(4S)-3-(tert-Butyloxycarbonyl)thiazolidine-4-carboxamide | 739365-93-6

• 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: (4S)-3-(tert-Butyloxycarbonyl)thiazolidine-4-carboxamide
• 英文别名: (4S)-N-BOC-1,3-thiazolane-4-carboxamide；(S)-Tert-butyl 4-carbamoylthiazolidine-3-carboxylate；tert-butyl (4S)-4-carbamoyl-1,3-thiazolidine-3-carboxylate
• CAS: 739365-93-6
• 化学式: C₉H₁₆N₂O₃S
• 分子量: 232.304
• InChiKey: OXGKKJVYQKKOIS-ZCFIWIBFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  97.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4S)-3-(tert-Butyloxycarbonyl)thiazolidine-4-carboxamide 以 1,4-二氧六环 、 盐酸 为溶剂， 生成 (4R)-thiazolidine-4-carboxamide hydrochloride
  参考文献：
  名称：

  Inhibitors of dipeptidyl peptidase IV

  摘要：

  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。

  公开号：

  US20040082497A1
• 作为产物：
  描述：

  Boc-d-噻唑烷-4-羧酸 在 氯甲酸乙酯 、 三乙胺 、 氨 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 18.5h， 以71%的产率得到(4S)-3-(tert-Butyloxycarbonyl)thiazolidine-4-carboxamide
  参考文献：
  名称：

  [EN] NOVEL DIPEPTIDYL PEPTIDASE IV INHIBITORS; PROCESSES FOR THEIR PREPARATION AND COMPOSITIONS THEREOF
  [FR] NOUVEAUX INHIBITEURS DE DIPEPTIDYLE PEPTIDASE IV, LEUR PROCEDES DE PREPARATION ET COMPOSITIONS EN COMPORTANT

  摘要：

  本发明涉及一种新型二肽基肽酶IV（DPP-IV）抑制剂，其一般式（1）用于治疗糖尿病、非胰岛素依赖型糖尿病、糖耐量受损、炎症性肠病、溃疡性结肠炎、克罗恩病、肥胖症和代谢综合征。

  公开号：

  WO2005075426A1

文献信息

• [EN] NOVEL DIPEPTIDYL PEPTIDASE IV INHIBITORS, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM, AND PROCESS FOR THEIR PREPARATION<br/>[FR] NOUVEAUX INHIBITEURS DE DIPEPTIDYLE PEPTIDASE IV, COMPOSITIONS PHARMACEUTIQUES EN CONTENANT, ET LEUR PROCEDE DE PREPARATION
  申请人：GLENMARK PHARMACEUTICALS SA

  公开号：WO2006040625A1

  公开（公告）日：2006-04-20

  The present invention relates to novel compounds useful as dipeptidyl peptidase IV (DPP-IV) inhibitors of the formula: (I) wherein Y is -S(O)m, -CH2-, CHF, or -CF2; m is 0, 1, or 2; X is a bond, C1-C5 alkyl (e.g., -CH2-), or -C(=0)-; the dotted line [----] in the carbocyclic ring represents an optional double bond; R1 is substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclic ring, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted heteroarylalkyl, CN, -COOR3, CONR3R4, -OR3, -NR3R4, or NR3COR3; R2 is hydrogen, cyano, COOH, or an isostere of a carboxylic acid (such as SO3H, CONOH, B(OH)2, PO3R3R4, SO2NR3R4, tetrazole, -COOR3, -CONR3R4, NR3COR4, or -COOCOR3).

  本发明涉及一种新型化合物，其作为二肽基肽酶IV（DPP-IV）抑制剂的公式如下：(I)，其中Y为-S(O)m，-CH2-，CHF或-CF2；m为0，1或2；X为键，C1-C5烷基（例如，-CH2-），或-C(=0)-；在环状碳环中的虚线[----]表示可选的双键；R1为取代或未取代的环烷基，取代或未取代的环烷基烷基，取代或未取代的环烯基，取代或未取代的芳基，取代或未取代的芳基烷基，取代或未取代的杂芳基，取代或未取代的杂环戊基，取代或未取代的杂环烷基，取代或未取代的杂芳基烷基，CN，-COOR3，CONR3R4，-OR3，-NR3R4或NR3COR3；R2为氢，氰基，COOH或羧酸的同分异构体（例如SO3H，CONOH，B(OH)2，PO3R3R4，SO2NR3R4，四唑，-COOR3，-CONR3R4，NR3COR4或-COOCOR3）。
• 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。
• (3-HYDROXY-4-AMINO-BUTAN-2-YL) -3- (2-THIAZOL-2-YL-PYRROLIDINE-1-CARBONYL) BENZAMIDE DERIVATIVES AND RELATED COMPOUNDS AS BETA-SECRETASE INHIBITORS FOR TREATING
  申请人：Ghosh Arun K.

  公开号：US20100286170A1

  公开（公告）日：2010-11-11

  The present invention provides novel beta-secretase inhibitors and methods for their use, including methods of treating of Alzheimer's disease.

  本发明提供了新型β-秘鲁酶抑制剂及其使用方法，包括治疗阿尔茨海默病的方法。
• WO2006/90244
  申请人：——

  公开号：——

  公开（公告）日：——