ethyl 6-aminochroman-3-acetate | 188350-66-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: ethyl 6-aminochroman-3-acetate
• 英文别名: Ethyl 2-(6-aminochroman-3-yl)acetate；ethyl 2-(6-amino-3,4-dihydro-2H-chromen-3-yl)acetate
• CAS: 188350-66-5
• 化学式: C₁₃H₁₇NO₃
• 分子量: 235.283
• InChiKey: MHFFWCUFQLUBNB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 6-aminochroman-3-acetate 在 盐酸 、 ammonium acetate 、 三乙胺 作用下， 以 氯仿 为溶剂， 反应 26.0h， 生成 ethyl 6-[(4-amidinobenzoyl)amino]chroman-3-acetate
  参考文献：
  名称：

  New Platelet Fibrinogen Receptor Glycoprotein IIb-IIIa Antagonists:  Orally Active Series of N-Alkylated Amidines with a 6,6-Bicyclic Template

  摘要：

  The design, synthesis, and pharmacological evaluation of (S)-(-)-ethyl [6-[4-(morpholino-formimidoyl)benzamido]-3,4-dihydro-2H-1-benzopyran-3-yl]acetate hydrochloride ((S)-4 . HCl, MS-180), an orally active glycoprotein IIb-IIIa (GPIIb-IIIa) antagonist, are reported. Pharmacophore mapping of amidino and carboxyl groups of already known GPIIb-IIIa antagonists led to the synthesis of nine amidino acids containing 6,6-bicyclic ring skeletons (10a-i). Among them, the compounds 10a,c,e having an amide bond and 1,2,3,4-tetrahydronaphthalene or 3,4-dihydro-2H-1-benzopyran skeleton showed marked inhibitions with IC50 values of 46-57 nM in human platelet aggregation assay in vitro, but low oral activities. N-Alkylation of the amidino group coupled with the ester prodrug approach afforded MS-180 ((S)-4 . HCl), which generates in vivo the corresponding carboxylic acid (S)-3 as an active species. In vitro, (S)-3 inhibited ADP-induced aggregation of guinea pig, dog, and human platelets (IC50 = 110, 253, and 35 nM, respectively) and inhibited the binding of fibrinogen to immobilized GPIIb-IIIa of human platelets (IC50 = 0.12 nM). After oral administration of MS-180 ((S)-4 . HCl) to fasted beagle dog, ex vivo inhibition of platelet aggregation was observed. The maximal inhibitions were observed 2-4 h after dosing with dose dependency (60% inhibition at a dose of 1 mg/kg, 85% at 3 mg/kg, and 100% at 10 mg/kg, respectively) and the extent of the inhibitions paralleled the plasma concentration of the active species (S)-3. On the basis of these studies, we selected MS-180 ((S)-4 . HCl) as a candidate for clinical evaluation as a drug for the treatment and prevention of thrombosis in patients.

  DOI：

  10.1021/jm9801859
• 作为产物：
  描述：

  6-硝基苯并二氢吡喃-4-酮 在 palladium on activated charcoal 硫酸 、 氢气 作用下， 以 1,4-二氧六环 为溶剂， 60.0 ℃ 、1000.0 kPa 条件下， 反应 25.0h， 生成 ethyl 6-aminochroman-3-acetate
  参考文献：
  名称：

  New Platelet Fibrinogen Receptor Glycoprotein IIb-IIIa Antagonists:  Orally Active Series of N-Alkylated Amidines with a 6,6-Bicyclic Template

  摘要：

  The design, synthesis, and pharmacological evaluation of (S)-(-)-ethyl [6-[4-(morpholino-formimidoyl)benzamido]-3,4-dihydro-2H-1-benzopyran-3-yl]acetate hydrochloride ((S)-4 . HCl, MS-180), an orally active glycoprotein IIb-IIIa (GPIIb-IIIa) antagonist, are reported. Pharmacophore mapping of amidino and carboxyl groups of already known GPIIb-IIIa antagonists led to the synthesis of nine amidino acids containing 6,6-bicyclic ring skeletons (10a-i). Among them, the compounds 10a,c,e having an amide bond and 1,2,3,4-tetrahydronaphthalene or 3,4-dihydro-2H-1-benzopyran skeleton showed marked inhibitions with IC50 values of 46-57 nM in human platelet aggregation assay in vitro, but low oral activities. N-Alkylation of the amidino group coupled with the ester prodrug approach afforded MS-180 ((S)-4 . HCl), which generates in vivo the corresponding carboxylic acid (S)-3 as an active species. In vitro, (S)-3 inhibited ADP-induced aggregation of guinea pig, dog, and human platelets (IC50 = 110, 253, and 35 nM, respectively) and inhibited the binding of fibrinogen to immobilized GPIIb-IIIa of human platelets (IC50 = 0.12 nM). After oral administration of MS-180 ((S)-4 . HCl) to fasted beagle dog, ex vivo inhibition of platelet aggregation was observed. The maximal inhibitions were observed 2-4 h after dosing with dose dependency (60% inhibition at a dose of 1 mg/kg, 85% at 3 mg/kg, and 100% at 10 mg/kg, respectively) and the extent of the inhibitions paralleled the plasma concentration of the active species (S)-3. On the basis of these studies, we selected MS-180 ((S)-4 . HCl) as a candidate for clinical evaluation as a drug for the treatment and prevention of thrombosis in patients.

  DOI：

  10.1021/jm9801859
• 作为试剂：
  描述：

  、 Racemic 6-aminochroman-3-acetic acid ethyl ester hydrochloride 、 氢氧化钾 在 amine 、 氯化钠 、 potassium dihydrogenphosphate 、 Phosphoric Acid Dipotassium 、 magnesium sulfate 、 starch 、 ethyl 6-aminochroman-3-acetate 、 甲苯 、 2-(6-amino-3,4-dihydro-2H-chromen-3-yl)acetic acid 作用下， 以 甲苯 为溶剂， 反应 78.0h， 以(S) 6-aminochroman-3-acetic acid ethyl ester with a purity of more than 99% was obtained的产率得到ethyl 6-aminochroman-3-acetate
  参考文献：
  名称：

  Esterase and methods for the production of optically active chroman

  摘要：

  通过处理公式（I）的（3R）-和（3S）- chroman-3-acetic酯的混合物，可以获得光学活性的chroman-3-acetic酸和光学活性的chroman-3-acetic酸酯。[其中R1是具有1-5个碳原子的直链或支链烷基，R2是氢原子或取代或未取代的氨基]与具有光学选择性水解活性的酯酶或携带该水解酶的微生物，或其制剂处理。也可以使用从Pseudonocardia属细菌中获得的新型酯酶作为所述的酯酶。

  公开号：

  US06060290A1

文献信息

• Bicyclic compound and platelet aggregation inhibitor containing the same
  申请人：Mitsui Toatsu Chemicals, Inc.

  公开号：US05629321A1

  公开（公告）日：1997-05-13

  The invention relates to a novel compound which is represented by the formula (1) and has an excellent platelet aggregation inhibiting action based on fibrinogen antagonism. The platelet aggregation inhibitor containing the compound of the formula (1) as an effective ingredient are effective for prevention and curing of thrombosis and restenosis or reocclusion after percutaneous transluminal coronary angioplasty or percutaneous transluminal coronary recanalization.

  该发明涉及一种新型化合物，其化学式表示为（1），基于纤维蛋白原拮抗作用具有出色的抑制血小板聚集作用。含有化合物（1）的血小板聚集抑制剂作为有效成分对预防和治疗血栓形成以及经皮透支式冠状动脉成形术或经皮透支式冠状动脉再通术后的再狭窄或再闭塞具有有效性。
• Esterase and methods for the production of optically active chroman compounds
  申请人：Mitsui Chemicals, Inc.

  公开号：US06303349B1

  公开（公告）日：2001-10-16

  Optically active chroman-3-acetic acids and optically active chroman-3-acetic acid esters can be obtained by treating a mixture of (3R)- and (3S)-chroman-3-acetic esters of formula (I) [wherein R1 is a straight or branched alkyl group having 1-5 carbon atoms and R2 is a hydrogen atom or substituted or unsubstituted amino group] is treated with an esterase which has an optically selective hydrolyzing activity or microorganisms which carry said hydrolase, or a preparation therefrom. A novel esterase derived from bacteria of genus Pseudonocardia can also be used as said esterase.

  光学活性的3-羟基香豆酸和光学活性的3-羟基香豆酸酯可以通过处理式（I）的（3R）和（3S）-香豆酸酯混合物而获得[其中R1是1-5个碳原子的直链或支链烷基，R2是氢原子或取代或未取代的氨基]，处理时使用具有光学选择性水解活性的酯酶或携带该水解酶的微生物或其制剂。也可以使用源自假单胞菌属细菌的新型酯酶作为该酯酶。
• Bicyclic compounds useful as platelet aggregation inhibitors
  申请人：MITSUI TOATSU CHEMICALS, Inc.

  公开号：EP0709370A1

  公开（公告）日：1996-05-01

  The invention relates to a novel compound which is represented by the formula (1) and has an excellent platelet aggregation inhibiting action based on fibrinogen antagonism. The platelet aggregation inhibitor containing the compound of the formula (1) as an effective ingredient is effective for prevention and therapy of thrombosis and restenosis or reocclusion after percutaneous transluminal coronary angioplasty or percutaneous transluminal coronary recanalization.

  本发明涉及一种新型化合物，该化合物由式（1）表示，在纤维蛋白原拮抗作用的基础上具有优异的血小板聚集抑制作用。含有式（1）化合物作为有效成分的血小板聚集抑制剂可有效预防和治疗血栓形成以及经皮腔内冠状动脉成形术或经皮腔内冠状动脉再通术后的再狭窄或再闭塞。
• Esterase and its use for the production of optically active chroman compounds
  申请人：MITSUI CHEMICALS, INC.

  公开号：EP0892044A2

  公开（公告）日：1999-01-20

  Optically active chroman-3-acetic acids and optically active chroman-3-acetic acid esters can be obtained by treating a mixture of (3R)- and (3S)-chroman-3-acetic esters of formula (I) [wherein R1 is a straight or branched alkyl group having 1-5 carbon atoms and R2 is a hydrogen atom or substituted or unsubstituted amino group] is treated with an esterase which has an optically selective hydrolyzing activity or microorganisms which carry said hydrolase, or a preparation therefrom. A novel esterase derived from bacteria of genus Pseudonocardia can also be used as said esterase.

  通过处理式 (I) 的 (3R)- 和 (3S)- 色满-3-乙酸酯混合物，可获得光学活性色满-3-乙酸和光学活性色满-3-乙酸酯 [其中 R1 是具有 1-5 个碳原子的直链或支链烷基，R2 是氢原子或取代或未取代的氨基］ 用具有光学选择性水解活性的酯酶或携带上述水解酶的微生物或其制备物处理。也可以使用从假心属细菌中提取的新型酯酶作为所述酯酶。
• Amidine derivatives and platelet aggregation inhibitor containing the same
  申请人：MITSUI CHEMICALS, INC.

  公开号：EP0760364B1

  公开（公告）日：2000-07-19