Modeling of LIM-Kinase 2 inhibitory activity of pyrrolopyrimidine analogues: useful in treatment of ocular hypertension and glaucoma.
The LIM-Kinase 2 (LIMK2) inhibitory activity of a series of pyrrolopyrimidine analogs has been analyzed through combinatorial protocol in multiple linear regressions (CP-MLR) and partial least square (PLS) using different descriptors obtained from DRAGON software. The empirical, topological and charge descriptors have led to statistically significant QSAR models and showed good external predictivity as reflected in test set R2 values (0.782 to 0.888). The obtained structure-activity correlations underlined the significance of bulkiness and molecular polarizability in improving the activity. The topological descriptors suggested that open chain or branched substituents are favorable while cyclic /ring substituents are unfavorable for the activity. The descriptors identified in the study showed that pyrrolopyrimidine scaffold holds scope for modulating LIMK2 inhibitory activity. The study gives a direction for further exploration of chemical space of pyrrolopyrimidine analogs as LIMK2 inhibitors.
Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga, India.
Gagandip
G
Singh
Manish K
MK
Gupta
Viney
V
Kumar
Yenamandra S
YS
Prabhakar
D020650:Combinatorial Chemistry Techniques; D005901:Glaucoma / Q000188:drug therapy; D016018:Least-Squares Analysis; D054461:Lim Kinases / Q000037:antagonists & inhibitors*; D016014:Linear Models; D008954:Models, Biological; D009798:Ocular Hypertension / Q000188:drug therapy; D011743:Pyrimidines / Q000737:chemistry* / Q000627:therapeutic use; D011758:Pyrroles / Q000737:chemistry* / Q000627:therapeutic use
D011743:Pyrimidines; D011758:Pyrroles; C527741:pyrrolopyrimidine; C102895:LIMK2 protein, human; D054461:Lim Kinases