珍米洛非班 | 149820-74-6

• 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
• 中文名称: 珍米洛非班
• 英文名称: xemilofiban
• 英文别名: CS-551；ethyl 3S-[[4-[[4-(aminoiminomethyl)phenyl]amino]-1,4-dioxobutyl] amino]-4-pentynoate；ethyl 3S[[4-[[4-(aminoiminomethyl)phenyl]amino]-1,4-dioxobutyl]-amino]-4-pentynoate；xemlofiban；ethyl (3S)-3-[[4-(4-carbamimidoylanilino)-4-oxobutanoyl]amino]pent-4-ynoate
• CAS: 149820-74-6
• 化学式: C₁₈H₂₂N₄O₄
• 分子量: 358.397
• InChiKey: ZHCINJQZDFCSEL-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  26
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  134
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  珍米洛非班 在 硫酸氢铵 、 phosphate buffer 作用下， 反应 20.0h， 生成 SC-54701
  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：

  ethyl (S)-3-amino-5-(trimethylsilyl)-4-pentynoate 在 N-甲基吗啉 、 四丁基氟化铵 、 氯甲酸异丁酯 作用下， 生成 珍米洛非班
  参考文献：
  名称：

  A very short, efficient and inexpensive synthesis of the prodrug form of SC-54701A a platelet aggregation inhibitor

  摘要：

  A short and efficient synthesis of the prodrug form of SC-54701A has been achieved from (trimethylsilyl)acetylene in 6 steps with an overall yield of 19%. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00293-x

文献信息

• [EN] PHOSPHONIC ACID DERIVATES AND THEIR USE AS P2Y12 RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS D'ACIDE PHOSPHONIQUE ET LEUR UTILISATION EN TANT QU'ANTAGONISTES DU RÉCEPTEUR P2Y12
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2009069100A1

  公开（公告）日：2009-06-04

  The invention relates to 2-phenyl-pyrimidine derivatives containing a phosphonic acid motif and their use as P2Y12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals. (I).

  这项发明涉及含有膦酸基团的2-苯基嘧啶衍生物，以及它们作为P2Y12受体拮抗剂在治疗和/或预防外周血管、内脏-、肝脏和肾脏血管、心血管和脑血管疾病或与血小板聚集有关的疾病或状况中的使用，包括人类和其他哺乳动物中的血栓形成。（I）。
• Methods for synthesizing organoboronic compounds and products thereof
  申请人：Walter Armin

  公开号：US20050119226A1

  公开（公告）日：2005-06-02

  Organoboronic acids, for example Cbz-(R)-Phe-(S)-Pro-(R)-Mpg-B(OH) 2 , are made by hydrolysing their diethanolamine adducts under conditions which avoid substantial C—B bond breakage. The product acids are substantially free of degradation product derived from cleavage of the C—B bond thereof. The acids are used to make base addition salts thereof. The salts are formulated into anti-thrombotic pharmaceutical formulations.

  有机硼酸，例如Cbz-(R)-Phe-(S)-Pro-(R)-Mpg-B(OH)2，是通过在避免大量C—B键断裂的条件下水解它们的二乙醇胺加合物制备的。所得的产物酸基本上不含有从C—B键裂解产生的降解产物。这些酸用于制备它们的碱盐。这些盐被配制成抗血栓药物配方。
• Combinations of lipid modulating agents and substituted azetidinones and treatments for vascular conditions
  申请人：Graziano P. Michael

  公开号：US20050096307A1

  公开（公告）日：2005-05-05

  The present invention provides compositions, therapeutic combinations and methods including: (a) at least one lipid modulating agent; and (b) at least one substituted azetidinone or substituted β-lactam sterol absorption inhibitor which can be useful for treating vascular conditions, diabetes, obesity and lowering plasma levels of sterols or 5α-stanols.

  本发明提供了包括以下内容的组合物、治疗组合和方法：(a)至少一种脂质调节剂；和(b)至少一种取代的噁唑烷酮或取代的β-内酰胺甾醇吸收抑制剂，可用于治疗血管疾病、糖尿病、肥胖以及降低血浆中甾醇或5α-甾烷醇的水平。
• Combinations of substituted azetidinones and CB1 antagonists
  申请人：Veltri P. Enrico

  公开号：US20060069080A1

  公开（公告）日：2006-03-30

  The present invention provides compositions, therapeutic combinations and methods including: (a) at least one selective CB 1 antagonist; and (b) at least one substituted azetidinone or substituted β-lactam sterol absorption inhibitor which can be useful for treating vascular conditions, diabetes, obesity, metabolic syndrome and lowering plasma levels of sterols or 5α-stanols.

  本发明提供了包括以下内容的组合物、治疗组合和方法：(a)至少一种选择性CB1拮抗剂；和(b)至少一种取代的氮杂环丁烷或取代的β-内酰胺甾醇吸收抑制剂，可用于治疗血管疾病、糖尿病、肥胖、代谢综合征以及降低血浆中的甾醇或5α-甾烷醇水平。
• [EN] DIPHENYLAZETIDINONE DERIVATES PROCESSING CHOLESTEROL ABSORPTION INHIBITORY ACTIVITY<br/>[FR] DERIVES DIPHENYLAZETIDINONE PRESENTANT UNE ACTIVITE D'INHIBITION D'ABSORPTION DU CHOLESTEROL
  申请人：ASTRAZENECA AB

  公开号：WO2005061451A1

  公开（公告）日：2005-07-07

  Compounds of formula (XV): [Chemical formula should be inserted here. Please see paper copy] (XV) (wherein variable groups are as defined within) pharmaceutically acceptable salts, solvates, solvates of such salts and prodrugs thereof and their use as cholesterol absorption inhibitors for the treatment of hyperlipidaemia are described. Processes for their manufacture and pharmaceutical compositions containing them are also described.

  公式（XV）的化合物：[应在此处插入化学公式。请参见纸质副本]（XV）（其中变量组如内部定义）药物可接受的盐、溶剂化物、这些盐的溶剂化物和前药及其用作治疗高脂血症的胆固醇吸收抑制剂。还描述了它们的制造过程和含有它们的药物组合物。