Pharmacological Evaluation of Some New 6-Amino/Methyl Pyridine Derivatives.

Abstract

Pyridines were reported to possess anticonvulsant, 1,2) cardiotonic, 3) antihypertensive, 4) b-adrenergic blocking activity.5) Aryloxypropanolamines were reported to be associated with b-adrenergic blocking, 6,7) CNS depressant 8) and hypotensive 9) activities. In view of this potential nature of these moieties, it was thought worthwhile to study the effects of two pharmacophoric moieties like pyridine and propanolamine/ethanediamine in a single molecule. We have reported the potential anticonvulsant activity of arylaminopropanolamine 10) of pyridine and arylaminopropanolamine/ aryloxyaminopropane, [11][12][13] to continue our work with the same intention, it was envisaged that, chemical entities with both pyridine and arylaminopropanolamine/ethanediamine moieties would result in compounds of interesting biological activities.In the present study, we report the synthesis, the pharmacological evaluation, and structure-activity relationship of 2-(3Ј-substituted-2Ј-hydroxypropylamino/2Ј-substituted-ethylamino)-pyridine. The compounds were characterized by IR, 1 H-NMR spectral and elemental analysis. The compounds were investigated for anticonvulsant activity, the decrease in the elevated motor activity by introceptive chemical stimuli (amphetamine antagonistic activity) at the dose level of 25 and 50 mg/kg, cardiac activity on isolated frog heart and antihistaminic on guinea pig ileum. ChemistryMelting points were determined in open capillary tubes and are uncorrected. IR spectra were recorded (in KBr) on Bomem FT-IR spectrophotometer M.B Serial II. 1 H-NMR and IR spectra were consistent with the assigned structures. Synthesis of 2-(2-Chloroethylamino)-6-aminopyridine 2,6-Diaminopyridine was reacted with 1,2-dichloroethane, using the previously reported procedure.10) A solution of sodium methoxide (0.113 mol of sodium and 75 ml of methanol) was added to 0.113 mol of 2,6-diaminopyridine and refluxed for 1 h. Then the methanol was completely removed from the medium and 10 ml of anhydrous dimethyl formamide (DMF) was added to the dry residue. A solution of 1,2-dichloroethane (0.113 mol) in 10 ml anhydrous dimethyl formamide was then added dropwise to the reaction mixture with continuous stirring. The mixture was stirred for 1 h at room temperature. The product was filtered, dried in vacuum and recrystallised by using chloroform-diethylether (1 : 1). Yieldϭ56%, mp 175°C. , 49.12; H, 5.84; N, 24.56. Found: C, 49.36; H, 5.58; N, 24.34.General Method of Synthesis of 1a to m 2-(2-Chloroethylamino)-6-aminopyridine was reacted with various amines, using the previously reported procedure.10) A solution of 2-(2-chloroethylamino)-6-aminopyridine (0.013 mol) and the appropriate amine (0.013 mol) in 40 ml of methanol was refluxed for 24 h. The product obtained was filtered, vacuum dried and recrystallized using 1 : 1 acetone-diethylether (1c, 1e, 1f, 1l), 1 : 1 ethanol-diethylether (1a, 1h, 1k, 1m), 1 : 1 chloroform-diethylether (1b, 1g) and 1 : 1 methanol-diethylether (1d, 1i, 1j).2-(2-Morpholinoethylamino)-6-aminopyridine 1a:...

Synthesis, Anticonvulsant and Antihypertensive Activities of 8-Substituted Quinoline Derivatives

“…The increase in the carbon atom number at the 4th position of piperazine influenced the activity remarkably. In the propanol series (12)(13)(14)(15)(16)(17)(18)(19)(20), only compounds 13, 14, 19 and 20 were found to have a high degree of protection against MES-induced convulsions. 4-phenylpiperazino substituted compounds at the 3Ј position showed higher protection than the other substitutions at piperazine compounds.…”

“…We have already reported the potential anticonvulsant activity and the b-blocking activity of propanolamine, aminopropane and aminoethane from our laboratory. [14][15][16][17][18][19][20] To explore the heteroaryl and propanolamine/aminoethane combination, it was envisaged that chemical entities with both quinoline and aryloxypropanolamine/aminoethane moieties would result in compounds with interesting biological activities.…”

3-(2-Pyridylaminocarbonyl)propanoic acid

“…For background on the pharmaceutical applications of this family of compounds, see: Narendar et al (2003); Ravlee et al (2003).…”

One Pot Synthesis of Novel 4-[(5-Aryl-1,3,4-thiadiazol-2-ylamino)methyl]phenol Derivatives

“…1,3,4-噻二唑衍生物因其特殊结构而具有良好的杀 虫 [1] 、杀菌 [2,3] 、除草 [4] 、植物生长调节 [5] 、药物活性 [6,7] 等多种功效而倍受关注, 同时由于其环上的 N, S 原子均 能参与生命活动, 因而也具有广泛的生理活性, 如抗 炎 [8] 、 抗菌 [9] 、 抗癌 [10,11] 等作用, 已成为当今的研究热点.…”