2-(5-(((2S)-2-Benzyloxycarbonylamino-2-tert-butoxycarbonyl-ethyl)carbamoyl)-2-thienyl)-cyclopropancarboxylic Acid Methyl Ester | 250688-88-1

• 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: 2-(5-(((2S)-2-Benzyloxycarbonylamino-2-tert-butoxycarbonyl-ethyl)carbamoyl)-2-thienyl)-cyclopropancarboxylic Acid Methyl Ester
• 英文别名: methyl 2-[5-[[(2S)-3-[(2-methylpropan-2-yl)oxy]-3-oxo-2-(phenylmethoxycarbonylamino)propyl]carbamoyl]thiophen-2-yl]cyclopropane-1-carboxylate
• CAS: 250688-88-1
• 化学式: C₂₅H₃₀N₂O₇S
• 分子量: 502.588
• InChiKey: WHSHMSMECJMEIO-ABHNRTSZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  35
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  148
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-(5-(((2S)-2-Benzyloxycarbonylamino-2-tert-butoxycarbonyl-ethyl)carbamoyl)-2-thienyl)-cyclopropancarboxylic Acid Methyl Ester 在 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 (2S)-2-Benzyloxycarbonylamino-3-((5-(2-(1,4,5,6-tetrahydropyrimidin-2-ylcarbamoyl)-cyclopropyl)-thiophene-2-carbonyl)-amino)-propionic Acid
  参考文献：
  名称：

  αvβ3 Antagonists Based on a Central Thiophene Scaffold

  摘要：

  A series of novel, highly potent alpha (v)beta (3) antagonists based on a thiophene scaffold and containing an acylguanidine as an Arg-mimetic is described. A number of structural features, such as cyclic versus open guanidine and a variety of lipophilic side chains, carbamates, sulfonamides and beta -amino acids were explored with respect to inhibition of alpha (v)beta (3) mediated cell adhesion and selectivity versus alpha (IIb)beta (3) binding. In addition, compound 19 was found to be active in the TPTX model of osteoporosis. (C) 2001 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(01)00357-2
• 作为产物：
  描述：

  5-溴-2-羧基噻吩 在 palladium diacetate 、 O-[(ethoxycarbonyl)cyanomethyleneamino]-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 PdCl₂(PPh₂ferrocene)2 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醚 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 30.0h， 生成 2-(5-(((2S)-2-Benzyloxycarbonylamino-2-tert-butoxycarbonyl-ethyl)carbamoyl)-2-thienyl)-cyclopropancarboxylic Acid Methyl Ester
  参考文献：
  名称：

  αvβ3 Antagonists Based on a Central Thiophene Scaffold

  摘要：

  A series of novel, highly potent alpha (v)beta (3) antagonists based on a thiophene scaffold and containing an acylguanidine as an Arg-mimetic is described. A number of structural features, such as cyclic versus open guanidine and a variety of lipophilic side chains, carbamates, sulfonamides and beta -amino acids were explored with respect to inhibition of alpha (v)beta (3) mediated cell adhesion and selectivity versus alpha (IIb)beta (3) binding. In addition, compound 19 was found to be active in the TPTX model of osteoporosis. (C) 2001 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(01)00357-2

文献信息

• Thienyl substituted acylguanidines as inhibitors of bone resorption and vitronectin receptor antagonists
  申请人：Aventis Pharma Deutschland GmbH and Genentech, Inc.

  公开号：US20030153557A1

  公开（公告）日：2003-08-14

  The present invention relates to thienyl substituted acylguanidine derivatives, such as compounds of formula (I) in which R 1 , R 2 , R 4 , R 6 , A, B and D have the meanings indicated in the claims, their physiologically tolerable salts and their prodrugs. The compounds of the present invention are valuable pharmaceutical active compounds. They are vitronectin receptor antagonists and inhibitors of bone resorption by osteoclasts. They are suitable, for example, for the therapy and prophylaxis of diseases which are caused at least partially by an undesired extent of bone resorption, for example of osteoporosis. The invention furthermore relates to processes for the preparation of thienyl substituted acylguanidines, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.

  本发明涉及噻吩取代的酰基胍衍生物，例如公式(I)中R1、R2、R4、R6、A、B和D所示含义的化合物，它们的生理耐受性盐和前药。本发明的化合物是有价值的药物活性化合物。它们是玻璃蛋白受体拮抗剂和破骨细胞骨吸收抑制剂。例如，它们适用于治疗和预防由于骨吸收不良造成的至少部分疾病，例如骨质疏松症。此外，本发明还涉及制备噻吩取代的酰基胍衍生物的方法，它们的使用，特别是作为药物中的活性成分，并包括它们的制剂。
• THIENYL SUBSTITUTED ACYLGUANIDINES AS INHIBITORS OF BONE RESORPTION AND VITRONECTIN RECEPTOR ANTAGONISTS
  申请人：Aventis Pharma Deutschland GmbH

  公开号：EP1086098A1

  公开（公告）日：2001-03-28
• US6566366B1
  申请人：——

  公开号：US6566366B1

  公开（公告）日：2003-05-20
• US6660728B2
  申请人：——

  公开号：US6660728B2

  公开（公告）日：2003-12-09
• [EN] THIENYL SUBSTITUTED ACYLGUANIDINES AS INHIBITORS OF BONE RESORPTION AND VITRONECTIN RECEPTOR ANTAGONISTS<br/>[FR] ACYLGUANIDINES A SUBSTITUTION THIENYL EN TANT QU'INHIBITEURS DE LA RESORPTION OSSEUSE OSTEOCLASTIQUE ET ANTAGONISTES DU RECEPTEUR DE LA VITRONECTINE
  申请人：AVENTIS PHARMA DEUTSCHLAND GMBH

  公开号：WO1999059992A1

  公开（公告）日：1999-11-25

  (EN) The present invention relates to thienyl substituted acylguanidine derivatives, such as compounds of formula (I) in which R1, R2, R4, R6, A, B and D have the meanings indicated in the claims, their physiologically tolerable salts and their prodrugs. The compounds of the present invention are valuable pharmaceutical active compounds. They are vitronectin receptor antagonists and inhibitors of bone resorption by osteoclasts. They are suitable, for example, for the therapy and prophylaxis of diseases which are caused at least partially by an undesired extent of bone resorption, for example of osteoporosis. The invention furthermore relates to processes for the preparation of thienyl substituted acylguanidines, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.(FR) Cette invention, qui a trait à des acylguanidines à substitution thiényl en tant qu'inhibiteurs de la résorption osseuse ostéoclastique et antagonistes du récepteur de la vitronectine, concerne également des dérivés d'acylguanidine à substitution thiényl, notamment des composés correspondant à la formule (I) ainsi que leurs sels physiologiquement acceptables et leurs bioprécurseurs. Dans cette formule, R1, R2, R4, R6, A, B et D sont tels que décrit dans les revendications. Les composés selon l'invention constituent d'intéressants composés pharmaceutiques actifs. Ils sont des antagonistes du récepteur de la vitronectine et des inhibiteurs de la résorption osseuse par les ostéoclastes. Ils participent du mieux à la thérapie et à la prophylaxie de maladies dues, au moins en partie, à une extension indésirable de la résorption osseuse, l'ostéoporose notamment. L'invention porte, en outre, sur des procédés de préparation d'acylguanidines à substitution thiényl, sur leur utilisation, notamment en tant qu'ingrédients actifs de médicaments, ainsi que sur des préparations pharmaceutiques renfermant ces ingrédients.