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1. 发明申请

WO2006078331A2 CRYSTALLIZATION VIA HIGH-SHEAR TRANSFORMATION 审中-公开
标题翻译：通过高剪切变形的结晶
公开(公告)号：WO2006078331A2
公开(公告)日：2006-07-27
申请号：PCT/US2005/034552
申请日：2005-09-27
申请人： BRISTOL-MYERS SQUIBB COMPANY , WEI, Chenkou , YANG, Bing-Shiou
发明人： WEI, Chenkou , YANG, Bing-Shiou
IPC分类号： C07D471/02 , A61K31/4745
CPC分类号： A61K31/4745 , B01D9/0059
摘要： The invention relates to a process or apparatus for transforming a first polymorph of a chemical material into a second polymorph of the same chemical material, utilizing an apparatus comprising a vessel connected to a re-circulation system, the process comprising the steps of: suspending said first polymorph in a solution to form a slurry in the vessel, re-circulating the slurry and removing the slurry from the vessel.
摘要翻译：本发明涉及一种用于将化学材料的第一多晶型物转化为相同化学材料的第二多晶型物的方法或装置，利用包括连接到再循环系统的容器的装置，该方法包括以下步骤：将所述在溶液中的第一多晶型物，以在容器中形成浆料，重新循环浆料并从容器中除去浆料。

2. 发明申请

WO2011097331A1 CRYSTALLINE FORMS OF (S)-1-(4-(5-CYCLOPROPYL-1H-PYRAZOL-3- YLAMINO)PYRROLO [1,2-F] [1,2,4] TRIAZIN-2-YL)-N-(6-FLUOROPYRIDIN- 3-YL)-2-METHYLPYRROLIDINE-2-CARBOXAMIDE 审中-公开
标题翻译：（S）-1-（4-（5-环丙基）-1H-吡唑-3-基氨基]吡咯并[1,2-F] [1,2,4]三嗪-2-基）-N-（ 6-氟吡啶-3-基）-2-甲基吡咯烷-2-羧酰胺
公开(公告)号：WO2011097331A1
公开(公告)日：2011-08-11
申请号：PCT/US2011/023521
申请日：2011-02-03
申请人： BRISTOL-MYERS SQUIBB COMPANY , SCHLAM, Roxana F. , NG, Alicia Tee Fuay , WEI, Chenkou
发明人： SCHLAM, Roxana F. , NG, Alicia Tee Fuay , WEI, Chenkou
IPC分类号： C07D487/04 , A61K31/53 , A61P35/00
CPC分类号： C07D487/04
摘要： Crystalline forms of (S)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrrolo[1,2-f][1,2,4]triazin-2-yl)-N-(6-fluoropyridin-3-yl)-2-methylpyrrolidine-2-carboxamide of the formula (I)are provided. Also provided is a pharmaceutical composition comprising one or more crystalline forms of (3R,4R)-4-amino-1-[[4-[(3-methoxyphenyl)amino]pyrrolo[2,1-f][1,2,4]triazin-5-yl]methyl]piperidin-3-ol, as well as a method of using one or more crystalline forms of (3R,4R)-4-amino-1-[[4-[(3-methoxyphenyl)amino]pyrrolo[2,1-f][1,2,4]triazin-5-yl]methyl]piperidin-3-ol in the treatment of cancer and other proliferative diseases.
摘要翻译：（S）-1-（4-（5-环丙基-1H-吡唑-3-基氨基）吡咯并[1,2-f] [1,2,4]三嗪-2-基）-N-（ 6-氟吡啶-3-基）-2-甲基吡咯烷-2-甲酰胺。还提供了包含一种或多种结晶形式的（3R，4R）-4-氨基-1 - [[4 - [（3-甲氧基苯基）氨基]吡咯并[2,1-f] [1,2， 4]三嗪-5-基]甲基]哌啶-3-醇，以及使用一种或多种结晶形式的（3R，4R）-4-氨基-1 - [[4 - [（3-甲氧基苯基））氨基]吡咯并[2,1-f] [1,2,4]三嗪-5-基]甲基]哌啶-3-醇用于治疗癌症和其它增殖性疾病。

3. 发明申请

WO2008157291A3 CRYSTALLINE FORMS OF (3Aα, 4β, 5α, 7β, 7Aα)-4-(OCTAHYDRO-5-ETHYLSULFONAMIDO-4,7-DIMETHYL-1,3-DIOXO-4,7-EPOXY-2H-ISOINDOL-2-YL)-2-(TRIFLUOROMETHYL)BENZONITRILE AND METHOD OF PREPARATION 审中-公开
公开(公告)号：WO2008157291A3
公开(公告)日：2008-12-24
申请号：PCT/US2008/066835
申请日：2008-06-13
申请人： BRISTOL-MYERS SQUIBB COMPANY , KACSUR, David James , LO, Ehrlic , RAMPULLA, Richard A. , WANG, Jianji , WEI, Chenkou
发明人： KACSUR, David James , LO, Ehrlic , RAMPULLA, Richard A. , WANG, Jianji , WEI, Chenkou
IPC分类号： C07D491/04 , A61K31/407 , A61P35/00
摘要： Crystalline forms of (3aα,4β,5α,7β,7aα)-4- (octahydro-5-ethylsulfonamido-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile are provided. Also provided are at least one pharmaceutical composition comprising at least one crystalline form of (3aα,4β,5α,7β,7aα)-4-(octahydro-5-ethylsulfonamido-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile, at least one method of using at least one crystalline form of (3aα,4β,5α,7β,7a α )-4- (octahydro-5-ethylsulfonamido-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile to treat cancer and/or other proliferative diseases, and processes to prepare crystalline forms of (3a α,4β,5α,7β,7aα )-4-(octahydro-5-ethylsulfonamido-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile.

4. 发明申请

WO2002088664A2 CONTROL OF COMPACTABILITY THROUGH CRYSTALLIZATION 审中-公开
标题翻译：通过结晶控制可压缩性
公开(公告)号：WO2002088664A2
公开(公告)日：2002-11-07
申请号：PCT/US2002/013055
申请日：2002-04-23
申请人： BRISTOL-MYERS SQUIBB COMPANY , SPROCKEL, Omar, Leopold , LAI, Chiajen , DISCORDIA, Robert, Paul , WEI, Chenkou , KOTHARI, Sanjeev, H. , KIM, Soojin
发明人： SPROCKEL, Omar, Leopold , LAI, Chiajen , DISCORDIA, Robert, Paul , WEI, Chenkou , KOTHARI, Sanjeev, H. , KIM, Soojin
IPC分类号： G01N
CPC分类号： A61K9/2009 , A61K9/2054 , A61K9/2059 , A61K31/16 , A61K31/40 , A61K31/44 , A61K38/05
摘要： The invention is directed toward a method for increasing the compactability of an active ingredient by determining the crystallization parameters of the active ingredient that affect compactability; and controlling the crystallization parameters to achieve increased compactability.
摘要翻译：本发明涉及通过确定影响可压实性的活性成分的结晶参数来提高活性成分的压实性的方法; 并控制结晶参数以实现增加的紧实性。

5. 发明申请

WO2012135082A1 PRODRUGS OF LXR MODULATING IMIDAZOLE DERIVATIVES 审中-公开
标题翻译： LXR调节咪唑衍生物的产品
公开(公告)号：WO2012135082A1
公开(公告)日：2012-10-04
申请号：PCT/US2012/030499
申请日：2012-03-26
申请人： BRISTOL-MYERS SQUIBB COMPANY , KICK, Ellen, K. , HAGEMAN, Michael, J. , GUARINO, Victor, R. , SU, Ching-Chiang , WEI, Chenkou , WARRIER, Jayakumar Sankara , NAIR, Satheesh Kesavan
发明人： KICK, Ellen, K. , HAGEMAN, Michael, J. , GUARINO, Victor, R. , SU, Ching-Chiang , WEI, Chenkou , WARRIER, Jayakumar Sankara , NAIR, Satheesh Kesavan
IPC分类号： C07D233/64 , A61K31/4164 , A61P3/00 , C07F9/141 , C07F9/145
CPC分类号： C07D233/64 , A61K31/4174 , A61K31/675 , A61K45/06 , C07F9/12 , C07F9/65061
摘要： Imidazole prodrugs, pharmaceutically acceptable salts, or isomers thereof, of the invention are disclosed, which are useful as modulators of the activity of liver X receptors (LXR). Pharmaceutical compositions containing the compounds and methods of using the compounds are also disclosed.
摘要翻译：公开了本发明的咪唑前药，药学上可接受的盐或异构体，其可用作肝脏X受体（LXR）活性的调节剂。还公开了含有化合物的药物组合物和使用该化合物的方法。

6. 发明申请

WO2007095632A1 CRYSTALLINE FORMS OF (3R,4R)-4-AMINO-1-[[4-[(3-METHOXYPHENYL)AMINO]PYRROLO[2,1-F][1,2,4]TRIAZIN-5-YL]METHOL]PIPERIDIN-3-OL 审中-公开
标题翻译：（3R，4R）-4-氨基-1- [[4 - [（3-甲氧基苯基）氨基]吡咯并[2,1-F] [1,2,4]三氮杂-5-YL]甲醇的晶体形式哌啶-3-醇
公开(公告)号：WO2007095632A1
公开(公告)日：2007-08-23
申请号：PCT/US2007/062276
申请日：2007-02-16
申请人： BRISTOL-MYERS SQUIBB COMPANY , WEI, Chenkou , NORRIS, Derek, J.
发明人： WEI, Chenkou , NORRIS, Derek, J.
IPC分类号： C07D487/04 , A61K31/53 , A61P35/00
CPC分类号： C07D487/04
摘要： Crystalline forms of (3R,4R)-4-amino-1-[[4-[(3-methoxyphenyl)amino]pyrrolo[2,1-f][1,2,4]triazin-5-yl]methyl]piperidin-3-ol of the formula (I) are provided. Also provided is a pharmaceutical composition comprising one or more crystalline forms of (3R,4R)-4-amino-1-[[4-[(3-methoxyphenyl)amino]pyrrolo[2,1-f][1,2,4]triazin-5-yl]methyl]piperidin-3-ol, as well as a method of using one or more crystalline forms of (3R,4R)-4-amino-1-[[4-[(3-methoxyphenyl)amino]pyrrolo[2,1-f][1,2,4]triazin-5-yl]methyl]piperidin-3-ol in the treatment of cancer and other proliferative diseases.
摘要翻译：（3R，4R）-4-氨基-1 - [[4 - [（3-甲氧基苯基）氨基]吡咯并[2,1-f] [1,2,4]三嗪-5-基]甲基] 提供式（I）的哌啶-3-醇。还提供了包含一种或多种结晶形式的（3R，4R）-4-氨基-1 - [[4 - [（3-甲氧基苯基）氨基]吡咯并[2,1-f] [1,2， 4]三嗪-5-基]甲基]哌啶-3-醇，以及使用一种或多种结晶形式的（3R，4R）-4-氨基-1 - [[4 - [（3-甲氧基苯基））氨基]吡咯并[2,1-f] [1,2,4]三嗪-5-基]甲基]哌啶-3-醇用于治疗癌症和其它增殖性疾病。

7. 发明申请

WO2005108380A3 PROCESS EMPLOYING CONTROLLED CRYSTALLIZATION IN FORMING CRYSTALS OF A PHARMACEUTICAL 审中-公开
公开(公告)号：WO2005108380A3
公开(公告)日：2005-11-17
申请号：PCT/US2005/015338
申请日：2005-05-03
申请人： BRISTOL-MYERS SQUIBB COMPANY , KIM, Soojin , WEI, Chenkou , LINDRUD, Mark , CHUNG, Hyei-Jha
发明人： KIM, Soojin , WEI, Chenkou , LINDRUD, Mark , CHUNG, Hyei-Jha
IPC分类号： B01D9/00
摘要： A process is provided which employs reactive controlled crystallization to produce drug substance having desirable crystal properties which process involves providing reactants A and B in liquid or solution form and adding reactant B to reactant A using a cubic or incremental addition technique to control extent of reaction and thus crystallization kinetics, including supersaturation and nucleation, to produce crystals of drug substance which are generally larger, better quality and with few fines and narrow particle size distribution than normally obtainable employing prior art crystallization techniques. In addition, crystals of drug substance produced by the above process is also provided.

8. 发明申请

WO2006039639A1 CRYSTALLINE FORMS AND PROCESS FOR PREPARING SPIRO-HYDANTOIN COMPOUNDS 审中-公开
标题翻译：晶体形式和制备SPIRO-HYDANTOIN化合物的方法
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

9. 发明申请

WO2003095059A1 CRYSTALLIZATION SYSTEM USING HOMOGENIZATION 审中-公开
标题翻译：使用均匀化的结晶体系
公开(公告)号：WO2003095059A1
公开(公告)日：2003-11-20
申请号：PCT/US2003/012314
申请日：2003-04-21
申请人： BRISTOL-MYERS SQUIBB COMPANY , WEI, Chenkou , AKITI, Otute
发明人： WEI, Chenkou , AKITI, Otute
IPC分类号： B01D9/00
CPC分类号： B01F7/008 , B01D9/005 , B01F5/104
摘要： A first solution and a second solution are supplied to the inlet conduit of a chamber. The chamber includes a stator formed of spaced stationery blades within which a rotor with spaced blades is rotatably received. As the rotor is rotated, high shear mixing forces are applied to the solutions and crystallization take place within the chamber. Additional mixing of the product can take place after it leaves the chamber. Seed material can be introduced to the chamber and recirculated from the inlet to the outlet as the process is performed. The process can be used to combine a solution of the material to be crystallized dissolved in a solvent and an anti-solvent solution. Alternatively, solutions containing first and second reactive intermediates in solvents can be combined under conditions of temperature and pressure that permit reaction of the first and second reactive intermediates to produce a reaction product of limited solubility in the solvent mixture.
摘要翻译：将第一溶液和第二溶液供应到室的入口导管。腔室包括由间隔开的文具刀片形成的定子，其中具有间隔开的叶片的转子被可旋转地接收。当转子旋转时，将高剪切混合力施加到溶液中，并且在室内发生结晶。产品的进一步混合可以在离开室之后进行。当进行处理时，种子材料可以被引入到室中并且从入口再循环到出口。该方法可用于将溶解在溶剂中的待结晶材料的溶液与抗溶剂溶液组合。或者，在溶剂中含有第一和第二反应性中间体的溶液可以在温度和压力的条件下进行组合，其允许第一和第二反应中间体反应产生在溶剂混合物中溶解度有限的反应产物。

10. 发明申请

WO2003092852A1 CRYSTALLIZATION SYSTEM UTILIZING ATOMIZATION 审中-公开
标题翻译：使用原子化的结晶体系
公开(公告)号：WO2003092852A1
公开(公告)日：2003-11-13
申请号：PCT/US2003/012312
申请日：2003-04-21
申请人： BRISTOL-MYERS SQUIBB COMPANY , WEI, Chenkou , AKITI, Otute , GLEESON, Margaret, M.
发明人： WEI, Chenkou , AKITI, Otute , GLEESON, Margaret, M.
IPC分类号： B01D9/00
CPC分类号： B01J19/0066 , A61K9/1688 , B01D9/0027 , B01D9/005 , B01D9/0054 , B01D9/0059 , B01D9/0081 , B01F3/0865 , B01F3/0876 , B01F5/0206 , B01F7/16 , B01J19/10 , B01J19/18 , B01J19/24 , B01J19/26 , B01J2219/00011 , B01J2219/00029 , B01J2219/00033 , B01J2219/00074 , B01J2219/00121
摘要： Crystallization of an organic pharmaceutical compound is achieved by atomization of one solution and introduction of the atomized solution into a vessel containing a second solution where the solutions are mixed to form a product. The process can be performed on non-reactive constituents such as a solution containing the compound to be crystallized dissolved in a solvent and an anti-solvent solution. Alternatively, the process can be performed on reactive constituents, such as solutions of solvents containing different reactive intermediates, under proper reactive conditions. The process may be practiced continuously or in batch mode. Atomizers of the non-pressure-driven ultrasonic type or of the ultrasonic or non-ultrasonic pressure-driven type can be utilized.
摘要翻译：通过雾化一种溶液并将雾化溶液引入含有溶液混合以形成产物的第二溶液的容器中来实现有机药物化合物的结晶。该方法可以对非反应性成分进行，例如含有待结晶化合物溶解在溶剂中的溶液和反溶剂溶液。或者，该方法可以在适当的反应条件下对反应性组分如含有不同反应性中间体的溶剂的溶液进行。该过程可以连续地或以批处理模式进行。可以使用非压力驱动超声波型或超声波或非超声波压力驱动型的雾化器。

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