(S)-3-amino-2-butoxycarbonylamino-propionic acid methyl ester | 169605-35-0

• 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: (S)-3-amino-2-butoxycarbonylamino-propionic acid methyl ester
• 英文别名: methyl (2S)-3-amino-2-(butoxycarbonylamino)propanoate
• CAS: 169605-35-0
• 化学式: C₉H₁₈N₂O₄
• 分子量: 218.253
• InChiKey: UIUXDKPCDMGHHY-ZETCQYMHSA-N

物化性质

• 沸点：
  350.9±37.0 °C(Predicted)
• 密度：
  1.108±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  15
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  90.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-3-amino-2-butoxycarbonylamino-propionic acid methyl ester 在 盐酸 、 氨 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 螺内酯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-2-Butoxycarbonylamino-3-{[2-(4-carbamimidoyl-phenyl)-1H-benzoimidazole-5-carbonyl]-amino}-propionic acid methyl ester
  参考文献：
  名称：

  Design, synthesis and in vitro activities of a series of benzimidazole/benzoxazole glycoprotein IIb/IIIa inhibitors

  摘要：

  A potent centrally constrained series of benzimidazole and benzoxazole glycoprotein IIb/IIIa inhibitors has been discovered based on the solution conformation of a cyclic RGD-containing peptide, DMP 728. The high potency of this series of compounds in the inhibition of platelet aggregation requires a benzamidine as the basic moiety and an alpha-carbamate or sulfonamide substituted beta-alanine as the acidic moiety.

  DOI：

  10.1016/0960-894x(95)00590-p
• 作为产物：
  描述：

  methyl (2S)-2-(butoxycarbonylamino)-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 以100%的产率得到(S)-3-amino-2-butoxycarbonylamino-propionic acid methyl ester
  参考文献：
  名称：

  Design, synthesis and in vitro activities of a series of benzimidazole/benzoxazole glycoprotein IIb/IIIa inhibitors

  摘要：

  A potent centrally constrained series of benzimidazole and benzoxazole glycoprotein IIb/IIIa inhibitors has been discovered based on the solution conformation of a cyclic RGD-containing peptide, DMP 728. The high potency of this series of compounds in the inhibition of platelet aggregation requires a benzamidine as the basic moiety and an alpha-carbamate or sulfonamide substituted beta-alanine as the acidic moiety.

  DOI：

  10.1016/0960-894x(95)00590-p

文献信息

• Discovery of an Orally Active Series of Isoxazoline Glycoprotein IIb/IIIa Antagonists
  作者：Chu-Biao Xue、John Wityak、Thais M. Sielecki、Donald J. Pinto、Douglas G. Batt、Gary A. Cain、Michael Sworin、Arlene L. Rockwell、John J. Roderick、Shuaige Wang、Michael J. Orwat、William E. Frietze、Lori L. Bostrom、Jie Liu、C. Anne Higley、F. Wayne Rankin、A. Ewa Tobin、George Emmett、George K. Lalka、Jean Y. Sze、Susan V. Di Meo、Shaker A. Mousa、Martin J. Thoolen、Adrienne L. Racanelli、Elizabeth A. Hausner、Thomas M. Reilly、William F. DeGrado、Ruth R. Wexler、Richard E. Olson

  DOI：10.1021/jm960799i

  日期：1997.6.1

  Using isoxazoline XR299 (1a) as a starting point for the design of highly potent, long-duration GPIIb/IIIa antagonists, the effect of placing lipophilic substituents at positions alpha and beta to the carboxylate moiety was evaluated. Of the compounds studied, it was found that the n-butyl carbamate 24u exhibited superior potency and duration of ex vivo antiplatelet effects in dogs. Replacement of

  使用异恶唑啉XR299（1a）作为设计高效，长效GPIIb / IIIa拮抗剂的起点，评估了将亲脂性取代基置于羧酸酯部分的α和β处的效果。在所研究的化合物中，发现氨基甲酸正丁酯24u在狗中表现出优异的效力和离体抗血小板作用的持续时间。用可替代的碱性基团取代苯并胺丁-4-基部分，消除异恶唑啉立体中心，并改变异恶唑啉环的方向，导致效力和/或作用时间降低。
• Platelet glycoprotein IIb/IIIa receptor antagonists derived from isoxazolidines
  作者：Pat N. Confalone、Fuqiang Jin、Shaker A. Mousa

  DOI：10.1016/s0960-894x(98)00686-6

  日期：1999.1

  A series of isoxazolidines has been synthesized as mimetics of the RGD sequence and was evaluated as antagonists of the platelet glycoprotein IIb/IIIa receptor. These compounds were shown to be highly potent GPIIb/IIIa antagonists, exhibiting submicromolar potencies.

  已经合成了一系列异恶唑烷作为RGD序列的模拟物，并被评估为血小板糖蛋白IIb / IIIa受体的拮抗剂。这些化合物被证明是高效的GPIIb / IIIa拮抗剂，表现出亚微摩尔效价。
• Novel Chiral Auxiliary for Attempted Resolution of Key Roxifiban Intermediate: A Simple Diastereoselective Coupling Approach for the Synthesis of Roxifiban
  作者：Ashok K. Gangopadhyay、Gopal V. Gole、Ravindra D. Jadhav、Bansi Lal

  DOI：10.1080/00397910701575012

  日期：2007.12

  a simple method for the synthesis of roxifiban, a potent glycoprotein GP IIb‐IIIa receptor antagonist, by a diastereoselective coupling approach to give >99.9% optical purity. We have also described an attempt to resolve the key synthetic intermediate by diastereomeric ester formation. Although we have been able to separate two diastereomeric esters, the removal of the chiral auxiliary led to partial

  摘要 本文介绍了一种通过非对映选择性偶联方法合成 roxifiban（一种有效的糖蛋白 GP IIb-IIIa 受体拮抗剂）的简单方法，可提供 >99.9% 的光学纯度。我们还描述了通过形成非对映体酯来解决关键合成中间体的尝试。尽管我们已经能够分离两种非对映体酯，但手性助剂的去除导致部分外消旋化。
• [EN] NOVEL ISOXAZOLINE AND ISOXAZOLE FIBRINOGEN RECEPTOR ANTAGONISTS<br/>[FR] NOUVEAUX ANTAGONISTES DE RECEPTEUR DE FIBRINOGENE, A BASE D'ISOXAZOLINE ET D'ISOXAZOLE
  申请人：THE DU PONT MERCK PHARMACEUTICAL COMPANY

  公开号：WO1995014683A1

  公开（公告）日：1995-06-01

  (EN) This invention relates to novel isoxazolines and isoxazoles which are useful as antagonists of the platelet glycoprotein IIb/IIIa fibrinogen receptor complex, to pharmaceutical compositions containing such compounds, processes for preparing such compounds, and to methods of using these compounds, alone or in combination with other therapeutic agents, for the inhibition of platelet aggregation, as thrombolytics and/or for the treatment of thromboembolic disorders.(FR) L'invention se rapporte à de nouveaux isoxazoles et isoxazolines aptes à être utilisés comme antagonistes du complexe récepteur de fibrinogène/glycoprotéine plaquettaire IIb/IIIa, à des compositions pharmaceutiques contenant ces composés, à des procédés de préparation de ces derniers ainsi qu'à des procédés permettant de les utiliser, seuls ou en combinaison avec d'autres agents thérapeutiques, comme agents thrombolytiques pour inhiber l'agrégation plaquettaire, et/ou pour le traitement de troubles thromboemboliques.

  该发明涉及新型异氧化吲唑和异氧化吡唑，可用作血小板糖蛋白IIb/IIIa纤维蛋白原受体复合物的拮抗剂，以及含有这些化合物的制药组合物，制备这些化合物的方法，以及使用这些化合物的方法，单独或与其他治疗剂联合使用，用于抑制血小板聚集，作为溶栓剂和/或用于治疗血栓栓塞性疾病。
• [EN] NOVEL CARBOXAMIDES AS PLATELET AGGREGATION INHIBITORS<br/>[FR] NOUVEAUX CARBOXAMIDES INHIBITEURS D'AGREGATION PLAQUETTAIRE
  申请人：J. URIACH & CIA. S.A.

  公开号：WO1998046599A1

  公开（公告）日：1998-10-22

  (EN) Compounds of formula (I) and their salts and solvates wherein: one of Y1 or Y2 represents N and the other represents NR5, O or S, or one of Y1 or Y2 represents S and the other represents CR5, wherein R5 represents hydrogen or C1-4 alkyl; m represents 0, 1 or 2; A represents C0-2 alkylene which may be optionally substituted with one or more groups independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, C3-7 cycloalkylC1-4 alkyl, aryl, arylC1-4 alkyl, arylC3-7 cycloalkyl, heteroaryl, heteroarylC1-4 alkyl, R6SO2NR2C1-4 alkyl, R6CONR2C1-4 alkyl, R6OCONR2C1-4 alkyl, R2R7NCONR2C1-4 alkyl, R6SO2C1-4 alkyl, R2R7NSO2C1-4 alkyl, R2R7NCOC1-4 alkyl, R6COC1-4 alkyl, R7OOCC1-4 alkyl, R6OC1-4 alkyl, R2R7NC1-4 alkyl, R8OOC-, or R2R7NCO-; R2 represents independently hydrogen or C1-4 alkyl; B represents carboxy or a metabolically labile ester or amide thereof; R4 represents a group of formula (i) or (ii): wherein the terminal ring in both groups can be optionally substituted with one or more C1-4 alkyl or halogen groups and wherein R1 and R3, as defined in the description, are platelet aggregation inhibitors and are useful for the treatment or prevention of thromboembolic disorders. Pharmaceutical compositions including these compounds and processes for their preparation are also provided.(FR) L'invention concerne des composés de formule (I) et leurs sels et solvates, formule dans laquelle l'un des éléments Y1 ou Y2 représente N et l'autre représente NR5, O ou S ou bien l'un des éléments Y1 ou Y2 représente S et l'autre représente CR5, R5 représentant hydrogène ou alkyle C1-4; m vaut 0, 1 ou 2; A représente alcylène C0-2 éventuellement substitué par un ou plusieurs groupes sélectionnés indépendamment parmi alkyle C1-6, alcényle C2-6, alcynyle C2-6, haloalkyle C1-6, cycloalkyle C3-7, cycloalkyle C3-7 alkyle C1-4, aryle, arylalkyle C1-4, arylcycloalkyle C3-7, hétéroaryle, hétéroarylalkyle C1-4, R6SO2NR2 alkyle C1-4, R6CONR2 alkyle C1-4, R6OCONR2 alkyle C1-4, R2R7NCONR2 alkyle C1-4, R6SO2 alkyle C1-4, R2R7NSO2 alkyle C1-4, R2R7NCO alkyle C1-4, R6CO alkyle C1-4, R7OOC alkyle C1-4, R6O alkyle C1-4, R2R7N alkyle C1-4, R8OOC- ou R2R7NCO-; R2 représente indépendamment hydrogène ou alkyle C1-4; B représente carboxy ou un de ses esters ou amides instable métaboliquement; R4 représente un groupe de formule (i) ou (ii), le cycle terminal dans ces deux groupes pouvant être facultativement susbtitué par un ou plusieurs groupes halogène ou alkyle C1-4. R1 et R3, tels qu'ils sont définis dans la description, sont des inhibiteurs d'agrégation plaquettaire et sont utiles pour le traitement ou la prévention de désordres thromboemboliques. L'invention concerne également les compositions pharmaceutiques contenant ces composés et les procédés pour leur préparation.

  化合物的化学式为（I），其盐和溶剂化合物，其中：Y1或Y2中的一个代表N，另一个代表NR5，O或S，或者Y1或Y2中的一个代表S，另一个代表CR5，其中R5代表氢或C1-4烷基；m代表0，1或2；A代表C0-2烷基，可以选择性地用一个或多个从C1-6烷基，C2-6烯基，C2-6炔基，C1-6卤代烷基，C3-7环烷基，C3-7环烷基C1-4烷基，芳基，芳基C1-4烷基，芳基C3-7环烷基，杂环芳基，杂环芳基C1-4烷基，R6SO2NR2C1-4烷基，R6CONR2C1-4烷基，R6OCONR2C1-4烷基，R2R7NCONR2C1-4烷基，R6SO2C1-4烷基，R2R7NSO2C1-4烷基，R2R7NCOC1-4烷基，R6COC1-4烷基，R7OOCC1-4烷基，R6OC1-4烷基，R2R7NC1-4烷基，R8OOC-或R2R7NCO-中独立选择的一个或多个基团替换；R2独立地代表氢或C1-4烷基；B代表羧基或其代谢易耗酯或酰胺；R4代表式（i）或（ii）的基团：其中两个基团中的末端环可以选择性地用一个或多个C1-4烷基或卤代基团替换，其中R1和R3如描述中所定义，是血小板聚集抑制剂，用于治疗或预防血栓栓塞性疾病。还提供包括这些化合物的制药组合物和它们的制备方法。