公开(公告)号：EP1000080A1

公开(公告)日：2000-05-17

申请号：EP98937254.5

申请日：1998-07-29

申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN ,  GLAXO GROUP LIMITED

发明人： TOWNSEND, Leroy, B. ,  DRACH, John, C. ,  BIRON, Karen,K. ,  BOYD, Frank,L. Jr.

IPC分类号： C07H19/052 ,  A61K31/70

CPC分类号： C07H19/052 ,  Y02P20/55

摘要： The present invention pertains to D- and L-lyxofuranosyl benzimidazole compounds. In one embodiment, the present invention pertains to D- and L-lyxofuranosyl benzimidazole compounds selected from the group consisting of compounds having a formula selected from the following: (beta-D), (beta-L), (alpha-L) and (alpha-D) wherein R?2, R4, R5, R6, and R7¿ are independently the same or different and independently selected from the group consisting of: -H, -F, -Cl, -Br, -I, -NO¿2?, -N(R?8)¿2, -OR?8, -SR12¿, and -CF¿3?, wherein R?8¿ is independently -H or an alkyl group having 1-6 carbon atoms and wherein R12 is independently -H or a hydrocarbyl group having 1-10 carbon atoms; and R?9, R10 and R11¿ are independently the same or different and are H or a hydroxyl protecting group; anomeric and optical isomers thereof; and pharmaceutically acceptable salts and prodrug derivatives thereof. The present invention also pertains to antiviral compositions using these compounds, methods of treating a viral infection using these compounds, and the use of these compounds in the preparation of a medicament for use in the treatment of a viral infection.

摘要翻译： 本发明涉及D-和L-左旋呋喃糖基苯并咪唑化合物。 在一个实施方案中，本发明涉及选自具有选自以下结构式的化合物的D-和L-来苏呋喃糖基苯并咪唑化合物：（β-D），（β-L），（α-L）和 （α-D）其中R 2，R 4，R 5，R 6和R 7'独立地相同或不同并且独立地选自：-H，-F，-Cl，-Br，-I， - -N（R 8）2，-OR 8，-SR 12和-CF 3，其中R 8独立地为-H或具有1-6个碳原子的烷基 并且其中R 12独立地为-H或具有1-10个碳原子的烃基; R9，R10和R11独立地是相同或不同的，并且是H或羟基保护基; 它们的端基异构体和光学异构体; 及其药学上可接受的盐和前药衍生物。 本发明还涉及使用这些化合物的抗病毒组合物，使用这些化合物治疗病毒感染的方法，以及这些化合物在制备用于治疗病毒感染的药物中的用途。

公开(公告)号：EP1019425A1

公开(公告)日：2000-07-19

申请号：EP97902982.4

申请日：1997-01-22

申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN ,  GLAXO GROUP LIMITED

发明人： TOWNSEND, Leroy, B. ,  DRACH, John, C. ,  FREEMAN, George, A.

IPC分类号： C07H19/052 ,  A61K31/70

CPC分类号： C07D471/04 ,  C07H7/06 ,  C07H9/04 ,  C07H11/00 ,  C07H19/052

摘要： 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 R1 is a fluorinated sugar-like moiety; and R?2, R4, R5, R6 and R7¿ are benzimidazole substituents, such as -H, halogens (e.g., -F, -C1, -Br, -I), -NO¿2?, -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?1¿ is 2'-fluoro-furanosyl or 3'-fluoro-furanosyl; R2 is -H, -F, -C1, -Br, -I, or -NR¿2?, wherein R is independently -H or an alkyl group having 1-6 carbon atoms; R?4, R5, R6 and R7¿ are independently -H, -F, -C1, -Br, or -I.

公开(公告)号：EP1490015B1

公开(公告)日：2009-09-23

申请号：EP03764294.9

申请日：2003-03-13

申请人： WAYNE STATE UNIVERSITY ,  THE REGENTS OF THE UNIVERSITY OF MICHIGAN

发明人： ZEMLICKA, Jiri ,  DRACH, John, C. ,  CHEN, Xinchao

IPC分类号： A61K6/00 ,  C07D473/18 ,  C07D473/16 ,  C07D473/24 ,  A61K31/522 ,  A61P31/18 ,  A61P31/22 ,  C07F9/6506

CPC分类号： C07D473/00 ,  C07F9/65616

摘要： 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.

公开(公告)号：EP1490015A2

公开(公告)日：2004-12-29

申请号：EP03764294.9

申请日：2003-03-13

申请人： Wayne State University ,  THE REGENTS OF THE UNIVERSITY OF MICHIGAN

发明人： ZEMLICKA, Jiri ,  DRACH, John, C.

IPC分类号： A61K6/00

CPC分类号： C07D473/00 ,  C07F9/65616

摘要： 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.

公开(公告)号：EP1165560A1

公开(公告)日：2002-01-02

申请号：EP00913872.8

申请日：2000-03-10

申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN ,  BOARD OF GOVERNORS OF WAYNE STATE UNIVERSITY

发明人： ZEMLICKA, Jiri ,  QIU, Yao-Ling ,  DRACH, John, C. ,  PTAK, Roger, G.

IPC分类号： C07D473/16 ,  C07D473/18 ,  A61K31/52 ,  A61K31/522

CPC分类号： C07D239/47 ,  C07D239/54 ,  C07D473/00 ,  C07D473/16 ,  C07D473/18 ,  C07D473/34 ,  C07F9/65061 ,  C07F9/65616

摘要： Compounds which are active against viruses have Formulas (1, 2, 3 and 4) wherein B is a purine or pyrimidine heterocyclic ring and is preferably selected from the group consisting of 6-aminopurine (adenine), 2,6-diaminopurine, 2-amino-6-azidopurine, 2-amino-6-cyclopropylaminopurine, 6-hydroxypurine (hypoxanthine), 2-amino-6-halo substituted purines, 2-amino-6-alkoxy substituted purines, 2-amino-6-hydroxypurine (guanine), 3-deazapurines, 7-deaza-purines, 8-azapurines, cytosine, 5-halo substituted cytosines, 5-alkyl substituted cytosines, thymine, uracil and 6-azapyrimidines; X is O; and, R1 and R2 are alkyl or aryl groups. The compounds of the present invention also include the R- and S-enantiomers of the above compounds. The R1X and/or R2X can also be amino acid residues with X as NH.

摘要翻译： 对病毒具有活性的化合物具有式（1,2,3和4），其中B是嘌呤或嘧啶杂环并且优选选自6-氨基嘌呤（腺嘌呤），2,6-二氨基嘌呤，2-氨基嘌呤， 氨基-6-叠氮基嘌呤，2-氨基-6-环丙基氨基嘌呤，6-羟基嘌呤（次黄嘌呤），2-氨基-6-卤代嘌呤，2-氨基-6-烷氧基取代的嘌呤，2-氨基-6-羟基嘌呤（鸟嘌呤 ），3-脱氮嘌呤，7-脱氮嘌呤，8-氮杂嘌呤，胞嘧啶，5-卤代取代的胞嘧啶，5-烷基取代的胞嘧啶，胸腺嘧啶，尿嘧啶和6-氮杂嘧啶; X是O; 并且，R1和R2是烷基或芳基。 本发明的化合物还包括上述化合物的R-和S-对映体。 R1X和/或R2X也可以是X为NH的氨基酸残基。

公开(公告)号：EP1165560B1

公开(公告)日：2004-11-17

申请号：EP00913872.8

申请日：2000-03-10

申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN ,  BOARD OF GOVERNORS OF WAYNE STATE UNIVERSITY

发明人： ZEMLICKA, Jiri ,  QIU, Yao-Ling ,  DRACH, John, C. ,  PTAK, Roger, G.

IPC分类号： C07D473/16 ,  C07D473/18 ,  A61K31/52 ,  A61K31/522 ,  A61P31/18 ,  A61P31/22

CPC分类号： C07D239/47 ,  C07D239/54 ,  C07D473/00 ,  C07D473/16 ,  C07D473/18 ,  C07D473/34 ,  C07F9/65061 ,  C07F9/65616

摘要： Compounds which are active against viruses have Formulas (1, 2, 3 and 4) wherein B is a purine or pyrimidine heterocyclic ring and is preferably selected from the group consisting of 6-aminopurine (adenine), 2,6-diaminopurine, 2-amino-6-azidopurine, 2-amino-6-cyclopropylaminopurine, 6-hydroxypurine (hypoxanthine), 2-amino-6-halo substituted purines, 2-amino-6-alkoxy substituted purines, 2-amino-6-hydroxypurine (guanine), 3-deazapurines, 7-deaza-purines, 8-azapurines, cytosine, 5-halo substituted cytosines, 5-alkyl substituted cytosines, thymine, uracil and 6-azapyrimidines; X is O; and, R1 and R2 are alkyl or aryl groups. The compounds of the present invention also include the R- and S-enantiomers of the above compounds. The R1X and/or R2X can also be amino acid residues with X as NH.

摘要翻译： 对病毒具有活性的化合物具有式（1,2,3和4），其中B是嘌呤或嘧啶杂环并且优选选自6-氨基嘌呤（腺嘌呤），2,6-二氨基嘌呤，2-氨基嘌呤， 氨基-6-叠氮基嘌呤，2-氨基-6-环丙基氨基嘌呤，6-羟基嘌呤（次黄嘌呤），2-氨基-6-卤代嘌呤，2-氨基-6-烷氧基取代的嘌呤，2-氨基-6-羟基嘌呤（鸟嘌呤 ），3-脱氮嘌呤，7-脱氮嘌呤，8-氮杂嘌呤，胞嘧啶，5-卤代取代的胞嘧啶，5-烷基取代的胞嘧啶，胸腺嘧啶，尿嘧啶和6-氮杂嘧啶; X是O; 并且，R1和R2是烷基或芳基。 本发明的化合物还包括上述化合物的R-和S-对映体。 R1X和/或R2X也可以是X为NH的氨基酸残基。

公开(公告)号：EP0746559A1

公开(公告)日：1996-12-11

申请号：EP95911092.0

申请日：1995-02-23

申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN

发明人： TOWNSEND, Leroy, B. ,  DRACH, John, C. ,  RENAU, Thomas, E.

IPC分类号： A61K31 ,  A61P31 ,  C07D487

CPC分类号： C07D487/04

摘要： This invention relates to a novel class of 4,5,6,7-substituted non-nucleoside, non-phosphorylatable pyrrolo[2,3-d]pyrimidines which exhibit both significantly lower levels of cytotoxicity and superior antiviral activity than known nucleoside, non-nucleoside, and non-nucleoside, non-phosphorylatable pyrrolo[2,3-d]pyrimidine derivatives, particularly against human DNA viruses such as cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1). These compounds are represented by formula (I) wherein R4 is -NH¿2? or -NHCH3; R?5¿ is -CN, -CSNH¿2?, or -CSeNH2; R?6¿ is -H or -NH¿2?; and R?7¿ is selected from the group consisting of aryls and aralkyls having 6 to 30 carbon atoms; aliphatic oxy-hydrocarbyls having 2 to 15 carbon atoms, lacking free hydroxyl groups and further lacking acyl or acyl derivatized groups; and oxy-hydrocarbyls having 6 to 30 carbon atoms, at least one aryl or aralkyl group, and only one oxy-group; with the proviso that if R5 is -CN and R6 is -H, then R4 is -NH¿2? and R?7¿ is -CH¿2?C6H4-2-CH3.

公开(公告)号：EP0556334A1

公开(公告)日：1993-08-25

申请号：EP92901986.0

申请日：1991-10-31

申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN

发明人： TOWNSEND, Leroy, B. ,  DRACH, John, C.

IPC分类号： A61K31 ,  C07D235 ,  C07H19

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

摘要： L'invention se rapporte à de nouveaux benzimidazoles polysubstitués et leurs compositions, ainsi qu'à leur utilisation dans le traitement d'infections virales. Les benzimidazoles polysubstitués et leurs compositions décrits par l'invention présentent des propriétés antivirales contre des virus de la famille des herpès, particulièrement le cytomégalovirus humain (HCMV) et les virus de l'herpès simplex (HSV).

公开(公告)号：EP1677784A1

公开(公告)日：2006-07-12

申请号：EP04794300.6

申请日：2004-10-06

申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN

发明人： TOWNSEND, Leroy, B. ,  DRACH, John, C.

IPC分类号： A61K31/405 ,  C07H19/04 ,  C07D209/04

CPC分类号： A61K31/405 ,  A61K31/655 ,  A61K31/7052 ,  C07H19/04

摘要： 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.

公开(公告)号：EP0845001B1

公开(公告)日：2002-11-13

申请号：EP96928176.5

申请日：1996-08-16

申请人： The Regents of The University of Michigan

发明人： TOWNSEND, Leroy, B. ,  DRACH, John, C.

IPC分类号： C07H19/052 ,  A61K31/70

CPC分类号： C07H19/052

摘要： 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.