1259327-69-9Relevant articles and documents
N-aromatic amide compound and preparation method and application thereof
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Paragraph 0085-0091; 0099-0103; 0176-0180; 0188-0192, (2020/04/17)
The invention relates to N-aromatic amide compounds represented by general formulas (I) and (II), a preparation method thereof, a pharmaceutical composition and a pharmaceutical preparation containingthe compound represented by the general formula (I) or (II), and applications of the compounds represented by the general formulas (I) and (II) in preparation of drugs used for treating androgen-related diseases. The definitions of R1, R2, R3, R4, R5, R6, W1, W2, W3, W4 and W5 in the general formulas are the same as those in the specifications. The compounds of the general formulas (I) and (II) are capable of binding to androgen receptors, have activity against androgens and degrade androgen receptors. The compound can be used for treating various androgen-related diseases such as prostate cancer, benign prostatic hyperplasia, breast cancer, bladder cancer, ovarian cancer and the like alone or as a composition, and can also be used for treating diseases such as acnes, hirsutism, alopeciaand the like.
Bromo-nitro substitution on a tertiary α carbon - A previously uncharacterized facet of the Kornblum substitution
Leonard, Matthew J.,McKay, Peter G.,Lingham, Anthony R.
, p. 76401 - 76418 (2015/09/22)
Sodium nitrite in dimethylformamide substitutes nitro for bromine alpha to an amide carbonyl in high yield at a tertiary site. Hammett plots show a strongly positive ρ value (+0.67), indicating a negatively-charged transition state, in contrast to the typical SN1/SN2 mechanism domain for Kornblum substitutions. 2015
Antitumor agents 290. Design, synthesis, and biological evaluation of new LNCaP and PC-3 cytotoxic curcumin analogs conjugated with anti-androgens
Shi, Qian,Wada, Koji,Ohkoshi, Emika,Lin, Li,Huang, Rong,Morris-Natschke, Susan L.,Goto, Masuo,Lee, Kuo-Hsiung
experimental part, p. 4020 - 4031 (2012/09/08)
In our continuing study of curcumin analogs as potential anti-prostate cancer drug candidates, 15 new curcumin analogs were designed, synthesized and evaluated for cytotoxicity against two human prostate cancer cell lines, androgen-dependent LNCaP and androgen-independent PC-3. Twelve analogs (5-12, 15, 16, 19, and 20) are conjugates of curcumin (1) or methyl curcumin (2) with a flutamide- or bicalutamide-like moiety. Two compounds (22 and 23) are C4-mono- and difluoro-substituted analogs of dimethyl curcumin (DMC, 21). Among the newly synthesized conjugates compound 15, a conjugate of 2 with a partial bicalutamide moiety, was more potent than bicalutamide alone and essentially equipotent with 1 and 2 against both prostate tumor cell lines with IC 50 values of 41.8 μM (for LNCaP) and 39.1 μM (for PC-3). A cell morphology study revealed that the cytotoxicity of curcumin analogs or curcumin-anti-androgen conjugates detected from both prostate cancer cell lines might be due to the suppression of pseudopodia formation. A molecular intrinsic fluorescence experiment showed that 1 accumulated mainly in the nuclei, while conjugate 6 was distributed in the cytosol. At the tested conditions, anti-androgens suppressed pseudopodia formation in PC-3 cells, but not in LNCaP cells. The evidence suggests that distinguishable target proteins are involved, resulting in the different outcomes toward pseudopodia suppression.
