(1R,3S)-1-(aminomethyl)-3-tert-butyl-3,4-dihydro-1H-isochromene-5,6-diol;hydrochloride | 134456-61-4

• 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: (1R,3S)-1-(aminomethyl)-3-tert-butyl-3,4-dihydro-1H-isochromene-5,6-diol;hydrochloride
• CAS: 134456-61-4
• 化学式: C₁₄H₂₁NO₃*ClH
• 分子量: 287.787
• InChiKey: SHWRTPUJMGNQGE-FXMYHANSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.51
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  75.7
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  环己酮缩邻苯二酚 在 盐酸 、 lithium aluminium tetrahydride 、 正丁基锂 、 叠氮化锂 、 三氟化硼乙醚 作用下， 以 乙醚 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.0h， 生成 (1R,3S)-1-(aminomethyl)-3-tert-butyl-3,4-dihydro-1H-isochromene-5,6-diol;hydrochloride
  参考文献：
  名称：

  Synthesis and dopaminergic activity of 3-substituted 1-(aminomethyl)-3,4-dihydro-5,6-dihydroxy-1H-2-benzopyrans: characterization of an auxiliary binding region in the D1 receptor

  摘要：

  The synthesis and dopaminergic activity of a series of C3 and nitrogen-substituted 1-(aminomethyl)-3,4-dihydro-5,6-dihydroxy-1H-2-benzopyrans (isochromans) is described. The synthesis of the compounds was stereospecific for the 1,3 cis isomer, and the enantioselective synthesis of both enantiomers of one of the analogoues (20) was achieved. It was determined that all of the dopaminergic activity resides in the [1R,3S] isomer. Generally, substitution at the C3 position provided compounds with very high potency (< 10 nm EC50) and selectivity for the D1 receptor, with a wide range of intrinsic activities (60-160%). Analogues containing C3 substituents including aryl, arylalkyl, and cyclic and acyclic alkyl groups showed a marked enhancement of dopaminergic activity compared to the unsubstituted compound. As a class, the drugs were orally active in the rat rotation model with a very long duration of action.

  DOI：

  10.1021/jm00112a034

文献信息

• DOPAMINE AGONISTS
  申请人：ABBOTT LABORATORIES

  公开号：EP0474767B1

  公开（公告）日：1996-02-21
• US4963568A
  申请人：——

  公开号：US4963568A

  公开（公告）日：1990-10-16
• [EN] DOPAMINE AGONISTS
  申请人：ABBOTT LABORATORIES

  公开号：WO1990015056A1

  公开（公告）日：1990-12-13

  (EN) Novel compounds are provided of formula (I), or a pharmaceutically acceptable salt, ester or amide thereof, wherein A is O, S, CHR2, CR2 or C when n is 0 and A and R6 taken together form a nitrogen-containing 5-, 6- or 7-membered ring, and n is zero or 1. The dotted lines represent optional double bonds. R1 is selected from hydrogen and a readily cleavable group. R2 is selected from hydrogen, alkyl, substituted alkyl, alkenyl and alkynyl. R3 is selected from alkyl, substituted alkyl, alkenyl, alkynyl, cycloalkyl, carbocyclic aryl, carbocyclic arylalkyl and heterocycle. R4 is selected from hydrogen and alkyl or, taken together with R3 and the carbon atom to which they are attached, forms a spirocycloalkyl ring of from 3 to 7 carbons. R5 is selected from hydrogen, alkyl and substituted alkyl or, taken together with R3 and the carbon atoms to which they are attached forms a cycloalkyl ring of from 5 to 7 carbons. R6 is selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, carbocyclic arylalkyl, alkanoyl of from 1 to 8 carbons, amino acid and dipeptide or, taken together with A when A is C and when n is 0, forms a nitrogen-containing 5-, 6-, or 7-membered ring. R7 is hydrogen or alkyl or, taken together with R6 or R8, forms a nitrogen-containing 5-, 6- or 7-membered ring, provided that when R6 is carbocyclic arylalkyl, R7 is not alkyl. R8 is hydrogen or alkyl or, taken together with R6 or R7, forms a nitrogen-containing 5-, 6-, or 7-membered ring or, taken together with the catechol ring at the 8-position and the carbon atoms to which they are attached, forms a 5-, 6- or 7-membered ring. The compounds of the invention are useful for treating dopamine-related neurological, psychological and cardiovascular disorders as well as in the treatment of cognitive impairment, attention deficit disorder, and substance abuse and other addictive behavior disorders.(FR) L'invention concerne des nouveaux composés de la formule (I), où un sel, un esther ou un amide pharmaceutiquement acceptables de ceux-ci, dans laquelle A représente O, S, CHR2, CR2 ou C lorsque n est égal à 0, et A ainsi que R6 forment ensemble un anneau à 5, 6 ou 7 éléments contenant de l'azote, et n est égal à 0 ou à 1. Les lignes pointillées représentent des doubles liaisons facultatives. R1 est choisi entre l'hydrogène et un groupe facilement clivable. R2 est choisi entre hydrogène, alkyle, alkyle substitué, alcényle et alkynyle. R3 est choisi entre alkyle, alkyle substitué, alcényle, alkynyle, cycloalkyle, aryle carbocyclique, arylalkyle carbocyclique et un hétérocycle. R4 est choisi entre hydrogène et alkyle ou, pris avec R3 et l'atome de carbone auquel ils sont fixés, il forme un anneau spirocycloalkyle comportant 3 à 7 atomes de carbone. R5 est choisi entre hydrogène, alkyle et alkyle substitué ou, pris avec R3 et les atomes de carbone auxquels ils sont fixés, il forme un anneau cycloalkyle comprenant 5 à 7 atomes de carbone. R6 est choisi entre hydrogène, alkyle, acényle, alkynyle, cycloalkyle, arylalkylcarbocyclique, alcanoyle comportant 1 à 8 atomes de carbone, un acide aminé et bipeptide ou, pris ensemble avec A lorsque A représente C et lorsque n est égal à 0, il forme un anneau à 5, 6 ou 7 éléments contenant de l'azote. R7 représente hydrogène ou alkyle ou, pris avec R7 ou R8, il forme un anneau à 5, 6 ou 7 éléments contenant de l'azote, à condition que lorsque R6 représente arylalkyl carbocyclique, R7 ne représente pas alkyle. R8 représente hydrogène ou alkyle ou, pris avec R6 ou R7, il forme un anneau à 5, 6 ou 7 éléments contenant de l'azote, ou pris avec l'anneau de pyrocatéchine à la position 8 et les atomes de carbone auxquels ils sont fixés, il forme un anneau à 5, 6 ou 7 éléments. Les composés de l'invention sont utiles pour traiter les troubles neurologiques, psychologiques et cardiovasculaires liés à la dopamine, ainsi que dans le traitement de l'insuffisance cognitive, des troubles déficitaires de l'attention, des abus de substances chimiques et d'autres troubles du comportement provoqués par une accoutumance.
• Synthesis and dopaminergic activity of 3-substituted 1-(aminomethyl)-3,4-dihydro-5,6-dihydroxy-1H-2-benzopyrans: characterization of an auxiliary binding region in the D1 receptor
  作者：Michael P. DeNinno、Robert Schoenleber、Richard J. Perner、Linda Lijewski、Karen E. Asin、Donald R. Britton、Robert MacKenzie、John W. Kebabian

  DOI：10.1021/jm00112a034

  日期：1991.8

  The synthesis and dopaminergic activity of a series of C3 and nitrogen-substituted 1-(aminomethyl)-3,4-dihydro-5,6-dihydroxy-1H-2-benzopyrans (isochromans) is described. The synthesis of the compounds was stereospecific for the 1,3 cis isomer, and the enantioselective synthesis of both enantiomers of one of the analogoues (20) was achieved. It was determined that all of the dopaminergic activity resides in the [1R,3S] isomer. Generally, substitution at the C3 position provided compounds with very high potency (< 10 nm EC50) and selectivity for the D1 receptor, with a wide range of intrinsic activities (60-160%). Analogues containing C3 substituents including aryl, arylalkyl, and cyclic and acyclic alkyl groups showed a marked enhancement of dopaminergic activity compared to the unsubstituted compound. As a class, the drugs were orally active in the rat rotation model with a very long duration of action.