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    CRYSTALLINE FORMS AND PROCESS FOR PREPARING SPIRO-HYDANTOIN COMPOUNDS
    2.
    发明公开
    CRYSTALLINE FORMS AND PROCESS FOR PREPARING SPIRO-HYDANTOIN COMPOUNDS 审中-公开
    结晶形式及其制造方法螺乙内酰脲CONNECTIONS

    公开(公告)号：EP1802628A1

    公开(公告)日：2007-07-04

    申请号：EP05812262.3

    申请日：2005-09-30

    申请人： Bristol-Myers Squibb Company

    发明人： DELMONTE, Albert, J. ,  DHAR, T., G. Murali ,  FAN, Yu ,  GOUGOUTAS, Jack, Z. ,  MALLEY, Mary, F. ,  MCLEOD, Douglas, D. ,  WALTERMIRE, Robert ,  WEI, Chenkou

    IPC分类号： C07D487/10 ,  A61K31/4188 ,  A61P29/00

    CPC分类号： C07D487/10

    摘要： A process is provided for preparing spiro-hydantoin compounds of the formula (II), wherein Z is N or CR4b; K and L are independently O or S; Ar is an optionally substituted aryl or heteroaryl; A2 is a linker, G' is a linker; Q is a linker; and R2, R4a, R4c, and Rh are defined in the specification. The process optionally includes the enantiomeric separation of intermediates to allow preparation of enantiomers of the spiro-hydantoin compounds of formula II. Substituted spiro-hydantoin compounds may be prepared from the spiro-hydantoin compounds of formula (II). The spiro-hydantoin compound of formula (II) and the substituted spiro-hydantoin compounds are useful in the treatment of immune or inflammatory diseases. Also, provided are products made by the instant inventive process and crystalline forms (prepared by any process) of the substituted spiro-hydantoin compound, 5-[(5S, 9R)-9-(4-Cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-7-ylmethyl]-thiophene-3- carboxylic acid, including solvates and salts thereof, as well as methods of use thereof. Crystalline forms of certain intermediates are provided.

    N-(5S,6S,9R)-5-AMINO-6-(2,3-DIFLUOROPHENYL)-6,7,8,9-TETRAHYDRO-5H-CYCLOHEPTA[B]PYRIDIN-9-YL-4-(2-OXO-2,3-DIHYDRO-1H-IMIDAZO[4,5-B]PYRIDIN-1-YL)PIPERIDINE-1-CARBOXYLATE SALT
    5.
    发明公开
    N-(5S,6S,9R)-5-AMINO-6-(2,3-DIFLUOROPHENYL)-6,7,8,9-TETRAHYDRO-5H-CYCLOHEPTA[B]PYRIDIN-9-YL-4-(2-OXO-2,3-DIHYDRO-1H-IMIDAZO[4,5-B]PYRIDIN-1-YL)PIPERIDINE-1-CARBOXYLATE SALT 审中-公开
    N-（5S，6S，9R）-5-氨基-6-（2,3-二氟苯基）-6,7,8,9-四氢-5H-环庚并[b]吡啶-9-基-4-（2- - 氧代-2,3-二氢-1H-咪唑并[4,5-b]吡啶-1-基）哌啶-1-羧酸酯盐

    公开(公告)号：EP3254681A1

    公开(公告)日：2017-12-13

    申请号：EP17180587.2

    申请日：2013-02-25

    申请人： Bristol-Myers Squibb Company

    发明人： ROBERTS, Daniel Richard ,  SCHARTMAN, Richard Raymond ,  WEI, Chenkou

    IPC分类号： A61K31/437 ,  C07D471/04 ,  A61P11/00 ,  A61P25/00

    CPC分类号： A61K31/444 ,  C07D401/14 ,  C07D471/04

    摘要： Disclosed is a hemisulfate salt of Compound (I): and crystalline forms of the hemisulfate salt. Also disclosed are methods of using the hemisulfate salt of Compound (1) as a CGRP receptor antagonist, and pharmaceutical compositions comprising the hemisulfate salt of Compound (I). The hemisulfate salt of Compound (I) is useful in treating, preventing, or ameliorating disorders including migraine and other headaches, neurogenic vasodilation, neurogenic inflammation, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases such as asthma, and chronic obstructive pulmonary disease (COPD).

    摘要翻译： 公开了化合物（I）的半硫酸盐：和半硫酸盐的结晶形式。 还公开了使用化合物（1）的半硫酸盐作为CGRP受体拮抗剂的方法，以及包含化合物（I）的半硫酸盐的药物组合物。 化合物（I）的半硫酸盐可用于治疗，预防或改善包括偏头痛和其他头痛，神经源性血管舒张，神经源性炎症，热损伤，循环休克，与绝经相关的潮红，气道炎性疾病如哮喘和慢性 阻塞性肺病（COPD）。