3-Arylisothiazolo[5,4-b]quinolin-4(9H)-ones and 3-arylisoxazolo[5,4-b]quinolin-4(9H)-ones were synthesized and assayed for affinity for the benzodiazepine binding site of the GABAA receptors. While the 3-arylisothiazo...3-Arylisothiazolo[5,4-b]quinolin-4(9H)-ones and 3-arylisoxazolo[5,4-b]quinolin-4(9H)-ones were synthesized and assayed for affinity for the benzodiazepine binding site of the GABAA receptors. While the 3-arylisothiazoloquinolin-4-ones were found to be potent ligands, with affinities (expressed as the affinity Ki value) down to 1 nM, the 3-arylisoxazoloquinolin-4-ones are less potent. This is suggested to depend on sterical repulsive interaction of the 3-arylisoxazoloquinolin-4-ones with the receptor essential volume of the binding site, and a higher electron density at the nitrogen in the azole ring (N-2) as well as the carbonyl oxygen in the isothiazoloquinolin-4-ones enabling them to interact stronger with hydrogen bond donor sites at the binding site.展开更多
According to the classification presented by Lehmann BD(2016),triple-negative breast cancer(TNBC)is a heterogeneous group of malignant tumors with four specific subtypes:basal-like(subtype 1 and subtype 2),mesenchymal...According to the classification presented by Lehmann BD(2016),triple-negative breast cancer(TNBC)is a heterogeneous group of malignant tumors with four specific subtypes:basal-like(subtype 1 and subtype 2),mesenchymal,and luminal androgen receptor(LAR)subtypes.The basal-like subtypes of carcinomas predominate in this group,accounting for up to 80%of all cases.Despite the significantly lower proportions of mesenchymal and LAR variants in the group of breast carcinomas with a TNBC profile,such tumors are characterized by aggressive biological behavior.To this end,the LAR subtype is of particular interest,since the literature on such tumors presents different and even contradictory data concerning the disease course and prognosis.This review is devoted to the analysis of the relevant literature,reflecting the main results of studies on the molecular properties and clinical features of the disease course of LAR-type TNBC carcinomas.展开更多
基金Financial support from the Swedish Board for Scientific Research(VR),the Knut and Alice Wallenberg Foundation,the Research School for Pharmaceutical Sciences at Lund University,Carlsberg Foundation,Denmark,and the NeuroScience PharmaBiotec Research Center,Den-mark,is gratefully acknowledged.
文摘3-Arylisothiazolo[5,4-b]quinolin-4(9H)-ones and 3-arylisoxazolo[5,4-b]quinolin-4(9H)-ones were synthesized and assayed for affinity for the benzodiazepine binding site of the GABAA receptors. While the 3-arylisothiazoloquinolin-4-ones were found to be potent ligands, with affinities (expressed as the affinity Ki value) down to 1 nM, the 3-arylisoxazoloquinolin-4-ones are less potent. This is suggested to depend on sterical repulsive interaction of the 3-arylisoxazoloquinolin-4-ones with the receptor essential volume of the binding site, and a higher electron density at the nitrogen in the azole ring (N-2) as well as the carbonyl oxygen in the isothiazoloquinolin-4-ones enabling them to interact stronger with hydrogen bond donor sites at the binding site.
文摘According to the classification presented by Lehmann BD(2016),triple-negative breast cancer(TNBC)is a heterogeneous group of malignant tumors with four specific subtypes:basal-like(subtype 1 and subtype 2),mesenchymal,and luminal androgen receptor(LAR)subtypes.The basal-like subtypes of carcinomas predominate in this group,accounting for up to 80%of all cases.Despite the significantly lower proportions of mesenchymal and LAR variants in the group of breast carcinomas with a TNBC profile,such tumors are characterized by aggressive biological behavior.To this end,the LAR subtype is of particular interest,since the literature on such tumors presents different and even contradictory data concerning the disease course and prognosis.This review is devoted to the analysis of the relevant literature,reflecting the main results of studies on the molecular properties and clinical features of the disease course of LAR-type TNBC carcinomas.
