Acryloylamino-salicylanilides as EGFR PTK inhibitors
摘要:
A series of acryloylamino-salicylanilides were synthesized as inhibitors of EGFR PTK. A strategy of pseudo six-membered ring formed through intramolecular hydrogen bonding in salicylanilides is employed to mimic the planar pyrimidine ring of quinazoline EGFR inhibitors. Acrylamido moiety is incorporated to target the Cys-773 of EGFR specifically. Some of the obtained compounds exhibited good activity as EGFR inhibitors. (c) 2005 Elsevier Ltd. All rights reserved.
Acryloylamino-salicylanilides as EGFR PTK inhibitors
摘要:
A series of acryloylamino-salicylanilides were synthesized as inhibitors of EGFR PTK. A strategy of pseudo six-membered ring formed through intramolecular hydrogen bonding in salicylanilides is employed to mimic the planar pyrimidine ring of quinazoline EGFR inhibitors. Acrylamido moiety is incorporated to target the Cys-773 of EGFR specifically. Some of the obtained compounds exhibited good activity as EGFR inhibitors. (c) 2005 Elsevier Ltd. All rights reserved.
Structure-activity relationships of antifilarial antimycin analogs: a multivariate pattern recognition study
作者:David L. Selwood、David J. Livingstone、John C. W. Comley、Alan B. O'Dowd、Alan T. Hudson、Peter Jackson、Karamjit S. Jandu、Valerie S. Rose、Jeremy N. Stables
DOI:10.1021/jm00163a023
日期:1990.1
The structure-activity relationships of a series of novel antifilarial antimycin A1 analogues have been investigated by using computational chemistry and multivariate statistical techniques. The physiochemical descriptors calculated in this way contained information which was useful in the classification of compounds according to their in vitro antifilarial activity. This approach generated a 53 parameter descriptor set, which was reduced with a multivariate pattern recognition package, ARTHUR. Regression analysis of the reduced set yielded several statistically significant regression equations; e.g.-log in vitro activity = 0.017 mp + 0.65 log P - 0.81ESDL10-7.33 (R = 0.9). With use of this equation, it was possible to make predictions for further untested analogues. The analysis indicated that membrane or lipid solubility is an important determinant in biological activity agreeing with the proposed primary mode of action of the compounds as disrupters of cuticular glucose uptake.
Acryloylamino-salicylanilides as EGFR PTK inhibitors
A series of acryloylamino-salicylanilides were synthesized as inhibitors of EGFR PTK. A strategy of pseudo six-membered ring formed through intramolecular hydrogen bonding in salicylanilides is employed to mimic the planar pyrimidine ring of quinazoline EGFR inhibitors. Acrylamido moiety is incorporated to target the Cys-773 of EGFR specifically. Some of the obtained compounds exhibited good activity as EGFR inhibitors. (c) 2005 Elsevier Ltd. All rights reserved.