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    Isoquinoline derivative hydrochloride anhydrate crystal
    2.
    发明专利
    Isoquinoline derivative hydrochloride anhydrate crystal 有权
    异喹啉衍生物氢氯酸盐晶体

    公开(公告)号：JP2013100247A

    公开(公告)日：2013-05-23

    申请号：JP2011245229

    申请日：2011-11-09

    Applicant: Kowa Co ,  興和株式会社

    Inventor： OSHIMA TAKESHI ,  ISHIKAWA TETSUYA ,  HARA TAKEAKI ,  ASHIKAWA MASANORI ,  TAGASHIRA JUNYA

    IPC: C07D401/12 ,  A61K31/551 ,  A61P9/00 ,  A61P25/00

    Abstract: PROBLEM TO BE SOLVED: To provide a stable (S)-(-)-1-(4-fluoroisoquinolin-5-yl)sulfonyl-2-methyl-1,4 homopiperazine hydrochloride anhydrate, and to provide a method of producing the same.SOLUTION: An (S)-(-)-1-(4-fluoroisoquinolin-5-yl)sulfonyl-2-methyl-1,4 homopiperazine hydrochloride dihydrate is heated to be dried under low pressure, thereby obtaining stable crystal different from conventionally known anhydrate.

    Abstract translation: 待解决的问题：提供稳定的（S） - （ - ） - 1-（4-氟异喹啉-5-基）磺酰基-2-甲基-1,4-高哌嗪盐酸盐水合物，并提供一种 生产相同。 解决方案：将（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加热至低压干燥，得到稳定的结晶 与常规已知的无水物不同。 版权所有（C）2013，JPO＆INPIT

    ENDOTHELIN ANTAGONIST
    5.
    发明专利
    ENDOTHELIN ANTAGONIST 失效

    公开(公告)号：JPH07330601A

    公开(公告)日：1995-12-19

    申请号：JP12874694

    申请日：1994-06-10

    Applicant: KOWA CO

    Inventor： HIRATA MITSUTERU ,  OSHIMA TAKESHI ,  SOGI HIROYUKI ,  TAMURA MASAHIRO ,  ODA TOSHIAKI ,  SHIRATO SHOZO

    IPC: C07D487/22 ,  A61K31/40 ,  A61K31/555 ,  A61P9/08 ,  A61P9/10 ,  A61P43/00

    Abstract: PURPOSE:To obtain an endothelin antagonist containing a specific protoporphyrin or its salt as an effective component and capable of exhibiting strong binding- inhibition activity against endothelin which has strong blood vessel dilating activity and to obtain a blood vessel dilating agent. CONSTITUTION:An endothelin antagonist containing, as an effective component, a porphyrin of formula I [R and R are each H, a lower alkyl optionally containing OH and/or COOH, a lower alkenyl or acetyl; R , R and R are each H or a lower alkyl; R is H or methoxyphenyl; R is H, a carboxy lower alkyl or a lower alkyl; R and R are each H, a lower alkyl or ACO2B (A is a single bond or a lower alkylene; B is H or a lower alkylene); R is H, formyl, methoxyphenyl, QCOOX (Q is a lower alkylene or a lower alkenylene; X is H or a lower alkyl)], its metal complex or its salt and a blood vessel dilating agent. Examples of a porphyrin expressed by formula I include compounds of from formula II to formula VII, etc.

    PYRIMIDINE DERIVATIVE AND MANUFACTURE OF THE SAME
    6.
    发明专利
    PYRIMIDINE DERIVATIVE AND MANUFACTURE OF THE SAME 失效

    公开(公告)号：JP2000143637A

    公开(公告)日：2000-05-26

    申请号：JP24715699

    申请日：1999-09-01

    Applicant: KOWA CO

    Inventor： TAKAHASHI YOSHIO ,  TAIMA TSUTOMU ,  OSHIMA TAKESHI ,  ISHIKAWA TETSUYA ,  YAMAGUCHI TAKASHI ,  HIRATA MITSUTERU ,  SATO YUKIHIRO ,  YAMADA HAJIME

    IPC: C07D239/52 ,  A61K31/505 ,  A61K31/5377 ,  A61P9/00 ,  A61P9/12 ,  A61P43/00

    Abstract: PROBLEM TO BE SOLVED: To obtain a new pyrimidine derivative having potent endothelin antagonism useful for medicine as a therapeutic agent of circulatory system disease or the like. SOLUTION: This derivative is expressed by formula I [R1 is a lower alkyl; R2 is a (substituted) pyrimidyl, morpholino; n is 1 to 3], preferably, 3-[6-(4-t- butylphenylsulfonylamino)-5-(2-methoxyphenoxy)-2-(2-pyrimidyl)-4-pyrim idyloxy) propanal or the like. The compound of formula I is preferably obtained by reacting a compound expressed by formula III [R3 is a (substituted) alkyl, an aralkyl or the like] (for example; 3,3-diethoxy-1-propanol or the like) to a compound expressed by formula II (X is a halogen) for example; 4-t-butyl-N-[6- chloro-5-(2-methoxyphenoxy)-2-(2-pyrimidyl)-4-pyrimidyl]benzenesulfona mide or the like} to obtain the compound of formula IV, and deprotecting the product.

    TRIPEPTIDES CONTAINING ACIDIC AMINO ACID
    7.
    发明专利
    TRIPEPTIDES CONTAINING ACIDIC AMINO ACID 失效

    公开(公告)号：JPH08311097A

    公开(公告)日：1996-11-26

    申请号：JP11993795

    申请日：1995-05-18

    Applicant: KOWA CO ,  MICROBIAL CHEM RES FOUND

    Inventor： HIRATA MITSUTERU ,  TAMURA MASAHIRO ,  SUZUKI CHIYOTAKA ,  OSHIMA TAKESHI ,  ODA TOSHIAKI ,  SOGI HIROYUKI ,  SHIRATO SHOZO ,  HAMADA MASA ,  MAEDA KENJI ,  TAKEUCHI TOMIO

    IPC: A61K38/00 ,  A61K38/22 ,  A61P9/08 ,  A61P9/10 ,  C07K5/083

    Abstract: PURPOSE: To provide the subject new compound consisting of a tripeptide containing a specific acidic amino acid, having strong inhibiting action on endothelin and vasodilating action and useful as an endothelin antagonistic agent, a vasodilator, etc., for the treatment of myocardial infarction, stenocardia, etc. CONSTITUTION: This new tripeptide (its salt or hydrate) is expressed by formula (R is an alkyl, an aryl, an aryl-lower alkyl, an alkoxy, an aryloxy, etc.; R is H, an alkyl, an aryl, an aryl-lower alkyl, formyl, a lower acyl, etc.; one of R and R is hydroxyl and the other is an alkoxy or an alkylamino; A is methylene or ethylene). It has endothelin antagonistic action and vasodilating action and useful e.g. as an agent for the treatment of heart diseases, respiratory tract diseases, cardiovascular diseases, renal diseases, hepatic diseases, bone diseases, vascular disorders, etc. The compound can be produced either by condensing amino acids one by one or condensing condensation products each composed of plural amino acids and optionally removing the protective groups by alkali hydrolysis, catalytic hydrogenative decomposition, etc.

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