公开(公告)号：WO1990006996A1

公开(公告)日：1990-06-28

申请号：PCT/US1989005671

申请日：1989-12-18

Applicant: SEPRACOR, INC.

Inventor： SEPRACOR, INC. ,  LOPEZ, Jorge, L. ,  MATSON, Stephen, L.

IPC: C12N11/02

CPC classification number: C12N11/02 ,  C12M25/10 ,  C12M29/16 ,  C12N11/08 ,  C12N11/10

Abstract: Apparatus for catalysis in multiphase reaction systems is provided in which catalysts are confined within various membranes without the use of covalent coupling. Confinement of the catalysts is achieved by a combination of a small-pore skin on one side of the membrane and the use of a solvent in which the catalysts are not appreciably soluble on the other. Methods are also provided for the preparation of such apparatus and for their regeneration by incorporation of fresh catalyst.

Abstract translation: 提供了多相反应体系中的催化装置，其中催化剂被限制在各种膜中，而不使用共价偶联。 催化剂的限制通过膜的一侧上的小孔表皮与使用其中催化剂在另一方面不易溶解的溶剂的组合来实现。 还提供了用于制备这种装置并通过掺入新鲜催化剂进行再生的方法。

公开(公告)号：WO1990004643A1

公开(公告)日：1990-05-03

申请号：PCT/US1989004784

申请日：1989-10-26

Applicant: SEPRACOR, INC.

Inventor： SEPRACOR, INC. ,  DODDS, David, R. ,  LOPEZ, Jorge, L. ,  ZEPP, Charles, M. ,  BRANDT, Steven ,  ROSSI, Richard, F.

IPC: C12P41/00

CPC classification number: C07D303/48 ,  C07D281/10 ,  C12P17/02 ,  C12P41/005

Abstract: This invention relates to a method for the production of (2R,3S)-3-(4-methoxyphenyl)glycidic acids and esters thereof, which are synthetic intermediate for the production of the calcium antagonist diltiazem. The method involves the stereoselective enzymatic ester hydrolysis of racemic trans-3-(4-methoxyphenyl)glycidic acid ester to yield the resolved (2R,3S) compound as the ester. Membrane reactor methods and apparatus for the conduct of this enzymatic resolution process are also disclosed herein, as is the use of bisulfite anion in the aqueous reaction phase as a means of minimizing the inhibitory effect of an aldehyde reaction by-product on the reaction's progress. The benefits of selected solvent systems from which may be obtained highly resolved ester product are also disclosed. These enriched organic solutions may be used in subsequent transformations. Alternatively, optically pure product may be obtained directly therefrom.

Abstract translation: 本发明涉及制备（2R，3S）-3-（4-甲氧基苯基）缩水甘油酸及其酯的方法，它们是钙拮抗剂地尔硫卓的合成中间体。 该方法涉及外消旋反式-3-（4-甲氧基苯基）缩水甘油酸酯的立体选择性酶酯水解，得到分解的（2R，3S）化合物，为酯。 本文还公开了用于进行该酶解析方法的膜反应器方法和装置，以及在水反应相中使用亚硫酸氢盐阴离子作为使醛反应副产物对反应进程的抑制作用最小化的手段。 还公开了可以获得高度拆分的酯产物的选择的溶剂体系的益处。 这些富集的有机溶液可用于随后的转化。 或者，可以直接从其获得光学纯的产物。

公开(公告)号：WO1988007582A1

公开(公告)日：1988-10-06

申请号：PCT/US1988001098

申请日：1988-03-31

Applicant: SEPRACOR, INC.

Inventor： SEPRACOR, INC. ,  MATSON, Stephen, L.

IPC: C12P41/00

CPC classification number: C12N11/02 ,  B01J19/2475 ,  B01J2219/00159 ,  B01J2219/00162 ,  B01J2219/00177 ,  C07C219/10 ,  C07C305/04 ,  C07C305/10 ,  C07C309/65 ,  C07C309/66 ,  C07C327/32 ,  C07F9/091 ,  C12M21/18 ,  C12M25/02 ,  C12M29/04 ,  C12M29/16 ,  C12N11/08 ,  C12P1/00 ,  C12P7/40 ,  C12P41/00 ,  C12P41/005

Abstract: This invention relates to the resolution of racemic mixtures of optically active compounds, including but not limited to the stereochemical purification of chiral organic esters, amides, carboxylic acids, alcohols, and amines. Novel methods utilizing multiphase and extractive enzyme membrane bioreactors are disclosed that selectively produce pure or substantially purified optically active compounds from achiral precursors or mixtures of isomers in which one or several of those isomers are biologically inactive or otherwise lack desirable characteristics. The invention involves the use of fluids immiscible with one another on the opposite sides of the enzyme membrane.

公开(公告)号：WO1998000109A1

公开(公告)日：1998-01-08

申请号：PCT/US1997011639

申请日：1997-06-27

Applicant: SEPRACOR, INC. ,  FABIANO, Vincent, L. ,  McCULLOUGH, John, R.

Inventor： SEPRACOR, INC.

IPC: A61K09/08

CPC classification number: C07D207/12 ,  A61K31/40 ,  C07B2200/07

Abstract: A method for treating urinary incontinence, such as incontinence resulting from bladder detrusor muscle instability, using enantiomerically enriched (S,R)-glycopyrrolate. The method comprises administering a therapeutically effective amount of enantiomerically enriched (S,R)-glycopyrrolate, or a pharmaceutically acceptable salt thereof, substantially free of the (R,S)-glycopyrrolate enantiomer. Pharmaceutical compositions for the treatment of urinary incontinence comprising enantiomerically enriched (S,R)-glycopyrrolate, or a pharmaceutically acceptable salt thereof, and an acceptable carrier are also disclosed.

Abstract translation: 使用对映异构体富集的（S，R） - 乙酰丙酸酯治疗尿失禁的方法，例如由膀胱逼尿肌不稳定引起的失禁。 该方法包括施用治疗有效量的基本上不含（R，S） - 乙酰丙酸酰对映异构体的对映异构体富集的（S，R） - 乙酰基吡咯烷酸酯或其药学上可接受的盐。 还公开了用于治疗尿失禁的药物组合物，其包含对映异构体富集的（S，R） - 乙酰丙酸酯，或其药学上可接受的盐和可接受的载体。

公开(公告)号：WO1997039729A1

公开(公告)日：1997-10-30

申请号：PCT/US1997006627

申请日：1997-04-21

Applicant: SEPRACOR, INC.

Inventor： SEPRACOR, INC. ,  ABERG, Gunnar ,  JERUSSI, Thomas, P. ,  McCULLOUGH, John, R.

IPC: A61K07/16

CPC classification number: A61Q11/00 ,  A61K8/21 ,  A61K8/36 ,  A61K8/365 ,  A61K8/368 ,  A61K8/492 ,  A61K33/16 ,  A61K2300/00

Abstract: A method for preventing dental caries by administering fluoride and, at the same time controlling periodontal bone loss precipitated by the fluoride, by providing a combination of fluoride and NSAID is disclosed. Topical medicament compositions including NSAIDS and fluoride are also disclosed.

Abstract translation: 公开了一种通过施用氟化物防止龋齿的方法，并且同时通过提供氟化物和NSAID的组合来控制由氟化物沉淀的牙周骨损失。 还公开了包含NSAIDS和氟化物的局部药物组合物。

公开(公告)号：WO1997007110A1

公开(公告)日：1997-02-27

申请号：PCT/US1996012666

申请日：1996-08-02

Applicant: SEPRACOR, INC.

Inventor： SEPRACOR, INC. ,  GAO, Yun ,  ZEPP, Charles, M.

IPC: C07D305/14

CPC classification number: C07D305/14 ,  C07C271/22 ,  C07F7/1804

Abstract: A process for the preparation of taxol and derivatives of taxol (I) is disclosed. The process involves reacting a beta -alkoxycarbonylamino-phenylpropionic acid with a 13-hydroxy taxane to produce an ester of the taxane at C-13; and then deprotecting the beta -alkoxycarbonylamino-phenylpropionic ester to produce a beta -amino- alpha -hydroxybenzenepropanoic ester of the taxane. Intermediates useful in the process are also disclosed.

Abstract translation: 披露了紫杉醇和紫杉醇衍生物（I）的制备方法。 该方法包括使β-烷氧基羰基氨基 - 苯基丙酸与13-羟基紫杉烷反应以在C-13处产生紫杉烷的酯; 然后脱保护β-烷氧基羰基氨基 - 苯基丙酸酯以产生紫杉烷的β-氨基-α-羟基苯丙酸酯。 还公开了在该方法中有用的中间体。

公开(公告)号：WO1995032937A1

公开(公告)日：1995-12-07

申请号：PCT/US1995006615

申请日：1995-05-24

Applicant: SEPRACOR, INC.

Inventor： SEPRACOR, INC. ,  GAO, Yun ,  HONG, Yaping ,  ZEPP, Charles, M.

IPC: C07C35/08

CPC classification number: C07D207/325 ,  C07B2200/07 ,  C07C29/143 ,  C07C211/20 ,  C07C2602/08 ,  C07D307/52 ,  C07F5/02 ,  C07F5/025 ,  C07C33/22

Abstract: A method for the enantioselective reduction of prochiral ketones using catalytic amounts of tetrahydroindeno[1,2-d][1,3,2]oxazaboroles of formula (II) is disclosed. The oxazaboroles can be generated in situ from the corresponding cis-1-amino-2-indanols or imino indanols (III). Novel compounds of formulas (II) and (III) are also disclosed.

Abstract translation: 公开了使用催化量的式（II）的四氢茚并[1,2-d] [1,3,2]恶唑硼烷来对映选择性还原前手性酮的方法。 可以从相应的顺式-1-氨基-2-茚满醇或亚氨基茚满醇（III）原位产生恶唑烷。 还公开了新的式（II）和（III）化合物。

公开(公告)号：WO1995028156A1

公开(公告)日：1995-10-26

申请号：PCT/US1995004453

申请日：1995-04-11

Applicant: SEPRACOR, INC.

Inventor： SEPRACOR, INC. ,  GRAY, Nancy, M.

IPC: A61K31/44

CPC classification number: A61K31/44

Abstract: Methods and compositions are disclosed utilizing optically pure (-)-fadrozole for the treatment of estrogen-dependent breast cancer, gynecomastia, systemic lupus erythematosus and premature labor while substantially reducing the concomitant liability of adverse effects associated with the racemic mixture of fadrozole. (-)-Fadrozole is an inhibitor of aromatase and is therefore useful in the treatment of other conditions supported by estrogen or caused by elevated estrogen levels.

Abstract translation: 公开了使用光学纯的（ - ） - fadrozole来治疗雌激素依赖性乳腺癌，男子乳腺发育症，系统性红斑狼疮和早产的方法和组合物，同时显着减少与法多唑的外消旋混合物相关的副作用的伴随责任。 （ - ） - 法多唑是芳香酶的抑制剂，因此可用于治疗由雌激素支持或由升高的雌激素水平引起的其他病症。

公开(公告)号：WO1995019770A1

公开(公告)日：1995-07-27

申请号：PCT/US1995000871

申请日：1995-01-20

Applicant: SEPRACOR, INC.

Inventor： SEPRACOR, INC. ,  GRAY, Nancy, M.

IPC: A61K31/275

CPC classification number: A61K31/277 ,  A61K31/275 ,  Y10S514/859

Abstract: Methods and compositions are disclosed utilizing optically pure R-(-)-casodex for the treatment of androgen-dependent prostate cancer, while substantially reducing the concomitant liability of adverse effects associated with the central antiandrogen activity of the racemic mixture of casodex. R-(-)-casodex is a peripherally selective antiandrogen and is therefore useful in the treatment of other conditions supported by androgen or caused by elevated androgen levels. Such conditions include benign prostatic hypertrophy or hyperplasia, acne and hirsutism.

Abstract translation: 公开利用光学纯的R - （ - ） - casodex用于治疗雄激素依赖性前列腺癌的方法和组合物，同时显着降低与casodex的外消旋混合物的中枢抗雄激素活性相关的副作用的伴随的责任。 R - （ - ） - casodex是外周选择性抗雄激素，因此可用于治疗由雄激素支持或由升高的雄激素水平引起的其他病症。 这些病症包括良性前列腺肥大或增生，痤疮和多毛症。

公开(公告)号：WO1994016700A1

公开(公告)日：1994-08-04

申请号：PCT/US1994000920

申请日：1994-01-27

Applicant: SEPRACOR, INC. ,  GEORGETOWN UNIVERSITY

Inventor： SEPRACOR, INC. ,  GEORGETOWN UNIVERSITY ,  GRAY, Nancy, M. ,  WOOSLEY, Raymond, L.

IPC: A61K31/495

CPC classification number: A61K31/495

Abstract: Methods and compositions are disclosed utilizing the optically pure (2R,4S) isomer of itraconazole. This compound is a potent drug for the treatment of local and systemic fungal, yeast, and dermatophyte infections, while avoiding the concomitant liability of adverse effects associated with the racemic mixture of itraconazole.

Abstract translation: 公开利用伊曲康唑的光学纯的（2R，4S）异构体的方法和组合物。 该化合物是治疗局部和全身真菌，酵母和皮肤癣菌感染的有效药物，同时避免与伊曲康唑外消旋混合物相关的副作用的伴随责任。