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公开(公告)号：US6043250A
公开(公告)日：2000-03-28
申请号：US472296
申请日：1995-06-07
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。
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公开(公告)号：US5837703A
公开(公告)日：1998-11-17
申请号：US152650
申请日：1993-11-12
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。
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公开(公告)号：US5807862A
公开(公告)日：1998-09-15
申请号：US478112
申请日：1995-06-07
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。
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公开(公告)号：US5629423A
公开(公告)日：1997-05-13
申请号：US449400
申请日：1995-05-23
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。
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公开(公告)号：US5780476A
公开(公告)日：1998-07-14
申请号：US468660
申请日：1995-06-06
申请人： Gail E. Underiner , David Porubek , J. Peter Klein , Paul Woodson
发明人： Gail E. Underiner , David Porubek , J. Peter Klein , Paul Woodson
IPC分类号： A61K31/519 , A61K31/522 , A61K31/52 , C07D473/04
CPC分类号： A61K31/522 , A61K31/519
摘要： Disclosed are therapeutic compounds having the formula: (R)j - (core moiety), including resolved enantiomers, diastereomers, hydrates, salts, solvates and mixtures thereof. j is an integer from one to three, the core moiety is either non-cyclic or comprises at least one five- to seven-membered ring structure, R may be selected from the group consisting of hydrogen, halogen, hydroxyl, amino, substituted or unsubstituted benzyl, C.sub.1-6 alkyl or C.sub.1-6 alkenyl, and at least one R has the formula I: ##STR1## n is an integer from seven to twenty and at least one of X or Y is --OH. The other of X or Y, which is not --OH, is hydrogen, CH.sub.3 --, CH.sub.3 --CH.sub.2 --, CH.sub.3 --(CH.sub.2).sub.2 -- or (CH.sub.3).sub.2 --CH.sub.2 --, and each W.sub.1, W.sub.2, and W.sub.3 is independently hydrogen, CH.sub.3 --, CH.sub.3 --CH.sub.2 --, CH.sub.3 --(CH.sub.2).sub.2 -- or (CH.sub.3).sub.2 --CH.sub.2 --. The X, Y, W.sub.1, W.sub.2, or W.sub.3 alkyl groups may be unsubstituted or substituted by an hydroxyl, halo or dimethylamino group. The disclosed compounds and therapeutic compositions thereof are useful in treating individuals having a disease or treatment-induced toxicity, mediated by second messenger activity.
摘要翻译： 公开了具有下式的治疗化合物：（R）j-（核心部分），包括拆分的对映异构体，非对映体，水合物，盐，溶剂合物及其混合物。 j是1至3的整数，核心部分是非环状的或包含至少一个五至七元环结构，R可以选自氢，卤素，羟基，氨基，取代或 未取代的苄基，C 1-6烷基或C 1-6烯基，并且至少一个R具有式I：I是7至20的整数，X或Y中的至少一个是-OH。 不是-OH的X或Y中的另一个是氢，CH 3 - ，CH 3 -CH 2 - ，CH 3 - （CH 2）2 - 或（CH 3）2 -CH 2 - ，并且每个W 1，W 2和W 3独立地 氢，CH 3 - ，CH 3 -CH 2 - ，CH 3 - （CH 2）2 - 或（CH 3）2 -CH 2 - 。 X，Y，W1，W2或W3烷基可以是未取代的或被羟基，卤素或二甲基氨基取代。 所公开的化合物及其治疗组合物可用于治疗由第二信使活性介导的患有疾病或治疗诱导的毒性的个体。
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公开(公告)号：US5817662A
公开(公告)日：1998-10-06
申请号：US468656
申请日：1995-06-06
IPC分类号： A61K31/522 , A61K31/52
CPC分类号： A61K31/522 , Y10S424/824 , Y10S424/825
摘要： Compounds and pharmaceutical compositions thereof comprise the formula: (R)j-(core moiety), including resolved enantiomers and/or diastereomers, hydrates, salts, solvates and mixtures thereof, wherein J is an integer from one to three, the core moiety is non-cyclic or comprises at least one, five- to seven-membered ring structure, R may be selected from the group consisting of hydrogen, halogen, hydroxyl, amino, substituted or unsubstituted benzyl, alkyl (C.sub.1-6) or alkenyl (C.sub.1-6), and at least one R has the formula I: ##STR1## wherein n is an integer from four to eighteen; each R'.sub.1 and R'.sub.2 is independently hydrogen, alkyl (C.sub.1-4) or alkenyl (C.sub.1-4), the alkyl or alkenyl groups being preferably substituted by a halogen, hydroxyl, ketone or dimethylamino group and/or may be interrupted by an oxygen or hydrogen atom or an alkyl (C.sub.1-4) group; and each R'.sub.3 and R'.sub.4 is independently hydrogen or methyl. Preferably, n is an integer from six to ten, R'.sub.1 and R'.sub.2 are independently hydrogen or methyl and R'.sub.3 and R'.sub.4 are hydrogen. The compounds are useful in treating or preventing, for example, sepsis syndrome, hematopoietic or organ toxicity, baldness, hair loss or allopecia caused by cytotoxic therapies, and progression of an inflammatory or autoimmune disease.
摘要翻译： 化合物及其药物组合物包含式（R）j-（核心部分），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J为1至3的整数，核心部分为 非环状或包含至少一个五元至七元环结构，R可以选自氢，卤素，羟基，氨基，取代或未取代的苄基，烷基（C 1-6）或烯基（C 1 -6），并且至少一个R具有式I：其中n是从4到18的整数; 每个R'1和R'2独立地是氢，烷基（C1-4）或烯基（C1-4），烷基或烯基优选被卤素，羟基，酮或二甲基氨基取代和/或可被中断 通过氧或氢原子或烷基（C 1-4）基团; 并且每个R'3和R'4独立地是氢或甲基。 优选地，n是6至10的整数，R'1和R'2独立地是氢或甲基，R'3和R'4是氢。 该化合物可用于治疗或预防例如败血症综合症，造血或器官毒性，秃发，由细胞毒性治疗引起的脱发或脱发，以及炎性或自身免疫性疾病的进展。
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17.发明授权Therapeutic compounds containing a monocyclic five- to six- membered ring structure having one to two nitrogen atoms 失效含有1至2个氮原子的单环五至六元环结构的治疗化合物
公开(公告)号：US5804584A
公开(公告)日：1998-09-08
申请号：US468659
申请日：1995-06-06
申请人： Gail E. Underiner , David Porubek , J. Peter Klein , Paul Woodson
发明人： Gail E. Underiner , David Porubek , J. Peter Klein , Paul Woodson
IPC分类号： A61K31/519 , A61K31/522 , C07D239/54 , A61K31/52
CPC分类号： A61K31/522 , A61K31/519
摘要： Disclosed are therapeutic compounds having the formula: (R)j-(core moiety), including resolved enantiomers, diastereomers, hydrates, salts, solvates and mixtures thereof. j is an integer from one to three, the core moiety is either non-cyclic or comprises at least one five- to seven-membered ring structure, R may be selected from the group consisting of hydrogen, halogen, hydroxyl, amino, substituted or unsubstituted benzyl, C.sub.1-6 alkyl or C.sub.1-6 alkenyl, and at least one R has the formula I: ##STR1## n is an integer from seven to twenty and at least one of X or Y is --OH. The other of X or Y, which is not --OH, is hydrogen, CH.sub.3 --, CH.sub.3 --CH.sub.2 --, CH.sub.3 --(CH.sub.2).sub.2 -- or (CH.sub.3).sub.2 --CH.sub.2 --, and each W.sub.1, W.sub.2, and W.sub.3 is independently hydrogen, CH.sub.3 --, CH.sub.3 --CH.sub.2 --, CH.sub.3 --(CH.sub.2).sub.2 -- or (CH.sub.3).sub.2 --CH.sub.2 --. The X, Y, W.sub.1, W.sub.2, or W.sub.3 alkyl groups may be unsubstituted or substituted by an hydroxyl, halo or dimethylamino group. The disclosed compounds and therapeutic compositions thereof are useful in treating individuals having a disease or treatment-induced toxicity, mediated by second messenger activity.
摘要翻译： 公开了具有下式的治疗化合物：（R）j-（核心部分），包括拆分的对映异构体，非对映体，水合物，盐，溶剂合物及其混合物。 j是1至3的整数，核心部分是非环状的或包含至少一个五至七元环结构，R可以选自氢，卤素，羟基，氨基，取代或 未取代的苄基，C 1-6烷基或C 1-6烯基，并且至少一个R具有式I：I是7至20的整数，X或Y中的至少一个是-OH。 不是-OH的X或Y中的另一个是氢，CH 3 - ，CH 3 -CH 2 - ，CH 3 - （CH 2）2 - 或（CH 3）2 -CH 2 - ，并且每个W 1，W 2和W 3独立地 氢，CH 3 - ，CH 3 -CH 2 - ，CH 3 - （CH 2）2 - 或（CH 3）2 -CH 2 - 。 X，Y，W1，W2或W3烷基可以是未取代的或被羟基，卤素或二甲基氨基取代。 所公开的化合物及其治疗组合物可用于治疗由第二信使活性介导的患有疾病或治疗诱导的毒性的个体。
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公开(公告)号：US5470878A
公开(公告)日：1995-11-28
申请号：US164081
申请日：1993-12-08
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 , A61K31/20 , C07C233/00
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-(non-cyclic core moiety),j being an integer from one to three, the core moiety is non-cyclic and X is 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 alkane or alkene 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 alkoxy. 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 alkane or alkene 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 alkoxy, 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 hydroxy group.
摘要翻译： 治疗化合物具有下式：（X）j-（非环核心部分），j为1至3的整数，核心部分为非环状，X为外消旋混合物，R或S对映异构体，溶剂合物，水合物 或其盐：C是手性碳原子，n是1-4的整数（优选1至3），（CH 2）n的一个或多个碳原子可被酮或羟基取代 组，m是从1到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烃或烯烃，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，R 5上的取代基是羟基，氯，氟，溴或C 1-6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，治疗性化合物也可以具有下式：R 4是氢，长或多至八个碳原子的直链或支链烷烃或烯烃， - （CH 2）w R 5，w是2至14的整数， R5是一个，二或三取代或未取代的芳基，R 5上的取代基是羟基，氯，氟，溴或C 1-6烷氧基，或取代或未取代的饱和或不饱和杂环基， 八个碳原子。 r和s独立为从1到4的整数，并且（r + s）不大于5。 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。
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公开(公告)号：US6133274A
公开(公告)日：2000-10-17
申请号：US756703
申请日：1996-11-26
申请人： Gail E. Underiner , David Porubek , J. Peter Klein , Paul Woodson
发明人： Gail E. Underiner , David Porubek , J. Peter Klein , Paul Woodson
IPC分类号： A61K31/519 , A61K31/522 , C07D473/04 , A61K31/52
CPC分类号： A61K31/522 , A61K31/519
摘要： Disclosed are therapeutic compounds having the formula:(R)j-(core moiety),including resolved enantiomers, diastereomers, hydrates, salts, solvates and mixtures thereof. j is an integer from one to three, the core moiety is either non-cyclic or comprises at least one five- to seven-membered ring structure, R may be selected from the group consisting of hydrogen, halogen, hydroxyl, amino, substituted or unsubstituted benzyl, C.sub.1-6 alkyl or C.sub.1-6 alkenyl, and at least one R has the formula I: ##STR1## n is an integer from seven to twenty and at least one of X or Y is --OH. The other of X or Y, which is not --OH, is hydrogen, CH.sub.3 --, CH.sub.3 --CH.sub.2 --, CH.sub.3 --(CH.sub.2).sub.2 -- or (CH.sub.3).sub.2 --CH.sub.2 --, and each W.sub.1, W.sub.2, and W.sub.3 is independently hydrogen, CH.sub.3 --, CH.sub.3 --CH.sub.2 --, CH.sub.3 --(CH.sub.2).sub.2 -- or (CH.sub.3).sub.2 --CH.sub.2 --. The X, Y, W.sub.1, W.sub.2, or W.sub.3 alkyl groups may be unsubstituted or substituted by an hydroxyl, halo or dimethylamino group. The disclosed compounds and therapeutic compositions thereof are useful in treating individuals having a disease or treatment-induced toxicity, mediated by second messenger activity.
摘要翻译： 公开了具有下式的治疗化合物：（R）j-（核心部分），包括拆分的对映异构体，非对映体，水合物，盐，溶剂合物及其混合物。 j是1至3的整数，核心部分是非环状的或包含至少一个五至七元环结构，R可以选自氢，卤素，羟基，氨基，取代或 未取代的苄基，C 1-6烷基或C 1-6烯基，并且至少一个R具有式I：n是7至20的整数，X或Y中的至少一个是-OH。 不是-OH的X或Y中的另一个是氢，CH 3 - ，CH 3 -CH 2 - ，CH 3 - （CH 2）2 - 或（CH 3）2 -CH 2 - ，并且每个W 1，W 2和W 3独立地 氢，CH 3 - ，CH 3 -CH 2 - ，CH 3 - （CH 2）2 - 或（CH 3）2 -CH 2 - 。 X，Y，W1，W2或W3烷基可以是未取代的或被羟基，卤素或二甲基氨基取代。 所公开的化合物及其治疗组合物可用于治疗由第二信使活性介导的患有疾病或治疗诱导的毒性的个体。
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公开(公告)号：US5889011A
公开(公告)日：1999-03-30
申请号：US884037
申请日：1997-06-27
IPC分类号： A61K31/522 , C07D473/00 , A61K31/52
CPC分类号： A61K31/522 , Y10S424/824 , Y10S424/825
摘要： Compounds and pharmaceutical compositions thereof comprise the formula:(R)j- (core moiety),including resolved enantiomers and/or diastereomers, hydrates, salts, solvates and mixtures thereof, wherein J is an integer from one to three, the core moiety is non-cyclic or comprises at least one, five- to seven-membered ring structure, R may be selected from the group consisting of hydrogen, halogen, hydroxyl, amino, substituted or unsubstituted benzyl, alkyl (C.sub.1-6) or alkenyl (C.sub.1-6), and at least one R has the formula I: ##STR1## wherein n is an integer from four to eighteen; each R'.sub.1 and R'.sub.2 is independently hydrogen, alkyl (C.sub.1-4) or alkenyl (C.sub.1-4), the alkyl or alkenyl groups being preferably substituted by a halogen, hydroxyl, ketone or dimethylamino group and/or may be interrupted by an oxygen or hydrogen atom or an alkyl (C.sub.1-4) group; and each R'.sub.3 and R'.sub.4 is independently hydrogen or methyl. Preferably, n is an integer from six to ten, R'.sub.1 and R'.sub.2 are independently hydrogen or methyl and R'.sub.3 and R'.sub.4 are hydrogen. The compounds are useful in treating or preventing, for example, sepsis syndrome, hematopoietic or organ toxicity, baldness, hair loss or allopecia caused by cytotoxic therapies, and progression of an inflammatory or autoimmune disease.
摘要翻译： 化合物及其药物组合物包含式（R）j-（核心部分），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J为1至3的整数，核心部分为 非环状或包含至少一个五元至七元环结构，R可以选自氢，卤素，羟基，氨基，取代或未取代的苄基，烷基（C 1-6）或烯基（C 1 -6），并且至少一个R具有式I：其中n是从4到18的整数; 每个R'1和R'2独立地是氢，烷基（C1-4）或烯基（C1-4），烷基或烯基优选被卤素，羟基，酮或二甲基氨基取代和/或可被中断 通过氧或氢原子或烷基（C 1-4）基团; 并且每个R'3和R'4独立地是氢或甲基。 优选地，n是6至10的整数，R'1和R'2独立地是氢或甲基，R'3和R'4是氢。 该化合物可用于治疗或预防例如败血症综合症，造血或器官毒性，秃发，由细胞毒性治疗引起的脱发或脱发，以及炎性或自身免疫性疾病的进展。
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