Abstract
3,5-diaryl-4,5-dihydropyrazoles were discovered to be potent KSP inhibitors with excellent in vivo potency. These enzyme inhibitors possess desirable physical properties that can be readily modified by incorporation of a weakly basic amine. Careful adjustment of amine basicity was essential for preserving cellular potency in a multidrug resistant cell line while maintaining good aqueous solubility.
MeSH terms
-
ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
-
Amides / chemical synthesis*
-
Amides / pharmacology*
-
Antimitotic Agents / chemical synthesis*
-
Antimitotic Agents / pharmacology*
-
Antineoplastic Agents / chemical synthesis
-
Antineoplastic Agents / pharmacology
-
Cell Line, Tumor
-
Chemical Phenomena
-
Chemistry, Physical
-
Drug Design
-
Drug Resistance, Neoplasm
-
Genes, MDR / drug effects
-
Humans
-
Indicators and Reagents
-
Kinesins / antagonists & inhibitors*
-
Mitosis / drug effects*
-
Pyrazoles / chemical synthesis*
-
Pyrazoles / pharmacology*
-
Solubility
-
Stereoisomerism
-
Structure-Activity Relationship
Substances
-
ATP Binding Cassette Transporter, Subfamily B, Member 1
-
Amides
-
Antimitotic Agents
-
Antineoplastic Agents
-
Indicators and Reagents
-
KIF11 protein, human
-
Pyrazoles
-
Kinesins