N-(2,3-dihydro-1H-inden-2-yl)glycine ethyl ester hydrochloride | 80871-69-8

• 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: N-(2,3-dihydro-1H-inden-2-yl)glycine ethyl ester hydrochloride
• 英文别名: N-(2-indanyl)glycine ethyl ester hydrochloride；ethyl 2-(2,3-dihydro-1H-inden-2-ylamino)acetate;hydrochloride
• CAS: 80871-69-8
• 化学式: C₁₃H₁₇NO₂*ClH
• 分子量: 255.744
• InChiKey: SLJRZJIHVGUOJT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.73
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  38.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(2,3-dihydro-1H-inden-2-yl)glycine ethyl ester hydrochloride 在 氢氧化钾 、 1-羟基苯并三唑 、 戴斯-马丁氧化剂 、 氯磷酸二乙酯 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 55.75h， 生成 (3RS)-N-(carbobenzyloxy)-N-methyl-L-valyl-N-(2,3-dihydro-1H-inden-2-yl)glycine N-<3-(1,1,1-trifluoro-4-methyl-2-oxopentyl)>amide
  参考文献：
  名称：

  Inhibition of human leukocyte elastase (HLE) by N-substituted peptidyl trifluoromethyl ketones

  摘要：

  A series of tripeptides possessing trifluoromethyl or aryl ketone residues at P1 were prepared and evaluated both in vitro and in vivo as potential inhibitors of human leukocyte elastase (HLE). Tripeptides containing non naturally occurring N-substituted glycine residues at the P2-position have been demonstrated to be potent in vitro inhibitors of HLE, with IC50 values in the submicromolar range. Sterically demanding substituents on the P2-nitrogen have no detrimental effect on in vitro potency. The inhibition process presumably acts via hemiketal formation with the active site Ser195 of HLE, and is facilitated by the strongly electron withdrawing trifluoromethyl functionality. Deletion of the amino acid at the P3-subsite region affords inactive compounds. Valine is the preferred residue at the P1-position, whereas the corresponding glycine, alanine, alpha,alpha-dimethylglycine, or phenylalanine analogues are all inactive. The compounds described herein all confer a high degree of in vitro specificity when tested against representative cysteine, aspartyl, metallo, and other serine proteases. One of the most potent in vitro inhibitors is (3RS)-N-[4-[[[(4-chlorophenyl)sulfonyl]amino]carbonyl]phenyl]oxomethyl]-L-valyl-N-(2,3-dihydro-1H-inden-2-yl)glycine N-[3-(1,1,1-trifluoro-4-methyl-2-oxopentyl)]amide (20i; BI-RA-260) (IC50 = 0.084-mu-M). Compound 20i was also tested in hamsters in an elastase-induced pulmonary hemorrhage (EPH) model. In this model, intratracheal (it.) administration of 20i, 5 min prior to HLE challenge, effectively inhibited hemorrhage in a dose-dependent manner with an ED50 of 4.8-mu-g. The inhibitor 20i, 20-mu-g administered it. 24, 48, and 72 h prior to HLE challenge, exhibits significant inhibition against hemorrhage at all time points (97%, 64% and 49%, respectively). In a 21-day chronic model of emphysema in hamsters, 200-mu-g of HLE administered it. caused an elastase-induced emphysema in the lungs which can be quantitated histologically utilizing image analysis. In this assay, 20i significantly inhibited pulmonary lesions associated with septal destruction and increased alveolar spaces, when dosed at 20-mu-g it. 5 min prior to challenge with HLE.

  DOI：

  10.1021/jm00082a005
• 作为产物：
  描述：

  甘氨酸乙酯盐酸盐 、 2-茚酮 在 盐酸 、 3 A molecular sieve 、 sodium cyanoborohydride 作用下， 生成 N-(2,3-dihydro-1H-inden-2-yl)glycine ethyl ester hydrochloride
  参考文献：
  名称：

  Saito; Matsui; Fukushima, Arzneimittel-Forschung/Drug Research, 1989, vol. 39, # 12, p. 1558 - 1561

  摘要：

  DOI：

文献信息

• Imidazo[1,2-a]piperazines
  申请人：Boehringer Ingelheim Pharmaceuticals, Inc.

  公开号：US05166154A1

  公开（公告）日：1992-11-24

  Imidazo-[1,2-a]piperazines, inhibitors of human neutrophil elastase, having the following general structure ##STR1## wherein the substituents are defined hereinbelow, are disclosed.

  本发明揭示了人类中性粒细胞弹性蛋白酶抑制剂咪唑并[1,2-a]哌嗪，其具有以下一般结构##STR1##其中取代基在下文中定义。
• N-substituted amides
  申请人：Boehringer Ingelheim Pharmaceuticals, Inc.

  公开号：US05221665A1

  公开（公告）日：1993-06-22

  N-substituted amides which inhibit hydrolysis of elastin, are described, which compounds are tri-and di- fluoromethyl ketone amide and non-naturally occurring n-substituted amino acids derivatives.

  本文描述了抑制弹性蛋白水解的N-取代酰胺，这些化合物是三氟甲基酮酰胺和二氟甲基酮酰胺以及非天然的N-取代氨基酸衍生物。
• L-Alanyl-N-(indan-2-yl)glycine, its esters and salts thereof
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US04474692A1

  公开（公告）日：1984-10-02

  Useful intermediates for the preparation of hypotensives and inhibitors of angiotensin converting enzymes are L-alanyl-N-(indan-2-yl)glycine, its lower alkyl esters and the salts thereof.

  L-丙氨酸-N-(茚-2-基)甘氨酸及其较低的烷基酯和盐是制备降压药和血管紧张素转换酶抑制剂的有用中间体。
• Chromanyl glycines
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US04521607A1

  公开（公告）日：1985-06-04

  New bicyclic compounds, inclusive of salts thereof, of the formula: ##STR1## wherein R.sup.1 and R.sup.2, which may be the same or different, each represent hydrogen, halogen, lower alkyl, hydroxyl, lower alkyloxy or aralkyloxy, or R.sup.1 and R.sup.2 jointly represent lower alkylenedioxy; R.sup.3 and R.sup.4 each represent hydrogen or lower alkyl; R.sup.5 represents hydrogen, lower alkyl or --CH.sub.2 SR.sup.7 (R.sup.7 represents hydrogen or acyl); R.sup.6 represents hydrogen or acyl, or R.sup.6 and R.sup.7 jointly represent a single bond; X represents --CH.sub.2 --, --O-- or >N--R.sup.8 (R.sup.8 represents hydrogen, acyl or lower alkyl); and n represents 2, 3 or 4, have inhibitory activities of angiotensin converting enzyme and bradykinin decomposing enzyme, and are useful as antihypertensive agents.

  新的双环化合物及其盐，化学式如下：##STR1## 其中，R.sup.1和R.sup.2，可以相同也可以不同，分别表示氢、卤素、低级烷基、羟基、低级烷氧基或芳基烷氧基，或者R.sup.1和R.sup.2共同表示低级烷二氧基；R.sup.3和R.sup.4分别表示氢或低级烷基；R.sup.5表示氢、低级烷基或--CH.sub.2 SR.sup.7（其中R.sup.7表示氢或酰基）；R.sup.6表示氢或酰基，或者R.sup.6和R.sup.7共同表示单键；X表示--CH.sub.2 --、--O--或>N--R.sup.8（其中R.sup.8表示氢、酰基或低级烷基）；n表示2、3或4。该化合物具有抑制血管紧张素转换酶和激肽酶降解酶的活性，是一种有用的降压药。
• Bicycle compounds, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US04822818A1

  公开（公告）日：1989-04-18

  New bicyclic compounds, inclusive of salts thereof, of the formula: ##STR1## wherein R.sup.1 and R.sup.2 are the same or different and each represents hydrogen, hydroxyl or lower alkoxy, R.sup.3 is hydrogen or lower alkyl, R.sup.4 is hydrogen, lower alkyl, amino-lower-alkyl or acylamino-lower-alkyl, R.sup.5 is hydrogen, lower alkyl or aralkyl which may be substituted, R.sup.6 is hydroxyl, lower alkoxy, amino or lower alkylamino, and m and n each means 1 or 2, have inhibitory activities of angiotensin converting enzyme and bradykinin decomposing enzyme, and are useful as antihypertensive agents.

  新的双环化合物，包括其盐，化学式如下：##STR1## 其中，R.sup.1和R.sup.2相同或不同，分别代表氢、羟基或较低的烷氧基，R.sup.3代表氢或较低的烷基，R.sup.4代表氢、较低的烷基、氨基-较低-烷基或酰胺基-较低-烷基，R.sup.5代表氢、较低的烷基或可能被取代的芳基烷基，R.sup.6代表羟基、较低的烷氧基、氨基或较低的烷基氨基，m和n分别表示1或2，具有抑制血管紧张素转化酶和缓激肽降解酶的活性，并且可用作降压剂。