公开(公告)号：WO2005034943A1

公开(公告)日：2005-04-21

申请号：PCT/US2004/032895

申请日：2004-10-06

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN ,  TOWNSEND, Leroy, B. ,  DRACH, John, C.

Inventor： TOWNSEND, Leroy, B. ,  DRACH, John, C.

IPC: A61K31/405

CPC classification number: A61K31/405 ,  A61K31/655 ,  A61K31/7052 ,  C07H19/04

Abstract: The present invention provides novel chemical compounds and methods for their use. In particular, the present invention provides indole derivatives (e.g. as shown in Formula (I)) and related compounds and methods of using indole derivatives and related compounds as therapeutic agents to treat a number of conditions, including those associated with viral infection and cardiovascular diseases.

Abstract translation: 本发明提供了新颖的化合物及其使用方法。 特别地，本发明提供吲哚衍生物（例如如式（I）所示）和相关化合物和使用吲哚衍生物和相关化合物作为治疗剂的方法来治疗许多病症，包括与病毒感染和心血管疾病相关的病症 。

公开(公告)号：WO2004006867A2

公开(公告)日：2004-01-22

申请号：PCT/US2003/007909

申请日：2003-03-13

Applicant: WAYNE STATE UNIVERSITY ,  THE REGENTS OF THE UNIVERSITY OF MICHIGAN ,  ZEMLICKA, Jiri ,  DRACH, John, C.

Inventor： ZEMLICKA, Jiri ,  DRACH, John, C.

IPC: A61K

CPC classification number: C07D473/00 ,  C07F9/65616

Abstract: Compounds which are active against viruses have the Formulas (1) and (2), wherein B is 2-aminopurine-9-yl, which may be unsubstituted or substituted in the 6 position with NHR 1 , OR 2 , or SR 3 ; R l is selected from the group consisting of alkyl, alkenyl, alkynyl, and C 4-18 cycloalkyl, any of which may be optionally substituted with one or more members of the group consisting of hydroxy, halo, amino, acyl, cycloalkyl, heterocyclyl and aryl; R 2 is selected from the group consisting of C 2-18 alkyl, alkenyl, alkynyl, and cycloalkyl, any of which may be branched or unbranched and optionally substituted with one or more members of the group consisting of hydroxy, halo, amino, acyl, cycloalkyl, heterocyclyl, and aryl; and R 3 is selected from the group consisting of alkyl, alkenyl, alkynyl, and cycloalkyl, any of which may be branched or unbranched and optionally substituted with one or more members of the group consisting of hydroxy, halo, amino, acyl, cycloalkyl, heterocyclyl and aryl.

Abstract translation: 对病毒有活性的化合物具有式（1）和（2），其中B是2-氨基嘌呤-9-基，其可以是未取代的或在6位被NHR1，OR2或SR3取代; R 1选自烷基，烯基，炔基和C 4-18环烷基，其中任何一个可以任选地被羟基，卤素，氨基，酰基，环烷基，杂环基和芳基中的一个或多个成员取代 ; R2选自C2-18烷基，烯基，炔基和环烷基，其中任何一个可以是支链或非支链的，并且任选被一个或多个由羟基，卤素，氨基，酰基，环烷基 ，杂环基和芳基; 并且R 3选自烷基，烯基，炔基和环烷基，其中任何一个可以是支链或非支链的，并且任选被一个或多个由羟基，卤素，氨基，酰基，环烷基，杂环基 和芳基。

公开(公告)号：WO1997027205A1

公开(公告)日：1997-07-31

申请号：PCT/US1997001602

申请日：1997-01-22

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN ,  TOWNSEND, Leroy, B. ,  DRACH, John, C.

Inventor： THE REGENTS OF THE UNIVERSITY OF MICHIGAN

IPC: C07H19/052

CPC classification number: C07D471/04 ,  C07H7/06 ,  C07H9/04 ,  C07H11/00 ,  C07H19/052

Abstract: This invention pertains to nucleoside analogs which have antiviral activity and improved metabolic stability, compositions comprising them, and methods of antiviral treatment employing them. More particularly, this invention pertains to imidazo [1,2-a]pyridine C-nucleosides, as exemplified by compounds such imidazo[1,2-a]pyridine C5-nucleosides and imidazo[1,2-a]pyridine C3-nucleosides, and may be represented by formula (I), wherein exactly one of Q and Q is a sugar-like moiety; exactly one of Q and Q is -H; and Q , Q , Q and Q are independently imidazo[1,2-a]pyridine substituents, such as -H, -F, -Cl, -Br, and -I.

Abstract translation: 本发明涉及具有抗病毒活性和改善的代谢稳定性的核苷类似物，包含它们的组合物以及使用它们的抗病毒治疗方法。 更具体地，本发明涉及咪唑并[1,2-a]吡啶C-核苷，例如咪唑并[1,2-a]吡啶C5-核苷和咪唑并[1,2-a]吡啶C 3 - 核苷 并且可以由式（I）表示，其中Q 3和Q 5中的仅一个是糖状部分; Q 3和Q 5中的正好一个是-H; 和Q 2，Q 6，Q 7和Q 8独立地是咪唑并[1,2-a]吡啶取代基，例如-H，-F，-Cl，-Br和-I 。

公开(公告)号：WO2004006867A3

公开(公告)日：2004-10-21

申请号：PCT/US0307909

申请日：2003-03-13

Applicant: UNIV WAYNE STATE ,  UNIV MICHIGAN ,  ZEMLICKA JIRI ,  DRACH JOHN C

Inventor： ZEMLICKA JIRI ,  DRACH JOHN C

IPC: C07D473/16 ,  A61K31/52 ,  A61P31/12 ,  A61P31/18 ,  A61P31/20 ,  A61P31/22 ,  C07D473/00 ,  C07D473/18 ,  C07D473/24 ,  C07D473/32 ,  C07F9/6561 ,  A61K31/522

CPC classification number: C07D473/00 ,  C07F9/65616

Abstract: Compounds which are active against viruses have the Formulas (I) and (II), wherein B is 2-aminopurine-9-yl, which may be unsubstituted or substituted in the 6 position with NHR1, OR2, or SR3; Rl is selected from the group consisting of alkyl, alkenyl, alkynyl, and C4-18 cycloalkyl, any of which may be optionally substituted with one or more members of the group consisting of hydroxy, halo, amino, acyl, cycloalkyl, heterocyclyl and aryl; R2 is selected from the group consisting of C2-18 alkyl, alkenyl, alkynyl, and cycloalkyl, any of which may be branched or unbranched and optionally substituted with one or more members of the group consisting of hydroxy, halo, amino, acyl, cycloalkyl, heterocyclyl, and aryl; and R3 is selected from the group consisting of alkyl, alkenyl, alkynyl, and cycloalkyl, any of which may be branched or unbranched and optionally substituted with one or more members of the group consisting of hydroxy, halo, amino, acyl, cycloalkyl, heterocyclyl and aryl.

Abstract translation: 对病毒有活性的化合物具有式（I）和（II），其中B是2-氨基嘌呤-9-基，其可以是未取代的或在6位被NHR1，OR2或SR3取代; R 1选自烷基，烯基，炔基和C 4-18环烷基，其中任何一个可以任选地被羟基，卤素，氨基，酰基，环烷基，杂环基和芳基中的一个或多个成员取代 ; R2选自C2-18烷基，烯基，炔基和环烷基，其中任何一个可以是支链或非支链的，并且任选被一个或多个由羟基，卤素，氨基，酰基，环烷基 ，杂环基和芳基; 并且R 3选自烷基，烯基，炔基和环烷基，其中任何一个可以是支链或非支链的，并且任选被一个或多个由羟基，卤素，氨基，酰基，环烷基，杂环基 和芳基。

公开(公告)号：WO1992007867A1

公开(公告)日：1992-05-14

申请号：PCT/US1991008124

申请日：1991-10-31

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN ,  TOWNSEND, Leroy, B. ,  DRACH, John, C.

Inventor： THE REGENTS OF THE UNIVERSITY OF MICHIGAN

IPC: C07H17/02

CPC classification number: A61K31/70 ,  A61K31/415 ,  A61K31/4184 ,  A61K31/52 ,  A61K31/7056 ,  C07D235/24 ,  C07D235/26 ,  C07D235/30 ,  C07H19/052 ,  Y10S514/934 ,  A61K2300/00

Abstract: This invention relates to novel polysubstituted benzimidazoles and compositions and their use in the treatment of viral infections. The polysubstituted benzimidazoles and compositions of the present invention exhibit antiviral properties against viruses of the herpes family, particularly human cytomegalovirus (HCMV) and herpes simplex viruses (HSV).

公开(公告)号：WO1997027204A1

公开(公告)日：1997-07-31

申请号：PCT/US1997000764

申请日：1997-01-22

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN ,  GLAXO GROUP LIMITED ,  TOWNSEND, Leroy, B. ,  DRACH, John, C. ,  FREEMAN, George, A.

Inventor： THE REGENTS OF THE UNIVERSITY OF MICHIGAN ,  GLAXO GROUP LIMITED

IPC: C07H19/052

CPC classification number: C07D471/04 ,  C07H7/06 ,  C07H9/04 ,  C07H11/00 ,  C07H19/052

Abstract: This invention pertains to nucleoside analogs which have antiviral activity and improved metabolic stability. More specifically, this invention pertains to modified sugar benzimidazole nucleosides, as exemplified by compounds such as benzimidazole nucleosides possessing a fluorinated sugar-like moiety (for example, a 2'-fluoro-furanosyl moiety or a 3'-fluoro-furanosyl moiety), and may be represented by formula (I) wherein R is a fluorinated sugar-like moiety; and R , R , R , R and R are benzimidazole substituents, such as -H, halogens (e.g., -F, -C1, -Br, -I), -NO2, -NR2 (where R is independently -H or an alkyl group having 1-6 carbon atoms), -OR (where R is -H or an alkyl group having 1-6 carbon atoms), -SR (where R is -H or a hydrocarbyl of 1-10 carbon atoms), and -CF3. In one embodiment, R is 2'-fluoro-furanosyl or 3'-fluoro-furanosyl; R is -H, -F, -C1, -Br, -I, or -NR2, wherein R is independently -H or an alkyl group having 1-6 carbon atoms; R , R , R and R are independently -H, -F, -C1, -Br, or -I.

Abstract translation: 本发明涉及具有抗病毒活性和改善的代谢稳定性的核苷类似物。 更具体地，本发明涉及改性糖苯并咪唑核苷，例如化合物例如具有氟化糖样部分的苯并咪唑核苷（例如2'-氟 - 呋喃糖基部分或3'-氟 - 呋喃糖基部分）， 并且可以由式（I）表示，其中R 1是氟化糖样部分; R 2，R 4，R 5，R 6和R 7是苯并咪唑取代基，例如-H，卤素（例如-F，-C1，-Br，-I） ，-NO 2，-NR 2（其中R独立地是-H或具有1-6个碳原子的烷基），-OR（其中R是-H或具有1-6个碳原子的烷基），-SR（其中R 是-H或1-10个碳原子的烃基）和-CF 3。 在一个实施方案中，R 1是2'-氟 - 呋喃糖基或3'-氟 - 呋喃糖基; R 2是-H，-F，-C 1，-Br，-I或-NR 2，其中R独立地是-H或具有1-6个碳原子的烷基; R 4，R 5，R 6和R 7独立地是-H，-F，-C 1，-Br或-I。

公开(公告)号：WO2003104440A3

公开(公告)日：2003-12-18

申请号：PCT/US2003/007916

申请日：2003-03-14

Applicant: WAYNE STATE UNIVERSITY ,  THE REGENTS OF THE UNIVERSITY OF MICHIGAN ,  ZEMLICKA, Jiri ,  ZHOU, Shaoman ,  DRACH,John, C.

Inventor： ZEMLICKA, Jiri ,  ZHOU, Shaoman ,  DRACH,John, C.

IPC: C07D473/16

Abstract: Compounds which are active against viruses have the following formulas: Formula (I), Formula (II), wherein B is a purine or pyrimidine heterocyclic ring or base. In a preferred embodiment, the purine include 6-aminopurine (adenine), 6-hydroxypurine (hypoxanthine), 2-amino-6-hydroxypurine (guanine), 2,6-diamino-purine, 2-amino-6-azidopurine, 2-amino-6-halo substituted purines such as 2-amino­6-chloropurine, 2-amino-6-fluoropurine, 2-amino-6-alkoxypurines such as 2-amino-6-methoxypurine, 2-amino-6-cyclopropylaminopurine, 2-amino-­6-alkylamino or 2-amino-6-dialkylamino substituted purines, 2-amino-­6-thiopurine, 2-amino-6-alkylthio substituted purines, 3-deazapurines, 7-deazapurines and 8-azapurines. The pyrimidine incorporates cytosine, uracil and thymine, 5-halo substituted cytosines and uracils, 5-alkyl substituted cytosines and uracils including derivatives with a saturated or unsaturated alkyl group and 6-azapyrimidines.

公开(公告)号：WO2003104440A2

公开(公告)日：2003-12-18

申请号：PCT/US2003/007916

申请日：2003-03-14

Applicant: WAYNE STATE UNIVERSITY ,  THE REGENTS OF THE UNIVERSITY OF MICHIGAN ,  ZEMLICKA, Jiri ,  ZHOU, Shaoman ,  DRACH,John, C.

Inventor： ZEMLICKA, Jiri ,  ZHOU, Shaoman ,  DRACH,John, C.

IPC: C12N

CPC classification number: C07D239/36 ,  C07D239/54 ,  C07D473/18 ,  C07D473/30 ,  C07D473/34 ,  C07D473/40

Abstract: Compounds which are active against viruses have the following formulas: Formula (I), Formula (II), wherein B is a purine or pyrimidine heterocyclic ring or base. In a preferred embodiment, the purine include 6-aminopurine (adenine), 6-hydroxypurine (hypoxanthine), 2-amino-6-hydroxypurine (guanine), 2,6-diamino-purine, 2-amino-6-azidopurine, 2-amino-6-halo substituted purines such as 2-amino­6-chloropurine, 2-amino-6-fluoropurine, 2-amino-6-alkoxypurines such as 2-amino-6-methoxypurine, 2-amino-6-cyclopropylaminopurine, 2-amino-­6-alkylamino or 2-amino-6-dialkylamino substituted purines, 2-amino-­6-thiopurine, 2-amino-6-alkylthio substituted purines, 3-deazapurines, 7-deazapurines and 8-azapurines. The pyrimidine incorporates cytosine, uracil and thymine, 5-halo substituted cytosines and uracils, 5-alkyl substituted cytosines and uracils including derivatives with a saturated or unsaturated alkyl group and 6-azapyrimidines.

Abstract translation: 对病毒有活性的化合物具有下式：式（I），式（II），其中B是嘌呤或嘧啶杂环或碱基。 在优选的实施方案中，嘌呤包括6-氨基嘌呤（腺嘌呤），6-羟基嘌呤（次黄嘌呤），2-氨基-6-羟基嘌呤（鸟嘌呤），2,6-二氨基嘌呤，2-氨基-6-叠氮基嘌呤，2 2-氨基-6-氯嘌呤，2-氨基-6-氟嘌呤，2-氨基-6-氟代嘌呤，2-氨基-6-甲氧基嘌呤，2-氨基-6-环丙基氨基嘌呤，2 2-氨基-6-烷基氨基或2-氨基-6-二烷基氨基取代的嘌呤，2-氨基-6-硫嘌呤，2-氨基-6-烷硫基取代的嘌呤，3-脱氮嘌呤，7-脱氮嘌呤和8-氮杂嘌呤。 嘧啶含有胞嘧啶，尿嘧啶和胸腺嘧啶，5-卤素取代的胞嘧啶和尿嘧啶，5-烷基取代的胞嘧啶和尿嘧啶，包括具有饱和或不饱和烷基的衍生物和6-氮杂嘧啶。

公开(公告)号：WO1997007125A1

公开(公告)日：1997-02-27

申请号：PCT/US1996013187

申请日：1996-08-16

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN ,  TOWNSEND, Leroy, B. ,  DRACH, John, C.

Inventor： THE REGENTS OF THE UNIVERSITY OF MICHIGAN

IPC: C07H19/052

CPC classification number: C07H19/052

Abstract: The present invention relates to polysubstituted benzimidazoles, having formula (I), wherein Q is substituted benzimidazole group attached at the benzimidazole 1-position; R is a halogen or atomic number 9 to 53, inclusive (i.e., -F, -Cl, -Br, or -I); azido (i.e., -N3); or -X-R1, wherein X is a chalcogen of atomic number 8 to 16, inclusive (i.e., -O- or -S-), and R1 may be straight or branched chain alkyl of 1 to 8 carbon atoms; and R2 and R3 may be the same or different and are separately -O-C(=O)CH3 (i.e., -OAc) or hydroxy (i.e., -OH); and pharmaceutically acceptable salts and operative combinations thereof. Also provided by this invention are compositions comprising a polysubstituted benzimidazoles as defined above and methods of use thereof.

Abstract translation: 本发明涉及具有式（I）的多取代的苯并咪唑，其中Q是在苯并咪唑1-位连接的取代的苯并咪唑基; R是卤素或原子序数9至53，包括（即-F，-Cl，-Br或-I）; 叠氮基（即-N3）; 或-X-R 1，其中X是原子数为8〜16的硫族元素（即-O-或-S-），R 1可以是1〜8个碳原子的直链或支链烷基; 并且R 2和R 3可以相同或不同，并且分别是-O-C（= O）CH 3（即，-OAc）或羟基（即-OH）; 及其药学上可接受的盐和操作组合。 本发明还提供了包含如上所定义的多取代苯并咪唑及其使用方法的组合物。