Isopropylidene substitution increases activity and selectivity of biphenylmethylene 4-pyridine type CYP17 inhibitors.
CYP17 inhibition is a promising therapy for prostate cancer (PC) because proliferation of 80% of PC depends on androgen stimulation. Introduction of isopropylidene substituents onto the linker of biphenylmethylene 4-pyridines resulted in several strong CYP17 inhibitors, which were more potent and selective, regarding CYP 11B1, 11B2, 19 and 3A4, than the drug candidate abiraterone.
Hu
Qingzhong
Q
Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C23, D-66123 Saarbrucken, Germany.
Yin
Lina
L
Jagusch
Carsten
C
Hille
Ulrike E
UE
Hartmann
Rolf W
RW
D018931:Antineoplastic Agents, Hormonal / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000201:enzymology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000201:enzymology; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D018931:Antineoplastic Agents, Hormonal; D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D011725:Pyridines; D013254:Steroid 17-alpha-Hydroxylase