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BTK and PI3Kdelta play crucial roles in the progression of leukemia, and studies confirmed that the dual inhibition against BTK and PI3Kdelta could provide superior anticancer agents to single targeted therapies. Herein, a new series of novel benzofuro[3,2-b]pyridin-2(1H)-one derivatives were optimized based on a BTK/PI3Kdelta inhibitor 2 designed by our group. Biological studies clarified that compound 6f exhibited the most potent inhibitory activity (BTK: IC50 = 74 nM; PI3Kdelta: IC50 = 170 nM) and better selectivity than 2. Moreover, 6f significantly inhibited the proliferation of Raji and Ramos cells with IC50 values of 2.1 muM and 2.65 muM respectively by blocking BTK and PI3K signaling pathways. In brief, 6f possessed of the potency for further optimization as an anti-leukemic drug by inhibiting BTK and PI3Kdelta kinase.

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Benzofuran – Wikipedia,
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A series of substituted 3H-1,2,3,5-oxathiadiazole-2-oxides (6) was prepared and tested for antihyperglycemic activity in the db/db mouse, a model for type 2 (non-insulin dependent) diabetes mellitus. The oxathiadiazoles 6 were synthesized by a two-step sequence: treatment of a substituted acetonitrile (4) with hydroxylamine to give the corresponding amidoxime (5) and cyclization with thionyl chloride to yield 6. In terms of potency, the 2-naphthalenylmethyl group (as in compound 3) was found to be the optimal substituent in this series. Compound 3 was approximately 5 times more potent than ciglitazone (1).

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The first formal [3 + 2] cycloaddition reaction of in situ generated azaoxyallyl cation with cyclic ketones has been developed using mild reaction conditions. A variety of spiro-4-oxazolidinones was obtained in excellent yields (up to 99%). The high efficiency of this process, coupled with the operational simplicity, makes it an attractive method for the synthesis of spiro-4-oxazolidinones.

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Organohalogenite-Catalyzed Spiroketalization: Enantioselective Synthesis of Bisbenzannulated Spiroketal Cores

A new core structure-motivated strategy for the intramolecular aromatic spiroketalization process was found and used for the enantioselective synthesis of bisbenzannulated spiroketals, the bioactive core of rubromycins, with high levels of enantioselectivity (up to 98% ee) via an organohalogenite-mediated asymmetric intramolecular aromatic spiroketalization. This is the first organocatalytic method for the construction of optically pure bisbenzannulated spiroketals.

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PIPERIDINE DERIVATIVE AND PREPARATION METHOD AND PHARMACEUTICAL USE THEREOF

The present invention relates to a piperidine derivative and the preparation method and a pharmaceutical use thereof. In particular, the present invention relates to the piperidine derivative as shown by general formula (I) and the preparation method thereof and a pharmaceutical composition containing same, and the use thereof as an estrogen receptor modulator in the treatment of estrogen receptor mediated or dependent diseases or conditions, the diseases particularly preferably being breast cancer. In the abstract, the definition of each substituent of the general formula (I) is the same as that in the description.

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SPIROLACTAM CGRP RECEPTOR ANTAGONISTS

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.

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GLUCOPYRANOSIDE DERIVATIVES

Novel compounds of the formula (I), in which X has the meaning indicated in Patent Claim 1, are suitable as antidiabetics.

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Benzofuran – Wikipedia,
Benzofuran | C8H3602O – PubChem