(1S,2R)-cis-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin hydrochloride | 85378-81-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (1S,2R)-cis-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin hydrochloride
• 英文别名: (+)-UH 232 hydrochloride；cis-1S,2R-5-Methoxy-1-methyl-2-(di-n-propylamino)tetralin.HCl；(1S,2R)-5-Methoxy-1-methyl-N,N-dipropyl-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride
• CAS: 85378-81-0
• 化学式: C₁₈H₂₉NO*ClH
• 分子量: 311.895
• InChiKey: ADVQBNGWEGSMGY-SQQLFYIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.66
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  13.7
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1S,2R)-cis-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin hydrochloride 在 氢溴酸 作用下， 反应 2.0h， 生成 (1S,2R)-cis-5-hydroxy-1-methyl-2-(di-n-propylamino)tetralin hydrobromide
  参考文献：
  名称：

  Novel dopamine receptor agonists and antagonists with preferential action on autoreceptors

  摘要：

  The enantiomers of cis-5-hydroxy-1-methyl-2-(di-n-propylamino)tetralin and its methyl ether have been synthesized. The compounds were tested for central dopamine (DA) receptor activity, by using biochemical and behavioral tests in rats. The (1R,2S)-(-) enantiomers of 1 and 2 are characterized as centrally acting DA-receptor agonists while the corresponding (1S,2R)-(+) enantiomers are characterized as centrally acting DA-receptor antagonists. Compounds (+)-1 and (+)-2 differ from classical neuroleptics in being able to increase DA synthesis rate in a wide dose range without reducing locomotor activity, suggesting a pronounced selectivity for DA autoreceptors. Also the (-) enantiomers seem to act preferentially on DA autoreceptors.

  DOI：

  10.1021/jm00146a012
• 作为产物：
  描述：

  (1S,2R)-cis-2-amino-5-methoxy-1-methyltetralin hydrochloride 生成 (1S,2R)-cis-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin hydrochloride
  参考文献：
  名称：

  JOHANSSON A. M.; ARVIDSSON L. -E.; HACKSELL U.; NILSSON J. L. G.; SVENSSO+, J. MED. CHEM., 30,(1987) N 4, 602-611

  摘要：

  DOI：

文献信息

• Resolved cis- and trans-2-amino-5-methoxy-1-methyltetralins: central dopamine receptor agonists and antagonists
  作者：Anette M. Johansson、Lars Erik Arvidsson、Uli Hacksell、J. Lars G. Nilsson、Kjell Svensson、Arvid Carlsson

  DOI：10.1021/jm00387a004

  日期：1987.4

  A series of 35 stereochemically well-defined C1-methyl-substituted derivatives of the potent dopamine (DA) receptor agonist 5-hydroxy-2-(di-n-propylamino)tetralin (5-OH-DPAT) have been synthesized. The compounds were tested for central DA receptor agonistic and antagonistic activity, by use of biochemical and behavioral tests in rats. In addition, the compounds were tested for in vivo interactions with 5,6-dihydroxy-2-(di-n-propylamino)tetralin (DiPr-5,6-ADTN). On the basis of pharmacological activity profiles, the active compounds have been classified into four groups: classical pre- and postsynaptic DA receptor agonists, DA receptor agonists with preferential action at presynaptic receptors, pre- and postsynaptic DA receptor antagonists, and DA receptor antagonists with preferential action at presynaptic receptors. Results obtained indicate that both 2R and 2S enantiomers of C5-oxygenated 2-aminotetralins may be able to bind to DA receptors but that only 2S antipodes are able to activate the receptors. O-Methylation of the C5-oxygenated (1S,2R)-2-amino-1-methyltetralin derivatives tends to increase their DA receptor antagonistic activity, whereas decrease of the size of the N-substituent(s) from n-propyl to ethyl or methyl appears to increase their activity at postsynaptic DA receptors.
• C1-Methylated 5-hydroxy-2-(dipropylamino)tetralins: central dopamine-receptor stimulating activity
  作者：Uli Hacksell、Anette M. Johansson、Lars Erik Arvidsson、J. Lars G. Nilsson、Stephan Hjorth、Arvid Carlsson、Hakan Wikstroem、Domingo Sanchez、Per Lindberg

  DOI：10.1021/jm00374a012

  日期：1984.8

  C1-Methylated derivatives of the potent dopaminergic agonist 5-hydroxy-2-(di-n-propylamino)tetralin (6) have been synthesized and tested for central dopamine (DA) receptor stimulating activity, by using biochemical and behavioral tests in rats. Both cis- and trans-5-hydroxy-1-methyl-2-(di-n-propylamino) tetralin (4 and 3) may be classified as central DA-receptor agonists, albeit of lower potency than 6. The results obtained indicate that both 4 and 3 display DA-autoreceptor stimulation capacity. However, only one of the isomers, trans-3, is able to elicit clear-cut postsynaptic DA receptor agonist actions at larger doses. 5-Hydroxy-1,1-dimethyl-2-(n-propylamino) tetralin (5) was found to be inactive.
• HALO SUBSTITUTED AMINOTETRALINS
  申请人：THE UPJOHN COMPANY

  公开号：EP0452390B1

  公开（公告）日：1994-10-26
• US5225596A
  申请人：——

  公开号：US5225596A

  公开（公告）日：1993-07-06
• [EN] HALO SUBSTITUTED AMINOTETRALINS
  申请人：——

  公开号：WO1990007490A1

  公开（公告）日：1990-07-12

  [EN] This invention is therapeutically useful tetralins and pharmaceutically acceptable acid addition salts thereof of formula (I), wherein X1 is halogen, CF3, -OR3, or -SR4; wherein R3 is alkyl(C1-C8); alkenyl(C1-C8), -CH2-cycloalkyl(C3-C8) or benzyl; wherein R4 is alkyl(C1-C3); wherein X2 is hydrogen, CF3 or halogen; wherein R7 is hydrogen or methyl; wherein R1 is hydrogen, alkyl(C1-C3), or cyclopropylmethyl; wherein R2 is -CH2-cycloalkyl(C3-C8), alkyl(C1-C8), -(CH2)q-R5 or -CH2CH2-Z-(CH2)rCH3; wherein R5 is phenyl, 2-thiophene or 3-thiophene; wherein Z is oxygen or sulfur; and wherein p is 1 or 2, q is 2 or 3, and r is 0 to 3; with the provisos that (1) when X1 is -OR3, X2 is halogen or CF3; and (2) when X1 is halogen, X2 is hydrogen, and p is 2, X1 is in a position other than the 8-position. These compounds are useful to treat central nervous system disorders.
  [FR] Tétralines thérapeutiques utiles et sels de celles-ci obtenus par addition d'acide tolérables pharmaceutiquement, ayant la formule (I) où X1 est halogène, CF3, -OR3, ou -SR4; où R3 est alkyle(C1-C8); alkényle(C1-C8), -CH2-cycloalkyle(C3-C8) ou benzyle; où R4 est alkyle(C1-C3); où X2 est hydrogène, CF3 ou halogène; où R7 est hydrogène ou méthyle; où R1 est hydrogène, alkyle(C1-C3), ou cyclopropylméthyle; où R2 est -CH2-cyclo-alkyle(C3-C8), alkyle(C1-C8), -(CH2)q-R5 ou -CH2CH2-Z-(CH2)rCH3; où R5 est phényle, 2-thiophène ou 3-thiophène; où Z est oxygène ou soufre; et où p est égal à 1 ou 2, q est égal à 2 ou 3, et r est compris entre 0 et 3; à condition que (1) lorsque X1 est -OR3, X2 est halogène ou CF3; et que (2) lorsque X1 est halogène, X2 est hydrogène; et lorsque p est égal à 2, X1 se trouve dans une position autre que la position 8. Lesdits composés sont utiles dans le traitement des troubles du système nerveux central.