美索的平 | 62658-88-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 美索的平
• 中文别名: 甲硫地平
• 英文名称: diethyl 2,6-dimethyl-4-<2-(methylthio)-3-pyridyl>-1,4-dihydropyridine-3,5-dicarboxylate
• 英文别名: 2',6'-dimethyl-2-methylsulfanyl-1',4'-dihydro-[3,4']bipyridinyl-3',5'-dicarboxylic acid diethyl ester；4-(2-methylthiopyrid-3-yl)-3,5-dicarbethoxy-2,6-dimethyl-1,4-dihydropyridine；Mesudipine；diethyl 2,6-dimethyl-4-(2-methylsulfanylpyridin-3-yl)-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 62658-88-2
• 化学式: C₁₉H₂₄N₂O₄S
• 分子量: 376.477
• InChiKey: DYGIPCPWPHKLMC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  美索的平 在 镍 四氯苯醌 、 间氯过氧苯甲酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 二氯甲烷 、 甲苯 为溶剂， 反应 10.25h， 生成 diethyl 4-(3-pyridyl)-2,4,6-trimethyl-1,4-dihydropyridine-3,5-dicarboxylate
  参考文献：
  名称：

  Synthesis, pharmacological effects, and conformation of 4,4-disubstituted 1,4-dihydropyridines

  摘要：

  4,4-Disubstituted 1,4-dihydropyridines are synthesized by intramolecular addition of sulfinyl carbanions to pyridines. These disubstituted derivatives show a loss of Ca antagonistic potency of up to three powers of 10 both in vitro on aortic rings and in vivo on anaesthetized dogs as compared to examples that are monosubstituted at the 4-position of the DHP ring. As the X-ray structure shows, the 4-aryl substituent is present not in the accustomed axial conformation, but in an equatorial one. This dramatic change in conformation could be the reason for the major loss of activity and would indicate the need for axial conformation of the aryl residue in pharmacologically active 1,4-dihydropyridines. The change in conformation was also confirmed by quantum chemical calculations (AM1).

  DOI：

  10.1021/jm00167a021
• 作为产物：
  描述：

  2-methylthionicotinaldehyde 、 乙酰乙酸乙酯 在 氨 作用下， 以 乙醇 、 水 为溶剂， 生成 美索的平
  参考文献：
  名称：

  4-(2-Chloro- or

  摘要：

  本发明涉及替代的1,4-二氢吡啶，具有有趣的生理活性，特别是对心血管系统的影响。本发明中的1,4-二氢吡啶在4位被2-氯吡啶-3-基或2-甲硫基吡啶-3-基取代，在3和5位被甲氧羰基或乙氧羰基取代，在2和6位被甲基取代。这些化合物的酸盐也包括在本发明中。这些化合物可以通过将适当的2-取代烟醛和烷基乙酮酸酯反应制备而成。根据本发明的化合物在非常低的剂量下表现出降压活性。

  公开号：

  US04096270A1

文献信息

• [EN] TOPICAL OPHTHALMIC COMPOSITIONS COMPRISING A COMBINATION OF CALCIUM ANTAGONISTS WITH KNOWN ANTIGLAUCOMA AGENTS<br/>[FR] COMPOSITIONS OPHTALMIQUES A USAGE LOCAL CONTENANT UNE COMBINAISON D'ANTAGONISTES DU CALCIUM ET D'AGENTS ANTIGLAUCOME
  申请人：ALCON LABORATORIES, INC.

  公开号：WO1993023082A1

  公开（公告）日：1993-11-25

  (EN) Calcium antagonists and compounds which lower intraocular pressure are combined in ophthalmic compositions to treat glaucoma. The calcium antagonists prevent or reduce the loss of visual field, while the intraocular pressure-lowering compounds maintain the intraocular pressure at normal levels.(FR) L'invention concerne des antagonistes du calcium et des composés abaissant la pression intraoculaire combinés dans des compositions ophtalmiques afin de traiter le glaucome. Les antagonistes du calcium empêchent au minimum la perte de champ visuel et les composés abaissant la pression intraoculaire maintiennent la pression intraoculaire à des niveaux normaux.

  （中文翻译）钙拮抗剂和降低眼内压的化合物被组合在眼科制剂中用于治疗青光眼。钙拮抗剂可以预防或减少视野损失，而降低眼内压的化合物可以维持眼内压在正常水平。
• [EN] BRONCHORELAXING COMPOUNDS<br/>[FR] COMPOSES BRONCHO-RELACHANTS
  申请人：RESPIRATORIUS AB

  公开号：WO2005070887A1

  公开（公告）日：2005-08-04

  A compound of the general formula (I) including its pharmaceutically acceptable acid addition salts formula (I) wherein A is CHR9, wherein R9 is H, C1-C6 alkyl;n is 1-3; B is CHR10, wherein R10 is H, C1-C6 alkyl; m is 1 or 2; D is O or S; E is CR11R12 or NR13, wherein R11 and R12 are, independent of each other, H or C1-C6 alkyl, R13 is H or C1-C6 alkyl; F is C1-C18 alkyl or R4-R7 cycloalkyl, which may be mono- or di-unsaturated and/or substituted, is useful in treating and preventing pulmonary disease characterized by bronchoconstriction; also disclosed is a pharmaceutical composition comprising the compound of formula (I), a pharmaceutical carrier and, optionally, an anti-asthmatic, a method for its manufacture, and a method for treating or preventing such disease.

  通式（I）的化合物及其药学上可接受的酸加合盐，其中A为CHR9，其中R9为H，C1-C6烷基；n为1-3；B为CHR10，其中R10为H，C1-C6烷基；m为1或2；D为O或S；E为CR11R12或NR13，其中R11和R12独立地为H或C1-C6烷基，R13为H或C1-C6烷基；F为C1-C18烷基或R4-R7环烷基，可以是单烯或双烯和/或取代的，用于治疗和预防以支气管收缩为特征的肺部疾病；还公开了包含通式（I）的药物组合物、药物载体和可选的抗哮喘药、其制造方法以及治疗或预防该疾病的方法。
• Diagnostic/therapeutic agents
  申请人：Klaveness Jo

  公开号：US20050002865A1

  公开（公告）日：2005-01-06

  Targetable diagnostic and/or therapeutically active agents, e.g. ultrasound contrast agents, comprising a suspension in an aqueous carrier liquid of a reporter comprising gas-containing or gas-generating material, said agent being capable of forming at least two types of binding pairs with a target.

  可定位的诊断和/或治疗活性剂，例如超声对比剂，包括悬浮在水载体液中的报告物，该报告物包含含气体或生成气体的材料，该剂能够与目标形成至少两种结合对。
• Bronchorelaxing compounds
  申请人：Skogvall Staffan

  公开号：US20060040919A1

  公开（公告）日：2006-02-23

  A compound of the general formula (I) including its pharmaceutically acceptable acid addition salts wherein A is CHR 9 , wherein R 9 is H, C 1 -C 6 alkyl; n is 1-3; B is CHR 10 , wherein R 10 is H, C 1 -C 6 alkyl; m is 1 or 2; D is O or S; E is CR 11 R 12 or NR 13 , wherein R 11 and R 12 are, independent of each other, H or C 1 -C 6 alkyl, R 13 is H or C 1 -C 6 alkyl; F is C 1 -C 18 alkyl or R 4 -R 7 cycloalkyl, which may be mono- or di-unsaturated and/or substituted, is useful in treating and preventing pulmonary disease characterized by bronchoconstriction; also disclosed is a pharmaceutical composition comprising the compound of formula (I), a pharmaceutical carrier and, optionally, an anti-asthmatic, a method for its manufacture, and a method for treating or preventing such disease.

  化合物的一般式(I)及其药学上可接受的酸盐包括其中，其中A为CHR9，其中R9为H，C1-C6烷基；n为1-3；B为CHR10，其中R10为H，C1-C6烷基；m为1或2；D为O或S；E为CR11R12或NR13，其中R11和R12独立地为H或C1-C6烷基，R13为H或C1-C6烷基；F为C1-C18烷基或R4-R7环烷基，可以是单烯或双烯和/或取代的，用于治疗和预防以支气管收缩为特征的肺部疾病；还公开了包括式(I)化合物的药物组合物、药物载体和可选的抗哮喘药、其制造方法以及治疗或预防该疾病的方法。
• Long acting formulation
  申请人：SYNTEX (U.S.A.) INC.

  公开号：EP0301133A2

  公开（公告）日：1989-02-01

  A long acting sustained release pharmaceutical composition for dihydropyridine calcium channel blockers wherein the calcium channel blocker and a pH-dependent binder are intimately admixed in essentially spherically shaped non-rugose particles of up to 1.2 mm in diameter.

  一种用于二氢吡啶类钙通道阻滞剂的长效缓释药物组合物，其中钙通道阻滞剂和一种 pH 值依赖性粘合剂紧密混合在直径不超过 1.2 毫米的球形非rugose 颗粒中。