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To exploit the S3′ subsite of renin active site for renin inhibitor design, 42 aliskiren derivatives with modified P2′ portion were designed, synthesized and biologically evaluated. Some highly potent renin inhibitors (IC 50 < 3 nM) were identified, among which compounds 38 (IC 50 = 0.9 nM) and 39 (IC 50 = 0.7 nM) were over 2.5-fold more potent than aliskiren (IC 50 = 2.3 nM). SAR analysis indicated that incorporation of polar hydrophilic moieties into the P2′ portion of renin inhibitors generally enhanced the potency. Consistently with this, molecular modeling study revealed that the triazole part of 39 could provide additional interactions to the S3′ subsite of renin active site. Moreover, in vivo evaluation in the double transgenic mouse hypertension model demonstrated that 39 produced greater reduction of the mean arterial blood pressure than ariskiren at the doses of 17.0 and 34.0 μmol/kg, respectively. Taken together, the S3′ subsite of renin active site merits further consideration for renin inhibitor design. [ABSTRACT FROM AUTHOR]

Abstract: Twelve derivatives of oleanolic acid (1) have been synthesized and evaluated for their inhibitory activities against the growth of prostate PC3, breast MCF-7, lung A549, and gastric BGC-823 cancer cells by MTT assays. Within these series of derivatives, compound 17 exhibited the most potent cytotoxicity against PC3 cell line (IC50 =0.39μM) and compound 28 displayed the best activity against A549 cell line (IC50 =0.22μM). SAR analysis indicates that H-donor substitution at C-3 position of oleanolic acid may be advantageous for improvement of cytotoxicity against PC3, A549 and MCF-7 cell lines. [Copyright &y& Elsevier]

Abstract: The intramolecular Schmidt reaction of simple azido secondary benzyl alcohols has been realized for the first time. Investigation of the electronic and steric effects of the substrates on the product outcome was conducted. Unique intramolecular Schmidt rearrangements were observed with the formation of a cinnamaldehyde derivative and aryl aldehydes, respectively. Using this protocol, an efficient synthesis of dihydrobenzotriazine derivatives was achieved. Moreover, a practical approach to 2-aryl-1-pyrrolines was also accessed. [Copyright &y& Elsevier]

Structurally diverse aryl bromides are well tolerated in the α-arylation reaction with a chiral nickel(II) glycinate complex. [ABSTRACT FROM AUTHOR]