35155-09-0Relevant academic research and scientific papers
Toward a treatment of diabesity: In vitro and in vivo evaluation of uncharged bromophenol derivatives as a new series of PTP1B inhibitors
Li, Xiangqian,Xu, Qi,Li, Chao,Luo, Jiao,Li, Xiuxue,Wang, Lijun,Jiang, Bo,Shi, Dayong
supporting information, p. 178 - 185 (2019/02/05)
Protein tyrosine phosphatase 1B (PTP1B) has been considered as a validated biological target for type 2 diabetes treatment, but past endeavors to develop inhibitors of PTP1B into drugs have been unsuccessful. Two challenging aspects are selective inhibition and cell permeability. A structure-based strategy was employed to develop uncharged bromophenols as a new series of PTP1B inhibitors. The most potent compound 22 (LXQ46) inhibited PTP1B with an IC50 value of 0.190 μM, and showed remarkable selectivity over other protein tyrosine phosphatases (PTPs, 20–200 folds). In the SPR study, increasing concentrations of compound 22 led to concentration-dependent increases in binding responses, indicating that compound 22 could bind to the surface of PTP1B via noncovalent means. By treating insulin-resistant C2C12 myotubes with compound 22, enhanced insulin and leptin signaling pathways were observed. Long-term oral administration of compound 22 reduced the blood glucose level of diabetic BKS db mice. The glucose tolerance tests (OGTT) and insulin tolerance tests (ITT) in BKS db mice showed that oral administration of compound 22 could increase insulin sensitivity. In addition, long-term oral administration of compound 22 could protect mice from obesity, which was not the result of toxicity. Our pharmacokinetics results from the rat-based assays showed that orally administered compound 22 was absorbed rapidly from the gastrointestinal tract, extensively distributed to the tissues, and rapidly eliminated from the body. All these results indicate that compound 22 could serve as a qualified agent to treat type II diabetes.
Design, synthesis and biological evaluation of uncharged catechol derivatives as selective inhibitors of PTP1B
Li, Xiang-Qian,Xu, Qi,Luo, Jiao,Wang, Li-Jun,Jiang, Bo,Zhang, Ren-Shuai,Shi, Da-Yong
, p. 348 - 359 (2017/05/17)
Protein tyrosine phosphatases 1B (PTP1B) is a promising and validated therapeutic target to effectively treat T2DM and obesity. However, the development of charged PTP1B inhibitors was restricted due to their low cell permeability and poor bioavailability. Based on active natural products, two series of uncharged catechol derivatives were identified as PTP1B inhibitors by targeting a secondary aryl phosphate-binding site as well as the catalytic site. The most potent inhibitor 22 showed an IC50 of 0.487?μM against PTP1B and strong selectivity (27-fold) over TCPTP. Kinetic studies were also performed that 22 act as a competitive PTP1B inhibitor. The treatment of C2C12 myotubes with 22 markedly increased the phosphorylation levels of IRβ, Akt and IRS1 phosphorylation. The similarity of its action profiling with that produced by insulin suggested its potential as a new non-insulin-dependent drug candidate.
6-(4′-Aryloxy-phenyl)vinyl-1,2,4-trioxanes: A new series of orally active peroxides effective against multidrug-resistant Plasmodium yoelii in Swiss mice
Singh, Chandan,Verma, Ved Prakash,Naikade, Niraj Krishna,Singh, Ajit Shankar,Hassam, Mohammad,Puri, Sunil. K.
scheme or table, p. 4459 - 4463 (2010/10/02)
A new series of 6-(4′-aryloxy-phenyl)vinyl-1,2,4-trioxanes 10a-d, 11a-d, and 12a-d have been synthesized and evaluated for their antimalarial activity against multidrug-resistant Plasmodium yoelii in Swiss mice by oral route. Trioxanes 10b and 10c, the tw
SUBSTITUTED 4-ARYLOXY AND 4-ARYLSULFANYL-PHENYL-2-AMINOTHIAZOLES AS INHIBITORS OF CELL PROLIFERATION
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Page/Page column 30-33, (2008/06/13)
The invention discloses compounds which are substituted 4-aryloxy and 4-arylsulfanyl-phenyl-2-aminothiazoles with anti-cancer activity. The invention futher discloses methods of preparing compounds of the invention. The invention also discloses methods of inhibiting cell proliferation and tumor growth in a subject by administering compounds of the invention to the subject.
Synthesis and evaluation of substituted 4-aryloxy- and 4-arylsulfanyl- phenyl-2-aminothiazoles as inhibitors of human breast cancer cell proliferation
Gorczynski, Michael J.,Leal, Rachel M.,Mooberry, Susan L.,Bushweller, John H.,Brown, Milton L.
, p. 1029 - 1036 (2007/10/03)
Several substituted 4-aryloxy- and 4-arylsulfanyl-phenyl-2-aminothiazoles were synthesized and evaluated for cytotoxic activity against estrogen-positive, estrogen-negative, and adriamycin-resistant human breast cancer cell lines. 4-[4′-(3,4-Dichlorophenoxy)-phenyl]-thiazol-2-yl ammonium iodide demonstrated potent activity against both estrogen-positive and negative breast cancer cell lines with low micromolar (μM) GI50 values. In addition, we have identified several 2-aminothiazoles that demonstrated selective potency for the adriamycin-resistant and estrogen-negative breast cancer cell lines. The results suggest that these 2-aminothiazoles represent lead compounds for evaluation in animal models of breast cancer.
