAKESHI ,  TAMURA MASAHIRO ,  ODA TOSHIAKI ,  YAMAZAKI YUKIYOSHI ,  NISHIKAWA MASAHIRO ,  TAKEMURA SHUNJI ,  OHKUCHI MASAO

IPC: A61K31/4545 ,  C07D295/12 ,  A61K31/445 ,  A61K31/4468 ,  A61K48/00 ,  A61P35/00 ,  A61P43/00 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D491/10

Abstract: THE PRESENT INVENTION IS DIRECTED TO A MEDICINE FOR TREATING CANCER, A METHOD FOR INHIBITING HISTONE DEACETYLASE INHIBITOR, AND A GENE THERAPYFACILITATER, COMPRISING ADMINISTERING AN EFFECTIVE AMOUNT OF A CYCLIC AMINE COMPOUND REPRESENTED BY THE FOLLOWING FORMULA (1):(WHEREIN R1,R2 AND R3 EACH INDEPENDENTLY REPRESENT A HYDROGEN ATOM, A HALOGEN ATOM, A HYDROXY GROUP, AN ALKYL GROUP, A HALOGEN-SUBSTITUTED ALKYL GROUP, AN ALKOXY GROUP, AN ALKYLTHIO GROUP, A CARBOXYL GROUP, AN ALKOXYCARBONYL GROUP, OR AN ALKANOYL GROUP; W1 AND W2 , WHICH ARE IDENTICAL TO OR DIFFERENT FROM EACH OTHER, REPRESENT N OR CH; X REPRESENTS O, NR4, CONR4, OR NR4CO;R4 REPRESENTS A HYDROGEN ATOM, AN ALKYL GROUP, AN ALKENYL GROUP, AN ALKYNYL GROUP, A SUBSTITUTED OR UNSUBSTITUTED ARYL GROUP, A SUBSTITUTED OR UNSUBSTITUTED HETEROARYL GROUP, A SUBSTITUTED OR UNSUBSTITUTED ARALKYL GROUP, OR A SUBSTITUTED OR UNSUBSTITUTED HETEROARALKYL GROUP; AND 1,M, AND N EACH REPRESENT A NUMBER OF 0 OR 1), A SALT THE REOF , OR A HYDRATE THEREOF.

公开(公告)号：DE69630799T2

公开(公告)日：2004-08-12

申请号：DE69630799

申请日：1996-09-04

Applicant: KOWA CO

Inventor： HIRATA MITSUTERU ,  DEUSHI TAKEO ,  TAKAHASHI YOSHIO ,  TAMURA MASAHIRO ,  OHSHIMA TAKESHI ,  ODA TOSHIAKI ,  ISHIKAWA TETSUYA ,  SONOKI HIROYUKI ,  SHIRATSUCHI MASAMI

IPC: C07D403/04 ,  A61K31/506 ,  A61P9/00 ,  A61P9/12 ,  C07D213/00 ,  C07D239/52 ,  C07D239/545 ,  C07D295/00 ,  C07D401/14 ,  C07D239/48 ,  A61K31/505 ,  C07D239/69

Abstract: The present invention is directed to a pyrimidine derivative of the following formula (1) or a salt of the derivative: Äwherein R represents a hydroxyl group, a lower alkoxy group, a phenyloxy group which may have a substituent, an aralkyloxy group which may have a substituent, or -NR R ; X represents an oxygen atom or N-R ; m is 2 or 3; and n is 1 or 2 (wherein each of R and R , which are identical to or different from each other, represents a hydrogen atom, a hydroxyl group, a lower alkyl group which may have a substituent, a phenyl group which may have a substituent, an aralkyl group which may have a substituent, or a heterocyclic group which may have a substituent; R represents a lower alkyl group, a phenyl group, a formyl group, or a lower alkoxycarbonyl group)Ü, as well as to a medicine containing the derivative or salt as the active ingredient. The compounds exhibit strong binding inhibitory activity against endothelin having potent vasoconstrictive effect. Therefore, the compounds are effective as remedies for various diseases including circulatory diseases.