- Synthesis and bioactivity of phenyl substituted furan and oxazole carboxylic acid derivatives as potential PDE4 inhibitors
-
In this present study, a series of 5-phenyl-2-furan and 4-phenyl-2-oxazole derivatives were designed and synthesized as phosphodiesterase type 4 (PDE4) inhibitors. In vitro results showed that the synthesized compounds exhibited considerable inhibitory ac
- Lin, Yinuo,Ahmed, Wasim,He, Min,Xiang, Xuwen,Tang, Riyuan,Cui, Zi-Ning
-
-
- Discovery of Novel Aryl Carboxamide Derivatives as Hypoxia-Inducible Factor 1α Signaling Inhibitors with Potent Activities of Anticancer Metastasis
-
In order to discover novel hypoxia-inducible factor 1 (HIF-1) inhibitors for the cancer metastasis treatment, 68 new aryl carboxamide compounds were synthesized and evaluated for their inhibitory effect by dual luciferase-reporter assay. Based on five rounds of investigation on structure-activity relationships step by step, compound 30m was discovered as the most active inhibitor (IC50 = 0.32 μM) with no obvious cytotoxicity (CC50 > 50 μM). It effectively attenuated hypoxia-induced HIF-1α protein accumulation and reduced transcription of vascular epidermal growth factor in a dose-dependent manner, which was further demonstrated by its inhibitory potency on capillary-like tube formation, angiogenesis of zebrafish as well as cellular migration and invasion. Importantly, compound 30m exhibited antimetastatic potency in breast cancer lung metastasis in the mice model, indicating its promising therapeutic potential for prevention and treatment of tumor metastasis. These results definitely merit attention for further rational design of more efficient HIF-1 inhibitors in the future.
- Liu, Mingming,Liang, Yuru,Zhu, Zhongzhen,Wang, Jin,Cheng, Xingxing,Cheng, Jiayi,Xu, Binpeng,Li, Rong,Liu, Xinhua,Wang, Yang
-
p. 9299 - 9314
(2019/10/16)
-
- Design, synthesis and evaluation of aromatic heterocyclic derivatives as potent antifungal agents
-
To further enhance the anti-Aspergillus efficacy of our previously discovered antifungal lead compounds (1), a series of aromatic heterocyclic derivatives were designed, synthesized and evaluated for in vitro antifungal activity. Many of the target compounds showed good inhibitory activity against Candida albicans and Cryptococcus neoformans. In particular, the isoxazole nuclei were more suited for improving the activity against Aspergillus spp. Among these compounds, 2-F substituted analogues 23g and 23h displayed the most remarkable in vitro activity against Candida spp., C. neoformans, A. fumigatus and fluconazole-resistant C.alb. strains, which is superior or comparable to the activity of the reference drugs fluconazole and voriconazole. Notably, the compounds 23g and 23h exhibited low inhibition profiles for various isoforms of human cytochrome P450 and excellent blood plasma stability.
- Zhao, Shizhen,Zhang, Xiangqian,Wei, Peng,Su, Xin,Zhao, Liyu,Wu, Mengya,Hao, Chenzhou,Liu, Chunchi,Zhao, Dongmei,Cheng, Maosheng
-
-
- Design, synthesis and biological evaluation of 2,4-disubstituted oxazole derivatives as potential PDE4 inhibitors
-
In this study, a series of pyrazole derivatives containing 4-phenyl-2-oxazole moiety were designed and synthesized in a concise way, some of which exhibited considerable inhibitory activity against PDE4B and blockade of LPS-induced TNF-α release. Compound
- Li, Ya-Sheng,Hu, De-Kun,Zhao, Dong-Sheng,Liu, Xing-Yu,Jin, Hong-Wei,Song, Gao-Peng,Cui, Zi-Ning,Zhang, Lian-Hui
-
p. 1852 - 1859
(2017/03/08)
-
- Towards New Tricyclic Motifs: Intramolecular C–H Arylation as the Key Step in a Formal [3+3] Cyclocondensation Strategy
-
Tricyclic scaffolds structurally related to the well-known benzodiazepine class of drugs show diverse biological activities strikingly different from those of their benzodiazepine counterparts. Interested by this scaffold-hopping perspective, we previousl
- Vrijdag, Johannes L.,De Ruysscher, Dries,De Borggraeve, Wim M.
-
p. 1465 - 1474
(2017/04/01)
-
- Synthesis and Biological Investigation of Oxazole Hydroxamates as Highly Selective Histone Deacetylase 6 (HDAC6) Inhibitors
-
Histone deacetylase 6 (HDAC6) catalyzes the removal of an acetyl group from lysine residues of several non-histone proteins. Here we report the preparation of thiazole-, oxazole-, and oxadiazole-containing biarylhydroxamic acids by a short synthetic proce
- Senger, Johanna,Melesina, Jelena,Marek, Martin,Romier, Christophe,Oehme, Ina,Witt, Olaf,Sippl, Wolfgang,Jung, Manfred
-
supporting information
p. 1545 - 1555
(2016/03/08)
-
- HETEROCYCLIC COMPOUND
-
The present invention provides a heterocyclic compound having an IRAK-4 inhibitory action, which is useful for the prophylaxis or treatment of inflammatory disease, autoimmune disease, osteoarticular degenerative disease, neoplastic disease and the like, and a medicament containing thereof. The present invention relates to a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.
- -
-
Paragraph 1044
(2015/05/26)
-
- CXCR7 ANTAGONISTS
-
Compounds having formula I, or pharmaceutically acceptable salts, hydrates or N-oxides thereof are provided and are useful for binding to CXCR7, and treating diseases that are dependent, at least in part, on CXCR7 activity. Accordingly, the present invention provides in further aspects, compositions containing one or more of the above-noted compounds in admixture with a pharmaceutically acceptable excipient.
- -
-
Paragraph 0445; 0446
(2014/06/23)
-
- Generation and exploration of new classes of antitubercular agents: The optimization of oxazolines, oxazoles, thiazolines, thiazoles to imidazo[1,2-a]pyridines and isomeric 5,6-fused scaffolds
-
Tuberculosis (TB) is a devastating disease resulting in a death every 20 s. Thus, new drugs are urgently needed. Herein we report ten classes of compounds - oxazoline, oxazole, thiazoline, thiazole, pyrazole, pyridine, isoxazole, imidazo[1,2-a]pyridine, imidazo[1,2-a]pyrimidine and imidazo[1,2-c]pyrimidine - which have good (micromolar) to excellent (sub-micromolar) antitubercular potency. The 5,6-fused heteroaromatic compounds were the most potent with MIC's as low as 37Rv, clinically relevant drug sensitive, multi- and extensively resistant Mtb strains as well as having good in vitro metabolic stability.
- Moraski, Garrett C.,Markley, Lowell D.,Chang, Mayland,Cho, Sanghyun,Franzblau, Scott G.,Hwang, Chang Hwa,Boshoff, Helena,Miller, Marvin J.
-
p. 2214 - 2220
(2012/05/20)
-
- Hydroxamic Acids as Potent Inhibitors of FeII and MnII E. coli Methionine Aminopeptidase: Biological Activities and X-ray Structures of Oxazole Hydroxamate-EcMetAP-Mn Complexes
-
New series of acids and hydroxamic acids linked to five-membered heterocycles including furan, oxazole, 1,2,4- or 1,3,4-oxadiazole, and imidazole were synthesized and tested as inhibitors against the FeII, CoII, and MnII f
- Huguet, Florian,Melet, Armelle,Alves de Sousa, Rodolphe,Lieutaud, Aurelie,Chevalier, Jacqueline,Maigre, Laure,Deschamps, Patrick,Tomas, Alain,Leulliot, Nicolas,Pages, Jean-Marie,Artaud, Isabelle
-
p. 1020 - 1030
(2012/07/31)
-
- A flexible synthetic approach to the hennoxazoles
-
Three advanced intermediates corresponding to the carbon skeleton of the hennoxazoles have been prepared. Central to the strategy is the synthesis of the oxazoles prior to coupling with the other fragments and a dithiane addition to allow for the generati
- Zylstra, Eric J.,She, Miles W.-L.,Salamant, Walter A.,Leahy, James W.
-
p. 623 - 627
(2007/10/03)
-
- Ramoplanin derivatives possessing antibacterial activity
-
Novel ramoplanin derivatives are disclosed. These ramoplanin derivatives exhibit antibacterial activity. As the compounds of the subject invention exhibit potent activities against gram positive bacteria, they are useful antimicrobial agents. Methods of synthesis and of use of the compounds are also disclosed.
- -
-
Page/Page column 71
(2010/11/23)
-
- Synthesis of 2-aryl-oxazolo[4,5-c]quinoline-4(5H)-ones and 2-aryl-thiazolo[4,5-c]quinoline-4(5H)-ones
-
(Matrix presented) Novel and highly efficient syntheses of oxazolo[4,5-c]quinoline-4(5H)-ones (1) and thiazolo[4,5-c]quinoline-4(5H)-ones (2) from ethyl 2-chlorooxazole-4-carboxylate (4) and ethyl 2-bromo-5-chlorothiazole-4-carboxylate (13), respectively,
- Hodgetts, Kevin J.,Kershaw, Mark T.
-
p. 2911 - 2914
(2007/10/03)
-
- Preparation of new 2,4-disubstituted oxazoles from N-acylaziridines
-
The efficiency of the ring enlargement of 2-substituted N-acylaziridines to dihydrooxazoles followed by nickel peroxide oxidation to give 2,4-disubstituted oxazoles as a synthetic route is examined. Sodium iodide-promoted ring enlargements work well for N-acylaziridines bearing electron-donating 2-substituents. For N-acylaziridines bearing electron-withdrawing 2-substituents, the best results are obtained using acid-promoted rearrangement.
- Eastwood, Frank W.,Perlmutter, Patrick,Yang, Qi
-
-