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 。

公开(公告)号：US20050107445A1

公开(公告)日：2005-05-19

申请号：US10811332

申请日：2004-03-29

申请人： Clare Watkins ,  Maria Rosario Romero-Martin ,  Kathryn Moore ,  James Ritchie ,  Paul Finn ,  Ivars Kalvinsh ,  Einars Loza ,  Klara Dikovska ,  Vija Gailite ,  Maxim Vorona ,  Irina Piskunova ,  Igor Starchenkov ,  Victor Andrianov ,  C. Harris ,  James Duffy

发明人： Clare Watkins ,  Maria Rosario Romero-Martin ,  Kathryn Moore ,  James Ritchie ,  Paul Finn ,  Ivars Kalvinsh ,  Einars Loza ,  Klara Dikovska ,  Vija Gailite ,  Maxim Vorona ,  Irina Piskunova ,  Igor Starchenkov ,  Victor Andrianov ,  C. Harris ,  James Duffy

IPC分类号： A61K31/341 ,  A61K31/403 ,  A61K31/4406 ,  A61P17/06 ,  A61P35/00 ,  A61P43/00 ,  C07C311/06 ,  C07C311/08 ,  C07C311/10 ,  C07C311/13 ,  C07C311/16 ,  C07C311/17 ,  C07C311/19 ,  C07C311/20 ,  C07C311/21 ,  C07C311/29 ,  C07D209/82 ,  C07D209/88 ,  C07D213/40 ,  C07D213/42 ,  C07D213/65 ,  C07D213/71 ,  C07D307/52 ,  C07D317/58 ,  A61K31/44 ,  A61K31/19 ,  A61K31/4015 ,  C07C311/35

CPC分类号： C07D213/40 ,  C07C311/06 ,  C07C311/13 ,  C07C311/16 ,  C07C311/19 ,  C07C311/20 ,  C07C311/21 ,  C07C311/29 ,  C07C2602/08 ,  C07D209/88 ,  C07D213/42 ,  C07D213/65 ,  C07D213/71 ,  C07D307/52 ,  C07D317/58

摘要： This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the following formula: (I) A is an aryl group; Q1 is a covalent bond or an aryl leader group; J is a sulfonamide linkage selected from: —S(═O)2NR1— and —NR1S(═O)2—; R1 is a sulfonamido substituent; and, Q2 is an acid leader group; with the proviso that if J is —S(═O)2NR1—, then Q1 is an aryl leader group; 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, e.g., to inhibit proliferative conditions, such as cancer and psoriasis.

公开(公告)号：US20050143385A1

公开(公告)日：2005-06-30

申请号：US10509732

申请日：2003-04-03

申请人： Clare Watkins ,  Maria-Rosario Romero-Martin ,  James Ritchie ,  Paul Finn ,  Ivars Kalvinsh ,  Einars Loza ,  Klar Dikovska ,  Igor Starchenkov ,  Daina Lolya ,  Vija Gailite

发明人： Clare Watkins ,  Maria-Rosario Romero-Martin ,  James Ritchie ,  Paul Finn ,  Ivars Kalvinsh ,  Einars Loza ,  Klar Dikovska ,  Igor Starchenkov ,  Daina Lolya ,  Vija Gailite

IPC分类号： C07D295/16 ,  A61K31/495 ,  A61K31/496 ,  A61K31/506 ,  A61P17/06 ,  A61P35/00 ,  A61P43/00 ,  C07D209/14 ,  C07D209/16 ,  C07D209/18 ,  C07D209/42 ,  C07D213/36 ,  C07D213/74 ,  C07D239/42 ,  C07D241/04 ,  C07D295/18 ,  C07D295/185 ,  C07D295/192 ,  C07D295/22 ,  C07D295/26 ,  C07D317/58 ,  C07D333/60 ,  C07D43/02

CPC分类号： C07D213/74 ,  C07D239/42 ,  C07D295/185 ,  C07D295/192 ,  C07D295/26 ,  C07D317/58 ,  C07D333/60

摘要： This invention pertains to certain carbamic acid compounds which inhibit HDAC (histone deacetylase) activity of the following formula: wherein: Cy is independently a cyclyl group; Q1 is independently a covalent bond or cyclyl leader group; the piperazin-1,4-diyl group is optionally substituted; J1 is independently a covalent bond or —C(═;O)—; J2 is independently —C(═O)— or —S(═O)2—; Q2 is independently an acid leader group; wherein: Cy is independently: C3-20carbocyclyl, C3-20heterocyclyl, or C5-20aryl; and is optionally substituted; Q1 is independently: a covalent bond; C1-7alkylene; or C1-7alkylene-X—C1-7alkylene, —X—C1-7alkylene, or C1-7alkylene-X—, wherein X is —O— or —S—; and is optionally substituted; Q2 is independently: C4-8alkylene; and is optionally substituted; and has a backbone length of at least 4 atoms; or: Q2 is independently: C5-20arylene; C5-20arylene-C1-7alkylene; C1-7alkylene-C5-20arylene; or, C1-7alkylene-C5-20arylene-C1-7alkylene; and is optionally substituted; and has a backbone length of at least 4 atoms; or a pharmaceutically acceptable salt, solvate, amide, ester, ether, chemically protected form, or prodrug 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.

公开(公告)号：US20050085515A1

公开(公告)日：2005-04-21

申请号：US10953106

申请日：2004-09-30

申请人： Clare Watkins ,  Maria Rosario Romero-Martin ,  Kathryn Moore ,  James Ritchie ,  Paul Finn ,  Ivars Kalvinsh ,  Einars Loza ,  Klara Dikovska ,  Vija Gailite ,  Maxim Vorona ,  Irina Piskunova ,  Igor Starchenkov ,  Victor Andrianov ,  C. John Harris ,  James Duffy

发明人： Clare Watkins ,  Maria Rosario Romero-Martin ,  Kathryn Moore ,  James Ritchie ,  Paul Finn ,  Ivars Kalvinsh ,  Einars Loza ,  Klara Dikovska ,  Vija Gailite ,  Maxim Vorona ,  Irina Piskunova ,  Igor Starchenkov ,  Victor Andrianov ,  C. John Harris ,  James Duffy

IPC分类号： A61K31/341 ,  A61K31/403 ,  A61K31/4406 ,  A61P17/06 ,  A61P35/00 ,  A61P43/00 ,  C07C311/06 ,  C07C311/08 ,  C07C311/10 ,  C07C311/13 ,  C07C311/16 ,  C07C311/17 ,  C07C311/19 ,  C07C311/20 ,  C07C311/21 ,  C07C311/29 ,  C07D209/82 ,  C07D209/88 ,  C07D213/40 ,  C07D213/42 ,  C07D213/65 ,  C07D213/71 ,  C07D307/52 ,  C07D317/58 ,  C07D213/72 ,  A61K31/19 ,  A61K31/40 ,  A61K31/44

CPC分类号： C07D213/40 ,  C07C311/06 ,  C07C311/13 ,  C07C311/16 ,  C07C311/19 ,  C07C311/20 ,  C07C311/21 ,  C07C311/29 ,  C07C2602/08 ,  C07D209/88 ,  C07D213/42 ,  C07D213/65 ,  C07D213/71 ,  C07D307/52 ,  C07D317/58

摘要： This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the following formula: (I) A is an aryl group; Q1 is a covalent bond or an aryl leader group; J is a sulfonamide linkage selected from: —S(═O)2NR1— and —NR1S(═O)2—; R1 is a sulfonamido substituent; and, Q2 is an acid leader group; with the proviso that if J is —S(═O)2NR1—, then Q1 is an aryl leader group; 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, e.g., to inhibit proliferative conditions, such as cancer and psoriasis.

摘要翻译： 本发明涉及抑制HDAC活性的一些活性氨基甲酸化合物，其具有下式：（I）A为芳基; Q 1是共价键或芳基前导基团; J是选自以下的磺酰胺键：-S（-O）2 NR 1 - 和-NR 1 S（-O） _{2 - ; R 1是磺酰胺基取代基; 而Q 2是酸性引导基团; 条件是如果J是-S（-O）2 NR 1 - ，则Q 1是芳基前导基团; 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种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，并且例如抑制增殖性疾病如癌症和牛皮癣。}

公开(公告)号：US20060079528A1

公开(公告)日：2006-04-13

申请号：US10546153

申请日：2004-02-25

申请人： Paul Finn ,  Ivars Kalvinsh ,  Einars Loza ,  Victor Andrianov ,  Olga Habarova ,  Daina Lolya ,  Irina Piskunova

发明人： Paul Finn ,  Ivars Kalvinsh ,  Einars Loza ,  Victor Andrianov ,  Olga Habarova ,  Daina Lolya ,  Irina Piskunova

IPC分类号： A61K31/517 ,  A61K31/502 ,  A61K31/498 ,  A61K31/4745 ,  A61K31/47 ,  C07D471/02

CPC分类号： C07D263/56 ,  C07D215/12 ,  C07D215/14 ,  C07D215/18 ,  C07D215/20 ,  C07D241/42 ,  C07D241/44 ,  C07D277/64

摘要： This invention pertains to certain carbamic acid compounds of the following formula, which inhibit HDAC (histone deacetylase) activity wherein: A is independently an unsubstituted or substituted bicyclic C9-10heteroaryl group (e.g., quinolinyl; quinoxalinyl; benzoxazolyl; benzothiazolyl); Q is an acid leader group, and is independently an unsubstituted or substituted, saturated or unsaturated C17alkylene group having a backbone length of 4 or less; with the proviso that if A is unsubstituted benzothiazol-2-yl, then Q is an unsaturated group; and with the proviso that if A is unsubstituted quinolin-6-yl, then Q is unsubstituted at the a-position; and with the proviso that A is not benzimidazol-2-yl; 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）活性的某些下式的氨基甲酸化合物，其中：A独立地是未取代或取代的双环C 9-10杂芳基（例如，喹啉基;喹喔啉基 ;苯并恶唑基;苯并噻唑基）; Q是酸引导基团，独立地是主链长度为4以下的未取代或取代的，饱和或不饱和的C 17亚烷基; 条件是如果A是未取代的苯并噻唑-2-基，则Q是不饱和基团; 并且条件是如果A是未取代的喹啉-6-基，那么Q在a位是未取代的; 并且条件是A不是苯并咪唑-2-基; 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：US20100311741A1

公开(公告)日：2010-12-09

申请号：US12599855

申请日：2008-05-16

申请人： Aigars Jirgensons ,  Gundars Leitis ,  Ivars Kalvinsh ,  Daniel Robinson ,  Paul Finn ,  Nagma Khan

发明人： Aigars Jirgensons ,  Gundars Leitis ,  Ivars Kalvinsh ,  Daniel Robinson ,  Paul Finn ,  Nagma Khan

IPC分类号： A61K31/5377 ,  C07D275/06 ,  C07D417/10 ,  C07D417/04 ,  C07D513/04 ,  C07D333/52 ,  C12N5/07 ,  A61K31/428 ,  A61K31/426 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4709 ,  A61K31/381 ,  A61K31/437 ,  A61P19/02 ,  A61P29/00 ,  A61P17/06 ,  A61P31/18 ,  A61P35/00 ,  A61P11/06 ,  A61P11/00 ,  A61P1/00 ,  A61P9/04 ,  A61P9/10 ,  A61P3/04 ,  A61P31/00 ,  A61P37/00 ,  A61P25/00 ,  A61P5/48

CPC分类号： C07D417/10 ,  C07D275/06 ,  C07D417/04 ,  C07D417/12

摘要： This invention pertains generally to the field of therapeutic compounds, and more particularly, to certain bicyclosulfonyl acid (BCSA) compounds which act as inhibitors of Tumour Necrosis Factor-α Converting Enzyme (TACE). The compounds are useful in the treatment of conditions mediated by TNF-α, such as rheumatoid arthritis; inflammation; psoriasis; septic shock; graft rejection; cachexia; anorexia; congestive heart failure; post ischaemic reperfusion injury; inflammatory disease of the central nervous system; inflammatory bowel disease; insulin resistance; HIV infection; cancer; chronic obstructive pulmonary disease (COPD); and asthma. 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, in the inhibition of TACE, and in the treatment of conditions that are ameliorated by the inhibition of TACE.

摘要翻译： 本发明一般涉及治疗化合物领域，更具体地涉及作为肿瘤坏死因子-α转化酶（TACE）抑制剂的某些双环磺酰基酸（BCSA）化合物。 该化合物可用于治疗由TNF-α介导的病症，例如类风湿性关节炎; 炎; 银屑病; 败血性休克 移植排斥反应 恶病质 厌食症 充血性心力衰竭; 缺血后再灌注损伤; 中枢神经系统炎症性疾病; 炎症性肠病; 胰岛素抵抗; 艾滋病毒感染; 癌症; 慢性阻塞性肺疾病（COPD）; 和哮喘。 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在抑制TACE中的用途，以及用于治疗通过抑制TACE而改善的病症。

公开(公告)号：US20080113993A1

公开(公告)日：2008-05-15

申请号：US12015208

申请日：2008-01-16

申请人： Jackie DE BELIN ,  Maria-Rosario Romero-Martin ,  Paul Finn ,  Lee Sayers ,  Norman Law ,  David Billington ,  Stephen Ryley ,  Shoumo Bhattacharya

发明人： Jackie DE BELIN ,  Maria-Rosario Romero-Martin ,  Paul Finn ,  Lee Sayers ,  Norman Law ,  David Billington ,  Stephen Ryley ,  Shoumo Bhattacharya

IPC分类号： A61K31/525 ,  A61K31/522 ,  A61K31/515 ,  A61K31/517

CPC分类号： C07D403/06 ,  A61K31/515 ,  A61K31/519 ,  A61K31/522 ,  A61K31/525 ,  C07D239/62 ,  C07D405/06 ,  C07D409/06 ,  C07D409/14 ,  C07D473/06 ,  C07D473/08 ,  C07D487/04

摘要： This invention pertains to active barbituric acid analogs which inhibit HIF-1 activity (e.g., the interaction between HIF-1$g(a) and p300) and thereby inhibit angiogenesis, tumorigenesis, and proliferative conditions, such as cancer. 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 HIF-1 activity, and to inhibit angiogenesis, tumorigenesis, and proliferative conditions, such as cancer.

摘要翻译： 本发明涉及抑制HIF-1活性的活性巴比妥酸类似物（例如，HIF-1 $ g（a）和p300之间的相互作用），从而抑制血管生成，肿瘤发生和增殖性病症如癌症。 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都用于抑制HIF-1活性以及抑制血管生成，肿瘤发生和增殖性疾病如癌症的用途。

公开(公告)号：US20050033178A1

公开(公告)日：2005-02-10

申请号：US10625392

申请日：2003-07-23

申请人： Stefan Assmann ,  Oliver Schreck ,  Paul Finn ,  Stephanie Shors

发明人： Stefan Assmann ,  Oliver Schreck ,  Paul Finn ,  Stephanie Shors

IPC分类号： A61B5/055 ,  A61B5/05

CPC分类号： A61B5/7264 ,  A61B5/055

摘要： In a method and apparatus for classifying plaque in a blood vessel of a living subject using magnetic resonance imaging, a first magnetic resonance image is produced with a first intensity distribution of a cross-section of a vessel containing plaque, and a contrast agent is injected into the vascular system and a second magnetic resonance image of the cross-section of the vessel is produced with a second intensity distribution after a first time duration following the contrast agent injection, and a third magnetic resonance image of the cross-section of the vessel is produced with a third intensity distribution after a second time duration following the injection of the contrast agent, and the plaque is classified dependent on the respective intensity distributions of the magnetic resonance images.

摘要翻译： 在使用磁共振成像对生物体的血管分类斑块的方法和装置中，以包含斑块的血管的横截面的第一强度分布产生第一磁共振图像，并注射造影剂 进入血管系统，并且在造影剂注射之后的第一时间段之后以第二强度分布产生血管横截面的第二磁共振图像，以及血管横截面的第三磁共振图像 在注射造影剂之后的第二持续时间之后产生具有第三强度分布，并且根据磁共振图像的各自的强度分布对斑块进行分类。

公开(公告)号：US07328056B2

公开(公告)日：2008-02-05

申请号：US10625392

申请日：2003-07-23

申请人： Stefan Assmann ,  Oliver Schreck ,  Paul Finn ,  Stephanie Shors

发明人： Stefan Assmann ,  Oliver Schreck ,  Paul Finn ,  Stephanie Shors

IPC分类号： A61B5/05

CPC分类号： A61B5/7264 ,  A61B5/055

摘要： In a method and apparatus for classifying plaque in a blood vessel of a living subject using magnetic resonance imaging, a first magnetic resonance image is produced with a first intensity distribution of a cross-section of a vessel containing plaque, and a contrast agent is injected into the vascular system and a second magnetic resonance image of the cross-section of the vessel is produced with a second intensity distribution after a first time duration following the contrast agent injection, and a third magnetic resonance image of the cross-section of the vessel is produced with a third intensity distribution after a second time duration following the injection of the contrast agent, and the plaque is classified dependent on the respective intensity distributions of the magnetic resonance images.

摘要翻译： 在使用磁共振成像对生物体的血管分类斑块的方法和装置中，以包含斑块的血管的横截面的第一强度分布产生第一磁共振图像，并注射造影剂 进入血管系统，并且在造影剂注射之后的第一个持续时间之后以第二强度分布产生血管横截面的第二磁共振图像，以及血管横截面的第三磁共振图像 在注射造影剂之后的第二持续时间之后产生具有第三强度分布，并且根据磁共振图像的各自的强度分布对斑块进行分类。