Synthesis and pharmacological activity of derivatives of pyrano- and pyrido-[3,2]carbazoles

Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 23, No. 10, pp. 1197–1200, October, 1989.     

Synthesis and pharmacological examination of hydrogenated 8-phenyl-1H-pyrazino-[3,2,1-jk]carbazoles

Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 25, No. 2, pp. 27–29, February, 1991.     

A study on organic nitrates,Part VI. Synthesis and pharmacological activity of 1-isopropylamino-3-(1-naphthyloxy)-2-propyl nitrate

Basing on the studies on the relationship between the structure and activity, we have synthesized a nitrate analogue of propranolol as potential donor of nitric oxide. The obtained 1-isopropylamino-3-(1-naphthyloxy)-2-propyl nitrate decreases blood pressure more than propranolol and slows the heart rate less than propranolol. It also affects peripheral vascular resistance less than propranolol.     

Synthesis and pharmacological evaluation of novel potential ultrashort-acting beta-blockers

The basic relationship between chemical structure and pharmacological activity of eight newly developed potential ultrashort-acting beta-adrenergic blockers was evaluated. The compounds studied are derivatives of arylcarbonyloxyaminopropanols and were prepared by four-step synthesis. All the compounds evaluated showed weak antiisoprenaline (beta-adrenergic receptor blocking) activity and antiarrhythmic (antiouabain) activity.     

Synthesis of perhydro-1,2,5-dithiazepine derivatives of potential pharmacological activity

New derivatives of perhydro-1,2,5-dithiazepine, 1-18, were synthesized. Compounds 1 and 16 showed spasmolytic and antihistaminic activity stronger than their analogs containing perhydro-1,4-thiazepine system.     

Studies in the synthesis of furocoumarins. Part 29: Synthesis of aminomethyl psoralen and angelicin derivatives as potential photo-chemotherapeutic agents.

Bromination of 2,7-dimethylfuro[2,3-h]benzopyran-5[H]-one (1a) and 2,5-dimethylfuro[3,2-g]benzopyran-7[H]-one (2a) with N-bromosuccinimide gave 2-bromomethyl-7-methylfuro[2,3-h]benzopyran-5[H]-one (1b) and 2-bromomethyl-5-methylfuro[3,2-g]benzopyran-7[H]-one (2b), respectively. The derivatives 1b and 2b were converted to 2-aminomethyl derivatives 1 c-h and 2 c-f by treatment with the appropriate secondary amine. The structures of 2-bromomethyl derivatives 1b and 2b have been confirmed by 13C-NMR spectra.     

Sydnone derivatives. Part VII: Synthesis of some novel thiazoles and their pharmacological properties.

The synthesis of some 4-(arylsydnonyl)-2-(4-arylhydrazono-3-methyl-5-oxo-2-pyrazolin-1-yl)- thiazoles by reacting 1-thiocarboxamido-3-methyl-4-(aryihydrazono)-2-pyrazolin-5-ones with different 4-bromoacetyl-3-arylsydnones is described. A few compounds from this series were screened for their anti-inflammatory, analgesic, and CNS depressant activities. Among the tested compounds 6s, 6d, 6n, and 6u showed significant anti-inflammatory activity comparable with that of standard drug Ibuprofen. Compounds containing chlorine and carboxylic substituents are more active. 6f, 6r, and 6u showed marked analgesic activity and most of the compounds tested showed promising CNS depressant activity comparable with that of standard drug pentobarbitone.     

Synthesis and pharmacological evaluation of some quinoline derivatives as potential cognition enhancers

The present paper describes the synthesis of a series of substituted 6-amino (1a-c) and 8-aminoquinoline derivatives (2b-c) and the evaluation of their ability to prevent the memory decline using a behavioural model, i.e. the elevated plus maze test. The effect of the candidate drugs on the activity of acetylcholinesterase was studied using the enzyme source from the mouse brain. The structures of the synthesized compounds were confirmed by UV, IR, 1H-NMR and elemental analysis. The 6-aminoquinoline derivative [6-(4-pyridyl)methylaminoquinoline] (1c) oxalate showed maximum % retention (50% at 5 mg/kg and 75% at 10 mg/kg) in the elevated plus maze test and maximum % inhibition (71% at 25 microM) of AChE on biochemical evaluation.     

Synthesis and pharmacological evaluations of N-(substituted benzoylamino)-5-carbethoxymethyl-1,2,3,6-tetrahydropyridines as potential antiinflammatory agents

In a continuing effort to enhance antiinflammatory activities, a series of 1,2,3,6-tetrahydropyridines, 4-tert butyl (9a), 4-methoxy (9b), 2-fluoro (9c), 3-chloro (9d) and 3,4-dichloro (9e) benzoylamino-5-carbethoxymethyl-1,2,3,6-tetrahydropyridines, were synthesized and evaluated for their antiinflammatory activities. Antiinflammatory activities were screened in animal models employing carrageenan induced paw-edema assay on the male Sprague-Dawley rat. Relative potencies for carrageenan induced paw-edema assay were 1, 0.07, > 0.03, 0.14, 0.4 and 0.12 for indomethacin (IC50 = 3 mg/kg), 9a, 9b, 9c, 9d and 9e, respectively. These novel tetrahydropyridines were assessed for nonsteroidal antiinflammatory drug-mediated inhibition of nitric oxide generation in RAW 264.7 macrophage cell line using Griess' reagent. Relative potencies for inhibition of nitric oxide generation by macrophages stimulated with lipopolysaccharide (1 microgram/ml) were 1, 0.48, 0.44, 0.43, 0.45 and 0.45 for indomethacin (IC50 = 0.434 mM), 9a, 9b, 9c, 9d and 9e, respectively. The results show that novel tetrahydropyridines have moderate antiinflammatory activities and that they inhibit nitric oxide production by inhibiting inducible nitric oxide synthase.     

Dimethyl cathate: synthesis and pharmacological investigation

Dimethyl cathate was synthesized through a reaction sequence starting from 3,4-pyridinedicarboxylic acid anhydride, and hydrolyzed to the not yet described cathic acid. Pharmacological screening procedures only showed a protection against the convulsive effect of pentylenetetrazol.     

Synthesis of 1-amino-2-(4-chloro-2-mercaptobenzenesulfonyl)guanidine derivatives with potential pharmacological activity

Syntheses of 1-amino-3-R2-2-(4-chloro-2- mercaptobenzenesulfonyl)guanidines [Va-o], 1-benzylidencimino-3-R2-2-(4-chloro-2- mercaptobenzenesulfonyl)guanidines [X, XII-XIX] and N-(4-chlorobenzylidene)-N'-(6-chloro-7-methyl-l, 1-dioxo- 1,4,2-benzodithiazin-3-yl)hydrazine [XX] have been described. The moderate anticancer and weak anti-HIV activities were observed in vitro for compounds [Va, e.g]. The obtained compounds were evaluated for their in vitro antimycobacterial activity towards a strain of Mycobacterium tuberculosis H 37 Rv.