HIV protease inhibitors: Peptidomimetic drugs and future perspectives

被引:46
作者
Abdel-Rahman, HM [1 ]
Al-karamany, GS
El-Koussi, NA
Youssef, AF
Kiso, Y
机构
[1] Assiut Univ, Fac Pharm, Pharmaceut Med Chem Dept, Assiut 71526, Egypt
[2] Kyoto Pharmaceut Univ, Dept Med Chem, Kyoto 6078412, Japan
关键词
AIDS; antiviral drugs; enzyme inhibitors; HIV; peptidomimetics;
D O I
10.2174/0929867023368890
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A literature review on the human immunodeficiency virus (HIV), the causative agent of acquired immune deficiency syndrome (AIDS). This review includes its life cycle, HIV protease structure, function, and substrates, as well as the mechanism and the design of inhibitors including the clinically approved drugs. Moreover the review mentioned the problems that hindered the development of peptidomimetic drug candidates as HIV protease inhibitors and the different approaches used by medicinal chemists to overcome these problems. A special attention was made to the design rationale as well as the lead optimization processes that provided inhibitors that possess high potency, reduced molecular weight and lower lipophilicity of the allophenylnorstatine (Apns) containing HIV protease inhibitors.
引用
收藏
页码:1905 / 1922
页数:18
相关论文
共 116 条
[71]   Synthesis and biological evaluation of prodrug-type anti-HIV agents: Ester conjugates of carboxylic acid-containing dipeptide HIV protease inhibitors and a reverse transcriptase inhibitor [J].
Matsumoto, H ;
Matsuda, T ;
Nakata, S ;
Mitoguchi, T ;
Kimura, T ;
Hayashi, Y ;
Kiso, Y .
BIOORGANIC & MEDICINAL CHEMISTRY, 2001, 9 (02) :417-430
[72]   Controlled drug release: New water-soluble prodrugs of an HIV protease inhibitor [J].
Matsumoto, H ;
Sohma, Y ;
Kimura, T ;
Hayashi, Y ;
Kiso, Y .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (04) :605-609
[73]   'Double-drugs' - A new class of prodrug form of an HIV protease inhibitor conjugated with a reverse transcriptase inhibitor by a spontaneously cleavable linker [J].
Matsumoto, H ;
Hamawaki, T ;
Ota, H ;
Kimura, T ;
Goto, T ;
Sano, K ;
Hayashi, Y ;
Kiso, Y .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2000, 10 (11) :1227-1231
[74]   Human immunodeficiency virus type 1 protease inhibitors [J].
McDonald, CK ;
Kuritzkes, DR .
ARCHIVES OF INTERNAL MEDICINE, 1997, 157 (09) :951-959
[75]   Structure-activity relationship of small-sized HIV protease inhibitors containing allophenylnorstatine [J].
Mimoto, T ;
Kato, R ;
Takaku, H ;
Nojima, S ;
Terashima, K ;
Misawa, S ;
Fukazawa, T ;
Ueno, T ;
Sato, H ;
Shintani, M ;
Kiso, Y ;
Hayashi, H .
JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (10) :1789-1802
[76]  
MIMOTO T, 1991, CHEM PHARM BULL, V39, P3088
[77]  
MIMOTO T, 1991, CHEM PHARM BULL, V39, P2465
[78]  
Mimoto T, 2000, CHEM PHARM BULL, V48, P1310
[79]  
Mitoguchi T, 1996, PEPTIDE CHEMISTRY 1995, P373
[80]   MOLECULAR TARGETS FOR AIDS THERAPY [J].
MITSUYA, H ;
YARCHOAN, R ;
BRODER, S .
SCIENCE, 1990, 249 (4976) :1533-1544