公开(公告)号：US09174990B2

公开(公告)日：2015-11-03

申请号：US11707248

申请日：2007-02-15

申请人： Jiri Zemlicka ,  John C. Drach ,  Xinchao Chen

发明人： Jiri Zemlicka ,  John C. Drach ,  Xinchao Chen

IPC分类号： C07D473/00 ,  C07F9/6561

CPC分类号： C07D473/00 ,  C07F9/65616

摘要： Compounds which are active against viruses have the following Formulas: wherein B is 2-aminopurine-9-yl, which may be unsubstituted or substituted in the 6 position with NHR1, OR2, or SR3; R1 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.

摘要翻译： 对病毒有活性的化合物具有下式：其中B是2-氨基嘌呤-9-基，其可以是未被取代的或在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：US07183268B2

公开(公告)日：2007-02-27

申请号：US10942314

申请日：2004-09-15

申请人： Jiri Zemlicka ,  John C. Drach ,  Xinchao Chen

发明人： Jiri Zemlicka ,  John C. Drach ,  Xinchao Chen

IPC分类号： C07D473/32 ,  C07D473/16 ,  C07D473/18 ,  A61K31/522 ,  A61K31/52

CPC分类号： C07D473/00 ,  C07F9/65616

摘要： Compounds which are active against viruses have the following Formulas: wherein B is 2-aminopurine-9-yl, which may be unsubstituted or substituted in the 6 position with NHR1, OR2, or SR3; R1 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.

摘要翻译： 对病毒有活性的化合物具有下式：其中B是2-氨基嘌呤-9-基，其可以是未取代的或在6位被NHR 1或OR 2取代， SUB>或SR 3; 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一个或多个 由羟基，卤素，氨基，酰基，环烷基，杂环基和芳基组成的基团; R 2选自C 2-18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，并且任选地被一个或多个 由羟基，卤素，氨基，酰基，环烷基，杂环基和芳基组成的组中的更多成员; 和R 3 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，卤代 ，氨基，酰基，环烷基，杂环基和芳基。

公开(公告)号：US06413938B1

公开(公告)日：2002-07-02

申请号：US09367260

申请日：1999-08-25

申请人： Jeffrey H. Tidwell ,  Stanley D. Chamberlain ,  George A. Freeman ,  Joseph H. Chan ,  George W. Koszalka ,  Leroy B. Townsend ,  John C. Drach

发明人： Jeffrey H. Tidwell ,  Stanley D. Chamberlain ,  George A. Freeman ,  Joseph H. Chan ,  George W. Koszalka ,  Leroy B. Townsend ,  John C. Drach

IPC分类号： A61K3170

CPC分类号： C07H19/052 ,  A61K31/7056 ,  Y10S514/934

摘要： According to a first aspect of the invention there is provided compounds of formula (I): wherein: R1 is hydroxy; O-acetyl; or a halo atom; R2 is hydroxy; O-acetyl; or a halo atom; R3 is hydrogen; a halo atom; azido; C2-6alkenyl; C2-6alkynyl; C6-14aryl C2-6alkenyl; C6-14arylC2-6alkynyl —NR8R9 (where R8 and R9 may be the same or different and are hydrogen, C1-8alkyl, cyanoC1-8alkyl, hydroxyC1-8alkyl, haloC1-8alkyl, C3-7cycloalkyl, C1-8alkylC3-7cycloalkyl, C2-6alkenyl, C3-7cycloalkylC1-8alkyl, C2-6alkynyl, C6-14aryl, C6-14arylC1-8alkyl, heterocycleC1-8alkyl, C1-8alkylcarbonyl, C6-14arylsulfonyl, C1-8alkysulfonyl, or R8R9 together with the N atom to which they are attached form a 3,4,5 or 6 membered heterocyclic ring); —OR10 (where R10 is hydrogen, C1-8alkyl, C6-14aryl, or C6-14arylC1-8alkyl, C2-6alkenyl, C2-6alkynyl, C6-14aryl C2-6alkenyl or C6-14arylC2-6alkynyl); or —SR11 (where R11 is hydrogen, C1-8alkyl, C6-14aryl, or C6-14arylC1-8alkyl).

摘要翻译： 根据本发明的第一方面，提供式（I）的化合物：其中：R 1是羟基; O-乙酰基; 或卤原子; R 2为羟基; O-乙酰基; 或卤素原子; R 3是氢; 卤素原子 叠氮 C2-6烯基; C 2-6炔基; C6-14芳基C2-6烯基; C 6-14芳基C 2-6炔基-NR 8 R 9（其中R 8和R 9可以相同或不同，为氢，C 1-8烷基，氰基C 1-8烷基，羟基C 1-8烷基，卤代C 1-8烷基，C 3-7环烷基，C 1-8烷基C 3-7环烷基， C 1-6烷基，C 3-7环烷基C 1-8烷基，C 2-6炔基，C 6-14芳基，C 6-14芳基C 1-8烷基，杂环C 1-8烷基，C 1-8烷基羰基，C 6-14芳基磺酰基，C 1-8炔基磺酰基或R 8 R 9与它们所连接的N原子一起 形成3,4,5或6元杂环）; -OR 10（其中R 10是氢，C 1-8烷基，C 6-14芳基或C 6-14芳基C 1-8烷基，C 2-6烯基，C 2-6炔基，C 6-14芳基C 2-6烯基或C 6-14芳基C 2-6炔基）; 或-SR 11（其中R 11是氢，C 1-8烷基，C 6-14芳基或C 6-14芳基C 1-8烷基）。

公开(公告)号：US06342501B1

公开(公告)日：2002-01-29

申请号：US09229391

申请日：1999-01-11

申请人： Leroy B. Townsend ,  John C. Drach

发明人： Leroy B. Townsend ,  John C. Drach

IPC分类号： C07D48704

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 the following formula: wherein: R4 is —NR1R2 or oxo; R5 is —CN, or —CSNR1R2, or —CONR1R2; R6 is —H, or halo, or —NR1R2; wherein R1 and R2 are independently —H or an aliphatic group; and R7 is of the formula R3—Ar, wherein R3 is an aliphatic group and Ar is an unsubstituted aryl or an aryl independently substituted with halo, nitro, amino, or aliphatic groups; provided that when R5 is a —CN or —CSNH2, and R6 is a —H or —NH2, and Ar is a —C6H5 or a phenyl substituted with only one aliphatic group, R3 is an aliphatic group other than methyl such that —R3— is not a —CH2—; and pharmaceutically acceptable salts, prodrugs and derivatives thereof.

摘要翻译： 本发明涉及一类新颖的4,5,6,7-取代的非核苷，不可磷酸化的吡咯并[2,3-d]嘧啶，其显示出比已知的核苷非特异性的显着更低的细胞毒性水平和更好的抗病毒活性 核苷和非核苷，不可磷酸化的吡咯并[2,3-d]嘧啶衍生物，特别是针对人DNA病毒如巨细胞病毒（HCMV）和1型单纯疱疹病毒（HSV-1）。 这些化合物由下式表示：其中：R4是-NR1R2或氧代; R5是-CN或-CSNR1R2或-CONR1R2; R6是-H或卤素，或-NR1R2; 其中R1和R2独立地为-H或脂族基团; R7为式R3-Ar，其中R3为脂族基团，Ar为未取代的芳基或独立地被卤素，硝基，氨基或脂族基团取代的芳基; 条件是当R 5为-CN或-CSNH 2，且R 6为-H或-NH 2，且Ar为-C 6 H 5或被一个脂族基团取代的苯基时，R 3为甲基以外的脂族基团，使得-R 3 - 不是-CH2-; 及其药学上可接受的盐，前药和衍生物。

公开(公告)号：US5874413A

公开(公告)日：1999-02-23

申请号：US698715

申请日：1996-08-16

申请人： Leroy B. Townsend ,  John C. Drach

发明人： Leroy B. Townsend ,  John C. Drach

IPC分类号： C07H19/23 ,  A61K31/00 ,  A61K31/70 ,  A61K31/7042 ,  A61K31/7052 ,  A61K31/7056 ,  A61P31/00 ,  A61P31/12 ,  C07H19/052 ,  C07H17/02 ,  A61K31/415 ,  C07D235/04

CPC分类号： C07H19/052

摘要： The present invention relates to polysubstituted benzimidazoles, having the following formula: ##STR1## wherein Q is a substituted benzimidazole group attached at the benzimidazole 1-position; R is a halogen of atomic number 9 to 53, inclusive (i.e., --F, --Cl, --Br, or --I); azido (i.e., --N.sub.3); or --X--R.sub.1, wherein X is a chalcogen of atomic number 8 to 16, inclusive (i.e., --O-- or --S--), and R.sub.1 may be straight or branched chain alkyl of 1 to 8 carbon atoms; and R.sub.2 and R.sub.3 may be the same or different and are separately --O--C(.dbd.O)CH.sub.3 (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 benzimidazole as defined above and methods of use thereof.

摘要翻译： 本发明涉及具有下式的多取代苯并咪唑：其中Q是在苯并咪唑1-位连接的取代苯并咪唑基; R为原子序数为9〜53的卤素（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（含-O-或-S-）的硫族元素，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，分别为-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。

公开(公告)号：US5712255A

公开(公告)日：1998-01-27

申请号：US457391

申请日：1995-06-01

申请人： Leroy B. Townsend ,  John C. Drach

发明人： Leroy B. Townsend ,  John C. Drach

IPC分类号： A61K31/415 ,  A61K31/4184 ,  A61K31/52 ,  A61K31/7056 ,  C07D235/24 ,  C07D235/26 ,  C07D235/30 ,  C07H19/052 ,  A01N43/52 ,  A61K31/70 ,  C07D235/04

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

摘要： A method for treating a herpes viral infection comprising administering to the infected host a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt or formulation thereof, selected from the group consisting of compounds having the following formula: ##STR1## wherein: R.sub.1 is H, R.sub.2 is Cl, R.sub.3 is Cl, R.sub.4 is H, R.sub.5 is Br and R.sub.6 is .beta.-D-ribofuranosyl (denoted compound 52 in the text); R.sub.1 is H, R.sub.2 is NO.sub.2, R.sub.3 is NO.sub.2, R.sub.4 is H, R.sub.5 is Cl and R.sub.6 is .beta.-D-ribofuranosyl (denoted compound 61 in the text); R.sub.1 is Cl, R.sub.2 is H, R.sub.3 is Cl, R.sub.4 is H, R.sub.5 is Cl and R.sub.6 is .beta.-D-ribofuranosyl (denoted compound 81 in the text); R.sub.1 is H, R.sub.2 is Cl, R.sub.3 is Cl, R.sub.4 is H, R.sub.5 is I and R.sub.6 is .beta.-D-ribofuranosyl (denoted compound 83a in the text); R.sub.1 is Br, R.sub.2 is Br, R.sub.3 is H, R.sub.4 is H, R.sub.5 is Cl and R.sub.6 is .beta.-D-ribofuranosyl (denoted compound 85 in the text); R.sub.1 is H, R.sub.2 is Br, R.sub.3 is Cl, R.sub.4 is H, R.sub.5 is Cl and R.sub.6 is .beta.-D-ribofuranosyl (denoted compound 95 in the text); R.sub.1 is H, R.sub.2 is Cl, R.sub.3 is Br, R.sub.4 is H, R.sub.5 is Cl and R.sub.6 is .beta.-D-ribofuranosyl (denoted compound 99 in the text); R.sub.1 is H, R.sub.2 is I, R.sub.3 is I, R.sub.4 is H, R.sub.5 is Cl and R.sub.6 is .beta.-D-ribofuranosyl (denoted compound 107 in the text); R.sub.1 is H, R.sub.2 is Cl, R.sub.3 is Cl, R.sub.4 is H, R.sub.5 is Cl and R.sub.6 is 2'-deoxy-.beta.-D-erythro-pentofuranosyl (denoted compound 111 in the text); R.sub.1 is H, R.sub.2 is Cl, R.sub.3 is Cl, R.sub.4 is H, R.sub.5 is Br and R.sub.6 is 2'-deoxy-.beta.-D-erythro-pentofuranosyl (denoted compound 112 in the text); R.sub.1 is Cl, R.sub.2 is Cl, R.sub.3 is Cl, R.sub.4 is Cl, R.sub.5 is Cl and R.sub.6 is (1,3-dihydroxy-2-propoxy)methyl (denoted compound 155 in the text); R.sub.1 is Cl, R.sub.2 is Cl, R.sub.3 is Cl, R.sub.4 is Cl, R.sub.5 is NH.sub.2 and R.sub.6 is (1,3-dihydroxy-2-propoxy)methyl (denoted compound 156 in the text); R.sub.1 is Cl, R.sub.2 is Cl, R.sub.3 is Cl, R.sub.4 is Cl, R.sub.5 is OCH.sub.3 and R.sub.6 is 2-hydroxyethoxymethyl (denoted compound 166a in the text); R.sub.1 is Cl, R.sub.2 is Cl, R.sub.3 is Cl, R.sub.4 is Cl, R.sub.5 is NH.sub.2 and R.sub.6 is 2-hydroxyethoxymethyl (denoted compound 167 in the text); and R.sub.1 is H, R.sub.2 is Cl, R.sub.3 is Cl, R.sub.4 is H, R.sub.5 is NH.sub.2 and R.sub.6 is benzyl (denoted compound 182 in the text).

公开(公告)号：US5633235A

公开(公告)日：1997-05-27

申请号：US266847

申请日：1994-07-05

申请人： Leroy B. Townsend ,  John C. Drach ,  Louis S. Kucera

发明人： Leroy B. Townsend ,  John C. Drach ,  Louis S. Kucera

IPC分类号： A61K31/70

CPC分类号： A61K31/7064

摘要： Triciribine and analogs are effective antiviral agents.

摘要翻译： 特敏灵和类似物是有效的抗病毒剂。

公开(公告)号：US5574058A

公开(公告)日：1996-11-12

申请号：US050470

申请日：1993-05-03

申请人： Leroy B. Townsend ,  John C. Drach

发明人： Leroy B. Townsend ,  John C. Drach

IPC分类号： A61K31/415 ,  A61K31/4184 ,  A61K31/52 ,  A61K31/7056 ,  C07D235/24 ,  C07D235/26 ,  C07D235/30 ,  C07H19/052 ,  A01N43/52 ,  C07D235/04 ,  C07D235/22

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

摘要： Polysubstituted benzimidazoles and pharmaceutical compositions containing them as the active ingredients. These compounds and compositions exhibit antiviral activity against viruse of the herpes family, particularly human cytomegalovirus and herpes simplex viruses (HSV).

摘要翻译： 多取代苯并咪唑和含有它们作为活性成分的药物组合物。 这些化合物和组合物对疱疹家族的病毒特别是人巨细胞病毒和单纯疱疹病毒（HSV）表现出抗病毒活性。

公开(公告)号：US5543413A

公开(公告)日：1996-08-06

申请号：US357762

申请日：1994-12-15

申请人： Leroy B. Townsend ,  John C. Drach ,  Thomas E. Renau

发明人： Leroy B. Townsend ,  John C. Drach ,  Thomas E. Renau

IPC分类号： A61K31/505 ,  A61P31/12 ,  C07D487/04 ,  A61K31/52

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 the following formula: ##STR1## wherein R.sup.4 is -NH.sub.2 or -NHCH.sub.3 ;R.sup.5 is -CN,-CSNH.sub.2, or -CSeNH.sub.2 ;R.sup.6 is -H or -NH.sub.2 ; andR.sup.7 is selected from the group consisting ofaryls 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; andoxy-hydrocarbyls having 6 to 30 carbon atoms, at least one aryl or aralkyl group, and only one oxy-group;with the proviso that if R.sup.5 is -CN and R.sup.6 is -H then R.sup.4 is -NH.sub.2 and R.sup.7 is -CH.sub.2 C.sub.6 H.sub.4 -2-CH.sub.3.

摘要翻译： 本发明涉及一类新颖的4,5,6,7-取代的非核苷，不可磷酸化的吡咯并[2,3-d]嘧啶，其显示出比已知的核苷非特异性的显着更低的细胞毒性水平和更好的抗病毒活性 核苷和非核苷，不可磷酸化的吡咯并[2,3-d]嘧啶衍生物，特别是针对人DNA病毒如巨细胞病毒（HCMV）和1型单纯疱疹病毒（HSV-1）。 这些化合物由下式表示：其中R 4是-NH 2或-NHCH 3; R5是-CN，-CSNH2或-CSeNH2; R6是-H或-NH2; 并且R 7选自具有6至30个碳原子的芳基和芳烷基; 具有2至15个碳原子的脂族烃基，缺少游离羟基并进一步缺乏酰基或酰基衍生基团; 和具有6至30个碳原子的烃基，至少一个芳基或芳烷基和仅一个氧基; 条件是如果R5为-CN且R6为-H，则R4为-NH2，R7为-CH2C6H4-2-CH3。

公开(公告)号：US4596798A

公开(公告)日：1986-06-24

申请号：US363723

申请日：1982-03-30

申请人： Charles Shipman, Jr. ,  Daniel L. Klayman ,  Sandra H. Smith ,  John C. Drach

发明人： Charles Shipman, Jr. ,  Daniel L. Klayman ,  Sandra H. Smith ,  John C. Drach

IPC分类号： A61K31/44 ,  C07D213/53 ,  A61K31/33 ,  A61K31/395 ,  A61K31/535 ,  A61K31/55

CPC分类号： C07D213/53 ,  A61K31/44 ,  Y10S514/934

摘要： This invention relates to the use of various 2-acetylpyridine thiosemicarbazones which are substituted on the 4-nitrogen atom in the treatment of viral infections. Also disclosed are several synthetic procedures used to prepare the thiosemicarbazones.

摘要翻译： 本发明涉及在病毒感染治疗中在4-氮原子上取代的各种2-乙酰基吡啶缩氨基硫脲。 还公开了几种用于制备缩氨基硫脲的合成方法。