公开(公告)号：EP2035364A2

公开(公告)日：2009-03-18

申请号：EP07796585.3

申请日：2007-06-29

申请人： Schering Corporation

发明人： THIRUVENGADAM, Tiruvettipuram, K. ,  WANG, Tao ,  CHIU, John, S. ,  LIAO, Jing

IPC分类号： C07C201/06 ,  C07C205/55 ,  C07C251/44

CPC分类号： C07C251/44 ,  C07C201/06 ,  C07C249/08 ,  C07C2601/16 ,  C07C205/56 ,  C07C251/42

摘要： This application discloses provides a process for the introduction of nitro-group functionality into a compound which contains also a site of unsaturation and/or oxygen functionality by direct (one step) oxidation of an oxime functional group mediated by a molybdenum VI/VII peroxo complex, the process comprising: (a) providing a substrate of Formula I containing an oxime functional group; Chemical formula should be inserted here as it appears on the abstract in paper form. wherein R1 and R2 are selected independently from linear, branched or cyclic alkyl and linear, branched or cyclic alkenyl groups, optionally substituted, with the proviso that at least one of R1 or R2 contains a carbon/carbon double bond; and (b) contacting said substrate of Formula I with a molybdenum oxidation complex, thereby oxidizing said oxime functional group to a nitro functional group to yield the structure of Formula III. Chemical formula should be inserted here as it appears on the abstract in paper form. Where R1 and R2 are as defined above.

摘要翻译： 该申请公开提供了一种通过由钼VI / VII过氧配合物介导的肟官能团的直接（一步）氧化将硝基官能团引入到还含有不饱和位和/或氧官能团位点的化合物的方法 该方法包括：（a）提供含有肟官能团的式I的底物; 其中R 1和R 2独立地选自直链，支链或环状的烷基和直链，支链或环状的烯基，任选被取代，条件是R 1或R 2中的至少一个含有碳/碳双键; 和（b）使式I的底物与钼氧化络合物接触，从而将所述肟官能团氧化为硝基官能团，得到式III的结构。 其中R1和R2如上所定义。

公开(公告)号：EP0596015B1

公开(公告)日：1997-10-01

申请号：EP92916790.6

申请日：1992-07-21

申请人： SCHERING CORPORATION

发明人： BURNETT, Duane, A. ,  CLADER, John, W. ,  THIRUVENGADAM, Tiruvettipuram, K. ,  TANN, Chou-Hong ,  LEE, Junning ,  MC ALLISTER, Timothy ,  COLON, Cesar ,  BARTON, Derek, H., R. ,  BRESLOW, Ronald ,  DUGAR, Sundeep ,  VACCARO, Wayne

IPC分类号： C07D205/08 ,  C07D205/085 ,  C07D401/04 ,  C07D403/04 ,  C07D405/10 ,  C07D405/04 ,  C07D409/04 ,  A61K31/395

CPC分类号： C07D401/04 ,  C07D205/08 ,  C07D205/085 ,  C07D403/04 ,  C07D405/04 ,  C07D405/10 ,  C07D409/04 ,  C07F7/0812 ,  C07F7/186 ,  C07F7/1892

摘要： Novel compounds of formula (I) wherein A is -CH=CH-B; -C=C-B; -(CH2)p-X-B, wherein p is 0-2 and X is a bond, -NH- or -S(O)0-2-; optionally substituted heteroaryl or benzofused heteroaryl; -C(O)-B; or (Ia), wherein k is 1-2; D is B'-(CH2)mC(O)-, wherein m is 1-5; B'-(CH2)q-, wherein q is 2-6; B'-(CH2)e-Z-(CH2)r-, wherein Z is -O-, -C(O)-, phenylene, -NR8- or -S(O)0-2-, e is 0-5 and r is 1-5, provided that the sum of e and r is 1-6; B'-(alkenylene)-; B'-(alkadienylene)-; B'-(CH2)t-Z-(alkenylene), wherein t is 0-3, provided that the sum of t and the number of carbon atoms in the alkenylene chain is 2-6; B'-(CH2)f-V-(CH2)g-, wherein V is cycloalkylene, f is 1-5 and g is 0-5, provided that the sum of f and g is 1-6; B'-(CH2)t-V-(alkenylene) or B'-(alkenylene)-V-(CH2)t-, provided that the sum of t and the number of carbon atoms in the alkenylene chain is 2-6; B'-(CH2)a-Z-(CH2)b-V-(CH2)d-, wherein a, b and d are 0-6, provided that the sum of a, b and d is 0-6; T-(CH2)s-, wherein T is cycloalkyl and s is 1-6; naphthylmethyl or optionally substituted heteroarylmethyl; B is optionally substituted phenyl; B' is naphthyl, optionally substituted heteroaryl or optionally substituted phenyl; R is hydrogen, fluoro, alkyl, alkenyl, alkynyl, or B-(CH2)h-, wherein h is 0-3; R4 is optionally substituted phenyl, indanyl, benzofuranyl, tetrahydronaphthyl, pyridyl, pyrazinyl, pyrimidinyl or quinolyl; are disclosed, as well as their use as hypocholesterolemic agents; the method of using compounds of formula (II), wherein R20 is optionally substituted phenyl, optionally substituted naphthyl, optionally substituted heteroaryl, or optionally substituted benzofused heteroaryl, R21, R22 and R23 are independently selected from H or R20; E, F and G are independently a bond; cycloalkylene; alkylene; alkenylene; alkynylene; a substituted alkylene, alkenylene or alkynylene chain; an interrupted alkylene, alkenylene or alkynylene chain; or an interrupted alkylene, alkenylene or alkynylene chain substituted by one or more substituents; or one of R21-E and R22-F is selected from the group consisting of halogeno, OH, alkoxy, -OC(O)R5, -NR10R11, -SH or -S(alkyl); R5 is alkyl, phenyl, R14-phenyl, benzyl or R14-benzyl; R10 and R11 are independently selected from H and lower alkyl, or a pharmaceutically acceptable salt thereof, in a pharmaceutically acceptable carrier as hypocholesterolemic agents is also disclosed.

公开(公告)号：EP0873352A1

公开(公告)日：1998-10-28

申请号：EP96944777.0

申请日：1996-12-18

申请人： SCHERING CORPORATION

发明人： FU, Xiaoyong ,  THIRUVENGADAM, Tiruvettipuram, K. ,  TANN, Chou-Hong

IPC分类号： C07J5 ,  C07J7 ,  C07J71

CPC分类号： C07J7/0085 ,  C07J5/0076 ,  C07J71/0015

摘要： Disclosed is a process for producing the epoxy steroid (1.0) wherein R1 is selected from H, -OH, or C1, and R2 is selected from hydrogen or lower alkyl. The process comprises reacting the triene of Formula (2.0) with a brominating or chlorinating agent in DMF containing a catalytic amount of 70 % HC1O¿4?, at a temperature of about 0 to about +40 °C to produce the corresponding bromoformate (3.0) or chloroformate (3.0A) wherein when R?1¿ is H then R3 is H; and when R1 is -OH then R3 is a suitably protected -OH group; and when R1 is C1 then R3 is C1. The bromoformate or chloroformate is then reacted, at a temperature of about -20 to about +10 °C, with a strong base in an organic solvent mixture comprising: (a) THF or CH¿2?C12 and (b) a C1 to C6 alkanol or acetonitrile, to produce the epoxy steroid (1.0).

公开(公告)号：EP1846385A2

公开(公告)日：2007-10-24

申请号：EP06718128.9

申请日：2006-01-12

申请人： Schering Corporation

发明人： THIRUVENGADAM, Tiruvettipuram, K. ,  LIM, Ngiap, Kie ,  WANG, Tao ,  HUANG, Mingsheng ,  WU, George G. ,  SUDHAKAR, Anantha ,  GREEN, Michael D. ,  KWOK, Daw-iong

IPC分类号： C07D307/92 ,  C07D405/06 ,  C07D493/10 ,  C07C235/28 ,  C07D295/18 ,  C07D317/72

CPC分类号： C07D493/10 ,  C07C235/28 ,  C07D295/185 ,  C07D307/92 ,  C07D317/72 ,  C07D405/06

摘要： This application discloses a novel process for the synthesis of himbacine analogs, as well as the compounds produced thereby. The synthesis proceeds by alternative routes including the cyclic ketal amide route, the chiral carbamate amide route, and the chiral carbamate ester route. The compounds produced thereby are useful as thrombin receptor antagonists. The chemistry disclosed herein is exemplified in the following synthesis sequence: (Formulae 8A, 7B).

公开(公告)号：EP1556358B1

公开(公告)日：2007-06-20

申请号：EP03799375.5

申请日：2003-10-01

申请人： SCHERING CORPORATION

发明人： CHEN, Frank, X. ,  WONG, Yee-Shing ,  ECKERT, Jeffrey, M. ,  ZOU, Nanfei ,  LIANG, Feng ,  KIM-MEADE, Agnes, S. ,  POIRIER, Marc ,  THIRUVENGADAM, Tiruvettipuram, K. ,  WU, George, G.

IPC分类号： C07D221/00

CPC分类号： C07D401/14 ,  C07D221/16

摘要： An enantioselective process for preparing intermediates useful in the preparation of the chiral tricyclic compound of formula (I), is disclosed.

公开(公告)号：EP2046804A1

公开(公告)日：2009-04-15

申请号：EP07796592.9

申请日：2007-06-29

申请人： Schering Corporation

发明人： YONG, Kelvin, H. ,  ZAVIALOV, Ilia, A. ,  YIN, Jianguo ,  FU, Xiaoyong ,  THIRUVENGADAM, Tiruvettipuram, K.

IPC分类号： C07F9/58 ,  A61K31/443 ,  C07D405/06 ,  A61P9/10 ,  A61P7/02 ,  A61P29/00

CPC分类号： C07F9/582 ,  C07D405/06

摘要： This application discloses a novel process for the preparation of phosphonate esters useful as intermediates in the preparation of himbacine analogs, themselves useful as thrombin receptor antagonists. The chemistry taught herein can be exemplified by the following scheme: Formula (I) wherein R9 is selected from alkyl, aryl heteroaryl and arylalkyl groups having 1 to 10 carbon atoms, and R11 is selected independently for each occurrence from alkyl, aryl heteroaryl and arylalkyl groups having 1 to 10 carbon atoms and hydrogen, X2 is Cl, Br, or I; X3 is selected from Cl and Br; and PdLn is a supported palladium metal catalyst or a soluble heterogeneous palladium catalyst. The L-derivatizing reagent is a moiety which converts the alcohol functional group of compound 137D to any leaving group which can be displaced by a triorgano-phosphite phosphonating agent.

公开(公告)号：EP1853592A1

公开(公告)日：2007-11-14

申请号：EP06718299.8

申请日：2006-01-12

申请人： Schering Corporation

发明人： THIRUVENGADAM, Tiruvettipuram, K. ,  WANG, Tao ,  LIAO, Jing ,  CHIU, John, S. ,  TSAI, David, J. S. ,  LEE, Hong-chang ,  WU, Wenxue ,  FU, Xiaoyong

IPC分类号： C07D405/08 ,  C07D493/10 ,  C07D307/88

CPC分类号： C07D307/77 ,  C07D307/885 ,  C07D307/92 ,  C07D405/06

摘要： The present invention relates to an improved process for preparing imbacine analogs. The compounds are useful as thrombin receptor antagonists. The improved process may allow for at least one of easier purification by crystallization, easier scalability, and improved process yield on the desired enantiomer. An example of a step in the synthesis of such a himbacine analog is as follows: Formula (I)

摘要翻译： 本发明涉及制备伊巴辛类似物的改进方法。 该化合物可用作凝血酶受体拮抗剂。 改进的方法可允许通过结晶进行更容易的纯化，更容易的可缩放性和对所需对映体的改进的加工产率中的至少一个。 合成这种喜巴辛类似物的步骤的实例如下：式（I）

公开(公告)号：EP0763054B1

公开(公告)日：2000-01-05

申请号：EP95920650.9

申请日：1995-05-30

申请人： SCHERING CORPORATION

发明人： FU, Xiaoyong ,  THIRUVENGADAM, Tiruvettipuram, K. ,  TANN, Chou-Hong ,  LEE, Junning ,  COLON, Cesar

IPC分类号： C07J5/00 ,  C07J7/00 ,  C07J51/00

CPC分类号： C07J7/0085 ,  C07J5/0076 ,  C07J51/00

摘要： Described is a process for the regioselective dehydration of 11-hydroxy steroids using PCl5, PCl3, POCl3 or either SO2Cl2 and imidazole, or PPh3 and CCl4. The disclosed process selectively forms DELTA steroids from either 11- alpha - or 11- beta -hydroxy steroids, and can also be used for the one-step conversion of 11,21-dihydroxy steroids to 21-chloro- DELTA steroids. Also disclosed are processes for the regioselective conversion of 11- beta -chloro steroids to DELTA steroids, and for regioselectively converting an 11,17,21-trihydroxy steroid to a 21-chloro-11,17-dihydroxy steroid.

公开(公告)号：EP1853592B1

公开(公告)日：2011-03-02

申请号：EP06718299.8

申请日：2006-01-12

申请人： Schering Corporation

发明人： THIRUVENGADAM, Tiruvettipuram, K. ,  WANG, Tao ,  LIAO, Jing ,  CHIU, John, S. ,  TSAI, David, J. S. ,  LEE, Hong-chang ,  WU, Wenxue ,  FU, Xiaoyong

IPC分类号： C07D405/08 ,  C07D493/10 ,  C07D307/88

CPC分类号： C07D307/77 ,  C07D307/885 ,  C07D307/92 ,  C07D405/06

摘要： The present invention relates to an improved process for preparing imbacine analogs. The compounds are useful as thrombin receptor antagonists. The improved process may allow for at least one of easier purification by crystallization, easier scalability, and improved process yield on the desired enantiomer. An example of a step in the synthesis of such a himbacine analog is as follows: Formula (I)

公开(公告)号：EP1701953A1

公开(公告)日：2006-09-20

申请号：EP05705212.8

申请日：2005-01-07

申请人： SCHERING CORPORATION

发明人： THIRUVENGADAM, Tiruvettipuram, K. ,  WU, Wenxue ,  WANG, Tao ,  CHIU, John, S. ,  BOGDANOWICH-KNIPP, Susan ,  PAVLOVSKY, Anastasia ,  GREENLEE, William, J. ,  GRAZIANO, Michael, P. ,  KOSOGLOU, Teddy ,  CHINTALA, Madhu ,  CHACKALAMANNIL, Samuel

IPC分类号： C07D405/06 ,  C07D307/00 ,  C07D213/00

CPC分类号： C07D417/14 ,  C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D405/06 ,  C07D405/14 ,  C07D413/14

摘要： A crystalline polymorph of a bislulfate salt of a thrombin receptor antagonist compound, which exhibits a powder x-ray diffraction profile substantially the same as that shown in FIG. 1, or which exhibits a differential scanning calorimtery profile substantially the same as that shown in FIG. 3, and is represented by the formula for Compound 2: Chemical formula should be inserted here as it appears on the abstract in paper form. and processes for preparing Compound 2 are disclosed. Pharmaceutical compositions comprising the polymorph of the bisulfate salt and at least one excipient or carrier, and methods of using the polymorph of Compound 2 to treat a variety of physiological disorders, such as thrombosis, are also disclosed.