Upadhayaya Ram Shankar, Sinha Neelima, Jain Sanjay, Kishore Nawal, Chandra Ramesh, Arora Sudershan K
Medicinal Chemistry Division, New Chemical Entity Research, Lupin Research Park, 46/47 A, At Village Nande, Taluka Mulshi, Pune 411042, India.
Bioorg Med Chem. 2004 May 1;12(9):2225-38. doi: 10.1016/j.bmc.2004.02.014.
A series of (2R,3S)-2-(2,4-difluorophenyl)-3-(5-[2-[4-aryl-piperazin-1-yl]-ethyl]-tetrazol-2-yl)-1-[1,2,4]-triazol-1-yl-butan-2-ol (11a-n) and (2R,3S)-2-(2,4-difluorophenyl)-3-(5-[2-[4-aryl-piperazin-1-yl]-ethyl]-tetrazole-1-yl)-1-[1,2,4]-triazol-1-yl-butan-2-ol (12a-n) has been synthesized. The antifungal activity of compounds was evaluated by in vitro agar diffusion and broth dilution assay. Compounds 11d and its positional isomer 12d having 3-trifluoromethyl substitution on the phenyl ring of piperazine demonstrated significant antifungal activity against variety of fungal cultures (Candida spp. C. neoformans and Aspergillus spp.). The compound 12d showed MIC value of 0.12 microg/mL for C. albicans, C. albicans V-01-191A-261 (resistant strain); 0.25 microg/mL for C. tropicalis, C. parapsilosis ATCC 22019 and C. krusei and MIC value of 0.5 microg/mL for C. glabrata, C. krusei ATCC 6258, which is comparable to itraconazole and better than fluconazole. Further, compound 11d showed significant activity (MIC; 0.25-0.5 microg/mL) against Candida spp. and strong anticryptococcal activity (MIC; 0.25 microg/mL) against C. neoformans.
一系列(2R,3S)-2-(2,4-二氟苯基)-3-(5-[2-[4-芳基哌嗪-1-基]乙基]-四唑-2-基)-1-[1,2,4]-三唑-1-基丁-2-醇(11a-n)和(2R,3S)-2-(2,4-二氟苯基)-3-(5-[2-[4-芳基哌嗪-1-基]乙基]-四唑-1-基)-1-[1,2,4]-三唑-1-基丁-2-醇(12a-n)已被合成。通过体外琼脂扩散法和肉汤稀释法评估了这些化合物的抗真菌活性。在哌嗪苯环上具有3-三氟甲基取代的化合物11d及其位置异构体12d对多种真菌培养物（念珠菌属、新型隐球菌和曲霉菌属）表现出显著的抗真菌活性。化合物12d对白色念珠菌、白色念珠菌V-01-191A-261（耐药菌株）的最低抑菌浓度（MIC）值为0.12μg/mL；对热带念珠菌、近平滑念珠菌ATCC 22019和克柔念珠菌的MIC值为0.25μg/mL，对光滑念珠菌、克柔念珠菌ATCC 6258的MIC值为0.5μg/mL，与伊曲康唑相当且优于氟康唑。此外，化合物11d对念珠菌属表现出显著活性（MIC；0.25 - 0.5μg/mL），对新型隐球菌表现出较强的抗隐球菌活性（MIC；0.25μg/mL）。
