氮唑类抗真菌药物研究新进展
盛春泉, 季海涛, 张万年
[摘要] 近年来氮唑类抗真菌药物研究取得了许多新进展。氮唑类药物的作用机制得到了进一步阐明，并有多个广谱、低毒、高效的新化合物进入临床研究。本文综述了氮唑类抗真菌药物作用机制的研究进展，并介绍了5个正在研制中的新型氮唑类抗真菌药物 ：活力康唑、普沙康唑、拉夫康唑、Syn-2869和TAK-187。与临床上常用的氟康唑和伊曲康唑相比，这5个新化合物均有其显著的优点。
[关键词]抗真菌 ;活力康唑 ;普沙康唑; 拉夫康唑
New Progress in Azole Antifungal Drug Research
Sheng Chunquan, Ji Haitao ,Zhang wangnian
(College of Pharmacy, Second Military Medical University , Shanghai 200433)
, 百拇医药
[Abstract] There have been many new developments in azole antifungal drug reseach. The mechanism of azole antifungals has been further clarified. Moreover, several new compounds with broad spectrum, low toxicity and high efficiency are undergoing clinical trials. New progress in the mole of action of azole antifungals is reviewed. Five novel azole antifungal drugs (Voriconazole, Posaconazole, Ravuconazole, Syn-2869 and TAK-187) are also introduced. The five new compounds have remarkable advantages as compared with fluconazole and itraconazole which are widely used in clinical practice now.
, 百拇医药
[Keywords] Antifungal; Voriconazole ;Posaconazole; Ravuconazole
[参考文献]
[1.] 李健和，许树梧，陈孝治. 氟康唑与眼部真菌感染[J]. 中国新药杂志，1998,7(3):184-188.
[2.] Ji H, Zhang W, Zhou Y, et al. A three-dimensional model of lanosterol 14alpha-demethylase of Candida albicans and its interaction with azole antifungals[J]. J Med Chem. 2000, 43(13):2493-2505.
[3.] Pfaller MA, Messer SA, Hollis RJ, et al. In vitro susceptibilities of Candida bloodstream isolates to the new triazole antifungal agents BMS-207147, Sch 56592, and voriconazole[J]. Antimicrob Agents Chemother. 1998, 42(12):3242-3244.
, 百拇医药
[4.] Nguyen MH, Yu CY. Voriconazole against fluconazole-susceptible and resistant candida isolates: in-vitro efficacy compared with that of itraconazole and ketoconazole[J]. J Antimicrob Chemother. 1998, 42(2):253-256.
[5.] Belanger P, Nast CC, Fratti R, et al. Voriconazole (UK-109,496) inhibits the growth and alters the morphology of fluconazole-susceptible and -resistant Candida species[J]. Antimicrob Agents Chemother. 1997, 41(8):1840-1842.
, 百拇医药
[6.] Pfaller MA, Zhang J, Messer SA, et al. In vitro activities of voriconazole, fluconazole, and itraconazole against 566 clinical isolates of Cryptococcus neoformans from the United States and Africa[J]. Antimicrob Agents Chemother. 1999, 43(1):169-171.
[7.] Sutton DA, Sanche SE, Revankar SG, et al. In vitro amphotericin B resistance in clinical isolates of Aspergillus terreus, with a head-to-head comparison to voriconazole[J]. J Clin Microbiol. 1999, 37(7):2343-2345.
, http://www.100md.com
[8.] Murphy M, Bernard EM, Ishimaru T, et al. Activity of voriconazole (UK-109,496) against clinical isolates of Aspergillus species and its effectiveness in an experimental model of invasive pulmonary aspergillosis[J]. Antimicrob Agents Chemother. 1997, 41(3):696-8.
[9.] Law D, Moore CB, Denning DW. Activity of SCH 56592 compared with those of fluconazole and itraconazole against Candida spp[J]. Antimicrob Agents Chemother. 1997, 41(10):2310-2311.
, http://www.100md.com
[10.] Perfect JR, Cox GM, Dodge RK, et al. In vitro and in vivo efficacies of the azole SCH56592 against Cryptococcus neoformans[J]. Antimicrob Agents Chemother. 1996, 40(8):1910-1913.
[11.] Oakley KL, Morrissey G, Denning DW. Efficacy of SCH-56592 in a temporarily neutropenic murine model of invasive aspergillosis with an itraconazole-susceptible and an itraconazole-resistant isolate of Aspergillus fumigatus[J]. Antimicrob Agents Chemother. 1997, 41(7):1504-1507.
, 百拇医药
[12.] Barchiesi F, Arzeni D, Fothergill AW, et al. In vitro activities of the new antifungal triazole SCH 56592 against common and emerging yeast pathogens[J]. Antimicrob Agents Chemother. 2000, 44(1):226-229.
[13.] Hossain MA, Maesaki S, Mitsutake K, et al. In-vitro and in-vivo activities of SCH56592 against Cryptococcus neoformans[J]. J Antimicrob Chemother. 1999, 44(6):827-829.
[14.] Graybill JR, Bocanegra R, Najvar LK, et al. SCH56592 treatment of murine invasive aspergillosis[J]. J Antimicrob Chemother. 1998, 42(4):539-542.
, 百拇医药
[15.] Kirkpatrick WR, McAtee RK, Fothergill AW, et al. Efficacy of SCH56592 in a rabbit model of invasive aspergillosis[J]. Antimicrob Agents Chemother. 2000, 44(3):780-782.
[16.] Abdely HM, Najvar L, Bocanegra R, et al. SCH 56592, amphotericin B, or itraconazole therapy of experimental murine cerebral phaeohyphomycosis due to Ramichloridium obovoideum[J]. Antimicrob Agents Chemother. 2000, 44(5):1159-1162.
[17.] Nomeir AA, Kumari P, Hilbert MJ, et al. Pharmacokinetics of SCH 56592, a new azole broad-spectrum antifungal agent, in mice, rats, rabbits, dogs, and cynomolgus monkeys[J]. Antimicrob Agents Chemother. 2000, 44(3):727-731.
, 百拇医药
[18.] Fung-Tomc JC, Huczko E, Minassian B, et al. In vitro activity of a new oral triazole, BMS-207147 (ER-30346)[J]. Antimicrob Agents Chemother. 1998, 42(2):313-318.
[19.] Pfaller MA, Messer SA, Hollis RJ, et al. In vitro susceptibilities of Candida bloodstream isolates to the new triazole antifungal agents BMS-207147, Sch 56592, and voriconazole[J]. Antimicrob Agents Chemother. 1998, 42(12):3242-3244.
[20.] Moore CB, Walls CM, Denning DW. In vitro activity of the new triazole BMS-207147 against Aspergillus species in comparison with itraconazole and amphotericin B[J]. Antimicrob Agents Chemother. 2000, 44(2):441-443.
, http://www.100md.com
[21.] Robert A, Fromtling J, Castaner. Syn-2869[J]. Drugs Fut, 1999,24(1):30-37.
[22.] Johnson EM, Szekely A, Warnock DW. In vitro activity of Syn-2869, a novel triazole agent, against emerging and less common mold pathogens[J]. Antimicrob Agents Chemother. 1999, 43(5):1260-1263.
[23.] Salama SM, ed. Syn2869. a new potent antifungal triazole for the treatment of systemic and superficial fungal infections: In vitro activity against clinical isolate of yeast and dermatophytes[C]. 38th Intersci Conf Antimicrob Agents Chemother. San Diego:National Cancex Institute,1998, Abst F150.
[24.] Schell WA, De Almeida GM, Dodge RK, et al. In vitro and in vivo efficacy of the triazole TAK-187 against Cryptococcus neoformans[J]. Antimicrob Agents Chemother. 1998, 42(10):2630-2632., http://www.100md.com
[摘要] 近年来氮唑类抗真菌药物研究取得了许多新进展。氮唑类药物的作用机制得到了进一步阐明，并有多个广谱、低毒、高效的新化合物进入临床研究。本文综述了氮唑类抗真菌药物作用机制的研究进展，并介绍了5个正在研制中的新型氮唑类抗真菌药物 ：活力康唑、普沙康唑、拉夫康唑、Syn-2869和TAK-187。与临床上常用的氟康唑和伊曲康唑相比，这5个新化合物均有其显著的优点。
[关键词]抗真菌 ;活力康唑 ;普沙康唑; 拉夫康唑
New Progress in Azole Antifungal Drug Research
Sheng Chunquan, Ji Haitao ,Zhang wangnian
(College of Pharmacy, Second Military Medical University , Shanghai 200433)
, 百拇医药
[Abstract] There have been many new developments in azole antifungal drug reseach. The mechanism of azole antifungals has been further clarified. Moreover, several new compounds with broad spectrum, low toxicity and high efficiency are undergoing clinical trials. New progress in the mole of action of azole antifungals is reviewed. Five novel azole antifungal drugs (Voriconazole, Posaconazole, Ravuconazole, Syn-2869 and TAK-187) are also introduced. The five new compounds have remarkable advantages as compared with fluconazole and itraconazole which are widely used in clinical practice now.
, 百拇医药
[Keywords] Antifungal; Voriconazole ;Posaconazole; Ravuconazole
[参考文献]
[1.] 李健和，许树梧，陈孝治. 氟康唑与眼部真菌感染[J]. 中国新药杂志，1998,7(3):184-188.
[2.] Ji H, Zhang W, Zhou Y, et al. A three-dimensional model of lanosterol 14alpha-demethylase of Candida albicans and its interaction with azole antifungals[J]. J Med Chem. 2000, 43(13):2493-2505.
[3.] Pfaller MA, Messer SA, Hollis RJ, et al. In vitro susceptibilities of Candida bloodstream isolates to the new triazole antifungal agents BMS-207147, Sch 56592, and voriconazole[J]. Antimicrob Agents Chemother. 1998, 42(12):3242-3244.
, 百拇医药
[4.] Nguyen MH, Yu CY. Voriconazole against fluconazole-susceptible and resistant candida isolates: in-vitro efficacy compared with that of itraconazole and ketoconazole[J]. J Antimicrob Chemother. 1998, 42(2):253-256.
[5.] Belanger P, Nast CC, Fratti R, et al. Voriconazole (UK-109,496) inhibits the growth and alters the morphology of fluconazole-susceptible and -resistant Candida species[J]. Antimicrob Agents Chemother. 1997, 41(8):1840-1842.
, 百拇医药
[6.] Pfaller MA, Zhang J, Messer SA, et al. In vitro activities of voriconazole, fluconazole, and itraconazole against 566 clinical isolates of Cryptococcus neoformans from the United States and Africa[J]. Antimicrob Agents Chemother. 1999, 43(1):169-171.
[7.] Sutton DA, Sanche SE, Revankar SG, et al. In vitro amphotericin B resistance in clinical isolates of Aspergillus terreus, with a head-to-head comparison to voriconazole[J]. J Clin Microbiol. 1999, 37(7):2343-2345.
, http://www.100md.com
[8.] Murphy M, Bernard EM, Ishimaru T, et al. Activity of voriconazole (UK-109,496) against clinical isolates of Aspergillus species and its effectiveness in an experimental model of invasive pulmonary aspergillosis[J]. Antimicrob Agents Chemother. 1997, 41(3):696-8.
[9.] Law D, Moore CB, Denning DW. Activity of SCH 56592 compared with those of fluconazole and itraconazole against Candida spp[J]. Antimicrob Agents Chemother. 1997, 41(10):2310-2311.
, http://www.100md.com
[10.] Perfect JR, Cox GM, Dodge RK, et al. In vitro and in vivo efficacies of the azole SCH56592 against Cryptococcus neoformans[J]. Antimicrob Agents Chemother. 1996, 40(8):1910-1913.
[11.] Oakley KL, Morrissey G, Denning DW. Efficacy of SCH-56592 in a temporarily neutropenic murine model of invasive aspergillosis with an itraconazole-susceptible and an itraconazole-resistant isolate of Aspergillus fumigatus[J]. Antimicrob Agents Chemother. 1997, 41(7):1504-1507.
, 百拇医药
[12.] Barchiesi F, Arzeni D, Fothergill AW, et al. In vitro activities of the new antifungal triazole SCH 56592 against common and emerging yeast pathogens[J]. Antimicrob Agents Chemother. 2000, 44(1):226-229.
[13.] Hossain MA, Maesaki S, Mitsutake K, et al. In-vitro and in-vivo activities of SCH56592 against Cryptococcus neoformans[J]. J Antimicrob Chemother. 1999, 44(6):827-829.
[14.] Graybill JR, Bocanegra R, Najvar LK, et al. SCH56592 treatment of murine invasive aspergillosis[J]. J Antimicrob Chemother. 1998, 42(4):539-542.
, 百拇医药
[15.] Kirkpatrick WR, McAtee RK, Fothergill AW, et al. Efficacy of SCH56592 in a rabbit model of invasive aspergillosis[J]. Antimicrob Agents Chemother. 2000, 44(3):780-782.
[16.] Abdely HM, Najvar L, Bocanegra R, et al. SCH 56592, amphotericin B, or itraconazole therapy of experimental murine cerebral phaeohyphomycosis due to Ramichloridium obovoideum[J]. Antimicrob Agents Chemother. 2000, 44(5):1159-1162.
[17.] Nomeir AA, Kumari P, Hilbert MJ, et al. Pharmacokinetics of SCH 56592, a new azole broad-spectrum antifungal agent, in mice, rats, rabbits, dogs, and cynomolgus monkeys[J]. Antimicrob Agents Chemother. 2000, 44(3):727-731.
, 百拇医药
[18.] Fung-Tomc JC, Huczko E, Minassian B, et al. In vitro activity of a new oral triazole, BMS-207147 (ER-30346)[J]. Antimicrob Agents Chemother. 1998, 42(2):313-318.
[19.] Pfaller MA, Messer SA, Hollis RJ, et al. In vitro susceptibilities of Candida bloodstream isolates to the new triazole antifungal agents BMS-207147, Sch 56592, and voriconazole[J]. Antimicrob Agents Chemother. 1998, 42(12):3242-3244.
[20.] Moore CB, Walls CM, Denning DW. In vitro activity of the new triazole BMS-207147 against Aspergillus species in comparison with itraconazole and amphotericin B[J]. Antimicrob Agents Chemother. 2000, 44(2):441-443.
, http://www.100md.com
[21.] Robert A, Fromtling J, Castaner. Syn-2869[J]. Drugs Fut, 1999,24(1):30-37.
[22.] Johnson EM, Szekely A, Warnock DW. In vitro activity of Syn-2869, a novel triazole agent, against emerging and less common mold pathogens[J]. Antimicrob Agents Chemother. 1999, 43(5):1260-1263.
[23.] Salama SM, ed. Syn2869. a new potent antifungal triazole for the treatment of systemic and superficial fungal infections: In vitro activity against clinical isolate of yeast and dermatophytes[C]. 38th Intersci Conf Antimicrob Agents Chemother. San Diego:National Cancex Institute,1998, Abst F150.
[24.] Schell WA, De Almeida GM, Dodge RK, et al. In vitro and in vivo efficacy of the triazole TAK-187 against Cryptococcus neoformans[J]. Antimicrob Agents Chemother. 1998, 42(10):2630-2632., http://www.100md.com