4-([4-(Aminoiminomethyl)phenyl]-amino)-4-oxobutanoic acid hydrochloride | 149177-92-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-([4-(Aminoiminomethyl)phenyl]-amino)-4-oxobutanoic acid hydrochloride
• 英文别名: 4-[[4-(aminoiminomethyl)phenyl]amino]-4-oxobutanoic acid, monohydrochloride；[Amino-[4-(3-carboxypropanoylamino)phenyl]methylidene]azanium;chloride；[amino-[4-(3-carboxypropanoylamino)phenyl]methylidene]azanium;chloride
• CAS: 149177-92-4
• 化学式: C₁₁H₁₃N₃O₃*ClH
• 分子量: 271.703
• InChiKey: LCGYSICNTXOCAI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  116
• 氢给体数：
  5
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-([4-(Aminoiminomethyl)phenyl]-amino)-4-oxobutanoic acid hydrochloride 在 N-甲基吗啉 、 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.08h， 生成 珍米洛非班
  参考文献：
  名称：

  Potent in Vitro and in Vivo Inhibitors of Platelet Aggregation Based Upon the Arg-Gly-Asp Sequence of Fibrinogen. (Aminobenzamidino)succinyl (ABAS) Series of Orally Active Fibrinogen Receptor Antagonists

  摘要：

  Our initial orally active fibrinogen receptor antagonist benzamidinopentanoyl (BAP) series which was discovered through truncation of our iv antiplatelet agent (SC-52012) demonstrated modest oral activity in canine studies (ethyl [5-(4-amidinophenyl)pentanoyl]3-3-amino-3 pyridyl)propionate, 1e). Introduction of an amide bond adjacent to the benzamidine led to a novel series with an (aminobenzamidino)succinyl (ABAS) Arg-Gly surrogate that had improved in vitro potency (5-17 times) relative to the BAP series. Four ester prodrug/acid active metabolite pairs (2a/2e, 60a/60e, 62a/62e, 63a/63e) from the ABAS series which varied in their 3-substituent on the beta-amino ester ''aspartate mimetic'' were prepared in enantiomerically enriched form (>95:5), and they were evaluated in canine studies for their ability to block collagen-induced aggregation in platelet-rich plasma, the elimination profile (t(1/2) beta-phase), repeated oral dosing studies, and oral systemic availability. Of the four ester prodrug/acid active metabolite pairs, 2e/2a (SC-54684A/SC-54701A) had the most favorable properties in the above studies with an IC50 = 67 +/- 5 nM (dog platelet-rich plasma, collagen), t(1/2) beta = 1.6 h tester) and 6.5 h (acid), no adverse effects upon repeated dosing, and a drug oral systemic availability of 62% (area under curve (AUG) of acid 2a (drug) following ig administration of ester 2e (prodrug, 2.5 mg/kg) divided by AUC of acid 2a (drug) following iv administration of ester 2e (prodrug, 2.5 mg/kg) as determined by HPLRC). In further pharmacokinetic studies using nonlabeled 2e/2a, the oral systemic availability tester 2e ig/ester 2e iv) of 2e was measured to be in the range of 44.7-53.0%. The more biologically relevant oral systemic availability tester 2e ig/acid 2a iv) of 2e was found to be in the range of 22.0-26.4%. A pharmacophore model. based on inhibitors from several different benzamidine classes including 2a (ABAS class) was developed using a combination of molecular modeling (MM2) and pharmacophore identification (APOLLO) methods.

  DOI：

  10.1021/jm00013a014
• 作为产物：
  描述：

  丁二酸酐 、 4-aminobenzamidine dihydrochloride 在 4-二甲氨基吡啶 吡啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以88%的产率得到4-([4-(Aminoiminomethyl)phenyl]-amino)-4-oxobutanoic acid hydrochloride
  参考文献：
  名称：

  A highly stereoselective Michael addition to an .alpha.,.beta.-unsaturated ester as the crucial step in the synthesis of a novel .beta.-amino acid-containing fibrinogen receptor antagonist

  摘要：

  DOI：

  10.1021/jo00079a054
• 作为试剂：
  描述：

  ethyl 3-amino-4-pentynoate 、 4-([4-(Aminoiminomethyl)phenyl]-amino)-4-oxobutanoic acid hydrochloride 在 4-([4-(Aminoiminomethyl)phenyl]-amino)-4-oxobutanoic acid hydrochloride 作用下， 以75的产率得到xemilofiban hydrochloride
  参考文献：
  名称：

  Bioorg. Med. Chem. Lett. 1997, 7, 1699-1700

  摘要：

  DOI：

文献信息

• Substituted .beta.-amino acid derivatives useful as platelet aggregation
  申请人：G.D. Searle & Co.

  公开号：US05344957A1

  公开（公告）日：1994-09-06

  Novel substituted .beta. amino acid derivatives are provided which inhibit platelet aggregation. This invention also pertains to pharmaceutical compositions and methods of using such derivatives.

  提供了一种新型的替代.beta.氨基酸衍生物，可以抑制血小板聚集。该发明还涉及制药组合物和使用这些衍生物的方法。
• Substituted heterocyclic derivatives useful as platelet aggregation
  申请人：Monsanto Company

  公开号：US05254573A1

  公开（公告）日：1993-10-19

  Novel substituted heterocyclic derivatives are provided which inhibit platelet aggregation. This invention also pertains to pharmaceutical compositions and methods of using such derivatives.

  提供了一种替代的新型杂环衍生物，可以抑制血小板聚集。该发明还涉及制药组合物和使用这些衍生物的方法。
• A synthesis of the platelet aggregation inhibitor xemilofiban from L-aspartic acid. Confirmation of the absolute configuration
  作者：Mark L. Boys

  DOI：10.1016/s0040-4039(98)00602-9

  日期：1998.5

  A synthesis of xemilofiban (SC-54684A) from L-aspartic acid has been achieved in an overall yield of 18 %, and the absolute configuration has been confirmed.

  已经由L-天冬氨酸合成西米洛非班（SC-54684A），总产率为18％，并且已经确认了绝对构型。
• IIB/IIIA ANTAGONISTS CO-ADMINISTERED WITH ASPIRIN
  申请人：——

  公开号：US20030054029A1

  公开（公告）日：2003-03-20

  The present invention is directed to coadministration of the fibrinogen receptor antagonists 3S-[[4-[[4-aminoiminomethyl)phenyl]amino]-1,4-dioxobutyl]amino]-4-pentynoic acid or ethyl 3S-[[4-[[4-(aminoiminomethyl)phenyl]amino]-1,4-dioxobutyl]amino]-4-pentynoate together with an anti-platelet agent such as aspirin and/or an anti-coagulant such as heparin.

  本发明涉及将纤维蛋白原受体拮抗剂3S-[[4-[(4-氨基亚甲基)苯基]氨基]-1,4-二氧戊基]-4-戊炔酸或乙酸乙酯3S-[[4-[(4-氨基亚甲基)苯基]氨基]-1,4-二氧戊基]-4-戊炔酸与抗血小板药物如阿司匹林和/或抗凝剂如肝素一起联合使用的方法。
• [EN] SUBSTITUTED (BETA)-AMINO ACID DERIVATIVES USEFUL AS PLATELET AGGREGATION INHIBITORS
  申请人：G.D. SEARLE & CO.

  公开号：WO1993007867A1

  公开（公告）日：1993-04-29

  (EN) Novel substituted beta-amino acid derivatives having general formula (I), are provided, in which e.g. R2 is selected from the group consisting of hydrogen, lower alkyl radicals, lower alkenyl radicals, lower alkynyl radicals, alicyclic hydrocarbon radicals, aromatic hydrocarbon radicals, wherein said radicals are optionally substituted with hydroxy, lower alkoxy, lower alkyl, halogen, nitro, cyano, azido, ureido, ureylene, carboxyl or carbonyl derivatives, trifluoromethyl, acyloxy, alkylthio, arylthio, alkylsulfenyl, arylsulfenyl, alkylsulfonyl, arylsulfonyl, amino, alkylamino, trialkylsilyl, aminosulfonyl, dialkylamino, alkanoylamino, aroylamino, phenyl, naphtyl, lower alkynyl which are optionally substituted with one or more of the following: halogen, nitro, lower alkoxy, lower alkyl, trialkylsilyl, azide and phenyl; the invention also pertains to pharmaceutical compositions comprising such derivatives.(FR) L'invention se rapporte à de nouveaux dérivés de bêta-aminoacides substitués, représentés par la formule générale (I), où notamment R2 est choisi dans le groupe constitué par l'hydrogène, par des radicaux d'alkyle inférieur, par des radicaux d'alcényle inférieur, par des radicaux d'alcynyle inférieur, par des radicaux d'hydrocarbure alicyclique, par des radicaux d'hydrocarbure aromatique, ces radicaux étant éventuellement substitués par hydroxy, alcoxy inférieur, alkyle inférieur, halogène, nitro, cyano, azydo, uréido, uréylène, des dérivés carboxyle ou carbonyle, trifluorométhyle, acyloxy, alkylthio, arylthio, alkylsulfényle, arylsulfényle, alkylsulfonyle, arylsulfonyle, amino, alkylamino, trialkylsilyle, aminosulfonyle, dialkylamino, alcanoylamino, aroylamino, phényle, naphtyle, alcynyle inférieur, éventuellement substitués par un ou plusieurs des éléments suivants: halogène, nitro, alcoxy inférieur, alkyle inférieur, trialkylsilyle, azide et phényle; l'invention se rapportant également à des compositions pharmaceutiques comprenant de tels dérivés.

  提供了具有一般式（I）的新型取代β-氨基酸衍生物，其中例如R2是从氢，低烷基基团，低烯基基团，低炔基基团，脂环烃基团，芳香族烃基团中选择的，其中所述基团可以用羟基，低烷氧基，低烷基，卤素，硝基，氰基，偶氮基，脲基，脲基烷基，羧基或羰基衍生物，三氟甲基，酰氧基，烷基硫基，芳基硫基，烷基磺酰基，芳基磺酰基，氨基，烷基氨基，三烷基硅基，氨基磺酰基，二烷基氨基，烷酰胺基，芳酰胺基，苯基，萘基，低炔基，其可以选择地被以下一种或多种替代：卤素，硝基，低烷氧基，低烷基，三烷基硅基，偶氮基和苯基；本发明还涉及包括这样的衍生物的制药组合物。