Synthesis of pyrazole-based hybrid molecules: Search for potent multidrug resistance modulators

被引:102
作者
Singh, Palwinder [1 ]
Paul, Kamaldeep
Holzer, Wolfgang
机构
[1] Guru Nanak Dev Univ, Dept Chem, Amritsar 143005, Punjab, India
[2] Univ Vienna, Inst Pharmaceut Chem, A-1090 Vienna, Austria
关键词
drugs; modulators; hybrid molecules; synthesis; P-glycoprotein; interactions;
D O I
10.1016/j.bmc.2006.02.046
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
The hybrid molecules have been designed on the basis of the structural features of pyrazole-based drugs and MDR modulator propafenone. A simple synthetic strategy and solvent-based regio selectivity have been used for the synthesis of newly designed molecules and they are evaluated for their interactions with P-glycoprotein (P-gp). Some of the molecules show considerable interactions with P-gp and compounds 15, 28 and 40 could be the potential candidates for their use as MDR modulators. (c) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码:5061 / 5071
页数:11
相关论文
共 30 条
[1]   3,4-DIPHENYL-1H-PYRAZOLE-1-PROPANAMINE ANTIDEPRESSANTS [J].
BAILEY, DM ;
HANSEN, PE ;
HLAVAC, AG ;
BAIZMAN, ER ;
PEARL, J ;
DEFELICE, AF ;
FEIGENSON, ME .
JOURNAL OF MEDICINAL CHEMISTRY, 1985, 28 (02) :256-260
[2]  
Behr L.C., 1967, CHEM HETEROCYCLIC CO, P1
[3]  
Busev A.I., 1965, RUSS CHEM REV+, V34, P237, DOI [10.1070/RC1965v034n03ABEH001426, DOI 10.1070/RC1965V034N03ABEH001426]
[4]  
CHAUHAN PMS, 1993, INDIAN J CHEM B, V32, P858
[5]   Substituted 4-acylpyrazoles and 4-acylpyrazolones: Synthesis and multidrug resistance-modulating activity [J].
Chiba, P ;
Holzer, W ;
Landau, M ;
Bechmann, G ;
Lorenz, K ;
Plagens, B ;
Hitzler, M ;
Richter, E ;
Ecker, G .
JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (21) :4001-4011
[6]   SYNTHESIS, PHARMACOLOGICAL ACTIVITY, AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF A SERIES OF PROPAFENONE-RELATED MODULATORS OF MULTIDRUG-RESISTANCE [J].
CHIBA, P ;
BURGHOFER, S ;
RICHTER, E ;
TELL, B ;
MOSER, A ;
ECKER, G .
JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (14) :2789-2793
[7]   Reversal of multidrug resistance by the P-glycoprotein modulator, LY335979, from the bench to the clinic [J].
Dantzig, AH ;
Law, KL ;
Cao, J ;
Starling, JJ .
CURRENT MEDICINAL CHEMISTRY, 2001, 8 (01) :39-50
[8]  
DUTRA GA, Patent No. 8206962
[9]  
FAHMY BSM, 1980, J CHEM TECH B, P30
[10]  
GARCIA H, 1991, HETEROCYCLES, V32, P1745