公开(公告)号：US06340756B1

公开(公告)日：2002-01-22

申请号：US09497319

申请日：2000-02-03

Applicant: Charles A. Dvorak ,  Douglas L. Wren ,  Lawrence E. Fisher ,  Steven D. Axt ,  Eric R. Humphreys ,  Humberto B. Arzeno ,  Colin C. Beard ,  Sam Linh Nguyen ,  Yeun-Kwei Han ,  Christopher R. Roberts ,  Jan P. Lund ,  Paul R. Fatheree

Inventor： Charles A. Dvorak ,  Douglas L. Wren ,  Lawrence E. Fisher ,  Steven D. Axt ,  Eric R. Humphreys ,  Humberto B. Arzeno ,  Colin C. Beard ,  Sam Linh Nguyen ,  Yeun-Kwei Han ,  Christopher R. Roberts ,  Jan P. Lund ,  Paul R. Fatheree

IPC: C07D47318

CPC classification number: C07D473/00 ,  C07D473/18 ,  Y02P20/55

Abstract: wherein Z1 is hydrogen or an amino-protecting group selected from the group consisting of acyl of the formula R—C(O)—, wherein R is alkyl of 1-6 carbon atoms; trityl, optionally substituted with methoxy; and N-(9-fluorenylmethoxycarbonyl); Y1 is halo, aralkyloxy or acyloxy, wherein acyl is as defined above; and Y2 is aralkyloxy. These intermediates are useful in a novel process for preparing the mono-L-valine ester of 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl) methoxy-1,3-propanediol (ganciclovir). The mono-L-valine ester of ganciclovir and its pharmaceutically acceptable salts are of value as antiviral agents with improved absorption.

Abstract translation: 其中Z1是氢或选自式R-C（O） - 的酰基的氨基保护基，其中R是1-6个碳原子的烷基; 三苯甲基，任选被甲氧基取代; 和N-（9-芴基甲氧基羰基）; Y1是卤素，芳烷氧基或酰氧基，其中酰基如上所定义; 而Y2是芳烷氧基。 这些中间体可用于制备2-（2-氨基-1,6-二氢-6-氧代 - 嘌呤-9-基）甲氧基-1,3-丙二醇（更昔洛韦）的单-L-缬氨酸酯的新方法 ）。 更昔洛韦的单-L-缬氨酸酯及其药学上可接受的盐具有改善吸收的抗病毒剂的价值。

公开(公告)号：US06218568B1

公开(公告)日：2001-04-17

申请号：US09497538

申请日：2000-02-03

Applicant: Charles A. Dvorak ,  Douglas L. Wren ,  Lawrence E. Fisher ,  Steven D. Axt ,  Eric R. Humphreys ,  Humberto B. Arzeno ,  Colin C. Beard ,  Sam Linh Nguyen ,  Yeun-Kwei Han ,  Christopher R. Roberts ,  Jan P. Lund ,  Paul R. Fatheree

Inventor： Charles A. Dvorak ,  Douglas L. Wren ,  Lawrence E. Fisher ,  Steven D. Axt ,  Eric R. Humphreys ,  Humberto B. Arzeno ,  Colin C. Beard ,  Sam Linh Nguyen ,  Yeun-Kwei Han ,  Christopher R. Roberts ,  Jan P. Lund ,  Paul R. Fatheree

IPC: C07C67743

CPC classification number: C07D473/00 ,  C07D473/18 ,  Y02P20/55

Abstract: Process for preparing intermediates of formula (III) wherein Y1 is acyloxy, wherein acyl is of the formula R—C(O)—, wherein R is alkyl of 1-6 carbon atoms, Y2 is aralkyloxy, and Z is benzoyloxy or acyloxy, wherein acyl is as defined above. Intermediates of formula (III) are useful in a novel process for preparing the mono-L-valine ester of 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy-1,3-propanediol (ganciclovir). The mono-L-valine ester of ganciclovir and its pharmaceutically acceptable salts are of value as antiviral agents with improved absorption.

Abstract translation: 制备式（III）的中间体的方法，其中Y1是酰氧基，其中酰基是式RC（O） - ，其中R是1-6个碳原子的烷基，Y2是芳烷氧基，Z是苯甲酰氧基或酰氧基，其中酰基 式（III）的中间体可用于制备2-（2-氨基-1,6-二氢-6-氧代 - 嘌呤-9-基） - 的单-L-缬氨酸酯的新方法， 甲氧基-1,3-丙二醇（更昔洛韦）。 更昔洛韦的单-L-缬氨酸酯及其药学上可接受的盐具有改善吸收的抗病毒剂的价值。

公开(公告)号：US6040446A

公开(公告)日：2000-03-21

申请号：US127380

申请日：1998-07-31

Applicant: Charles A. Dvorak ,  Douglas L. Wren ,  Lawrence E. Fisher ,  Steven D. Axt ,  Eric R. Humphreys ,  Humberto B. Arzeno ,  Colin C. Beard ,  Sam Linh Nguyen ,  Yeun-Kwei Han ,  Christopher R. Roberts ,  Jan P. Lund ,  Paul R. Fatheree

Inventor： Charles A. Dvorak ,  Douglas L. Wren ,  Lawrence E. Fisher ,  Steven D. Axt ,  Eric R. Humphreys ,  Humberto B. Arzeno ,  Colin C. Beard ,  Sam Linh Nguyen ,  Yeun-Kwei Han ,  Christopher R. Roberts ,  Jan P. Lund ,  Paul R. Fatheree

IPC: C07D473/00 ,  C07D473/18

CPC classification number: C07D473/00 ,  C07D473/18 ,  Y02P20/55

Abstract: Process and novel intermediates for preparing the L-mono-valine ester of 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy-1,3-propanediol and its pharmaceutically acceptable salts. The present process and intermediates provide for reduced impurities in the mono-valine ester end-product and lower overall production costs. The process involves the condensation of a silylated guanine compound with a substituted glycerol derivative and esterification of this product with an L-valine derivative. These mono-valine products are of value as antiviral agents with improved absorption.

Abstract translation: 用于制备2-（2-氨基-1,6-二氢-6-氧代 - 嘌呤-9-基）甲氧基-1,3-丙二醇的L-缬氨酸酯的方法和新型中间体及其药学上可接受的盐。 本方法和中间体提供了单缬氨酸酯最终产物中减少的杂质，降低了总体生产成本。 该方法包括将甲硅烷基化鸟嘌呤化合物与取代的甘油衍生物缩合，并将该产物与L-缬氨酸衍生物酯化。 这些单缬氨酸产品具有改善吸收的抗病毒剂的价值。

公开(公告)号：US06215017B1

公开(公告)日：2001-04-10

申请号：US09497537

申请日：2000-02-03

Applicant: Charles A. Dvorak ,  Douglas L. Wren ,  Lawrence E. Fisher ,  Steven D. Axt ,  Eric R. Humphreys ,  Humberto B. Arzeno ,  Colin C. Beard ,  Sam Linh Nguyen ,  Yeun-Kwei Han ,  Christopher R. Roberts ,  Jan P. Lund ,  Paul R. Fatheree

Inventor： Charles A. Dvorak ,  Douglas L. Wren ,  Lawrence E. Fisher ,  Steven D. Axt ,  Eric R. Humphreys ,  Humberto B. Arzeno ,  Colin C. Beard ,  Sam Linh Nguyen ,  Yeun-Kwei Han ,  Christopher R. Roberts ,  Jan P. Lund ,  Paul R. Fatheree

IPC: C07C67743

CPC classification number: C07D473/00 ,  C07D473/18 ,  Y02P20/55

Abstract: Intermediates of Formula (III) wherein Y1 is acyloxy, wherein acyl is of the formula R—C(O)—, wherein R is alkyl of 1-6 carbon atoms, Y2 is aralkyloxy, and Z is benzoyloxy or acyloxy, wherein acyl is as defined above. Intermediates of formula (III) are useful in a novel process for preparing the mono-L-valine ester of 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy-1,3-propanediol (ganciclovir). The mono-L-valine ester of ganciclovir and its pharmaceutically acceptable salts are of value as antiviral agents with improved absorption.

Abstract translation: 式（III）的中间体，其中Y1是酰氧基，其中酰基是式RC（O） - ，其中R是1-6个碳原子的烷基，Y2是芳烷氧基，Z是苯甲酰氧基或酰氧基，其中酰基如所定义 式（III）的中间体可用于制备2-（2-氨基-1,6-二氢-6-氧代 - 嘌呤-9-基）甲氧基-1的单-L-缬氨酸酯的新方法 ，3-丙二醇（更昔洛韦）。 更昔洛韦的单-L-缬氨酸酯及其药学上可接受的盐具有改善吸收的抗病毒剂的价值。