bimatoprost

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: bimatoprost
• 英文别名: (Z)-7-[(1R,2R,3R,5S)-3,5-Dihydroxy-2-[(E)-3-hydroxy-5-phenylpent-1-enyl]cyclopentyl]-N-ethylhept-5-enamide
• 化学式: C₂₅H₃₇NO₄
• 分子量: 415.573
• InChiKey: AQOKCDNYWBIDND-GCYMYIANSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  30
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  89.8
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  科立内脂二醇 在 咪唑 、 硫酸 、 potassium tert-butylate 、 四丁基氟化铵 、 二异丁基氢化铝 、 三乙胺 、 1H-benzotriazol-1-yl methanesulfonate 、 (-)-diisopinocamphenylborane chloride 、 lithium chloride 、 2-碘酰基苯甲酸 作用下， 以 四氢呋喃 、 甲醇 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 28.25h， 生成 bimatoprost
  参考文献：
  名称：

  Process for the synthesis of prostaglandins and intermediates thereof

  摘要：

  公开号：

  EP2495235B1

文献信息

• [EN] PROCESS FOR THE PREPARATION OF BIMATOPROST<br/>[FR] PROCÉDÉ DE PRÉPARATION DE BIMATOPROST
  申请人：GENTEC S A

  公开号：WO2017182465A1

  公开（公告）日：2017-10-26

  It is provided a process for the preparation of bimatoprost, which comprises: a) reacting a compound of formula (III) with ethylamine in the presence of a suitable solvent; and b) deprotecting compound obtained in step a) to obtain bimatoprost, wherein R1 is selected from (C1-C16)alkyl, (C1C16)haloalkyl, (C2-C16)alkenyl, (C2-C16)haloalkenyl, (C1-C16)alkoxy(C1-C16)alkyl, aryl, (C1-C16)alkylaryl, allyl, - (CH2-CH2-O)n-CH3 wherein n = 1, 2, 3 or 4, and -CH(O-CH2-CH2)2; R2 is selected from H, (C1-C16)alkyl, (C1-C16)haloalkyl, (C2-C16)alkenyl, (C2- C16)haloalkenyl, (C1-C16)alkoxy(CrC16)alkyl, aryl, (C1-C16)alkylaryl, allyl; or, alternatively, R1 and R2 taken together are selected from -CH2-CH2-CH2-, -CH2-CH2-, -O-CH2-CH2-, and -O-CH=CH-. There are also provided intermediates useful in such preparation process.

  提供了一种制备比马前列素的方法，包括：a）在适当的溶剂存在下，将化合物（III）与乙胺发生反应；b）去保护步骤a）中得到的化合物，以获得比马前列素，其中R1选自（C1-C16）烷基，（C1-C16）卤代烷基，（C2-C16）烯基，（C2-C16）卤代烯基，（C1-C16）烷氧基（C1-C16）烷基，芳基，（C1-C16）烷基芳基，烯丙基，-（CH2-CH2-O）n-CH3其中n = 1, 2, 3或4，和-CH（O-CH2-CH2）2；R2选自H，（C1-C16）烷基，（C1-C16）卤代烷基，（C2-C16）烯基，（C2-C16）卤代烯基，（C1-C16）烷氧基（C1-C16）烷基，芳基，（C1-C16）烷基芳基，烯丙基；或者，R1和R2一起选自-CH2-CH2-CH2-，-CH2-CH2-，-O-CH2-CH2-，和-O-CH=CH-。还提供了在这种制备过程中有用的中间体。
• [EN] A NOVEL PROCESS FOR THE PREPARATION OF PROSTAGLANDINS AND INTERMEDIATES THEREOF<br/>[FR] NOUVEAU PROCÉDÉ DE PRÉPARATION DE PROSTAGLANDINES ET DE LEURS INTERMÉDIAIRES
  申请人：BIOCON LTD

  公开号：WO2011055377A1

  公开（公告）日：2011-05-12

  This invention relates to novel process for the preparation of prostaglandin compounds having formula (K), wherein R is selected from the group consisting of C1-C7 alkyl; C7-C17 aralkyl wherein the aryl group is unsubstituted or substituted with one to three substituents selected from the group consisting of C1-C6 alkyl, halo and CF3; and (CH2)nOR2 wherein n is from 1 to 3 and R2 represents a C6-C10 aryl group which is unsubstituted or substituted with one to three substituents selected from the group consisting of C1-C6 alkyl, halo and CF3; and R1 is selected from OR3 and NHR3 wherein R3 is C1-C6 alkyl, H; and dashed lines represents a double bond or a single bond, is disclosed. Novel intermediates are also disclosed.

  本发明涉及一种制备公式（K）的前列腺素化合物的新工艺，其中R选自以下组中的一组：C1-C7烷基；C7-C17芳基烷基，其中芳基基团未取代或取代有1-3个取自C1-C6烷基，卤素和CF3的取代基；以及（CH2）nOR2，其中n为1-3，R2代表未取代或取代有1-3个取自C1-C6烷基，卤素和CF3的取代基的C6-C10芳基基团；R1选自OR3和NHR3，其中R3为C1-C6烷基，H；虚线表示双键或单键。本发明还揭示了新的中间体。
• NOVEL PROCESS FOR THE PREPARATION OF PROSTAGLANDINS AND INTERMEDIATES THEREOF
  申请人：Aswathanarayanappa Chandrashekar

  公开号：US20120209011A1

  公开（公告）日：2012-08-16

  This invention relates to novel process for the preparation of prostaglandin compounds having formula (K), wherein R is selected from the group consisting of C 1 -C 7 alkyl; C 7 -C 17 aralkyl wherein the aryl group is unsubstituted or substituted with one to three substituents selected from the group consisting of C 1 -C 6 alkyl, halo and CF 3 ; and (CH 2 ) n OR 2 wherein n is from 1 to 3 and R 2 represents a C 6 -C 10 aryl group which is unsubstituted or substituted with one to three substituents selected from the group consisting of C 1 -C 6 alkyl, halo and CF 3 ; and R 1 is selected from OR 3 and NHR 3 wherein R 3 is C 1 -C 6 alkyl, H; and dashed lines represents a double bond or a single bond, is disclosed. Novel intermediates are also disclosed.

  本发明涉及一种新型的制备具有式（K）的前列腺素化合物的方法，其中R选自以下组中的一种：C1-C7烷基；C7-C17芳基烷基，其中芳基基团未取代或取代有1至3个取代基，所述取代基选自C1-C6烷基，卤素和CF3；以及（CH2）nOR2，其中n为1至3，R2代表未取代或取代有1至3个取代基的C6-C10芳基基团，所述取代基选自C1-C6烷基，卤素和CF3；R1选自OR3和NHR3，其中R3为C1-C6烷基，H；虚线表示双键或单键。本发明还公开了新型中间体。
• PROCESS FOR THE PREPARATION OF BIMATOPROST
  申请人：Gentec, S.A.

  公开号：EP3235810A1

  公开（公告）日：2017-10-25

  It is provided a process for the preparation of bimatoprost, which comprises: a) reacting a compound of formula (III) with ethylamine in the presence of a suitable solvent; and b) deprotecting compound obtained in step a) to obtain bimatoprost, wherein R1 is selected from (C1-C16)alkyl , (C1-C16)haloalkyl, (C2-C16)alkenyl, (C2-C16)haloalkenyl, (C1-C16)alkoxy(C1-C16)alkyl, aryl, (C1-C16)alkylaryl, allyl,-(CH2-CH2-O)n-CH3 wherein n = 1, 2, 3 or 4, and -CH(O-CH2-CH2)2; R2 is selected from H, (C1-C16)alkyl , (C1-C16)haloalkyl, (C2-C16)alkenyl, (C2-C16)haloalkenyl, (C1-C16)alkoxy(C1-C16)alkyl, aryl, (C1-C16)alkylaryl, allyl; or, alternatively, R1 and R2 taken together are selected from -CH2-CH2-CH2-, -CH2-CH2-, -O-CH2-CH2-, and -O-CH=CH-. There are also provided intermediates useful in such preparation process.

  本发明提供了一种制备比马前列素的方法，包括：a）在适当的溶剂存在下，将式（III）化合物与乙基胺反应；和b）去保护步骤a）中得到的化合物以获得比马前列素，其中R1选自（C1-C16）烷基，（C1-C16）卤代烷基，（C2-C16）烯基，（C2-C16）卤代烯基，（C1-C16）烷氧基（C1-C16）烷基，芳基，（C1-C16）烷基芳基，丙烯基，-(CH2-CH2-O)n-CH3，其中n = 1, 2, 3或4，和-CH（O-CH2-CH2）2；R2选自H，（C1-C16）烷基，（C1-C16）卤代烷基，（C2-C16）烯基，（C2-C16）卤代烯基，（C1-C16）烷氧基（C1-C16）烷基，芳基，（C1-C16）烷基芳基，丙烯基；或者，R1和R2一起选自-CH2-CH2-CH2-，-CH2-CH2-，-O-CH2-CH2-和-O-CH=CH-。还提供了在该制备过程中有用的中间体。
• Drippable opthalmic bimatoprost gel
  申请人：MEDproject Pharma-Entwicklungs- und Vertriebsgesellschaft mbH

  公开号：US10314780B2

  公开（公告）日：2019-06-11

  The invention refers to a drippable ophthalmic gel, said gel having composition comprising bimatoprost in an amount of 0.003 to 0.03% by weight, polyacrylate in an amount of >0.2% by weight, povidone (PVP), dextrane, polyethylene glycols (PEG), carboxymethyl cellulose (CMC) or poly(vinyl alcohol) (PVA) in an amount of 0.2 to 10% by weight, an isotonizing agent in an amount to produce an osmolality of 200 to 400 mosml/kg, a salt for adjusting the viscosity in an amount of 0.05 to 0.4% by weight, a base in an amount to adjust the pH to 6 to 8 and excipients normally used in ophthalmic gels, having a viscosity in the range of 200 to 2000 mPa·s.

  本发明涉及一种可滴注的眼科凝胶，所述凝胶的成分包括重量百分比为 0.003 至 0.03% 的比马前列素、重量百分比大于 0.2% 的聚丙烯酸酯、重量百分比为 0.2 至 10%的聚维酮 (PVP)、糊精、聚乙二醇 (PEG)、羧甲基纤维素 (CMC) 或聚乙烯醇 (PVA)、可产生 200 至 400 毫升/千克渗透压的异渗剂、重量百分比为 0.05 至 0.0% 的用于调节粘度的盐。按重量计，可加入 0.2 至 10%的异构化剂，其用量可使渗透压达到 200 至 400 mosml/kg；按重量计，可加入 0.05 至 0.4%的用于调节粘度的盐；按重量计，可加入一定量的碱，其用量可将 pH 值调节到 6 至 8；以及通常用于眼科凝胶的赋形剂，其粘度范围为 200 至 2000 mPa-s。