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    PROCESS FOR PREPARING PHARMACOLOGICALLY ACCEPTABLE SALTS OF N-(1(S)-ETHOXYCARBONYL-3-PHENYLPROPYL)-L-ALANYL AMINO ACIDS
    32.
    发明专利
    PROCESS FOR PREPARING PHARMACOLOGICALLY ACCEPTABLE SALTS OF N-(1(S)-ETHOXYCARBONYL-3-PHENYLPROPYL)-L-ALANYL AMINO ACIDS 未知

    公开(公告)号：CA2266757A1

    公开(公告)日：1999-02-04

    申请号：CA2266757

    申请日：1998-07-21

    Applicant: KANEKA CORP

    Inventor： UEDA YASUYOSHI ,  KINOSHITA KOICHI ,  MOROSHIMA TADASHI ,  FUSE YOSHIHIDE ,  YANAGIDA YOSHIFUMI

    IPC: A61P9/12 ,  C07K1/02 ,  C07K1/08 ,  C07K5/02 ,  C07K5/06 ,  C07K5/062

    Abstract: A process for preparing pharmacologically acceptable salts of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl amino acids, comprising the steps of: condensing an amino acid with N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanine N-carboxyanhydride under basic conditions; decarboxylating the condensate under neutral to acidic conditions to prepare an N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl amino acid; and converting the product to a pharmacologically acceptable salt thereof, characterized in that a series of procedures up to the formation of a pharmacologically acceptable salt or up to the withdrawal of the pharmaceutically acceptable salt thereof are carried out in an aqueous liquid to inhibit the production of a by-product (3). According to this process, high-quality pharmacologically acceptable salts of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl amino acids can be prepared in high yields in a cost-effective manner on a commercial scale.

    PROCESS FOR PREPARING PHARMACOLOGICALLY ACCEPTABLE SALTS OF N-(1(S)-ETHOXYCARBONYL-3-PHENYLPROPYL)-L-ALANYL-AMINO ACIDS
    33.
    发明专利
    PROCESS FOR PREPARING PHARMACOLOGICALLY ACCEPTABLE SALTS OF N-(1(S)-ETHOXYCARBONYL-3-PHENYLPROPYL)-L-ALANYL-AMINO ACIDS 未知

    公开(公告)号：CA2266757C

    公开(公告)日：2010-10-19

    申请号：CA2266757

    申请日：1998-07-21

    Applicant: KANEKA CORP

    Inventor： UEDA YASUYOSHI ,  KINOSHITA KOICHI ,  MOROSHIMA TADASHI ,  YANAGIDA YOSHIFUMI ,  FUSE YOSHIHIDE

    IPC: C07K5/062 ,  A61P9/12 ,  C07K1/02 ,  C07K1/08 ,  C07K5/02 ,  C07K5/06

    Abstract: There is provided a process for preparing a pharmacologically acceptable salt of N-(1(S)--ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid which comprises condensing an amino acid and N--(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanine- N-carboxy-anhydride under basic condition, carrying out decarboxylation under between neutral and acidic condition to obtain N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid, and forming a pharmacologically acceptable salt thereof, wherein the production of a by-product (3): (see formula 3) is suppressed by carrying out in an aqueous liquid a series of operations till formation of the pharmacologically acceptable salt or till isolation of the pharmacologically acceptable salt. The present invention enables to prepare the pharmacologically acceptable salt of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid having high quality, in a commercial scale with high yield and economical efficiency.

    PROCEDIMIENTO PARA PREPARAR SALES FARMACOLOGICAMENTE ACEPTABLES DE N-1(S)-ETOXICARBONIL-3-FENILPROPIL)-L-ALANIL AMINOACIDOS.
    35.
    发明专利
    PROCEDIMIENTO PARA PREPARAR SALES FARMACOLOGICAMENTE ACEPTABLES DE N-1(S)-ETOXICARBONIL-3-FENILPROPIL)-L-ALANIL AMINOACIDOS. 未知

    公开(公告)号：ES2241149T3

    公开(公告)日：2005-10-16

    申请号：ES98932585

    申请日：1998-07-21

    Applicant: KANEKA CORP

    Inventor： UEDA YASUYOSHI ,  KINOSHITA KOICHI ,  MOROSHIMA TADASHI ,  YANAGIDA YOSHIFUMI ,  FUSE YOSHIHIDE

    IPC: A61P9/12 ,  C07K1/02 ,  C07K1/08 ,  C07K5/02 ,  C07K5/06 ,  C07K5/062

    Abstract: UN PROCEDIMIENTO PARA LA PREPARACION DE SALES DE N - (1(S) ETOXICARBONIL - 3 - FENILPROPIL) - L - ALANILAMINOACIDOS FARMACOLOGICAMENTE ACEPTABLES QUE CONSISTE EN LOS PASOS SIGUIENTES: SE CONDENSA UN AMINOACIDO CON N - CARBOXIANHIDRIDO DE N - (1(S) - ETOXICARBONIL - 3 - FENILPROPIL) - L - ALANINA BAJO CONDICIONES BASICAS; SE DESCARBOXILA EL CONDENSADO BAJO CONDICIONES DE NEUTRAS A ACIDAS PARA PREPARAR UN N - (1(S) ETOXICARBONIL 3 - FENILPROPIL) - L - ALANILAMINOACIDO; Y SE CONVIERTE EL PRODUCTO EN UNA SAL FARMACOLOGICAMENTE ACEPTABLE DEL MISMO, QUE SE CARACTERIZA PORQUE SE LLEVAN A CABO UNA SERIE DE PROCEDIMIENTOS HASTA LA FORMACION DE UNA SAL FARMACOLOGICAMENTE ACEPTABLE O HASTA LA RETIRADA DE LA SAL FARMACOLOGICAMENTE ACEPTABLE DEL MISMO EN UN LIQUIDO ACUOSO PARA INHIBIR LA PRODUCCION DE UN SUBPRODUCTO (4). SEGUN ESTE PROCEDIMIENTO, SE PUEDEN PREPARAR SALES DE N - (1(S) ETOXICARBONIL - 3 - FENILPROPIL) - L - ALANILAMINOACIDOS FARMACOLOGICAMENTE ACEPTABLES EN GRANDES CANTIDADES DE MANERA ECONOMICA A ESCALA COMERCIAL.

    PROCESS FOR THE PREPARATION OF N2-(1(S)-CARBOXY-3-PHENYLPROPYL)-L-LYSYL-L-PROLINE
    36.
    发明专利
    PROCESS FOR THE PREPARATION OF N2-(1(S)-CARBOXY-3-PHENYLPROPYL)-L-LYSYL-L-PROLINE 未知

    公开(公告)号：HU0100831A2

    公开(公告)日：2001-08-28

    申请号：HU0100831

    申请日：1999-09-22

    Applicant: KANEKA CORP

    Inventor： FUSE YOSHIHIDE ,  MOROSHIMA TADASHI ,  UEDA YASUYOSHI ,  YANAGIDA YOSHIFUMI

    IPC: C07K5/068 ,  A61K38/05 ,  A61P9/12 ,  C07K5/02

    Abstract: The process for producing N -(1(S)-carboxy-3-phenylpropyl)-L-lysyl-L-proline in a simple, efficient and industrially advantageous manner, which comprises: the first step of subjecting the N -(1(S)-alkoxycarbonyl-3-phenylpropyl)-N -trifluoroacetyl-L-lysyl -L-proline (1) to alkali hydrolysis in a mixed solution composed of water and a hydrophilic organic solvent using an inorganic base in an amount of n molar equivalents (n >/= 3) per mole of the above compound (1), the second step of neutralizing the hydrolysis product using an inorganic acid in an amount of (n - 1) to n molar equivalents (n >/= 3) and removing the inorganic salt formed by causing the same to precipitate out from a solvent system suited for decreasing the solubility of the inorganic salt, and the third step of causing the compound (2) existing in the mixture after removal of the inorganic salt to crystallize out at the isoelectric point thereof and thereby recovering the compound (2) in the form of crystals while retaining the salts comprising the trifluoroacetic acid-derived organic acid salt in a state dissolved in the mother liquor.

    METHOD OF OBTAINING N2-(1(S)-CARBOXY-3-PHENYLPROPYL)-L-LYSIL-L-PROLINE
    37.
    发明专利
    METHOD OF OBTAINING N2-(1(S)-CARBOXY-3-PHENYLPROPYL)-L-LYSIL-L-PROLINE 未知

    公开(公告)号：PL340685A1

    公开(公告)日：2001-02-26

    申请号：PL34068599

    申请日：1999-09-22

    Applicant: KANEKA CORP

    Inventor： MOROSHIMA TADASHI ,  YANAGIDA YOSHIFUMI ,  FUSE YOSHIHIDE ,  UEDA YASUYOSHI

    IPC: C07K5/068 ,  A61K38/05 ,  A61P9/12 ,  C07K5/02

    Abstract: The process for producing N -(1(S)-carboxy-3-phenylpropyl)-L-lysyl-L-proline in a simple, efficient and industrially advantageous manner, which comprises: the first step of subjecting the N -(1(S)-alkoxycarbonyl-3-phenylpropyl)-N -trifluoroacetyl-L-lysyl -L-proline (1) to alkali hydrolysis in a mixed solution composed of water and a hydrophilic organic solvent using an inorganic base in an amount of n molar equivalents (n >/= 3) per mole of the above compound (1), the second step of neutralizing the hydrolysis product using an inorganic acid in an amount of (n - 1) to n molar equivalents (n >/= 3) and removing the inorganic salt formed by causing the same to precipitate out from a solvent system suited for decreasing the solubility of the inorganic salt, and the third step of causing the compound (2) existing in the mixture after removal of the inorganic salt to crystallize out at the isoelectric point thereof and thereby recovering the compound (2) in the form of crystals while retaining the salts comprising the trifluoroacetic acid-derived organic acid salt in a state dissolved in the mother liquor.

    HEAT SHOCK FACTOR ACTIVITY INHIBITOR
    39.
    发明专利
    HEAT SHOCK FACTOR ACTIVITY INHIBITOR 未知

    公开(公告)号：CA2295055A1

    公开(公告)日：1999-01-07

    申请号：CA2295055

    申请日：1998-06-25

    Applicant: KANEKA CORP

    Inventor： YOKOTA SHIN-ICHI ,  KITAHARA MIKIO ,  FUSE YOSHIHIDE ,  MORIKAWA SOUICHI ,  YAMAMOTO KOZO

    IPC: C07D405/06 ,  A61K31/40 ,  A61K31/445

    Abstract: Remedies for diseases which function by regulating the expression of a protein induced by a heat shock factor (HSF). Specifically, HSF activity inhibitors or agents inhibiting the induction of the production of a protein regulated by HSF, wherein novel benzo-1,3-dioxole compounds represented by general formula (I) inhibit the transcription of a structural gene having a heat shock element sequence, which is a transcriptional regulatory factor, in a gene region participating in the transcription into RNA, thus inhibit the translation of this gene into a protein and, in its turn, suppress the induction of the production of the RNA, protein, etc. encoded by the gene; and remedies and preventives usable in thermotherapy for cancer and remedies and preventives for stress-induced diseases such as depression. Compounds represented by general formula (I): wherein X is -CH2- and R1 represents C1-2 alkyl, formyl or halogeno; or X is -(CH2)2- and R1 represents C1-3 alkyl, formyl, acetyl, hydrogen or halogeno.

    40.
    发明专利
    未知

    公开(公告)号：AT346086T

    公开(公告)日：2006-12-15

    申请号：AT99944783

    申请日：1999-09-22

    Applicant: KANEKA CORP

    Inventor： MOROSHIMA TADASHI ,  YANAGIDA YOSHIFUMI ,  FUSE YOSHIHIDE ,  UEDA YASUYOSHI

    IPC: C07K5/068 ,  A61K38/05 ,  A61P9/12 ,  C07K5/02 ,  C07K5/06

    Abstract: The process for producing N -(1(S)-carboxy-3-phenylpropyl)-L-lysyl-L-proline in a simple, efficient and industrially advantageous manner, which comprises: the first step of subjecting the N -(1(S)-alkoxycarbonyl-3-phenylpropyl)-N -trifluoroacetyl-L-lysyl -L-proline (1) to alkali hydrolysis in a mixed solution composed of water and a hydrophilic organic solvent using an inorganic base in an amount of n molar equivalents (n >/= 3) per mole of the above compound (1), the second step of neutralizing the hydrolysis product using an inorganic acid in an amount of (n - 1) to n molar equivalents (n >/= 3) and removing the inorganic salt formed by causing the same to precipitate out from a solvent system suited for decreasing the solubility of the inorganic salt, and the third step of causing the compound (2) existing in the mixture after removal of the inorganic salt to crystallize out at the isoelectric point thereof and thereby recovering the compound (2) in the form of crystals while retaining the salts comprising the trifluoroacetic acid-derived organic acid salt in a state dissolved in the mother liquor.

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