(4R)-thiazolidine-4-carboxamide hydrochloride

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (4R)-thiazolidine-4-carboxamide hydrochloride
• 英文别名: (4R)-1,3-thiazolidine-4-carboxamide hydrochloride；(4R)-thiazolidine-4-carbamide hydrochloride；(4R)-1,3-thiazolidine-4-carboxamide;hydrochloride
• 化学式: C₄H₈N₂OS*ClH
• 分子量: 168.647
• InChiKey: SWTCRXVGKJOXJA-DFWYDOINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.44
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  80.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  氯乙酰氯 、 (4R)-thiazolidine-4-carboxamide hydrochloride 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 (4R)-3-(氯乙酰基)-1,3-噻唑烷-4-甲酰胺
  参考文献：
  名称：

  WO2007/113634

  摘要：

  公开号：
• 作为产物：
  描述：

  tert-butyl (R)-4-carbamoylthiazolidine-3-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 以99%的产率得到(4R)-thiazolidine-4-carboxamide hydrochloride
  参考文献：
  名称：

  4-cyanothiazolidides as very potent, stable inhibitors of dipeptidyl peptidase IV

  摘要：

  A series of stable, very potent inhibitors of dipeptidyl peptidase IV has been developed. A number of dipeptide analogues, incorporating a 4-cyanothiazolidide were found to have K-i values of less than 1 nM versus human DP-IV and half-lives of between 5 and 27h in aqueous solution (pH 7.4). Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/s0960-894x(96)00491-x

文献信息

• NITROGEN-CONTAINING COMPOUNDS
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1535906A1

  公开（公告）日：2005-06-01

  A compound represented by formula (I); wherein ring A represents a nitrogen containing heterocyclic ring, ring B represents 5-membered heterocyclic ring which may have substituents, R represents a hydrogen atom or cyano and the other symbols represent as described in the specification; or a salt thereof. The compound represented by formula (I) has an inhibitory activity of DPP-IV, and therefore is useful as a preventive and/or treatment agent for type 2 diabetes mellitus, obesity, autoimmune disease, cancer metastasis, AIDS virus infection, dermatosis, prostatic hypertrophy and the like

  公式（I）所代表的化合物； 其中环A代表含氮的杂环，环B代表可能具有取代基的5-成员杂环，R代表氢原子或氰基，其他符号如规范中所述；或其盐。公式（I）所代表的化合物具有DPP-IV的抑制活性，因此可用作2型糖尿病、肥胖症、自身免疫疾病、癌转移、艾滋病毒感染、皮肤病、前列腺肥大等的预防和/或治疗剂。
• Inhibitors of dipeptidyl peptidase IV
  申请人：——

  公开号：US20040082497A1

  公开（公告）日：2004-04-29

  Compounds according to formula (1), wherein R 1 is H or CN, X 1 is S, O, SO 2 or CH 2 , X 2 is CO, CH 2 or a covalent bond, Het is a nitrogen-containing heterocycle and n is 1-5 are new. The compounds of the invention are inhibitors of dipeptidyl peptidase IV. Pharmaceutical compositions of the compounds of the invention, or pharmaceutically acceptable salts thereof, are useful in the treatment of, inter alia, type 2 diabetes. 1

  根据公式（1），其中R1为H或CN，X1为S、O、SO2或CH2，X2为CO、CH2或共价键，Het为含氮杂环，n为1-5的化合物是新的。本发明的化合物是二肽基肽酶IV的抑制剂。本发明的化合物的药物组合物或其药用盐在治疗2型糖尿病等疾病中是有用的。
• Novel dipeptidyl peptidase iv (dp-iv) inhibitors as anti-diabetic agents
  申请人：Evans M David

  公开号：US20050004205A1

  公开（公告）日：2005-01-06

  The present invention relates to a series of prodrugs of inhibitors of DP-IV with improved properties. The compounds can be used for the treatment of a number of human diseases, including impaired glucose tolerance and type II diabetes. The compounds of the invention are described by general formula (1); wherein R 1 is H or CN; R 2 is selected from CH 2 R 5 , CH 2 CH 2 R 5 and C(R 3 )(R 4 )—X 2 —(CH 2 ) a R 5 ; R 3 and R 4 are each independently selected from H and Me; R 5 is selected from CON(R 6 )(R 7 ), N(R 8 )C(=0)R 9 , N(R 8 )C(═S)R 9 , N(R 8 )SO 2 R 10 and N(R 8 )R 10 ; R 6 and R 7 are each independently R 11 (CH 2 ) b or together they are —(CH 2 ) 2 -Z-(CH 2 ) 2 — or CH 2 -o-C 6 H 4 -Z-CH 2 —; R 8 is H or Me; R 9 is selected from R 11 (CH 2 ) b , R 11 (CH 2 ) b O and N(R 6 )(R 7 ); R 10 is R 11 (CH 2 ) b ; R 11 is selected from H, alkyl, optionally substituted aryl, optionally substituted aroyl, optionally substituted arylsulphonyl and optionally substituted heteroaryl; R 12 is selected from H 2 NCH(R 13 )CO, H 2 NCH(R 14 )CONHCH(R 15 )CO, C(R 16 )═C(R 17 )COR 18 and R 19 OCO; R 13 , R 14 and R 15 are selected from the side chains of the proteinaceous amino acids; R 16 is selected from H, lower alkyl (C 1 -C 6 ) and phenyl; R 17 is selected from H and lower alkyl (C 1 -C 6 ); R 18 is selected from H, lower alkyl (C 1 -C 6 ), OH, O-(lower alkyl (C 1 -C 6 )) and phenyl; R 19 is selected from lower alkyl (C 1 -C 6 ), optionally substituted phenyl and R 20 C(=0)OC(R 21 )(R 22 ); R 20 , R 21 and R 22 are each independently selected from H and lower alkyl (C 1 -C 6 ); Z is selected from a covalent bond, —(CH 2 ) c —, —O—, —SO d — and —N(R 10 )—; X 1 is S or CH 2 ; X 2 is O, S or CH 2 ; a is 1, 2 or 3; b is 0-3; c is 1 or 2; and d is 0, 1 or 2.

  本发明涉及一系列具有改进性能的DP-IV抑制剂的前药。这些化合物可用于治疗多种人类疾病，包括糖耐量受损和2型糖尿病。该发明的化合物由通式（1）描述；其中，R1为H或CN；R2选自CH2R5，CH2CH2R5和C（R3）（R4）-X2-（CH2）aR5；R3和R4各自独立地选自H和Me；R5选自CON（R6）（R7），N（R8）C（=0）R9，N（R8）C（═S）R9，N（R8）SO2R10和N（R8）R10；R6和R7各自独立地为R11（CH2）b，或者它们为-（CH2）2-Z-（CH2）2-或CH2-o-C6H4-Z-CH2-；R8为H或Me；R9选自R11（CH2）b，R11（CH2）bO和N（R6）（R7）；R10选自R11（CH2）b；R11选自H，烷基，可选择取代的芳基，可选择取代的酰芳基，可选择取代的芳基磺酰基和可选择取代的杂环芳基；R12选自H2NCH（R13）CO，H2NCH（R14）CONHCH（R15）CO，C（R16）═C（R17）COR18和R19OCO；R13，R14和R15选自蛋白质氨基酸的侧链；R16选自H，低烷基（C1-C6）和苯基；R17选自H和低烷基（C1-C6）；R18选自H，低烷基（C1-C6），OH，O-（低烷基（C1-C6））和苯基；R19选自低烷基（C1-C6），可选择取代的苯基和R20C（=0）OC（R21）（R22）；R20，R21和R22各自独立地选自H和低烷基（C1-C6）；Z选自共价键，-（CH2）c-，-O-，-SOd-和-N（R10）-；X1为S或CH2；X2为O，S或CH2；a为1、2或3；b为0-3；c为1或2；d为0、1或2。
• Dipeptidyl peptidase IV (DP-IV) inhibitors as anti-diabetic agents
  申请人：Ferring B.V.

  公开号：US07144886B2

  公开（公告）日：2006-12-05

  The present invention relates to a series of prodrugs of inhibitors of DP-IV with improved properties. The compounds can be used for the treatment of a number of human diseases, including impaired glucose tolerance and type II diabetes. The compounds of the invention are described by general formula (1); wherein R1 is H or CN; R2 is selected from CH2R5, CH2CH2R5 and C(R3)(R4)—X2—(CH2)aR5; R3 and R4 are each independently selected from H and Me; R5 is selected from CON(R6)(R7), N(R8)C(═O)R9, N(R8)C(═S)R9, N(R8)SO2R10 and N(R8)R10; R6 and R7 are each independently R11(CH2)b or together they are —(CH2)2—Z—(CH2)2— or CH2—o—C6H4—Z—CH2—; R8 is H or Me; R9 is selected from R11(CH2)b, R11(CH2)bO and N(R6)(R7); R10 is R11(CH2)b; R11 is selected from H, alkyl, optionally substituted aryl, optionally substituted aroyl, optionally substituted arylsulphonyl and optionally substituted heteroaryl; R12 is selected from H2NCH(R13)CO, H2NCH(R14)CONHCH(R15)CO, C(R16)═C(R17)COR18 and R19OCO; R13, R14 and R15 are selected from the side chains of the proteinaceous amino acids; R16 is selected from H, lower alkyl (C1–C6) and phenyl; R17 is selected from H and lower alkyl (C1–C6); R18 is selected from H, lower alkyl (C1–C6), OH, O-(lower alkyl (C1–C6)) and phenyl; R19 is selected from lower alkyl (C1–C6), optionally substituted phenyl and R20C(═O)OC(R21)(R22); R20, R21 and R22 are each independently selected from H and lower alkyl (C1–C6); Z is selected from a covalent bond, —(CH2)c—, —O—, —SOd— and —N(R10)—; X1 is S or CH2; X2 is O, S or CH2; a is 1, 2 or 3; b is 0–3; c is 1 or 2; and d is 0, 1 or 2.

  本发明涉及一系列DP-IV抑制剂的前药，具有改善的性能。这些化合物可用于治疗多种人类疾病，包括糖耐量受损和2型糖尿病。本发明的化合物由通式（1）描述；其中R1为H或CN；R2从CH2R5，CH2CH2R5和C（R3）（R4）-X2-（CH2）aR5中选择；R3和R4各自独立地选自H和Me；R5从CON（R6）（R7），N（R8）C（═O）R9，N（R8）C（═S）R9，N（R8）SO2R10和N（R8）R10中选择；R6和R7各自独立地为R11（CH2）b或在一起它们是-（CH2）2-Z-（CH2）2-或CH2-o-C6H4-Z-CH2-；R8为H或Me；R9从R11（CH2）b，R11（CH2）bO和N（R6）（R7）中选择；R10为R11（CH2）b；R11从H，烷基，可选取代芳基，可选取代芳酰基，可选取代芳基磺酰基和可选取代杂环芳基中选择；R12从H2NCH（R13）CO，H2NCH（R14）CONHCH（R15）CO，C（R16）═C（R17）COR18和R19OCO中选择；R13，R14和R15从蛋白质氨基酸的侧链中选择；R16从H，低烷基（C1-C6）和苯基中选择；R17从H和低烷基（C1-C6）中选择；R18从H，低烷基（C1-C6），OH，O-（低烷基（C1-C6））和苯基中选择；R19从低烷基（C1-C6），可选取代苯基和R20C（═O）OC（R21）（R22）中选择；R20，R21和R22各自独立地选自H和低烷基（C1-C6）；Z从共价键，-（CH2）c-，-O-，-SOd-和-N（R10）-中选择；X1为S或CH2；X2为O，S或CH2；a为1、2或3；b为0-3；c为1或2；d为0、1或2。
• FAP inhibitors
  申请人：EVANS David Michael

  公开号：US20100081701A1

  公开（公告）日：2010-04-01

  The present invention concerns compounds, according to general formula (I), which find utility preferably for the treatment of cancer.

  本发明涉及一般式（I）的化合物，其主要用于癌症治疗。