Synthesis and Antibacterial and Antifungal Activity of 3-(Azol-1-Yl)-6-R-1,2,4,5-Tetrazines

Pharmaceutical Chemistry Journal - Nucleophilic substitution and 1,3-dipolar cycloaddition reactions were used to synthesize 3,6-disubstituted derivatives of simm-tetrazine containing azolyl,...     

7-[(2S)-2-羟甲基-4-氨基-1-吡咯烷基]氟喹诺酮类化合物的合成及体外抗菌活性

用反式-L-羟脯氨酸经对甲苯磺酰氯保护、甲酯化、氧化、肟化、四氢铝锂还原、叔丁氧基羰基保护后脱除对甲苯磺酰保护基,与不同的氟喹诺酮中间体缩合,最后经脱除叔丁氧基羰基等反应得到目标物,结构经1HNMR和FAB-MS确证,并进行了体外抗菌活性试验.结果表明,除化合物13对供试的大部分菌株,特别是对链球菌的体外活性相当于或优于对照药加替沙星和环丙沙星外,其余3个目标物总体活性均低于对照品.     

Synthesis and Biological Activity of Ethyl 2-[8-Arylmethylidenehydrazino-3-Methyl-7-(1-Oxothietan-3-YL)Xanth-1-YL]Acetates

Pharmaceutical Chemistry Journal - Ethyl 2-[8-Arylmethylidenehydrazino-3-methyl-7-(1-oxothietan-3-yl)xanth-1-yl]acetates (IV) were synthesized via reactions of ethyl...     

Synthesis and Pharmacological Activity of 2-(Diethylamino)Ethyl 9-Hydroxy-9H-Fluorene-9-Carboxylate Hydrochloride

Pharmaceutical Chemistry Journal - New fluorenecarboxylic acid derivatives (structural analogs of amizil) were synthesized. A compound with low toxicity (LD50 = 45 ± 9.9 mg/kg) and...     

Synthesis and Cardiotropic Activity of 1-(Methoxybenzyl)-4-{2-[(Methoxybenzyl)-Amino]Ethyl}Piperazines

Pharmaceutical Chemistry Journal - A group of new 1-(methoxybenzyl)-4-{2-[(methoxybenzyl)amino]ethyl}piperazines (1) were synthesized. The relationship of the structure of the triazaalkane linker...     

Synthesis and Antibacterial Activity of Sodium Salts of 7-[1-(4-Alkoxyphenyl)-1-cyclo-pentylcarbonylamino]-3-methyl-3-cephem-4-carboxylic Acid R-Sulfoxides

Pharmaceutical Chemistry Journal -     

Synthesis and Antiaggregant and Anticoagulant Activity of New 1-(4-Alkyloxybenzyl)-1H-Azoles and 1-(Adamantyl-1)-2-[4-(1H-Azol-1-Ylmethyl)-Phenoxy]Ethanones

Pharmaceutical Chemistry Journal - The development and optimization of synthetic methods for alkyl esters of 4-[(1H-azol-1-yl)methyl]phenols enabled the expansion of organic synthesis methodology,...     

Synthesis of Ethyl 4(1H)-Oxopyrimido[1,2-a]perimidine-3-carboxylate

In a recent communication¹), we reported the synthesis of some biologically interesting 1-substituted 3-(2-perimidyl)- ureas starting from 2-aminoperimidine ( 1a ). Because of the presence of a 1,3-dinucleophilic center in this molecule, 1a might undergo cyclocondensation with appropriate dielectrophiles. So this compound might be a useful synthon for the generation of novel fused perimidine derivatives. In an orientation experiment, we found that the reaction of 1a HBr with dimethyl acetylenedicarboxylate in the presence of Et₃N proceeded smoothly and afforded methyl 4(1H)-oxopyrimido[1,2-a]perimidine-2-carboxylate 2a in 52% yield²). The structure ov 2a was assigned on the basis of spectral analysis.     

Synthesis and antiarrhythmic activity of new 1-[1-[2-[3-(alkylamino)-2-hydroxypropoxy]phenyl]vinyl]-1 H-imidazoles and related compounds

Various 1-[1-[2-[3-(alkylamino)-2-hydroxypropoxy]phenyl]vinyl]-1 H-azoles were synthesized and investigated for beta-adrenoceptor-blocking and antiarrhythmic activities. Although no compounds showed more potent beta-blocking effects than propranolol in the isolated guinea pig right atria, many compounds exhibited significant antiarrhythmic effects against aconitine or ischemic arrhythmia in mice or dogs. 1-[2,5-Dichloro-6-[1-(1H-imidazol-1-yl)-ethenyl] phenoxy]-3-[(1-methylethyl)amino]-2-propanol hydrochloride (48) (711389-S) was selected as a candidate for clinical evaluation in man, since its antiarrhythmic effects were superior to those of quinidine, disopyramide, or propranolol. Asymmetric synthesis of (R)-(+)- and (S)-(-)-48 is described, and it is proven that there is no stereospecificity in the antiarrhythmic effect of 48.     

Synthesis and antinociceptive activity of 1-[2-(pyridyl)ethyl] and 1-[2-(dihydropyridyl)ethyl] analogues of fentanyl.

The syntheses and antinociceptive activities of all three isomeric 1-[2-(pyridyl)ethyl]-4-(propionanilido)-piperidine isosteres (11a-c) of fentanyl (1) are described. The 2- (11a), 3- (11b) and 4-pyridyl (11c) isomers exhibited 10, 2 and 0.2 times the antinociceptive activity of fentanyl, respectively. The ED50 values for 11a, 11b, 11c and fentanyl in the rat 4% NaCl-induced writhing test were 0.00023, 0.00085, 0.0087 and 0.0021 mg/kg sc, respectively. The 3-pyridyl (11b) and 4-pyridyl (11c) compounds were further elaborated to the 6-phenyl-1,6-dihydropyridine (12), C-2 H, Me, n-Bu and Ph 1,2-dihydropyridine (13a-d) analogues having a phenoxycarbonyl substituent on the dihydropyridine ring nitrogen. The most active compound in this series was 1-(2-[3-(1-phenoxycarbonyl-6-phenyl-1,6-dihydropyridyl)ethyl ])-4- (propionanilido)piperidine (12), which provided a 58% inhibition of writhing at a dose of 0.4 mg/kg sc. 1-(2-[4-(1-phenoxycarbonyl-1,2-dihydropyridyl)ethyl])-4- (propionanilido)piperidine (13a) exhibited an ED50 of 1.3 mg/kg sc, indicating a decrease in antinociceptive activity of about a 100 fold relative to the parent 4-pyridyl compound (11c). The dihydropyridine analogues 12 and 13 exhibit substantial antinociceptive activity relative to meperidine (ED50 = 0.6 mg/kg sc). The muscular rigidity effect induced by the pyridine compounds (11a-c) at a dose of 4 mg/kg sc, was not illicited by the dihydropyridine analogues at the same dose, or at a high dose of 40 mg/kg sc (13a). Compounds 12 and 13 may therefore be useful lead compounds for the development of more useful 4-anilidopiperidines if the antinociceptive activity can be dissociated from the muscular rigidity effect.     

Synthesis and Antiaggregant Activity of N-[4-Oxo-4-(4-ethoxycarbonylpiperazin-1-yl)butyryl]glicyl-D,L-β-phenyl-β-Alanine Ethyl Ester

Pharmaceutical Chemistry Journal -