1001669-22-2Relevant academic research and scientific papers
Synthesis, formulation and in vitro evaluation of a novel microtubule destabilizer, SMART-100
Li, Feng,Lu, Yan,Li, Wei,Miller, Duane D.,Mahato, Ram I.
, p. 151 - 158 (2010)
A novel microtubule destabilizer, substituted methoxybenzoyl-ary-thiazole (SMART)-100, was synthesized, which showed good anticancer activity in HepG2 cells. SMART-100 was able to circumvent multidrug resistance (MDR) and effectively inhibited the growth of cell lines that overexpress P-glycoprotein (P-gp). SMART-100 inhibited P-gp activity, which may be responsible for its ability to overcome MDR. Since SMART-100 is poorly soluble in water, it was formulated in polyethylene-b-poly(d,l-lactide) (PEG-PLA) micelles. The solubility of SMART-100 was increased by more than 1.1×105 folds. SMART-100 loaded PEG-PLA micelles could effectively inhibit HepG2 cell growth and arrest cell cycle progression at G2/M phase, followed by appearance of a sub-G1 phase, which is indicative of cell apoptosis. Increased Caspase-3 activity was also observed when HepG2 cells were treated with SMART-100. The anticancer activity of SMART-100 loaded PEG-PLA micelles was also evaluated on luciferase expressing C4-2-Luc cell lines by IVIS imaging. Our results suggest that SMART-100 has the potential to treat resistant cancers.
Rh(III)-catalyzed cyclization reaction of azoles with alkynes: Efficient synthesis of azole-fused-pyridines
Chen, Xuebing,Wu, Youzhi,Xu, Jinyi,Yao, Hequan,Lin, Aijun,Huang, Yue
supporting information, p. 9186 - 9189 (2015/09/07)
A Rh(III)-catalyzed cyclization of azoles with alkynes has been developed. A variety of azole-fused-pyridines were obtained in good to excellent yields and regioselectivity. Both the C5 and the C4 position of azoles were suitable for the reaction.
Concise synthesis of 2,4-disubstituted thiazoles from β-azido disulfides and carboxylic acids or anhydrides: Asymmetric synthesis of cystothiazole C
Liu, Yi,Sun, Xue,Zhang, Xing,Liu, Jun,Du, Yuguo
, p. 8453 - 8461 (2014/12/10)
A novel and efficient method for the one-pot synthesis of 2,4-disubstituted thiazoles from carboxylic acids or anhydrides is presented. Based on this new method, the total synthesis of the bis-2,4-disubstituted bis(thiazoles) natural product cystothiazole C is also presented. This journal is
Design, synthesis, and biological evaluation of stable colchicine binding site tubulin inhibitors as potential anticancer agents
Lu, Yan,Chen, Jianjun,Wang, Jin,Li, Chien-Ming,Ahn, Sunjoo,Barrett, Christina M.,Dalton, James T.,Li, Wei,Miller, Duane D.
, p. 7355 - 7366 (2015/01/30)
To block the metabolically labile sites of novel tubulin inhibitors targeting the colchicine binding site based on SMART, ABI, and PAT templates, we have designed, synthesized, and biologically tested three focused sets of new derivatives with modifications at the carbonyl linker, the para-position in the C ring of SMART template, and modification of A ring of the PAT template. Structure-activity relationships of these compounds led to the identification of new benzimidazole and imidazo[4,5-c]pyridine-fused ring templates, represented by compounds 4 and 7, respectively, which showed enhanced antitumor activity and substantially improved the metabolic stability in liver microsomes compared to SMART. MOM group replaced TMP C ring and generated a potent analogue 15, which showed comparable potency to the parent SMART compound. Further modification of PAT template yielded another potent analogue 33 with 5-indolyl substituent at A ring.
IMIDAZOTHIADIAZOLE AND IMIDAZOPYRAZINE DERIVATIVES AS PROTEASE ACTIVATED RECEPTOR 4 (PAR4) INHIBITORS FOR TREATING PLATELET AGGREGATION
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Paragraph 00218, (2013/11/18)
The present invention provides thiazole compounds of Formula I wherein W, Y, R0, R2, R4, R5, R6, R7, X1, X2, X3 and X4 are as defined herein, or a stereoisomer, tautomer, pharmaceutically acceptable salt, prodrug ester or solvate form thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of platelet aggregation and thus can be used as medicaments for treating or preventing thromboembolic disorders.
COMPOUNDS FOR TREATMENT OF CANCER
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Paragraph 00289, (2011/10/03)
The present invention relates to novel compounds having anti-cancer activity, methods of making these compounds, and their use for treating cancer and drug-resistant tumors, e.g. melanoma, metastatic melanoma, drug resistant melanoma, prostate cancer and drug resistant prostate cancer.
Design, synthesis, and SAR studies of 4-substituted methoxylbenzoyl-aryl- thiazoles analogues as potent and orally bioavailable anticancer agents
Lu, Yan,Li, Chien-Ming,Wang, Zhao,Chen, Jianjun,Mohler, Michael L.,Li, Wei,Dalton, James T.,Miller, Duane D.
, p. 4678 - 4693 (2011/09/14)
In a continued effort to improve upon the previously published 4-substituted methoxybenzoyl-aryl-thiazole (SMART) template, we explored chemodiverse "B" rings and "B" to "C" ring linkage. Further, to overcome the poor aqueous solubility of this series of agents, we introduced polar and ionizable hydrophilic groups to obtain water-soluble compounds. For instance, based on in vivo pharmacokinetic (PK) studies, an orally bioavailable phenyl-amino-thiazole (PAT) template was designed and synthesized in which an amino linkage was inserted between "A" and "B" rings of compound 1. The PAT template maintained nanomolar (nM) range potency against cancer cell lines via inhibiting tubulin polymerization and was not susceptible to P-glycoprotein mediated multidrug resistance in vitro, and markedly improved solubility and bioavailability compared with the SMART template (45a-c (PAT) vs 1 (SMART)).
COMPOUNDS FOR TREATMENT OF CANCER
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Page/Page column 17-18, (2010/01/31)
Compounds according to formula (I) are disclosed where Q is S, N, or O; X is optional, and can be O═, S═, ═N—NH2, ═N—OH, or —OH; Y is optional and can be —N(H)—, O, or C1 to C20 hydrocarbon; and R1 and R2 are each independently substituted or unsubstituted single-, fused- or multiple-ring aryl or (hetero)cyclic ring systems. Methods of making these compounds, pharmaceutical compositions containing the compounds, and their use, particularly for treating or preventing cancer, are also disclosed.
Discovery of 4-substituted methoxybenzoyl-aryl-thiazole as novel anticancer agents: Synthesis, biological evaluation, and structure-activity relationships
Lu, Yan,Li, Chien-Ming,Wang, Zhao,Ross, Charles R.,Chen, Jianjun,Dalton, James T.,Li, Wei,Miller, Duane D.
experimental part, p. 1701 - 1711 (2010/01/16)
A series of 4-substituted methoxybenzoyl-aryl-thiazoles (SMART) have been discovered and synthesized as a result of structural modifications of the lead compound 2-arylthiazolidine-4-carboxylic acid amides (ATCAA). The antiproliferative activity of the SMART agents against melanoma and prostate cancer cells was improved from μM to low nM range compared with the ATCAA series. The structure-activity relationship was discussed from modifications of "A", "B", and "C" rings and the linker. Preliminary mechanism of action studies indicated that these compounds exert their anticancer activity through inhibition of tubulin polymerization.
