公开(公告)号：WO2019006292A1

公开(公告)日：2019-01-03

申请号：PCT/US2018/040276

申请日：2018-06-29

申请人： BRISTOL-MYERS SQUIBB COMPANY ,  DELMONTE, Albert, J. ,  COHEN, Benjamin, M. ,  FRAUNHOFFER, Kenneth, Joseph ,  KOLOTUCHIN, Sergei ,  GONZALEZ-BOBES, Francisco ,  BEUTNER, Gregory, Louis ,  FREITAG, Adam, Joseph ,  BULTMAN, Michael, Scott ,  FAN, Yu ,  MAITY, Prantik ,  YOUNG, Ian, Scott ,  BECK, Hilary, Plake ,  OSPOV, Maksim ,  POWERS, Jay, Patrick ,  REILLY, Maureen, Kay ,  SHUNATONA, Hunter, Paul ,  WALKER, James, Ross ,  ZIBINSKY, Mikhail

发明人： DELMONTE, Albert, J. ,  COHEN, Benjamin, M. ,  FRAUNHOFFER, Kenneth, Joseph ,  KOLOTUCHIN, Sergei ,  GONZALEZ-BOBES, Francisco ,  BEUTNER, Gregory, Louis ,  FREITAG, Adam, Joseph ,  BULTMAN, Michael, Scott ,  FAN, Yu ,  MAITY, Prantik ,  YOUNG, Ian, Scott ,  BECK, Hilary, Plake ,  OSPOV, Maksim ,  POWERS, Jay, Patrick ,  REILLY, Maureen, Kay ,  SHUNATONA, Hunter, Paul ,  WALKER, James, Ross ,  ZIBINSKY, Mikhail

IPC分类号： A61K31/5365 ,  C07D498/04

摘要： The disclosure is directed to improved methods for preparing substituted quinolinylcyclohexylpropanamide compounds.

公开(公告)号：WO2006065908A1

公开(公告)日：2006-06-22

申请号：PCT/US2005/045251

申请日：2005-12-14

申请人： BRISTOL-MYERS SQUIBB COMPANY ,  DELMONTE, Albert J. ,  DHAR, T. G. Murali ,  GALELLA, Michael ,  GLEESON, Margaret ,  GOUGOUTAS, Jack Z. ,  MCLEOD, Douglas D. ,  ZHANG, Huiping ,  CHEN, Bang Chi

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.

摘要翻译： 本发明提供6 - [（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]非7-基]烟酸，其药学上可接受的盐或溶剂化物。此外，提供了制备式I的取代的螺 - 乙内酰脲化合物的方法，其中Z是N或CR4b; K和L独立地为O或S; Ar是任选取代的芳基或杂芳基; A1，A2，G和Q是接头; R2，R4a，R4c和R16在说明书中定义。 该方法包括N-取代的甘氨酸化合物和亚甲基前体化合物与烯烃化合物的反应。 式I和II的取代的螺 - 乙内酰脲化合物可用于治疗免疫和/或炎性疾病。

公开(公告)号：WO2006039639A1

公开(公告)日：2006-04-13

申请号：PCT/US2005/035467

申请日：2005-09-30

申请人： BRISTOL-MYERS SQUIBB COMPANY ,  DELMONTE, Albert, J. ,  DHAR, T., G. Murali ,  FAN, Yu ,  GOUGOUTAS, Jack, Z. ,  MALLEY, Mary, F. ,  MCLEOD, Douglas, D. ,  WALTERMIRE, Robert ,  WEI, Chenkou

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 CR 4b ; K and L are independently O or S; Ar is an optionally substituted aryl or heteroaryl; A 2 is a linker, G' is a linker; Q is a linker; and R 2 , R 4a , R 4c , and R h 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-[(5 S , 9 R )-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.

摘要翻译： 提供了制备式（II）的螺 - 乙内酰脲化合物的方法，其中Z为N或CR