公开(公告)号：US07465719B2

公开(公告)日：2008-12-16

申请号：US10542281

申请日：2004-01-19

申请人： Paul W. Finn ,  Ivars Kalvinsh ,  Einars Loza ,  Aleksandrs Gutcaits ,  Irena Olutnika ,  Ludmila Serpionova ,  Vija Gailite ,  Rasma Bokaldere

发明人： Paul W. Finn ,  Ivars Kalvinsh ,  Einars Loza ,  Aleksandrs Gutcaits ,  Irena Olutnika ,  Ludmila Serpionova ,  Vija Gailite ,  Rasma Bokaldere

IPC分类号： A61K31/55 ,  A61K31/445

CPC分类号： C07C251/48 ,  C07C259/10 ,  C07C2601/08 ,  C07C2601/14 ,  C07D211/32

摘要： This invention pertains to certain carbamic acid compounds of the formula (I), which inhibit HDAC (histone deacetylase) activity: wherein: J is a linking functional group and is independently:—O —C(═O)— or —C(═O)—O — or —C(═O)—; Cy is a cyclyl group and is independently: C3-20carbocyclyl, C3-20heterocyclyl, or C5-20aryl; and is optionally substituted; Q1 is a cyclyl leader group, and is independently a divalent bidentate group obtained by removing two hydrogen atoms from a ring carbon atom of a saturated monocyclic hydrocarbon having from 4 to 7 ring atoms, or by removing two hydrogen atoms from a ring carbon atom of saturated monocyclic heterocyclic compound having from 4 to 7 ring atoms including 1 nitrogen ring atom or 1 oxygen ring atom; and is optionally substituted; Q2 is an acid leader group, and is independently: C1-8alkylene; and is optionally substituted; or: Q2 is an acid leader group, and is independently: C5-20arylene; C5-20arylene-C1-7alkylene; C1-7alkylene-C5-20arylene; or C1-7alkylene-C5-20aryleneC1-7alkylene; and is optionally substituted; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC,and in the treatment of conditions mediated by HDAC, cancer, proliferative conditions, psoriasis, etc.

摘要翻译： 本发明涉及抑制HDAC（组蛋白脱乙酰酶）活性的某些式（I）的氨基甲酸化合物：其中：J为连接官能团，独立地为：-O-C（-O） - 或-C（ - O - ） - 或-C（ - O） - ; Cy是环状基团，独立地为：C 3-20碳环基，C 3-20杂环基或C 5-20芳基; 并且任选被取代; Q1是环状前导基团，并且独立地是通过从具有4至7个环原子的饱和单环烃的环碳原子中除去两个氢原子或通过从环碳原子中除去两个氢原子而获得的二价二齿基团 具有4至7个环原子的饱和单环杂环化合物，包括1个氮环原子或1个氧环原子; 并且任选被取代; Q2是酸性引导基团，独立地为：C1-8亚烷基; 并且任选被取代; 或：Q2是酸性引导基团，独立地为：C5-20亚芳基; C 5-20芳基-C 1-7亚烷基; C 1-7亚烷基-C 5 - 亚芳基; 或C 1-7亚烷基-C 5-20亚芳基C 1-7亚烷基; 并且任选被取代; 和其药学上可接受的盐，溶剂合物，酰胺，酯，醚，化学保护形式及其前药。 本发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物在体外和体内的用途，以抑制HDAC，以及治疗由HDAC，癌症，增殖性病症，牛皮癣等介导的病症 。

公开(公告)号：US20060058282A1

公开(公告)日：2006-03-16

申请号：US10542281

申请日：2004-01-19

申请人： Paul Finn ,  Ivars Kalvinsh ,  Einars Loza ,  Aleksandrs Gutcaits ,  Irena Olutnika ,  Ludmila Serpionova ,  Vija Gailite ,  Rasma Bokaldere

发明人： Paul Finn ,  Ivars Kalvinsh ,  Einars Loza ,  Aleksandrs Gutcaits ,  Irena Olutnika ,  Ludmila Serpionova ,  Vija Gailite ,  Rasma Bokaldere

IPC分类号： A61K31/55 ,  A61K31/445 ,  A61K31/40 ,  A61K31/397

CPC分类号： C07C251/48 ,  C07C259/10 ,  C07C2601/08 ,  C07C2601/14 ,  C07D211/32

摘要： This invention pertains to certain carbamic acid compounds of the formula (I), which inhibit HDAC (histone deacetylase) activity: wherein: J is a linking functional group and is independently: —O—C(═O)— or —C(═O)—O— or —C(═O)—; Cy is a cyclyl group and is independently: C3-20carbocyclyl, C3-20heterocyclyl, or C5-20aryl; and is optionally substituted; Q1 is a cyclyl leader group, and is independently a divalent bidentate group obtained by removing two hydrogen atoms from a ring carbon atom of a saturated monocyclic hydrocarbon having from 4 to 7 ring atoms, or by removing two hydrogen atoms from a ring carbon atom of saturated monocyclic heterocyclic compound having from 4 to 7 ring atoms including 1 nitrogen ring atom or 1 oxygen ring atom; and is optionally substituted; Q2 is an acid leader group, and is independently: C1-8alkylene; and is optionally substituted; or: Q2 is an acid leader group, and is independently: C5-20arylene; C5-20arylene-C1-7alkylene; C1-7alkylene-C5-20arylene; or C1-7alkylene-C5-20arylene-C1-7alkylene; and is optionally substituted; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC, and in the treatment of conditions mediated by HDAC, cancer, proliferative conditions, psoriasis, etc.

摘要翻译： 本发明涉及抑制HDAC（组蛋白脱乙酰酶）活性的某些式（I）氨基甲酸化合物：其中：J为连接官能团，独立地为-OC（-O） - 或-C（-O） -O-或-C（-O） - ; Cy是环基，并且独立地为：C 3-20碳环基，C 3-20杂环基或C 5-20芳基; 并且任选被取代; Q 1是环状前导基团，独立地是通过从具有4至7个环原子的饱和单环烃的环碳原子除去两个氢原子而获得的二价二齿基团，或者通过除去两个 具有4至7个环原子的饱和单环杂环化合物的环碳原子包括1个氮环原子或1个氧环原子的氢原子; 并且任选被取代; Q 2是酸前导基团，独立地是：C 1-8烷基; 并且任选被取代; 或：Q 2是酸前导基团，并且独立地为：C 5〜20亚芳基; C 5〜20亚芳基-C 1-7亚烷基; C 1-7亚烷基-C 5-20亚芳基; 或C 1-7亚烷基-C 5 - 亚芳基-C 1-7亚烷基; 并且任选被取代; 和其药学上可接受的盐，溶剂合物，酰胺，酯，醚，化学保护形式及其前药。 本发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物在体外和体内的用途，以抑制HDAC，以及治疗由HDAC，癌症，增殖性病症，牛皮癣等介导的病症 。