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：US4088771A

公开(公告)日：1978-05-09

申请号：US708651

申请日：1976-07-26

Applicant: Adolph P. Roszkowski ,  Colin C. Beard ,  Charles Dvorak ,  Klaus Weinhardt

Inventor： Adolph P. Roszkowski ,  Colin C. Beard ,  Charles Dvorak ,  Klaus Weinhardt

IPC: A61K31/415 ,  A61P21/02 ,  A61P25/00 ,  A61P25/08 ,  C07D233/46 ,  C07D233/48

CPC classification number: C07D233/46 ,  C07D233/48

Abstract: 1-Lower alkyl-4,5-dihydro-5-phenyl-2-lower alkoxycarbonylaminoimidazoles, and substituted phenyl derivatives thereof, and pharmaceutically acceptable salts thereof, and methods of preparing such compounds. In one method, the compounds can be prepared by treating the corresponding .beta.-lower alkylamino-.beta.-(phenyl or substituted phenyl)-ethylamine with the desired 1,3-bis (alkoxycarbonyl)-S-methylisothiourea or 1-alkoxycarbonyl-S-methylisothiourea. The compounds can also be prepared by treating the corresponding 1-lower alkyl-2-amino-4,5-dihydro-5-(phenyl or substituted phenyl)-imidazole with the desired dialkylcarbonate. The subject compounds are useful as psychotherapeutic agents in treating or palliating abnormal conditions, in mammals, which involve the central nervous system.

Abstract translation: 1-低级烷基-4,5-二氢-5-苯基-2-低级烷氧基羰基氨基咪唑及其取代的苯基衍生物及其药学上可接受的盐，以及制备这些化合物的方法。 在一种方法中，化合物可以通过用所需的1,3-双（烷氧基羰基）-S-甲基异硫脲或1-烷氧基羰基-S-苯基酯处理相应的β-低级烷基氨基-β-（苯基或取代的苯基） 甲基异硫脲 化合物也可以通过用所需的二烷基碳酸酯处理相应的1-低级烷基-2-氨基-4,5-二氢-5-（苯基或取代的苯基） - 咪唑来制备。 本发明化合物在涉及中枢神经系统的哺乳动物中用作治疗或缓解异常状况的心理治疗剂。

公开(公告)号：US4031234A

公开(公告)日：1977-06-21

申请号：US697499

申请日：1976-06-18

Applicant: Colin C. Beard ,  John A. Edwards ,  John H. Fried

Inventor： Colin C. Beard ,  John A. Edwards ,  John H. Fried

IPC: A61K31/415

Abstract: This application relates to 1,5(6)-disubstituted benzimidazole-2-carbamate derivatives represented by the following formula: ##STR1## where R is lower alkyl having 1 to 4 carbon atoms; R.sup.1 is --SOR.sup.2, --SR.sup.5, --OR.sup.5 or M'(CH.sub.2).sub.n MR.sup.7 ; R.sup.2 is lower alkyl having from 1 to 6 carbon atoms, cycloalkyl having 3 to 7 carbon atoms, lower alkenyl or lower alkynyl having 3 to 6 carbon atoms, or aralkyl or aryl; R.sup.5 is lower alkenyl, lower alkynyl or aralkyl; R.sup.7 is lower alkyl having 1 to 4 carbon atom, or aryl; M and M' are independently O, S, ##STR2## n is 1-4; and R.sup.8 is lower alkyl having 1 to 12 carbon atoms optionally substituted with a --COOR group where R is lower alkyl having 1 to 4 carbon atoms, aryl or aralkyl. The R.sup.1 substitution is at the 5(6)-position.The compounds are useful as pesticides, particularly as anthelmintic and antifungal agents.

Abstract translation: 本申请涉及由下式表示的1,5（6） - 二取代的苯并咪唑-2-氨基甲酸酯衍生物：其中R是具有1至4个碳原子的低级烷基; R 1是-SOR 2，-SR 5，-OR 5或M'（CH 2）nMR 7; R2是具有1至6个碳原子的低级烷基，具有3至7个碳原子的环烷基，具有3至6个碳原子的低级链烯基或低级炔基，或芳烷基或芳基; R5是低级烯基，低级炔基或芳烷基; R7是具有1至4个碳原子的低级烷基，或芳基; M和M'独立地为O，S，n为1-4; R8是具有1〜12个碳原子的低级烷基，任选被-COOR基团取代，其中R是具有1-4个碳原子的低级烷基，芳基或芳烷基。 R1取代为5（6）位。

公开(公告)号：US4009164A

公开(公告)日：1977-02-22

申请号：US675040

申请日：1976-04-05

Applicant: Colin C. Beard

Inventor： Colin C. Beard

IPC: C07D235/30 ,  C07D417/14

CPC classification number: C07D235/30

Abstract: Novel 2-substituted-1,2,4-thiadiazolo-[2,3-a]-benzimidazoles of the formula ##STR1## and the pharmaceutically acceptable salts thereof; and process for their preparation. These 2-substituted-1,2,4-thiadiazolo-[2,3-a]-benzimidazoles are useful as fungistatic and fungicidal agents.

Abstract translation: 式I的新型2-取代-1,2,4-噻二唑并[2,3-a] - 苯并咪唑及其药学上可接受的盐; 并进行准备。 这些2-取代-1,2,4-噻二唑并[2,3-a] - 苯并咪唑可用作抑菌和杀真菌剂。

公开(公告)号：US4005202A

公开(公告)日：1977-01-25

申请号：US615257

申请日：1975-09-22

Applicant: Colin C. Beard ,  John A. Edwards ,  John H. Fried

Inventor： Colin C. Beard ,  John A. Edwards ,  John H. Fried

IPC: C07D233/84 ,  C07D249/12 ,  A61K31/495

CPC classification number: C07D233/84 ,  C07D249/12

Abstract: Benzene ring substituted benzimidazole-2-carbamate derivatives represented by the formula: ##STR1## where R is a lower alkyl group having 1 to 4 carbon atoms; R.sup.1 is a heterocyclic ring having 1-4 hetero atoms; and M is O, S, or ##STR2##The R.sup.1 M-substitution is at the 5(6)-position. The compounds are useful as pesticides, particularly as anthelmintic and antifungal agents.

Abstract translation: 由下式表示的苯环取代的苯并咪唑-2-氨基甲酸酯衍生物：其中R是具有1至4个碳原子的低级烷基; R1是具有1-4个杂原子的杂环; 并且M是O，S或 R1M取代位于5（6）位。

公开(公告)号：US3976654A

公开(公告)日：1976-08-24

申请号：US622932

申请日：1975-10-16

Applicant: Colin C. Beard

Inventor： Colin C. Beard

IPC: C07D235/30 ,  C07D213/34

CPC classification number: C07D235/30

Abstract: Novel 2-substituted-1,2,4-thiadiazolo-[2,3-a]-benzimidazoles of the formula ##SPC1##And the pharmaceutically acceptable salts thereof; and process for their preparation. These 2-substituted-1,2,4-thiadiazolo-[2,3-a]-benzimidazoles are useful as fungistatic and fungicidal agents.

Abstract translation: 新颖的2-取代-1,2,4-噻二唑并[2,3-a] - 苯并咪唑及其药物接受的盐; 及其制备方法。 这些2-取代-1,2,4-噻二唑并[2,3-a] - 苯并咪唑可用作抑菌和杀真菌剂。

公开(公告)号：US3962437A

公开(公告)日：1976-06-08

申请号：US566014

申请日：1975-04-07

Applicant: Colin C. Beard

Inventor： Colin C. Beard

IPC: A61K31/41 ,  C07D513/04 ,  C07D513/08

CPC classification number: C07D513/04 ,  A61K31/41

Abstract: Benzene ring substituted benzimidazole-2-carbamate derivatives represented by the formula: ##SPC1##Where R is a lower alkyl group having 1 to 4 carbon atoms; and R.sup.1 is a fused, bicyclic heterocyclic ring moiety. The R.sup.1 S-substitution is at the 5(6)-position.The compounds are useful as pesticides, particularly as anthelmintic and antifungal agents.

公开(公告)号：US4191764A

公开(公告)日：1980-03-04

申请号：US946985

申请日：1978-09-29

Applicant: Colin C. Beard

Inventor： Colin C. Beard

IPC: C07C335/38 ,  C07D235/32 ,  A61K31/535 ,  C07D295/18

CPC classification number: C07D235/32 ,  C07C335/38

Abstract: Benzene ring substituted benzimidazole-2-carbamate derivatives represented by the formula: ##STR1## where R is a lower alkyl group having 1 to 4 carbon atoms; ##STR2## is a 5, 6, 7 or 8 membered heterocyclic ring containing 1 or 2 hetero atoms; the ##STR3## substitution being at the 5(6)-position; and the pharmaceutically acceptable salts thereof. The compounds are useful as pesticides, particularly as anthelmintic and antifungal agents.

Abstract translation: 由下式表示的苯环取代的苯并咪唑-2-氨基甲酸酯衍生物：其中R是具有1至4个碳原子的低级烷基; 是含有1或2个杂原子的5,6,7或8元杂环; 替换在5（6）位置; 及其药学上可接受的盐。 这些化合物可用作杀虫剂，特别是作为驱肠虫和抗真菌剂。

公开(公告)号：US4110463A

公开(公告)日：1978-08-29

申请号：US803016

申请日：1977-06-03

Applicant: Colin C. Beard ,  Marshall B. Wallach ,  Klaus Weinhardt

Inventor： Colin C. Beard ,  Marshall B. Wallach ,  Klaus Weinhardt

IPC: A61K31/415 ,  A61P21/02 ,  C07D233/44 ,  C07D233/48 ,  C07D233/46

CPC classification number: C07C255/00 ,  C07D233/48

Abstract: Compounds represented by the formula ##STR1## wherein R is hydrogen or alkyl of 1-4 carbons, R.sup.1 is alkyl of 1-6 carbons and the naphthyl group is attached to the imidazole ring at the 1 or 2 positions of the naphthyl ring and the pharmaceutically acceptable salts thereof are useful as centrally acting skeletal muscle relaxants.

Abstract translation: 由式CHEM表示的咪唑-2-氨基甲酸酯，其中R是氢或1-4个碳的烷基，R 1是1-6个碳的烷基，萘基在咪唑环上连接1或2个 萘环的位置及其药学上可接受的盐。 这些化合物可用作中枢作用的骨骼肌松弛剂。 该化合物通过闭合式（CHEM）化合物来制备