- INHIBITORS OF HUMAN ATGL
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The present invention relates to novel inhibitors of adipose triglyceride lipase (ATGL) having an improved inhibitory activity against human ATGL (hATGL) as well as pharmaceutical compositions comprising these inhibitors, and their therapeutic use, particularly in the treatment or prevention of a lipid metabolism disorder, including, e.g., obesity, non-alcoholic fatty liver disease, type 2 diabetes, insulin resistance, glucose intolerance, hypertriglyceridemia, metabolic syndrome, cardiac and skeletal muscle steatosis, congenital generalized lipodystrophy, familial partial lipodystrophy, acquired lipodystrophy syndrome, atherosclerosis, or heart failure.
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Page/Page column 207-209
(2021/02/05)
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- Identification of BR102910 as a selective fibroblast activation protein (FAP) inhibitor
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Fibroblast activation protein (FAP) belongs to the family of prolyl-specific serine proteases and displays both exopeptidase and endopeptidase activities. FAP expression is undetectable in most normal adult tissues, but is greatly upregulated in sites of tissue remodeling, which include fibrosis, inflammation and cancer. Due to its restricted expression pattern and dual enzymatic activities, FAP inhibition is investigated as a therapeutic option for several diseases. In the present study, we described the structure–activity relationship of several synthesized compounds against DPPIV and prolyl oligopeptidase (PREP). In particular, BR102910 (compound 24) showed nanomolar potency and high selectivity. Moreover, the in vivo FAP inhibition study of BR102910 (compound 24) using C57BL/6J mice demonstrated exceptional profiles and satisfactory FAP inhibition efficacy. Based on excellent in vitro and in vivo profiles, the potential of BR102910 (compound 24) as a lead candidate for the treatment of type 2 diabetes is considered.
- Jung, Hui Jin,Nam, Eun Hye,Park, Jin Young,Ghosh, Prithwish,Kim, In Su
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supporting information
(2021/02/26)
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- Design, synthesis and biological evaluation of novel thiazole-derivatives as mitochondrial targeting inhibitors of cancer cells
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Mitochondria are pivotal energy production sources for cells to maintain necessary metabolism activities. Targeting dysfunctional mitochondrial features has been a hotspot for mitochondrial-related disease researches. Investigation with cancerous mitochondrial metabolism is a continuing concern within tumor therapy. Herein, we set out to assess the anti-cancer activities of a novel family of TPP-thiazole derivatives based on our earlier research on mitochondrial targeting agents. Specifically, we designed and synthesized a series of TPP-thiazole derivatives and revealed by the MTT assay that most synthesized compounds effectively inhibited three cancer cell lines (HeLa, PC3 and MCF-7). After structure modifications, we explored the SAR relationships and identified the most promising compound R13 (IC50 of 5.52 μM) for further investigation. In the meantime, we performed ATP production assay to assess the selected compounds inhibitory effect on HeLa cells energy production. The results displayed the test compounds significantly restrained ATP production of cancer cells. Overall, we have designed and synthesized a series of compounds which exhibited significant cytotoxicity against cancer cells and effectively inhibited mitochondrial energy production.
- Dang, Xin,Lei, Shuwen,Luo, Shuhua,Hu, Yixin,Wang, Juntao,Zhang, Dongdong,Lu, Dan,Jiang, Faqin,Fu, Lei
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- I2/TBHP-Mediated tandem cyclization and oxidation reaction: Facile access to 2-substituted thiazoles and benzothiazoles
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The efficient synthesis of 2-substituted thiazoles and benzothiazoles has been accomplished employing readily available cysteine esters and 2-aminobenzenethiols as N and S sources. The reaction proceeds under an I2/TBHP system and involves a on
- Liu, Li,Tan, Chen,Fan, Rong,Wang, Zihan,Du, Hongguang,Xu, Kun,Tan, Jiajing
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supporting information
p. 252 - 256
(2019/01/10)
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- Powerful Antibacterial Activity of Phenyl-Thiolatobismuth(III) Complexes Derived from Oxadiazolethiones
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Seven novel 5-substituted phenylthiazole oxadiazolethiones: [Me-PTOT(H)], [MeO-PTOT(H)], [MeS-PTOT(H)], [F-PTOT(H)], [Cl-PTOT(H)], [Br-PTOT(H)], and [CF3-PTOT(H)], {where X-PTOT(H) = 5-[2-(4-X)thiazol-4-yl]-1,3,4-oxadiazole-2(3H)-thione, 4-X = C6H4}, were synthesised from their corresponding thioamides. From these seven heteroleptic thiolatobismuth complexes: BiPh(Me-PTOT)2 6, BiPh(MeO-PTOT)2 7, BiPh(MeS-PTOT)2 8, BiPh(F-PTOT)2 9, BiPh(Cl-PTOT)2 10, BiPh(Br-PTOT)2 11 and BiPh(CF3-PTOT)2 12 were synthesised and characterised. Complexes [10(DMSO)2] and [11(DMSO)2] were structurally characterised using X-ray diffraction. Evaluation of the antibacterial properties of the thiones and their BiIII complexes against Mycobacterium smegmatis, Staphylococcus aureus (S. aureus), Methicillin-resistant Staphylococcus aureus (MRSA), Vancomycin-resistant Enterococcus (VRE), Enterococcus faecalis (E. faecalis) and Escherichia coli (E. coli) showed that all bismuth(III) complexes were highly effective against all the bacteria, as demonstrated by very low MIC values (1.1-2.1 μM). Complexes BiPh(Me-PTOT)2 6, BiPh(Cl-PTOT)2 10 and BiPh(Br-PTOT)2 11, showed best activity against the multi-drug resistant bacteria VRE and MRSA with an MIC value of 1.0 μM. All these complexes and their corresponding thiones failed to show any prominent activity against M. smegmatis and E. coli, even at high concentrations. These complexes showed little or no toxicity towards mammalian COS-7 cells at 20 μg/mL. Seven heteroleptic thiolatobismuth(III) complexes [BiPh(X-PTOT)2] derived from a series of 5-substituted phenylthiazole oxadiazolethiones [X-PTOT(H)] provide powerful antibacterial action against the multi-resistant bacteria MRSA and VRE.
- Luqman, Ahmad,Blair, Victoria L.,Brammananth, Rajini,Crellin, Paul K.,Coppel, Ross L.,Andrews, Philip C.
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p. 4935 - 4945
(2015/11/02)
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- Synthesis of substituted esters of imidazoles, oxazoles, thiazoles, and diethyl pyrazine-2,5-dicarboxylate from a common acyclic precursor employing C-formylation strategy
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A novel synthetic route to substituted esters of imidazoles, oxazoles, thiazoles, and diethyl pyrazine-2,5-dicarboxylates via C-formylation of glycine ethyl ester hydrochloride is reported. This methodology is simple, robust, and gives good yields of different heterocyclic esters in one or two steps from a common acyclic precursor and is amenable to large scale synthesis.
- Khose, Goraksha,Shinde, Shailesh,Panmand, Anil,Kulkarni, Ravibhushan,Munot, Yogesh,Bandyopadhyay, Anish,Barawkar, Dinesh,Patil, Santoshkumar N.
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supporting information
p. 2671 - 2674
(2014/05/06)
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- Copper(II)-catalyzed oxidation of 4-carboxythiazolines and 4-carboxyoxazolines to 4-carboxythiazoles and 4-carboxyoxazoles
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A mild copper(II)-catalyzed oxidation of 4-carboxythiazolines and 4-carboxyoxazolines to 4-carboxythiazoles and 4-carboxyoxazoles has been developed. Various substrates with alkyl or aryl substitutions at 2-position on azoline ring could be smoothly oxidi
- Wang, Yiyun,Li, Ziyuan,Huang, Yue,Tang, Changhua,Wu, Xiaoming,Xu, Jinyi,Yao, Hequan
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supporting information; experimental part
p. 7406 - 7411
(2011/10/09)
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- Oxidation of 4-carboxylate thiazolines to 4-carboxylate thiazoles by molecular oxygen
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A facile and environment-benign oxidation by molecular oxygen was applied for the conversion of 4-carboxylate thiazolines to 4-carboxylate thiazoles. The substituent effect on thiazoline ring was investigated. It was found that electron-poor group on the thiazoline ring could facilitate the oxidation.
- Huang, Yue,Gan, Haifeng,Li, Shang,Xu, Jinyi,Wu, Xiaoming,Yao, Hequan
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supporting information; experimental part
p. 1751 - 1753
(2010/05/18)
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- BENZOAZEPIN-OXY-ACETIC ACID DERIVATIVES AS PPAR-DELTA AGONISTS USED FOR THE INCREASE OF HDL-C, LOWER LDL-C AND LOWER CHOLESTEROL
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The invention is directed to compounds of Formula (I) useful as PPAR agonists. Pharmaceutical compositions and methods of treating one or more conditions including, but not limited to, diabetes, nephropathy, neuropathy, retinopathy, polycystic ovary syndr
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Page/Page column 42
(2008/06/13)
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