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1.发明公开CRYSTALLINE FORMS OF6-[(5S,9R)-9-(4-CYANOPHENYL)-3-(3,5-DICHLOROPHENYL)-1-METHYL-2,4-DIOXO-1,3,7-TRIAZASPIRO[4.4]NON-7-YL]NICOTINIC ACID AS INHIBITORS OF CD18 INTEGRINS, ICAMS AND/OR THE LFA-1:ICAM INTERACTION FOR THE TREATMENT OF INFLAMMATIONS AND IMMUNE DISEASES 审中-公开6结晶形式 - [（5S，9R）-9-（4-氰基苯基）-3-（3,5-二氯苯基）-1-甲基-2,4-二氧代-1,3,7-三氮杂螺[4， 4]壬-7-基]烟酸AS CD18整合素，ICAM的AND / OR LFA-1的抑制剂：ICAM-相互作用治疗炎症和免疫性疾病
公开(公告)号：EP1836209A1
公开(公告)日：2007-09-26
申请号：EP05849629.0
申请日：2005-12-14
发明人： DELMONTE, Albert J. , DHAR, T. G. Murali , GALELLA, Michael , GLEESON, Margaret , GOUGOUTAS, Jack Z. , MCLEOD, Douglas D. , ZHANG, Huiping , CHEN, Bang Chi
IPC分类号： C07D487/10 , A61P37/06 , A61P19/02
CPC分类号： C07D487/10
摘要： The invention provides crystalline forms of 6-[(5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-7-yl]nicotinic acid, its pharmaceutically acceptable salts, or solvates, thereof Further, a process is provided for preparing substituted spiro-hydantoin compounds of the formula I, wherein Z is N or CR4b; K and L are independently O or S; Ar is an optionally substituted aryl or heteroaryl; A1, A2, G, and Q are linkers; and R2, R4a, R4c, and R16 are defined in the specification. The process includes the reaction of N-substituted glycine compound and methylene precursor compound with an alkene compound. The substituted spiro-hydantoin compounds of formulae I and II are useful in the treatment of immune and/or inflammatory diseases.
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