参考文献：M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. 用于研究药物诱导肝损伤的FDA批准药物标签，药物发现今天，16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007
M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank：根据人类发生药物诱导肝损伤风险排名的最大参考药物清单。药物发现今天2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015
References:M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007
M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015
Enantioselective Retention of 4‐Aryl‐1,4‐dihydropyridine Calcium‐Channel Blockers on Human Serum Albumin and
α1
‐Acid Glycoprotein HPLC Columns: Relationships with Different Scales of Lipophilicity
摘要：
The enantioselective retention of eight 4-aryl-1,4-dihydropyridine (DHP) calcium-channel blockers on HPLC stationary phases supporting human serum albumin (HSA) or alpha(1)-acid glycoprotein (AGP) was investigated. All chiral neutral DHPs were resolved on the AGP column, whereas, on the HSA column, only isradipine showed a split chromatographic peak. Analyses performed on AGP with eluents containing dimethyloctylamine (DMOA) as the displacer demonstrated that the protein has at least two binding sites for DHPs. The first family of binding sites is enantioselective, binds exclusively to the (R)-forms, and presumably interacts competitively with DMOA. The second family of binding sites appears to be non-enantioselective and is affected by a cooperative interaction with DMOA. For the selected set of DHPs, the lipophilicity scale in octan-1-ol/H2O (log P) was not collinear with log k(w)(IAM) values obtained with immobilized artificial membranes (IAM-HPLC) due to the inclusion of both neutral and basic congeners. Only for the neutral DHPs did log k(w)(IAM) behave as a better descriptor than log P for retention data on HSA and AGP. In fact, the behavior of the basic DHPs amlodipine and nicardipine on both proteins correlated better with the octan-1-ol/H2O log P values. We, therefore, infer that the amphipathic nature of the IAM phase only mimics the interaction of non-ionizable compounds with serum proteins. In contrast, the IAM-HPLC retention data of protonated bases encode additional interaction mechanisms that are specific for phospholipids and not involved in ligand-protein interactions.
[EN] NOVEL COMPOUNDS, THEIR PREPARATION AND USE<br/>[FR] NOUVEAUX COMPOSES, LEUR PREPARATION ET LEUR UTILISATION
申请人：NOVO NORDISK AS
公开号：WO2005105736A1
公开（公告）日：2005-11-10
Novel compounds of the general formula (I), the use of these compounds as phar- maceutical compositions, pharmaceutical compositions comprising the compounds and methods of treatment employing these compounds and compositions. The present compounds may be useful in the treatment and/or prevention of conditions mediated by Peroxisome Proliferator-Activated Receptors (PPAR), in particular the PPARδ suptype.
[EN] PHENOTHIAZINE DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS DE PHÉNOTHIAZINE ET LEURS UTILISATIONS
申请人：CAMP4 THERAPEUTICS CORP
公开号：WO2019195789A1
公开（公告）日：2019-10-10
The present invention provides phenothiazine compounds, processes for their preparation, pharmaceutical compositions comprising the compounds, and the use of the compounds or the compositions in the treatment of various diseases or conditions, for example ribosomal disorders and ribosomopathies, e.g. Diamond Blackfan anemia (DBA).
Dibenzyl amine compounds and derivatives, pharmaceutical compositions containing such compounds and the use of such compounds to elevate certain plasma lipid levels, including high density lipoprotein-cholesterol and to lower certain other plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by low levels of HDL cholesterol and/or high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases in some mammals, including humans.
Compounds and uses thereof for decreasing activity of hormone-sensitive lipase
申请人：——
公开号：US20030166644A1
公开（公告）日：2003-09-04
Use of compounds to inhibit hormone-sensitive lipase, pharmaceutical compositions comprising the compounds, methods of treatment employing these compounds and compositions, and novel compounds. The present compounds are inhibitors of hormone-sensitive lipase and may be useful in the treatment and/or prevention of medical disorders where a decreased activity of hormone-sensitive lipase is desirable.
[EN] SPIROLACTAM CGRP RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DE RÉCEPTEUR DE CGRP À BASE DE SPIROLACTAME
申请人：MERCK SHARP & DOHME
公开号：WO2013169567A1
公开（公告）日：2013-11-14
The present invention is directed to spirolactam analogues which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.
