N-(6,6-二甲基-2-庚烯-4-炔基)-N-甲基-α-取代-1-(4-取代)萘甲胺类的合成及抗真菌活性

根据氮唑类和烯丙胺类抗真菌化合物的构效关系、作用机理。设计合成了30个N-(6,6-二甲基-2-庚烯-4-炔基)-N-甲基-α-取代-1-(4-取代)萘甲胺类化合物。初步体外抑菌试验结果表明,大多数目标化合物对八种试验菌株都有不同程度的抗真菌活性。化合物Ⅰ_1a的真菌活性大致与克霉唑相当,对白念珠菌的活性明显高于naftifine和terbinafine,但对其它七种菌株的活性均不及naftifine和terbinafine;化合物Ⅲ_1a对八种试验菌株的活性均与terbinafine相当。

Synthesis and antifungal activity of N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-alpha-substituted -1-(4-substi tuted) naphthalenemethanamines

Thirty (E)- or (Z)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-alpha-subst itu ted-1-(4-substituted)naphthalenemethanamines were synthesized for searching of more potent and less toxic antimycotic agents. All title compounds and most of the intermediates are new. Results of preliminary biological tests showed that most of the title compounds exhibited activity against the common pathogenic fungi such as Cryptococcus neoformnas, Candida albicans, Aspergillus fumigatus, Cladosporium carrionii, Sporothrix schenckii, Microsporum gypseum, Trichophyton rubrum and Epidermophyton floccosum. The antifungal activity of compound I1a was roughly comparable to clotrimazole, and was more active against Candida albicans than naftifine and terbinafine. Compound III1a was as active as terbinafine against all fungi tested. Some improvements for the synthesis of tert-butylacetylene and the alkylating method of 1H-1,2,4-triazole and 1H-imidazole were made. Synthesis of 6,6-dimethyl-1-hepten-4-yn-3-ol and 2-alken-4-ynylamines were modified.