公开(公告)号：WO1998000122A1

公开(公告)日：1998-01-08

申请号：PCT/US1997011611

申请日：1997-06-27

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

Inventor： SEPRACOR, INC.

IPC: A61K31/14

CPC classification number: A61K31/14 ,  C07C215/30

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

Abstract translation: 使用对映异构体富集（S） - 二乙基己基治疗尿失禁的方法，例如由膀胱逼尿肌不稳定引起的失禁。 该方法包括施用基本上不含（R） - 十二乙基对映异构体的治疗有效量的对映异构体富集的（S） - 二乙基己基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） - 十二乙基或其药学上可接受的盐和可接受的载体。

公开(公告)号：WO1996036584A1

公开(公告)日：1996-11-21

申请号：PCT/US1996006901

申请日：1996-05-15

Applicant: SEPRACOR, INC.

Inventor： SEPRACOR, INC. ,  VAN EIKEREN, Paul ,  MC CONVILLE, Francis, X. ,  LOPEZ, Jorge

IPC: C07C51/487

CPC classification number: C07C51/487 ,  C07B57/00 ,  C07D307/24

Abstract: A process for the full or partial resolution of a mixture of enantiomers of a genus of chiral carboxylic acids is disclosed. The process uses a pure enantiomer of 1-aminoindan-2-ol as the resolving agent and achieves separation of the diastereomeric salts by fractional crystallizationn followed by liberation of the chiral acid from the salt by treatment with mineral acid. Diastereomeric salts and solvates of those salts are disclosed. The production of ketoprofen, flurbiprofen and other chiral medicaments and precursors thereto is disclosed.

Abstract translation: 公开了一种完全或部分拆分手性羧酸类的对映异构体混合物的方法。 该方法使用1-氨基茚满-2-醇的纯对映异构体作为拆分剂，并通过分级结晶实现非对映异构体盐的分离，然后用无机酸处理从盐中释放手性酸。 公开了这些盐的非对映异构盐和溶剂合物。 公开了酮洛芬，氟比洛芬和其他手性药物及其前体的生产。

公开(公告)号：WO1995032178A1

公开(公告)日：1995-11-30

申请号：PCT/US1995006539

申请日：1995-05-23

Applicant: SEPRACOR, INC.

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

IPC: C07C209/44

CPC classification number: C07C213/00 ,  C07C213/10 ,  C07C215/60 ,  C07C227/34

Abstract: The invention relates to a method for producing albuterol by the resolution of a mixture of enantiomers of 5-[2-[(1,1-dimethylethyl)amino]-1-hydroxyethyl]-2-hydroxybenzoate using di-toluoyltartaric acid. The invention further relates to a method for producing albuterol by the resolution of a mixture of enantiomers of methyl 5-[2-[(1,1-dimethylethyl)amino]-1-hydroxyethyl]-2-(phenylmethoxy)benzoate or alpha -[[(1,1-dimethylethyl)amino]methyl]-4-(phenylmethoxy)-1,3-benzenedimethanol using a chiral acid such as (+/-) di-toluoyltartaric acid or (+/-) di-benzoyltartaric acid.

Abstract translation: 本发明涉及通过使用二甲苯酰酒石酸分解5- [2 - [（1,1-二甲基乙基）氨基] -1-羟乙基] -2-羟基苯甲酸酯的对映异构体的混合物来生产沙丁胺醇的方法。 本发明还涉及通过拆分5- [2 - [（1,1-二甲基乙基）氨基] -1-羟乙基] -2-（苯基甲氧基）苯甲酸甲酯或α-甲氧基苯甲酸甲酯的对映异构体的混合物来生产沙丁胺醇的方法， [（1,1-二甲基乙基）氨基]甲基] -4-（苯基甲氧基）-1,3-苯二甲醇使用手性酸如（+/-）二甲苯甲酰酒石酸或（+/-）二苯甲酰酒石酸 。

公开(公告)号：WO1995031983A1

公开(公告)日：1995-11-30

申请号：PCT/US1995006446

申请日：1995-05-22

Applicant: SEPRACOR, INC.

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

IPC: A61K31/415

CPC classification number: A61K31/4184

Abstract: Methods and compositions are disclosed utilizing optically pure (+)-liarozole for the treatment of conditions supported by estrogen or caused by elevated estrogen levels such as 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 liarozole. Methods and compositions are also disclosed utilizing optically pure (+)-liarozole for the treatment of conditions supported by or caused by elevated testosterone levels, such as hormone dependent prostate cancer. Further disclosed are methods and compositions utilizing pure (+)-liarozole in combination with retinoic acid for enhancing therapy with retinoic acid, such as in the treatment of neuroectodermal and neuroepithelial malignancies, including glioma, promyelocytic leukemia and hormone-independent prostate cancer.

Abstract translation: 公开了使用光学纯的（+） - 利罗唑用于治疗由雌激素支持或由升高的雌激素水平引起的方法和组合物，例如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，同时显着降低伴随的责任 与利咯唑的外消旋混合物有关的不良反应。 还公开了使用光学纯的（+） - 利罗唑用于治疗由升高的睾酮水平如激素依赖性前列腺癌支持或由其引起的病症的方法和组合物。 进一步披露的是使用纯（+） - 利唑唑与视黄酸组合以增强视黄酸治疗的方法和组合，例如治疗神经外胚层和神经上皮性恶性肿瘤，包括神经胶质瘤，早幼粒细胞白血病和不依赖激素的前列腺癌。

公开(公告)号：WO1995029146A1

公开(公告)日：1995-11-02

申请号：PCT/US1995004869

申请日：1995-04-20

Applicant: SEPRACOR, INC.

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

IPC: C07C209/28

CPC classification number: C07C213/00

Abstract: A method for the enantioselective reduction of an alpha -iminoketone to an alpha -aminoalcohol is disclosed. The method utilizes a borane reducing agent as the reducing agent and a chiral 1,3,2-oxazaborole as the catalyst. The method is applied to the synthesis of R-albuterol from methyl 5-acetylsalicylate in high yield and high optical purity.

Abstract translation: 公开了将α-亚胺酮对映异构还原成α-氨基醇的方法。 该方法采用硼烷还原剂作为还原剂和手性1,3,2-恶唑硼烷作为催化剂。 该方法适用于以高产率和高光学纯度从5-乙酰水杨酸甲酯合成R-沙丁胺醇。

公开(公告)号：WO1995010269A1

公开(公告)日：1995-04-20

申请号：PCT/US1994011412

申请日：1994-10-07

Applicant: SEPRACOR, INC.

Inventor： SEPRACOR, INC. ,  GRAY, Nancy, M. ,  YOUNG, James, W.

IPC: A61K31/135

CPC classification number: A61K31/135

Abstract: Methods and compositions are disclosed utilizing the optically pure R-isomers of terodiline or of the hydroxylated derivatives of terodiline. These compounds are potent drugs for the treatment of urinary incontinence, obstructive pulmonary disease and such other conditions as are related to the compounds' activity as anticholinergic agents.

Abstract translation: 公开的方法和组合物利用光学纯的异噻唑啉的R-异构体或三苯胺的羟基化衍生物。 这些化合物是用于治疗尿失禁，阻塞性肺疾病和与化合物作为抗胆碱能药物的活性相关的其它病症的有效药物。

公开(公告)号：WO1995007880A1

公开(公告)日：1995-03-23

申请号：PCT/US1994010098

申请日：1994-09-09

Applicant: SEPRACOR, INC.

Inventor： SEPRACOR, INC. ,  GAO, Yun ,  HONG, Yaping ,  NIE, Xiaoyi ,  BAKALE, Roger, Paul ,  FEINBERG, Richard, Robert ,  ZEPP, Charles, Melvyn

IPC: C07C213/02

CPC classification number: C07C213/08 ,  C07C215/44 ,  C07C233/23 ,  C07C233/74 ,  C07C2601/08 ,  C07C2601/14 ,  C07C2602/08

Abstract: A two-step process for the conversion of a trans-1-amino-2-hydroxycycloalkane stereoselectively to a cis-1-amino-2-hydroxycycloalkane is disclosed. The novel step, a one-step hydrolysis with formal inversion, can be used to convert an amide of a trans-1-amino-2-hydroxycycloalkane to a cis-1-amino-2-hydroxycycloalkane. Methods for obtaining the trans-1-amino-2-hydroxycycloalkanes and their amides from alkenes are also disclosed. A preferred process converts indene to cis-1-amino-2-indanol.

Abstract translation: 公开了将立体选择性的反式-1-氨基-2-羟基环烷烃转化为顺式-1-氨基-2-羟基环烷烃的两步法。 新的步骤，用正式反转的一步水解可用于将反式-1-氨基-2-羟基环烷烃的酰胺转化为顺式-1-氨基-2-羟基环烷烃。 还公开了从烯烃获得反式-1-氨基-2-羟基环烷烃及其酰胺的方法。 优选的方法将茚转化为顺式-1-氨基-2-茚满醇。

公开(公告)号：WO1994026268A1

公开(公告)日：1994-11-24

申请号：PCT/US1994005191

申请日：1994-05-10

Applicant: SEPRACOR, INC.

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

IPC: A61K31/38

CPC classification number: A61K31/38

Abstract: Methods and compositions are disclosed utilizing optically pure (+)-zileuton for the treatment of asthma, rheumatoid arthritis and ulcerative colitis in humans while substantially reducing the concomitant liability of adverse effects associated with the racemic mixture of zileuton. (+)-Zileuton is an inhibitor of 5-lipoxygenase and is therefore useful in the treatment of other conditions related to elevated leukotriene levels. (+)-Zileuton is also an antioxidant and is therefore useful in treating or preventing atherosclerosis.

Abstract translation: 公开了使用光学纯的（+） - 齐卧子用于治疗人类的哮喘，类风湿性关节炎和溃疡性结肠炎的方法和组合物，同时基本上减少了与齐育酮的外消旋混合物相关的副作用的伴随责任。 （+） - Zileuton是5-脂氧合酶的抑制剂，因此可用于治疗与升高的白三烯水平相关的其他病症。 （+） - Zileuton也是抗氧化剂，因此可用于治疗或预防动脉粥样硬化。

公开(公告)号：WO1994024867A1

公开(公告)日：1994-11-10

申请号：PCT/US1994004543

申请日：1994-04-25

Applicant: SEPRACOR, INC.

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

IPC: A01N43/40

CPC classification number: A61K31/4439 ,  A61K31/44

Abstract: Methods and compositions are disclosed utilizing optically pure (-) pantoprazole for the treatment of ulcers in humans while substantially reducing the concomitant liability of adverse effects associated with the racemic mixture of pantoprazole. The optically pure (-) isomer is also useful for the treatment of gastroesophageal reflux. (-) Pantoprazole is an inhibitor of H release and is therefore useful in the treatment of other conditions related to gastric hypersecretion such as Zollinger-Ellison Syndrome.

Abstract translation: 公开了使用光学纯的（ - ）泮托拉唑用于治疗人类溃疡的方法和组合物，同时显着降低与泮托拉唑的外消旋混合物相关的副作用的伴随的责任。 光学纯的（ - ）异构体也可用于治疗胃食管反流。 （ - ）泮托拉唑是H +释放的抑制剂，因此可用于治疗与胃分泌异常有关的其他病症，如Zollinger-Ellison综合征。

公开(公告)号：WO1994014447A1

公开(公告)日：1994-07-07

申请号：PCT/US1993012357

申请日：1993-12-17

Applicant: SEPRACOR, INC.

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

IPC: A61K31/495

CPC classification number: A61K31/495

Abstract: Methods and compositions are disclosed utilizing the optically pure (-) isomer of ketoconazole. 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 ketoconazole.

Abstract translation: 公开利用光学纯的（ - ）酮康唑异构体的方法和组合物。 该化合物是用于治疗局部和全身真菌，酵母和皮肤癣菌感染的有效药物，同时避免与酮康唑外消旋混合物相关的副作用的伴随责任。