- Synthetic method of 4-(2-aminoethyl) tetrahydropyrane
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The invention belongs to the technical field of chemical medicine intermediate synthesis, and particularly relates to a synthetic method of medicine Bevenopran intermediate 4-(2-aminoethyl) tetrahydropyrane. The method comprises the following steps that (1) 4-chloro amylene oxide and methyl cyanoacetate take a reaction to obtain 2-cyano-2-(tetralin-4-pyranyl) methyl acetate; (2) the 2-cyano-2-(tetralin-4-pyranyl) methyl acetate is degreased to obtain (tetralin-4-pyranyl)-acetonitrile; (3) the (tetralin-4-pyranyl)-acetonitrile C takes a hydrogenation reaction to obtain 4-(2- aminoethyl) tetrahydropyrane. The method has the advantages that the 4-chloro amylene oxide and the methyl cyanoacetate are used as raw materials; the reaction time of the method is short; the cost is low; the raw materials are easy to obtain; no rank poison control or unstable chemical raw materials exist; safety and effectiveness are realized; the yield is high; the impurities are few.
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Paragraph 0011; 0018; 0019; 0020; 0021; 0022; 0023
(2017/04/29)
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- Diagnostic uses of 2-substituted adenosine carboxamides
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The present invention discloses a method for measuring myocardial function in a mammal in need of such measurement by: a) administering 2-substituted adenosine carboxamide derivatives at a dosage rate of less than 1 μg/kg/min, preferably between about 0.01 and 1 μg/kg/min; and then: b) performing a technique on the mammal to detect myocardial function. The method can be used to diagnose myocardial dysfunction by electrophysiologic analysis or by imaging the vasculature of the heart, especially under conditions that simulate stress.
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- 2-(SUBSTITUTED AMINO) ADENOSINES AS ANTIHYPERTENSIVES
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Disclosed are 2-substituted adenosine derivatives of the formula STR1 in which R represents a substituted amino grouping of the formula STR2 as defined herein; pharmaceutically acceptable ester derivatives thereof in which free hydroxy groups are esterified in the form of a pharmaceutically acceptable prodrug ester; and pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising said compounds; methods for their preparation; and their use in mammals as therapeutically effective adenosine-2 (A-2) agonists.
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- IMIDAZO[4,5-B]PYRIDINE DERIVATIVES AS CARDIOVASCULAR AGENTS
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Disclosed are the compounds of the formula STR1 wherein R represents hydrogen, lower alkyl, aryl or aryl-lower alkyl; R 1 represents hydrogen, lower alkyl, C 3-C 7-alkenyl, carbocyclic or heterocyclic aryl, carbocyclic or heterocyclic aryl-lower alkyl, C 3-C 7-cycloalkyl, or optionally lower alkyl substituted (C 3-C. sub.7-cycloalkyl, bicycloheptyl, bicycloheptenyl, adamantyl, tetrahydropyranyl or tetrahydrothiopyranyl)-lower alkyl, or diaryl-lower alkyl; R 2 represents hydrogen or lower alkyl; R 3 represents hydroxymethyl or--CONHR 4 in which R 4 represents hydrogen, lower alkyl, aryl-lower alkyl, C 3-C 7-cycloalkyl, C 3-C. sub.7-cycloalkyl-lower alkyl or hydroxy-lower alkyl; pharmaceutically acceptable ester derivatives thereof in which one or more of the hydroxy groups are esterified in form of a pharmaceutically acceptable ester; and pharmaceutically acceptable salts thereof; methods of preparation; pharmaceutical compositions; and their use as adenosine-2 agonists in mammals.
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- 2-substituted adenosine 5'-carboxamides as antihypertensive agents
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The compounds of the formula I STR1 wherein R represents hydrogen or lower alkyl; R 1 represents C 3 -C 6 -cycloalkyl optionally substituted by lower alkyl, C 3 -C 6 -cycloalkyl-lower alkyl optionally substituted by lower alkyl, bicycloalkyl, bicycloalkyl-lower alkyl, aryl, aryl-lower alkyl, aryl-C 3 -C 6 -cycloalkyl, 9-fluorenyl, diaryl-lower alkyl, 9-fluorenyl-lower alkyl, cycloalkenyl-lower alkyl, bicycloalkenyl-lower alkyl, tetrahydropyranyl-lower alkyl, tetrahydrothiopyranyl-lower alkyl or adamantyl-lower alkyl; or R 1 represents a bicyclic benzo-fused 5- or 6-membered saturated carbocyclic radical or a benzo-fused 5- or 6-membered saturated heterocyclic radical containing a heteroatom selected from oxygen and sulfur which is directly attached to the fused benzene ring, any said bicyclic radical being unsubstituted or substituted on the benzo portion by lower alkyl, lower alkoxy, hydroxy, halogen or trifluoromethyl, or by a substituent -W-Z in which W represents a direct bond, lower alkylene, lower alkenylene, thio-lower alkylene or oxy-lower alkylene and Z represents cyano, carboxy or carboxy derivatized in the form of a pharmaceutically acceptable ester or amide, or R 1 represents any said bicyclic radical substituted-lower alkyl; or R 1 represents aryl-hydroxy-lower alkyl; R 2 represents hydrogen, lower alkyl or aryl-lower alkyl; R 3 represents hydrogen or hydroxy; R 4 represents hydrogen, lower alkyl, aryl-lower alkyl, C 3 -C 6 -cycloalkyl or hydroxy-lower alkyl; aryl represents an optionally substituted carbocyclic aromatic radical, being preferably 1- or 2-naphthyl, phenyl, or naphthyl or phenyl substituted by one to three of lower alkyl, lower alkoxy, hydroxy, halogen or trifluoromethyl, or naphthyl or phenyl substituted by a substitutent -W-Z in which W represents a direct bond, lower alkylene, lower alkenylene, thio-lower alkylene or oxy-lower alkylene and Z represents cyano, carboxy or carboxy derivatized in the form of a pharmaceutically acceptable ester or amide; or aryl represents a heterocyclic aromatic radical, being preferably pyridyl or thienyl, each optionally substituted as described above for phenyl; pharmaceutically acceptable ester derivatives thereof in which free hydroxy groups are esterified in the form of a pharmaceutically acceptable ester; and pharmaceutically acceptable salts thereof; their preparation; and their use as adenosine-2 receptor agonists are disclosed.
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- N9 -cyclopentyl-substituted adenine derivatives having adenosine-2 receptor stimulating activity
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The compound of the formula I STR1 wherein R, R 3 and R 5 independently represent hydrogen or hydroxy provided that at least one of R, R 3 and R 5 represents hydroxy; R 1 represents hydrogen, lower alkyl, C 3 -C 7 -alkenyl, hydroxy-lower alkyl, optionally substituted cycloalkyl or optionally substituted cycloalkyl-lower alkyl, bicycloalkyl, bicycloalkyl-lower alkyl, adamantyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydropyranyl-lower alkyl, tetrahydrothiopyranyl-lower alkyl, adamantyl-lower alkyl, aryl-hydroxy-lower alkyl, aryl, aryl-lower alkyl, aryl-C 3 -C 6 -cycloalkyl, 9-fluorenyl, 9-fluorenyl-lower alkyl or cycloalkenyl-lower alkyl; or R 1 represents a bicyclic benzo-fused 5 or 6-membered saturated cyabocyclic radical or a benzo-fused 5 or 6-membered saturated heterocyclic radical containing a heteroatom selected from oxygen and sulfur directly attached to the fused benzene ring, any said bicyclic radicals being optionally substituted on the benzo portion by lower alkyl, lower alkoxy or halogen, or R 1 represents any said bicyclic radical substituted-lower alkyl; R 2 represents hydrogen, halogen, --S--R 1 '', --NR b --R 1 '', or --NH--R 1 '' in each of which R 1 '' has meaning as defined for R 1 provided that R 1 '' in --SR 1 '' does not represent hydrogen; R b represents lower alkyl; R 4 represents hydroxymethyl provided that R 2 does not represent either hydrogen or --NHR 1 '' in which R 1 '' represents either hydrogen or lower alkyl; or R 4 represents lower alkoxymethyl or lower alkylthiomethyl; or R 4 represents --CONHR 6 in which R 6 represents lower alkyl; aryl-lower alkyl, C 3 -C 6 -cycloalkyl or hydroxy-lower alkyl; pharmaceutically acceptable ester derivatives thereof in which free hydroxy groups are esterified in form of a pharmaceutically acceptable ester; and pharmaceutically acceptable salts thereof; methods for their preparation; and their use as adenosine receptor agonists are disclosed.
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