Ligand-based molecular design of 4-benzylpiperidinealkylureas and amides as CCR3 antagonists.
Asthma is an inflammatory disease of the lungs. Clinical studies suggest that eotaxin and chemokine receptor-3 (CCR3) play a primary role in the recruitment of eosinophils in allergic asthma. Development of novel and potent CCR3 antagonists could provide a novel mechanism for inhibition of this recruitment process, thereby preventing asthma. With the intention of designing new ligands with enhanced inhibitor potencies against CCR3, a 3D-QSAR CoMFA study was carried out on 41 4-benzylpiperidinealkylureas and amide derivatives. The best statistics of the developed CoMFA model were r (2) = 0.960, r(2)cv, n = 32 for the training set and r(2)pred, n = 9 for the test set. The generated 3D-QSAR contribution maps shed some light on the effects of the substitution pattern related to CCR3 antagonist activity.
Jain
Vaibhav
V
Centre for Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, 160 062, Punjab, India.
Pandey
Ashish
A
Gupta
Shikhar
S
Mohan
C Gopi
CG
D000577:Amides / Q000737:chemistry / Q000494:pharmacology*; D001249:Asthma / Q000473:pathology / Q000517:prevention & control; D001555:Benzene Derivatives; D015195:Drug Design; D006801:Humans; D008024:Ligands; D021281:Quantitative Structure-Activity Relationship; D054397:Receptors, CCR3 / Q000037:antagonists & inhibitors*; D014508:Urea / Q000737:chemistry / Q000494:pharmacology*
D000577:Amides; D001555:Benzene Derivatives; C515350:CCR3 protein, human; D008024:Ligands; D054397:Receptors, CCR3; D014508:Urea