Studies on cardiotonic agents. IV. Synthesis of novel 1-(6,7-dimethoxy-4-quinazolinyl)piperidine derivatives carrying substituted hydantoin and 2-thiohydantoin rings

A series of novel 1-(6,7-dimethoxy-4-quinazolinyl)piperidines carrying substituted hydantoin and 2-thiohydantoin rings was synthesized and examined for cardiotonic activity in anesthetized dogs. Introduction of isopropyl and sec-butyl group at the 5-position of the hydantoin and thiohydantoin rings led to potent inotropic activity. Effects of insertion of an alkyl chain between the piperidine and the hydantoin rings were also examined. The structural requirements necessary for optimal cardiotonic activity within the series were investigated.     

Studies on cardiotonic agents. III. Synthesis of 1-[1-(6,7-dimethoxy-4-quinazolinyl)-4-piperidinyl]-3-substituted 2-imidazolidinone and 2-imidazolidinethione derivatives

A series of 1-[1-(6,7-dimethoxy-4-quinazolinyl)-4-piperidinyl]-3-substituted 2-imidazolidinone and 2-imidazolidinethione derivatives was synthesized and examined for cardiotonic activity in anesthetized dogs. Alkylation of the 2-imidazolidinone (1) afforded the N-alkylated products, while alkylation of the 2-imidazolidinethione (12) afforded the S-alkylated derivatives accompanied with a small quantity of the N-alkylated products. The N-alkylated derivatives showed generally potent activity, and the S-alkylated ones exhibited weak activity. Insertion of an alkyl group between the piperidine and the imidazolidinone moiety generally resulted in a fall in activity.     

Studies on cardiotonic agents. VI. Synthesis of novel 4,5-dihydro-3(2H)-pyridazinone derivatives carrying some benzoheterocycles at the 6-position

Several benzothiazolyl, imidazobenzothiazolyl, benzothienyl, benzothienopyrimidinyl and quinazolinyl 4,5-dihydro-3(2H)-pyridazinones were synthesized and examined for cardiotonic activity in anesthetized dogs after i.v. administration. Among them, 4-methylamino-7-(2,3,4,5-tetrahydro-5-methyl-3-oxo-6- pyridazinyl)quinazoline (36) showed potent and long-lasting inotropic activity (relative potency = 2.11, milrinone = 1). The activity of 36 was more potent than indolidan (2) (relative potency = 1.53) which is one of the most potent inotropic agents to date.     

酰氨基硫脲及其相关杂环衍生物的研究III.1-(5-甲基异唑-3-甲酰基)-4-芳基氨基硫脲及其相关杂环衍生物

Eight 1-(5-methylisoxazol-3-ylcarbonyl)-4-substituted thiosemicarbazides (I), eight 3-(5-methylisoxazol-3-yl)-4-substituted-1,2,4-triazoline-5-thiones (II), seven 2-arylamino-5-(5-methylisoxazol-3-yl)-1,3,4-thiadiazoles, and five 2-arylamino-5-(5-methylisoxazol-3-yl)-1,3,4-oxadiazoles were prepared from isoxazole III and aryl isocyanates. The derivatives I and II showed antitubercular activity and promoted the growth of plumule of wheat in preliminary experiments     

Synthesis of new 2-substituted 6,7-dimethoxy-1-(methylcarbamoyl)-4-spirocyclopentane-1,2,3,4-tetrahydroisoquinolines

New 2-(heterylmethyl) derivatives were synthesized from 6,7-dimethoxy-4-spirocyclopentane-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid N-methylamide and heterylmethyl chlorides. The reactions of 2-chloroacetyl-substituted tetrahydroisoquinoline with versatile secondary amines and heterylthiols afforded the corresponding 2-aminoacetyl and 2-(heterylsulfanylacetyl) derivatives of tetrahydroisoquinoline series.     

Studies on cardiotonic agents. I. Synthesis of some quinazoline derivatives

A series of quinazoline derivatives with various 4-heterocyclylpiperidino groups at the 4-position was synthesized and tested for cardiotonic activity in anesthetized dogs. Among them, several 6,7-dimethoxyquinazoline derivatives showed potent cardiotonic activity.     

Studies on cardiotonic agents. II. Synthesis of novel phthalazine and 1,2,3-benzotriazine derivatives

A series of phthalazine and 1,2,3-benzotriazine derivatives which have heterocyclylpiperidino groups was synthesized and tested for cardiotonic activity in anesthetized dogs. Several 6,7-dimethoxyphthalazine derivatives showed relatively potent cardiotonic activity comparable to that of amrinone.     

Synthesis of some N-substituted 6,7-dimethoxy-1,2-benzothiazin(4H)-3-one 1,1-dioxides

Substituted 1,2-benzothiazin-3-ones have been prepared by cyclization of 4,5-dimethoxy-2-carboethoxymethybenzenesulfonamides. The latter were obtained by the action of ammonia and primary and secondary amines on 4,5-dimethoxy-2-carboethoxymethylbenzenesulfonyl chloride which in turn was obtained from ethyl 3,4-dimethoxyphenylacetate and chlorosulfonic acid.     

Synthesis of ferrocenyl-containing heterocyclic derivatives of 5-(4-aminophenyl)-10,15,20-triphenylporphyrin for sonodynamic therapy

The condensation of 1-(ferrocenylalkyl)pyrazole-3-carbaldehydes with 4′-aminotetraphenylporphyrin, followed by reduction with NaBH(OAc)₃ in 1,2-dichloroethane, provides a convenient method for the synthesis of 5-{4-[({1-[1-(ferrocen-1-yl)alkyl]-5-methyl-1H-pyrazol-3-yl}methyl)amino]phenyl}-10,15,20-triphenylporphyrins which exhibit pronounced cytotoxicity against Staphylococcus aureus under ultrasonic irradiation.     

Synthesis and characterization of trifluoromethyl heterocyclic compounds: 4-hydroxy-4-methyl-5-(2,2,2-trifluoro-1-trifluoromethylethyl)-1,3-thiazoline derivatives

We report the synthesis of two new bis-trifluoromethyl 4-hydroxy-1,3-thiazoline, and one thiazole derivatives from 5,5,5-trifluoro-4-(trifluoromethyl)-3-penten-2-one (1) by anti-Michael addition and condensation with thioamides. Spectroscopical properties, such as IR and Raman, ¹H, ¹³C and ¹⁹F NMR, as well as the crystalline structure of the 2-methyl-derivative are described. The crystalline structure shows short intermolecular F–F contacts. The 2-phenyl thiazole derivative was obtained by dehydration of the correspondent hydroxythiazoline, attempts to obtain the 2-methyl derivative were unsuccessful.     

Racematspaltung von (±)-5-äthyl-1-(3,4-dimethoxyphenyl)-6,7-dimethoxy-4-methyl-5H-2,3-benzodiazepin und anomales chiroptisches verhalten der enantiomeren

A process has been developed for resolving 1 , and the anomalous behaviour of the specific rotation of the enantiomers has been studied. It was shown that this is due to the shift in the conformational equilibrium la ? Ib , and not to an epimerization at C-5.