公开(公告)号：US6020337A

公开(公告)日：2000-02-01

申请号：US950810

申请日：1997-09-16

申请人： Alistair J. Leigh ,  John Michnick ,  Anil M. Kumar ,  J. Peter Klein ,  Gail Underiner

发明人： Alistair J. Leigh ,  John Michnick ,  Anil M. Kumar ,  J. Peter Klein ,  Gail Underiner

IPC分类号： C07D209/48 ,  C07D239/54 ,  C07D239/96 ,  C07D473/10 ,  A61K31/52 ,  C07D473/00

CPC分类号： C07D209/48 ,  C07D239/54 ,  C07D239/96 ,  C07D473/10

摘要： Therapeutic compounds, including resolved enantiomers and/or diastereomers, hydrates, salts, solvates and mixtures thereof, having a formula: ##STR1## wherein R.sub.0 is selected from the group consisting of hydrogen, halo, hydroxyl, amino, substituted or unsubstituted C.sub.(1-10) alkyl, C.sub.(2-10) alkenyl, cyclic or heterocyclic groups, wherein the substituents of substituted C.sub.(1-10) alkyl, C.sub.(2-10) alkenyl are other than halo; n is an integer from one to sixteen; R.sub.1, R.sub.2, and R.sub.3 are independently selected from the group consisting of a halo; haloacetoxy; hydrogen; hydroxy; oxo; --N.dbd.C.dbd.S; --N.dbd.C.dbd.O; --0--C.tbd.N; --C.tbd.N; --N.dbd.N.dbd.N; and --C--(R.sub.5).sub.3, R.sub.5 being independently a halo or hydrogen, at least one R.sub.5 being halo, at least one of R.sub.1, R.sub.2, and R.sub.3 being halo, cyano, isocyano, isothiocyano, azide or haloacetoxy group; R.sub.4 is hydrogen, C.sub.(1-6) alkyl, C.sub.(1-6) alkenyl, cyclo C.sub.(4-6) alkyl, or phenyl; one or more hydrogen atoms of (CH.sub.2).sub.n --CH.sub.a --CH.sub.b --CH.sub.c may be replaced with: i) at least one of halogen atom, hydroxyl, oxo, substituted or unsubstituted C.sub.(1-10) alkyl, C.sub.(1-10) alkoxyalkyl, or C.sub.(2-10) alkenyl; or ii) one or more unsaturated bonds; and any two adjacent carbon atoms of (CH.sub.2).sub.n --CH.sub.a --CH.sub.b --CH.sub.c may be instead separated by at least one oxygen atom. These compounds are useful in treating or preventing diseases by inhibiting selective second messenger pathways.

摘要翻译： 具有下式的治疗化合物，包括拆分的对映异构体和/或非对映异构体，水合物，盐，溶剂合物及其混合物，其中R 0选自氢，卤素，羟基，氨基，取代或未取代的C（1-10） 烷基，C（2-10）烯基，环状或杂环基团，其中取代的C（1-10）烷基，C（2-10）烯基的取代基不是卤素; n是从1到16的整数; R 1，R 2和R 3独立地选自卤素; 卤代乙酰氧基; 氢; 羟基; 氧代 -N = C = S; -N = C = O; -0-C 3BOND N; -C 3BOND N; -N = N = N; 和 - （R 5）3，R 5独立地为卤素或氢，至少一个R 5为卤素，R 1，R 2和R 3中的至少一个为卤素，氰基，异氰基，异硫氰基，叠氮基或卤代乙酰氧基; R4是氢，C（1-6）烷基，C（1-6）烯基，环C（4-6）烷基或苯基; （CH 2）n -CH-CHB-CHc的一个或多个氢原子可以被：i）卤素原子，羟基，氧代，取代或未取代的C（1-10）烷基，C（1-10 ）烷氧基烷基或C（2-10）烯基; 或ii）一个或多个不饱和键; 并且（CH 2）n -CH CH-CH c CH 2的任何两个相邻的碳原子可以被至少一个氧原子隔开。 这些化合物可用于通过抑制选择性第二信使途径来治疗或预防疾病。

公开(公告)号：US5629423A

公开(公告)日：1997-05-13

申请号：US449400

申请日：1995-05-23

申请人： J. Peter Klein ,  Alistair J. Leigh ,  John Michnick ,  Anil M. Kumar ,  Gail E. Underiner

发明人： J. Peter Klein ,  Alistair J. Leigh ,  John Michnick ,  Anil M. Kumar ,  Gail E. Underiner

IPC分类号： C07D303/02 ,  C07B41/02 ,  C07B53/00 ,  C07C29/147 ,  C07D301/02 ,  C07D473/10 ,  C07D513/04 ,  C07D301/00

CPC分类号： C07D473/10 ,  C07B53/00 ,  C07D301/02

摘要： A process for synthesizing enantiomerically pure chiral secondary alcohol compounds linked to a heterocyclic core moiety, using a natural chiral molecule starting material. The inventive process is particularly useful for bulk manufacturing of chiral secondary alcohol compounds.

摘要翻译： 使用天然手性分子原料合成与杂环核心部分连接的对映体纯的手性仲醇化合物的方法。 本发明方法特别适用于大量制造手性仲醇化合物。

公开(公告)号：US6100271A

公开(公告)日：2000-08-08

申请号：US483871

申请日：1995-06-07

申请人： J. Peter Klein ,  Alistair J. Leigh ,  Gail E. Underiner ,  Anil M. Kumar

发明人： J. Peter Klein ,  Alistair J. Leigh ,  Gail E. Underiner ,  Anil M. Kumar

IPC分类号： C07D239/54 ,  A61K31/42 ,  A61K31/421 ,  A61K31/496 ,  A61K31/505 ,  A61K31/52 ,  A61K31/522 ,  A61P9/10 ,  A61P9/14 ,  A61P11/16 ,  A61P13/02 ,  A61P15/00 ,  A61P25/28 ,  A61P29/00 ,  A61P31/12 ,  A61P31/18 ,  A61P35/00 ,  A61P37/04 ,  A61P37/08 ,  A61P43/00 ,  C07C47/198 ,  C07C47/277 ,  C07C49/175 ,  C07C49/255 ,  C07C57/46 ,  C07C59/64 ,  C07C65/21 ,  C07C69/06 ,  C07C69/14 ,  C07C69/24 ,  C07C69/608 ,  C07C69/612 ,  C07C225/06 ,  C07C233/01 ,  C07D239/56 ,  C07D241/18 ,  C07D263/30 ,  C07D473/04 ,  C07D473/06 ,  C07D473/10 ,  C07D487/04 ,  C07D513/04 ,  C07D521/00

CPC分类号： C07D487/04 ,  C07D473/04 ,  C07D473/06 ,  C07D473/10 ,  C07D513/04

摘要： Therapeutic compounds with at least one carboxylic acid, ester or amide-substituted side chain have the formula:CORE MOIETY --(R).sub.jwherein j is an integer from one to three. The core moiety is non-cyclic or cyclic (carbocyclic or heterocyclic). R may be selected from among hydrogen, halogen, hydroxyl, amino, substituted or unsubstituted C.sub.(1-10) alkyl, C.sub.(2-10) alkenyl, carbocyclic or heterocyclic groups and at least one R has the formula I: ##STR1## wherein: one or two p are the integer one, otherwise p is two; and n is an integer from three to twenty; R.sub.1 is selected from the group consisting of substituted and unsubstituted CH.sub.2 ; NR.sub.3, R.sub.3 being hydrogen, substituted or unsubstituted C.sub.(1-20) alkyl, C.sub.(1-20) alkoxyl, C.sub.(2-20) alkenyl or C.sub.(1-20) hydroxyalkyl, or carbocyclic or heterocyclic group; O; --CHR.sub.4 O--, R.sub.4 being substituted or unsubstituted C.sub.(1-20) alkyl, C.sub.(1-20) alkoxyl, C.sub.(2-20) alkenyl, C.sub.(1-20) hydroxyalkyl, or R.sub.2 and R.sub.4 join to form a substituted or unsubstituted heterocycle having four to seven ring atoms, the ether group --O-- of --CHR.sub.4 O-- being a member of the heterocycle. R.sub.2 is selected from the group consisting of hydrogen; halogen; substituted or unsubstituted C.sub.(1-10) alkyl; C.sub.(1-10) alkoxyl; C.sub.(2-10) alkenyl; C.sub.(1-10) hydroxyallyl; --A(R.sub.5).sub.m, A being N or O, m being one or two and R.sub.5 being hydrogen, a substituted or unsubstituted C.sub.(1-10) alkyl, C.sub.(1-10) alkoxyl, C.sub.(2-10) alkenyl or C.sub.(1-10) hydroxyalkyl), or carbocyclic or heterocyclic group. At least one of R.sub.1 is NR.sub.3, O or --CHR.sub.4 O--, or R.sub.2 is --A(R.sub.5).sub.m. The compounds and pharmaceutical compositions thereof are useful as therapies for diseases advanced via intracellular signaling through specific intracellular signaling pathways by mediating a signaling response to an external stimuli.

摘要翻译： 具有至少一个羧酸，酯或酰胺取代的侧链的治疗化合物具有下式：CORE MOIETY - （R）j，其中j是1至3的整数。 核心部分是非环状或环状的（碳环或杂环）。 R可以选自氢，卤素，羟基，氨基，取代或未取代的C（1-10）烷基，C（2-10）烯基，碳环或杂环基，并且至少一个R具有式I：其中： 或两个p为整数，否则p为2; n为3〜20的整数。 R1选自取代和未取代的CH 2; NR 1，R 3为氢，取代或未取代的C 1-20烷基，C（1-20）烷氧基，C（2-20）烯基或C（1-20）羟基烷基或碳环或杂环基; O; -CHR4O-，R4是取代或未取代的C（1-20）烷基，C（1-20）烷氧基，C（2-20）烯基，C（1-20）羟基烷基或R2和R4连接形成取代的 或具有4-7个环原子的未取代的杂环，-CHR4O-的醚基-O-是杂环的成员。 R2选自氢; 卤素; 取代或未取代的C（1-10）烷基; C（1-10）烷氧基; C（2-10）烯基; C（1-10）羟基烯基; -A（R5）m，A是N或O，m是一个或两个，R5是氢，取代或未取代的C（1-10）烷基，C（1-10）烷氧基，C（2-10）烯基 或C（1-10）羟烷基）或碳环或杂环基。 R 1中的至少一个为NR 3，O或-CHR 4 O-，或R 2为-A（R 5）m。 这些化合物及其药物组合物可用作通过介导对外部刺激的信号反应的特异性细胞内信号通路的细胞内信号传导的疾病的治疗。

公开(公告)号：US6043250A

公开(公告)日：2000-03-28

申请号：US472296

申请日：1995-06-07

申请人： J. Peter Klein ,  Alistair J. Leigh ,  Gail E. Underiner ,  Anil M. Kumar ,  Glenn C. Rice

发明人： J. Peter Klein ,  Alistair J. Leigh ,  Gail E. Underiner ,  Anil M. Kumar ,  Glenn C. Rice

IPC分类号： C07D239/54 ,  A61K31/42 ,  A61K31/421 ,  A61K31/496 ,  A61K31/505 ,  A61K31/52 ,  A61K31/522 ,  A61P9/10 ,  A61P9/14 ,  A61P11/16 ,  A61P13/02 ,  A61P15/00 ,  A61P25/28 ,  A61P29/00 ,  A61P31/12 ,  A61P31/18 ,  A61P35/00 ,  A61P37/04 ,  A61P37/08 ,  A61P43/00 ,  C07C47/198 ,  C07C47/277 ,  C07C49/175 ,  C07C49/255 ,  C07C57/46 ,  C07C59/64 ,  C07C65/21 ,  C07C69/06 ,  C07C69/14 ,  C07C69/24 ,  C07C69/608 ,  C07C69/612 ,  C07C225/06 ,  C07C233/01 ,  C07D239/56 ,  C07D241/18 ,  C07D263/30 ,  C07D473/04 ,  C07D473/06 ,  C07D473/10 ,  C07D487/04 ,  C07D513/04 ,  C07D521/00 ,  A61K3/52

CPC分类号： C07D487/04 ,  C07D473/04 ,  C07D473/06 ,  C07D473/10 ,  C07D513/04

摘要： Therapeutic compounds with at least one carboxylic acid, ester or amide-substituted side chain have the formula:CORE MOIETY --(R).sub.jwherein j is an integer from one to three. The core moiety is non-cyclic or cyclic (carbocyclic or heterocyclic). R may be selected from among hydrogen, halogen, hydroxyl, amino, substituted or unsubstituted C(.sub.1-10) alkyl, C(.sub.2-10) alkenyl, carbocyclic or heterocyclic groups and at least one R has the formula I: ##STR1## wherein: one or two p are the integer one, otherwise p is two; and n is an integer from three to twenty; R.sub.1 is selected from the group consisting of substituted and unsubstituted CH.sub.2 ; NR.sub.3, R.sub.3 being hydrogen, substituted or unsubstituted C(.sub.1-20) alkyl, C.sub.(1-20) alkoxyl, C.sub.(2-20) alkenyl or C.sub.(1-20) hydroxyalkyl, or carbocyclic or heterocyclic group; O; --CHR.sub.4 O--, R.sub.4 being substituted or unsubstituted C.sub.(1-20) alkyl, C.sub.(1-20) alkoxyl, C.sub.(2-20) alkenyl, C.sub.(1-20) hydroxyalkyl, or R.sub.2 and R.sub.4 join to form a substituted or unsubstituted heterocycle having four to seven ring atoms, the ether group --O-- of --CHR.sub.4 O-- being a member of the heterocycle. R.sub.2 is selected from the group consisting of hydrogen; halogen; substituted or unsubstituted C.sub.(1-10) alkyl; C.sub.(1-10) alkoxyl; C.sub.(2-10) alkenyl; C.sub.(1-10) hydroxyalkyl; --A(R.sub.5).sub.m, A being N or 0, m being one or two and R.sub.5 being hydrogen, a substituted or unsubstituted C.sub.(1-10) alkyl, C.sub.(1-10) alkoxyl, C.sub.(2-10) alkenyl or C.sub.(1-10) hydroxyalkyl), or carbocyclic or heterocyclic group. At least one of R.sub.1 is NR.sub.3, O or --CHR.sub.4 O--, or R.sub.2 is --A(R.sub.5).sub.m. The compounds and pharmaceutical compositions thereof are useful as therapies for diseases advanced via intracellular signaling through specific intracellular signaling pathways by mediating a signaling response to an external stimuli.

摘要翻译： 具有至少一个羧酸，酯或酰胺取代的侧链的治疗化合物具有下式：CORE MOIETY - （R）j，其中j是1至3的整数。 核心部分是非环状或环状的（碳环或杂环）。 R可以选自氢，卤素，羟基，氨基，取代或未取代的C（1-10）烷基，C（2-10）烯基，碳环或杂环基，并且至少一个R具有式I：其中： 或两个p为整数，否则p为2; n为3〜20的整数。 R1选自取代和未取代的CH 2; NR 1，R 3为氢，取代或未取代的C 1-20烷基，C（1-20）烷氧基，C（2-20）烯基或C（1-20）羟基烷基或碳环或杂环基; O; -CHR4O-，R4是取代或未取代的C（1-20）烷基，C（1-20）烷氧基，C（2-20）烯基，C（1-20）羟基烷基或R2和R4连接形成取代的 或具有4-7个环原子的未取代的杂环，-CHR4O-的醚基-O-是杂环的成员。 R2选自氢; 卤素; 取代或未取代的C（1-10）烷基; C（1-10）烷氧基; C（2-10）烯基; C（1-10）羟烷基; -A（R5）m，A为N或0，m为一个或两个，R5为氢，取代或未取代的C（1-10）烷基，C（1-10）烷氧基，C（2-10）烯基 或C（1-10）羟烷基）或碳环或杂环基。 R 1中的至少一个为NR 3，O或-CHR 4 O-，或R 2为-A（R 5）m。 这些化合物及其药物组合物可用作通过介导对外部刺激的信号反应的特异性细胞内信号通路的细胞内信号传导的疾病的治疗。

公开(公告)号：US5807862A

公开(公告)日：1998-09-15

申请号：US478112

申请日：1995-06-07

申请人： J. Peter Klein ,  Alistair J. Leigh ,  Gail E. Underiner ,  Anil M. Kumar

发明人： J. Peter Klein ,  Alistair J. Leigh ,  Gail E. Underiner ,  Anil M. Kumar

IPC分类号： C07D239/54 ,  A61K31/42 ,  A61K31/421 ,  A61K31/496 ,  A61K31/505 ,  A61K31/52 ,  A61K31/522 ,  A61P9/10 ,  A61P9/14 ,  A61P11/16 ,  A61P13/02 ,  A61P15/00 ,  A61P25/28 ,  A61P29/00 ,  A61P31/12 ,  A61P31/18 ,  A61P35/00 ,  A61P37/04 ,  A61P37/08 ,  A61P43/00 ,  C07C47/198 ,  C07C47/277 ,  C07C49/175 ,  C07C49/255 ,  C07C57/46 ,  C07C59/64 ,  C07C65/21 ,  C07C69/06 ,  C07C69/14 ,  C07C69/24 ,  C07C69/608 ,  C07C69/612 ,  C07C225/06 ,  C07C233/01 ,  C07D239/56 ,  C07D241/18 ,  C07D263/30 ,  C07D473/04 ,  C07D473/06 ,  C07D473/10 ,  C07D487/04 ,  C07D513/04 ,  C07D521/00

CPC分类号： C07D487/04 ,  C07D473/04 ,  C07D473/06 ,  C07D473/10 ,  C07D513/04

摘要： Therapeutic compounds with at least one carboxylic acid, ester or amide-substituted side chain have the formula: CORE MOIETY--(R).sub.j wherein j is an integer from one to three. The core moiety is non-cyclic or cyclic (carbocyclic or heterocyclic). R may be selected from among hydrogen, halogen, hydroxyl, amino, substituted or unsubstituted C.sub.(1-10) alkyl, C.sub.(2-10) alkenyl, carbocyclic or heterocyclic groups and at least one R has the formula I: ##STR1## wherein: one or two p are the integer one, otherwise p is two; and n is an integer from three to twenty; R.sub.1 is selected from the group consisting of substituted and unsubstituted CH.sub.2 ; NR.sub.3, R.sub.3 being hydrogen, substituted or unsubstituted C.sub.(1-20) alkyl, C.sub.(1-20) alkoxyl, C.sub.(2-20) alkenyl or C.sub.(1-20) hydroxyalkyl, or carbocyclic or heterocyclic group; O; --CHR.sub.4 O--, R.sub.4 being substituted or unsubstituted C.sub.(1-20) alkyl, C.sub.(1-20) alkoxyl, C.sub.(2-20) alkenyl, C.sub.(1-20) hydroxyalkyl, or R.sub.2 and R.sub.4 join to form a substituted or unsubstituted heterocycle having four to seven ring atoms, the ether group --O-- of --CHR.sub.4 O-- being a member of the heterocycle. R.sub.2 is selected from the group consisting of hydrogen; halogen; substituted or unsubstituted C.sub.(1-10) alkyl; C.sub.(1-10) alkoxyl; C.sub.(2-10) alkenyl; C.sub.(1-10) hydroxyalkyl; --A(R.sub.5).sub.m, A being N or O, m being one or two and R.sub.5 being hydrogen, a substituted or unsubstituted C.sub.(1-10) alkyl, C.sub.(1-10) alkoxyl, C.sub.(2-10) alkenyl or C.sub.(1-10) hydroxyalkyl), or carbocyclic or heterocyclic group. At least one of R.sub.1 is NR.sub.3, O or --CHR.sub.4 O--, or R.sub.2 is --A(R.sub.5).sub.m. The compounds and pharmaceutical compositions thereof are useful as therapies for diseases advanced via intracellular signaling through specific intracellular signaling pathways by mediating a signaling response to an external stimuli.

摘要翻译： 具有至少一个羧酸，酯或酰胺取代的侧链的治疗化合物具有下式：其中j是1至3的整数。 核心部分是非环状或环状的（碳环或杂环）。 R可以选自氢，卤素，羟基，氨基，取代或未取代的C（1-10）烷基，C（2-10）烯基，碳环或杂环基，并且至少一个R具有式I： I其中：一个或两个p是整数一个，否则p是两个; n为3〜20的整数。 R1选自取代和未取代的CH 2; NR 1，R 3为氢，取代或未取代的C 1-20烷基，C（1-20）烷氧基，C（2-20）烯基或C（1-20）羟基烷基或碳环或杂环基; O; -CHR4O-，R4是取代或未取代的C（1-20）烷基，C（1-20）烷氧基，C（2-20）烯基，C（1-20）羟基烷基或R2和R4连接形成取代的 或具有4-7个环原子的未取代的杂环，-CHR4O-的醚基-O-是杂环的成员。 R2选自氢; 卤素; 取代或未取代的C（1-10）烷基; C（1-10）烷氧基; C（2-10）烯基; C（1-10）羟烷基; -A（R5）m，A是N或O，m是一个或两个，R5是氢，取代或未取代的C（1-10）烷基，C（1-10）烷氧基，C（2-10）烯基 或C（1-10）羟烷基）或碳环或杂环基。 R 1中的至少一个为NR 3，O或-CHR 4 O-，或R 2为-A（R 5）m。 这些化合物及其药物组合物可用作通过介导对外部刺激的信号反应的特异性细胞内信号通路的细胞内信号传导的疾病的治疗。

公开(公告)号：US5837703A

公开(公告)日：1998-11-17

申请号：US152650

申请日：1993-11-12

申请人： Anil M. Kumar ,  John Michnick ,  Gail E. Underiner ,  J. Peter Klein ,  Glenn C. Rice

发明人： Anil M. Kumar ,  John Michnick ,  Gail E. Underiner ,  J. Peter Klein ,  Glenn C. Rice

IPC分类号： A61K31/404 ,  A61K31/45 ,  A61K31/47 ,  A61K31/513 ,  A61K31/519 ,  A61K31/522 ,  C07C215/08 ,  C07C215/56 ,  C07C217/62 ,  C07C229/22 ,  C07C233/36 ,  C07C233/78 ,  C07C233/91 ,  C07D207/40 ,  C07D207/404 ,  C07D209/48 ,  C07D211/76 ,  C07D211/88 ,  C07D217/24 ,  C07D239/54 ,  C07D239/90 ,  C07D239/96 ,  C07D295/13 ,  C07D473/10 ,  A61K31/55 ,  A61K31/445 ,  A61K31/515 ,  A61K31/52

CPC分类号： C07D207/404 ,  A61K31/404 ,  A61K31/45 ,  A61K31/47 ,  A61K31/513 ,  A61K31/519 ,  A61K31/522 ,  C07C215/08 ,  C07C215/56 ,  C07C217/62 ,  C07C229/22 ,  C07C233/36 ,  C07C233/78 ,  C07C233/91 ,  C07D209/48 ,  C07D211/76 ,  C07D211/88 ,  C07D217/24 ,  C07D239/54 ,  C07D239/90 ,  C07D239/96 ,  C07D295/13 ,  C07D473/10

摘要： Therapeutic compounds have the formula: (X)j-(core moiety), j being an integer from one to three, the core moiety comprising a core moiety, the core moiety being a heterocycle having one ring or two-fused rings, each ring having five or six ring atoms, A being a carbon atom of the core moiety and attached to a terminal carbon atom of (CH.sub.2).sub.m, and X has a structure and X being a racemic mixture, R or S enantiomer, solvate, hydrate, or salt of: ##STR1## *C is a chiral carbon atom, n is an integer from one to four (preferably from one to three), one or more carbon atoms of (CH.sub.2).sub.n may be substituted by a keto or hydroxy group, and m is an integer from one to fourteen. Independently, R.sub.1 and R.sub.2 may be a hydrogen, a straight or branched chain alkyl or alkenyl of up to twelve carbon atoms in length, or --(CH.sub.2).sub.w R.sub.5, w being an integer from two to fourteen and R.sub.5 being a mono-, di- or tri-substituted or unsubstituted aryl group, substituents on R.sub.5 being hydroxy, chloro, fluoro, bromo, or C.sub.1-6 alkoxyl. Or jointly, R.sub.1 and R.sub.2 form a substituted or unsubstituted, saturated or unsaturated heterocyclic group having from four to eight carbon atoms, N being a hetero atom. R.sub.3 is a hydrogen or C.sub.1-3. Or, therapeutic compounds may also have the formula: ##STR2## R.sub.4 is a hydrogen, a straight or branched chain alkyl or alkenyl of up to eight carbon atoms in length, --(CH.sub.2).sub.w R.sub.5, w being an integer from two to fourteen and R.sub.5 being a mono-, di- or tri-substituted or unsubstituted aryl group, substituents on R.sub.5 being hydroxy, chloro, fluoro, bromo, or C.sub.1-6 alkoxyl, or a substituted or unsubstituted, saturated or unsaturated heterocyclic group having from four to eight carbon atoms, r and s are independently integers from one to four, the sum (r+s) not being greater than five. t is an integer from one to fourteen and one or more carbon atoms of (CH.sub.2).sub.s or (CH.sub.2).sub.t may be substituted by a keto or hydroxyl group.

摘要翻译： 治疗性化合物具有下式：（X）j-（核心部分），j是1至3的整数，核心部分包含核心部分，核心部分是具有一个环或双稠环的杂环，每个环 具有五个或六个环原子，A是核心部分的碳原子并且连接到（CH 2）m的末端碳原子，X具有结构，X是外消旋混合物，R或S对映异构体，溶剂合物，水合物， 或盐：C是手性碳原子，n是1至4（优选1至3）的整数，（CH 2）n的一个或多个碳原子可以被酮基或羟基取代 ，m为1〜14的整数。 独立地，R 1和R 2可以是氢，长或多至十二个碳原子的直链或支链烷基或链烯基，或 - （CH 2）w R 5，w为2至14的整数，R 5为单 - ，二 - 或三取代或未取代的芳基，R5上的取代基是羟基，氯，氟，溴或C1-6烷氧基。 或者共同地，R 1和R 2形成具有4至8个碳原子的取代或未取代的饱和或不饱和杂环基，N是杂原子。 R3是氢或C1-3。 或者，治疗性化合物还可以具有如下分子式：长达8个碳原子的链长链烷基或链烯基， - （CH 2）w R 5，w为2至14的整数，R 5为单 - ，二 - 或三 - 取代或未取代的芳基，R 5上的取代基为羟基，氯，氟，溴或C 1-6烷氧基，或具有4至8个碳原子的取代或未取代的饱和或不饱和杂环基，r和s独立地为 一到四，总和（r + s）不大于五。 t是1至14的整数，（CH 2）s或（CH 2）t的一个或多个碳原子可以被酮基或羟基取代。

公开(公告)号：US06780865B1

公开(公告)日：2004-08-24

申请号：US08932834

申请日：1997-09-18

申请人： David Porubek ,  Anil M. Kumar ,  Charles R. Bredl ,  J. Peter Klein

发明人： David Porubek ,  Anil M. Kumar ,  Charles R. Bredl ,  J. Peter Klein

IPC分类号： C07D47310

CPC分类号： C07D473/04 ,  C07D473/10

摘要： Disclosed are compounds having selective hydrolytic potential. The disclosed compounds are useful as compounds having selective stability and are capable of undergoing programmed hydrolysis in biologic systems. The disclosed compounds have a structure of formula I:

摘要翻译： 公开了具有选择性水解电位的化合物。 所公开的化合物可用作具有选择性稳定性且能够在生物系统中进行程序水解的化合物。 所公开的化合物具有式I的结构：

公开(公告)号：US6103730A

公开(公告)日：2000-08-15

申请号：US486264

申请日：1995-06-07

申请人： J. Peter Klein ,  Gail E. Underiner ,  Anil M. Kumar ,  Lance H. Ridgers

发明人： J. Peter Klein ,  Gail E. Underiner ,  Anil M. Kumar ,  Lance H. Ridgers

IPC分类号： C07D239/54 ,  C07D473/04 ,  C07D473/06 ,  C07D487/04 ,  C07D513/04 ,  A61K31/522 ,  C07D473/10

CPC分类号： C07D239/54 ,  C07D473/04 ,  C07D473/06 ,  C07D487/04 ,  C07D513/04

摘要： Compounds and pharmaceutical compositions, including resolved enantiomers and/or diastereomers, hydrates, salts, solvates and mixtures thereof, have the formula:CORE MOIETY--(R).sub.jIn these compounds, j is an integer from one to three; the core moiety is a cyclic core, the cyclic core being non-cyclic or at least one five- to seven-member non-heterocyclic ring or heterocycle; and R is selected from the group consisting of amine, hydrogen, halogen, hydroxyl, substituted or unsubstituted C.sub.(1-10) alkyl, C.sub.(2-10) alkenyl, cyclic or heterocyclic group or formula I. At least one R having formula I: ##STR1## In formula I, n is an integer from four to twenty; and each R.sub.1 or R.sub.2 is independently hydrogen, substituted or unsubstituted C.sub.(1-20) alkyl, C.sub.(1-20) alkoxyl, C.sub.(2-20) alkenyl or cyclic or heterocyclic group. The compounds are useful in treating or preventing, for example, sepsis syndrome, hematopoietic or organ toxicity, cancer, viral activity, AIDS and AIDS-related indications, allopecia caused by cytotoxic therapies, and progression of an inflammatory or autoimmune disease.

摘要翻译： 化合物和药物组合物，包括拆分的对映异构体和/或非对映异构体，水合物，盐，溶剂合物及其混合物，具有下式：CORE MOIETY-（R）j在这些化合物中，j是1至3的整数; 核心部分是环核心，环核心是非环状的或至少一个五至七元的非杂环环或杂环; 并且R选自胺，氢，卤素，羟基，取代或未取代的C（1-10）烷基，C（2-10）烯基，环状或杂环基或式I。至少一个具有式 I：式I中，n为4〜20的整数。 并且每个R 1或R 2独立地为氢，取代或未取代的C 1-20烷基，C（1-20）烷氧基，C（2-20）烯基或环状或杂环基。 该化合物可用于治疗或预防例如败血症综合征，造血或器官毒性，癌症，病毒活性，AIDS和AIDS相关适应症，​​由细胞毒性疗法引起的脱发，以及炎性或自身免疫性疾病的进展。

公开(公告)号：US06774130B2

公开(公告)日：2004-08-10

申请号：US09288556

申请日：1999-04-09

申请人： J. Peter Klein ,  Stephen J. Klaus ,  Anil M. Kumar ,  Baoqing Gong

发明人： J. Peter Klein ,  Stephen J. Klaus ,  Anil M. Kumar ,  Baoqing Gong

IPC分类号： A61K31522

CPC分类号： C07D473/04 ,  A61K31/00 ,  C07D473/06 ,  C07D487/04 ,  C07D495/04 ,  C07D513/04

摘要： Novel heterocyclic compounds having a six membered ring structure fused to a five membered ring structure are found to be useful for the treatment and prevention of symptoms or manifestations associated with disorders affected by Interleukin-12 (“IL-12”) intracellular signaling, such as, for example, Th1 cell-mediated disorders. The therapeutic compounds, pharmaceutically acceptable derivatives (e.g., resolved enantiomers, diastereomers, tautomers, salts and solvates thereof) or prodrugs thereof, have the following general formula: Each X, Y and Z are independently selected from a member of the group consisting of C(R3), N, N(R3) and S. Each R1, R2 and R3 is substituted or unsubstituted and is independently selected from a member of the group consisting of hydrogen, halo, oxo, C(1-20)alkyl, C(1-20)hydroxyalkyl, C(1-20)thioalkyl, C(1-20)alkylamino, C(1-20)alkylaminoalkyl, C(1-20)aminoalkyl, C(1-20)aminoalkoxyalkenyl, C(1-20)aminoalkoxyalkynyl, C(1-20)diaminoalkyl, C(1-20)triaminoalkyl, C(1-20)tetraaminoalkyl, C(5-15)aminotrialkoxyamino, C(1-20)alkylamido, C(1-20)alkylamidoalkyl, C(1-20)amidoalkyl, C(1-20)acetamidoalkyl, C(1-20)alkenyl, C(1-20)alkynyl, C(3-8)alkoxyl, C(1-11)alkoxyalkyl, and C(1-20)dialkoxyalkyl.

摘要翻译： 发现具有与五元环结构稠合的六元环结构的新型杂环化合物可用于治疗和预防与受白细胞介素-12（“IL-12”）影响的紊乱相关的症状或表现， ，例如，Th1细胞介导的疾病。 治疗化合物，药学上可接受的衍生物（例如分解的对映异构体，非对映异构体，互变异构体，其盐和溶剂合物）或其前药具有以下通式：每个X，Y和Z独立地选自C （R 3），N，N（R 3）和S.每个R 1，R 2和R 3是取代或未取代的，并且独立地选自氢，卤素，氧代，C（1-20）烷基，C （1-20）羟基烷基，C（1-20）硫代烷基，C（1-20）烷基氨基，C（1-20）烷基氨基烷基，C（1-20）氨基烷基，C（1-20）氨基烷氧羰基，C（1 （1-20）氨基烷基，C（1-20）四氨基烷基，C（5-15）氨基三烷氧基氨基，C（1-20）烷基酰氨基，C（1-20）烷基氨基烷基，C（1-20） ）烷基酰氨基烷基，C（1-20）酰氨基烷基，C（1-20）乙酰氨基烷基，C（1-20）烯基，C（1-20）炔基，C（3-8）烷氧基，C（1-11）烷氧基烷基 ，和C（1-20）二烷氧基烷基。

公开(公告)号：US6075029A

公开(公告)日：2000-06-13

申请号：US2345

申请日：1998-01-02

申请人： J. Peter Klein ,  Anil M. Kumar ,  Paul Woodson

发明人： J. Peter Klein ,  Anil M. Kumar ,  Paul Woodson

IPC分类号： C07D473/04 ,  A61K31/52 ,  C07D473/06 ,  C07D473/10

CPC分类号： C07D473/04

摘要： A new class of xanthine compounds, variously substituted at the 1, 3, 7 and 8 positions, is characterized by an ability to modulate the activity of key enzymes involved in drug metabolism. These compounds generally are useful in affecting drug metabolism and, particularly, in extending the circulating half-life of compounds that are metabolized via P-450-mediated pathways.

摘要翻译： 在1,3,7和8位各种替代的新一类黄嘌呤化合物的特征在于调节参与药物代谢的关键酶的活性的能力。 这些化合物通常可用于影响药物代谢，特别是延长通过P-450介导途径代谢的化合物的循环半衰期。