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    24.
    发明专利
    未知

    公开(公告)号：DE69830307D1

    公开(公告)日：2005-06-30

    申请号：DE69830307

    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: Preparation of salts of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl amino acid derivatives of formula (R1)NH-CH(R2)-CO2H (I) comprises: (a) condensing an amino acid with N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanine N-carboxyanhydride of formula (II), under basic conditions; (b) decarboxylating the condensate under neutral to acidic conditions to give (I); and (c) and converting (I) to its salt. Steps (a), (b) and optionally (c) are carried out in aqueous liquid to inhibit the formation of by-products of formula (III): -N(R1)CH(R2)-C(O)- = e.g. group of formula (i).

    Process for preparing N2-(1(S)-carboxy-3-phenylpropyl)-L-lysyl-L-proline
    26.
    发明专利
    Process for preparing N2-(1(S)-carboxy-3-phenylpropyl)-L-lysyl-L-proline 未知

    公开(公告)号：CZ20001897A3

    公开(公告)日：2000-10-11

    申请号：CZ20001897

    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.

    PROCESS FOR PREPARING PHARMACOLOGICALLY ACCEPTABLE SALTS OF N-(1(S)-ETHOXYCARBONYL-3-PHENYLPROPYL)-L-ALANYL AMINO ACIDS
    28.
    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
    29.
    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.

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