公开(公告)号：WO1996008455A2

公开(公告)日：1996-03-21

申请号：PCT/US1995011522

申请日：1995-09-14

Applicant: ABBOTT LABORATORIES

Inventor： ABBOTT LABORATORIES ,  CHORGHADE, Mukund, S. ,  DOLPHIN, David, H. ,  HILL, David, R. ,  HINO, Fumio ,  LEE, Elaine, C.

IPC: C07B33/00

CPC classification number: B01J31/1815 ,  B01J2531/025 ,  B01J2531/16 ,  B01J2531/62 ,  B01J2531/72 ,  B01J2531/821 ,  B01J2531/842 ,  B01J2531/845 ,  B01J2531/847 ,  C07B33/00 ,  C07D231/44 ,  C07D233/36 ,  C07D405/04 ,  C07D413/04

Abstract: A method for the systematic and efficient synthetic preparation and identification of metabolites of a pharmaceutical product in order to study possible toxic and/or otherwise biologically-active metabolites of such pharmaceutical products as early and conveniently as possible in the very expensive drug development process, comprising adding samples of the pharmaceutical product to a series of combinations of a synthetic metalloporphyrin (SMP) with a synthetic metalloporphyrin-co-oxidizing reagent in the presence of a suitable solvent, under specified conditions, in a manner such that each sample of pharmaceutical product is reacted with a different combination of synthetic metalloporphyrin, SMP-co-oxidizing reagent and solvent, followed by separation and isolation of the resulting oxidative products, then confirmation of the identity of metabolites from the pre-identified oxidative products by appropriate animal model studies, and subjecting the actual metabolites prepared in larger quantities by the above method to toxicologic, pathologic, histopathologic, mechanistic or genotoxic testing in order to identify toxic and/or otherwise metabolically-active beneficial or detrimental individual metabolites.

Abstract translation: 一种用于系统和有效地合成制备和鉴定药物产品的代谢物的方法，以便在非常昂贵的药物开发过程中尽可能早地和方便地研究这些药物的可能的毒性和/或其他生物活性代谢物，包括 在合适的溶剂存在下，在规定的条件下，将药物产品的样品加入合成金属卟啉（SMP）与合成金属卟啉 - 辅助氧化剂的一系列组合，使得药物产品的每个样品为 与合成金属卟啉，SMP-辅助氧化试剂和溶剂的不同组合反应，然后分离和分离所得氧化产物，然后通过适当的动物模型研究从预先鉴定的氧化产物中鉴定代谢物的身份，以及 对在较大的q中制备的实际代谢物进行处理 通过上述方法对药物，病理，组织病理学，机械学或遗传毒性试验进行检测，以鉴别有毒和/或其他代谢活性的有益或有害的个体代谢物。

公开(公告)号：EP1044209A1

公开(公告)日：2000-10-18

申请号：EP98959481.7

申请日：1998-11-17

Applicant: Abbott Laboratories

Inventor： KU, Yi-Yin ,  RILEY, David, A. ,  LEE, Elaine, C. ,  TIEN, Jien-Heh, J.

IPC: C07H17/08

CPC classification number: C07H17/08

Abstract: The claimed invention provides a novel method of preparing 6-O-methyl erythromycin A. The process comprises the steps of reducing the 9-keto group of erythromycin A to form a 9-hydroxy erythromycin A, protecting the 9-, 2'-, and/or 4'-hydroxyl groups of erythromycin A, selectively methylating the 6-position of the 9-hydroxy erythromycin A derivative, deprotecting the hydroxyl groups and oxidizing the 9-hydroxyl to afford 6-O-methyl erythromycin A.

Abstract translation: 本发明提供了一种制备6-O-甲基红霉素A的新方法。该方法包括将红霉素A的9-酮基还原成9-羟基红霉素A，保护9-，2'-， 和/或红霉素A的4'-羟基，选择性甲基化9-羟基红霉素A衍生物的6-位，使羟基脱保护并氧化9-羟基，得到6-O-甲基红霉素A.

公开(公告)号：EP1044209B1

公开(公告)日：2004-08-18

申请号：EP98959481.7

申请日：1998-11-17

Applicant: Abbott Laboratories

Inventor： KU, Yi-Yin ,  RILEY, David, A. ,  LEE, Elaine, C. ,  TIEN, Jien-Heh, J.

IPC: C07H17/08

CPC classification number: C07H17/08

公开(公告)号：EP0781261A2

公开(公告)日：1997-07-02

申请号：EP95933078.0

申请日：1995-09-14

Applicant: Abbott Laboratories

Inventor： CHORGHADE, Mukund, S. ,  DOLPHIN, David, H. ,  HILL, David, R. ,  HINO, Fumio ,  LEE, Elaine, C.

IPC: G01N33 ,  B01J31 ,  C07B33 ,  C07D231 ,  C07D233 ,  C07D405 ,  C07D413 ,  C07D487

CPC classification number: B01J31/1815 ,  B01J2531/025 ,  B01J2531/16 ,  B01J2531/62 ,  B01J2531/72 ,  B01J2531/821 ,  B01J2531/842 ,  B01J2531/845 ,  B01J2531/847 ,  C07B33/00 ,  C07D231/44 ,  C07D233/36 ,  C07D405/04 ,  C07D413/04

Abstract: A method for the systematic and efficient synthetic preparation and identification of metabolites of a pharmaceutical product in order to study possible toxic and/or otherwise biologically-active metabolites of such pharmaceutical products as early and conveniently as possible in the very expensive drug development process, comprising adding samples of the pharmaceutical product to a series of combinations of a synthetic metalloporphyrin (SMP) with a synthetic metalloporphyrin-co-oxidizing reagent in the presence of a suitable solvent, under specified conditions, in a manner such that each sample of pharmaceutical product is reacted with a different combination of synthetic metalloporphyrin, SMP-co-oxidizing reagent and solvent, followed by separation and isolation of the resulting oxidative products, then confirmation of the identity of metabolites from the pre-identified oxidative products by appropriate animal model studies, and subjecting the actual metabolites prepared in larger quantities by the above method to toxicologic, pathologic, histopathologic, mechanistic or genotoxic testing in order to identify toxic and/or otherwise metabolically-active beneficial or detrimental individual metabolites.