1.Isolation, purification and identification of antioxidants in an aqueous aged garlic extract.
Wang X1, Liu R1, Yang Y1, Zhang M2. Food Chem. 2015 Nov 15;187:37-43. doi: 10.1016/j.foodchem.2015.03.109. Epub 2015 Apr 2.
An aqueous aged garlic extract (AGE) was prepared by soaking sliced garlic in water for 20days at room temperature (23-25 °C). In order to locate the antioxidant ingredients of the aqueous AGE, an activity-guided fractionation approach using ABTS assay, DPPH assay and FRAP assay were conducted to guide the fractionation by means of extraction, column chromatography and semi-preparative HPLC. Some phenols and organosulfur compounds were identified as antioxidants in AGE by GC-MS. Furthermore, UV, IR, ESI-MS, NMR and specific rotation experiments led to the identification of l-phenylalanine, l-tryptophan, (3S)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid, (1S,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid, and (1R,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid as the major antioxidants in the AGE. The EC50 values of these purified tetrahydro-β-carboline derivatives were 0.625-1.334 μmol/mL and 1.063-2.072 μmol/mL in ABTS assay and DPPH assay, respectively.
2.New Alkaloids from Green Vegetable Soybeans and Their Inhibitory Activities on the Proliferation of Concanavalin A-Activated Lymphocytes.
Wang T, Zhao J1, Li X, Xu Q, Liu Y, Khan IA1, Yang S. J Agric Food Chem. 2016 Mar 2;64(8):1649-56. doi: 10.1021/acs.jafc.5b06107. Epub 2016 Feb 17.
A comprehensive phytochemical study of the chemical constituents of green vegetable soybeans resulted in the isolation of two new alkaloids, soyalkaloid A, 1, and isoginsenine, 2, together with four known ones, ginsenine, 3, (1S,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid, 4, (1R,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid, 5, and indole-3-carboxylic acid, 6. The structures of compounds 1-6 were elucidated on the basis of spectroscopic and chemical analyses. All of the alkaloids were isolated from soybeans for the first time, and compound 1 was a new indole-type alkaloid with a novel carbocyclic skeleton. Their inhibitory activities on the proliferation of concanalin A-activated lymphocytes were assessed by CCK8 assay.
3.Identification of N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide (PIM447), a Potent and Selective Proviral Insertion Site of Moloney Murine Leukemia (PIM) 1, 2, and 3 Kinase Inhibitor in Clinical Trials for Hematological Malignancies.
Burger MT, Nishiguchi G, Han W, Lan J, Simmons R, Atallah G, Ding Y, Tamez V, Zhang Y, Mathur M, Muller K, Bellamacina C, Lindvall MK, Zang R, Huh K, Feucht P, Zavorotinskaya T, Dai Y, Basham S, Chan J, Ginn E, Aycinena A, Holash J, Castillo J, Langowski JL, Wang Y, Chen MY, Lambert A, Fritsch C1, Kauffmann A1, Pfister E1, Vanasse KG2, Garcia PD. J Med Chem. 2015 Nov 12;58(21):8373-86. doi: 10.1021/acs.jmedchem.5b01275. Epub 2015 Oct 27.
Pan proviral insertion site of Moloney murine leukemia (PIM) 1, 2, and 3 kinase inhibitors have recently begun to be tested in humans to assess whether pan PIM kinase inhibition may provide benefit to cancer patients. Herein, the synthesis, in vitro activity, in vivo activity in an acute myeloid leukemia xenograft model, and preclinical profile of the potent and selective pan PIM kinase inhibitor compound 8 (PIM447) are described. Starting from the reported aminopiperidyl pan PIM kinase inhibitor compound 3, a strategy to improve the microsomal stability was pursued resulting in the identification of potent aminocyclohexyl pan PIM inhibitors with high metabolic stability. From this aminocyclohexyl series, compound 8 entered the clinic in 2012 in multiple myeloma patients and is currently in several phase 1 trials of cancer patients with hematological malignancies.
4.Optimization of 3-aryl-3-ethoxypropanoic acids and discovery of the potent GPR40 agonist DS-1558.
Takano R1, Yoshida M2, Inoue M3, Honda T4, Nakashima R5, Matsumoto K5, Yano T5, Ogata T6, Watanabe N7, Hirouchi M7, Kimura T8, Toda N9. Bioorg Med Chem. 2015 Sep 1;23(17):5546-65. doi: 10.1016/j.bmc.2015.07.028. Epub 2015 Jul 23.
GPR40 agonists stimulate insulin secretion only under the presence of high glucose concentration. Based on this mechanism, GPR40 agonists are believed to be promising novel insulin secretagogues with low risk of hypoglycemia. The optimizations of 3-aryl-3-ethoxypropanoic acids were performed to improve in vitro activity. We discovered compound 29r (DS-1558), (3S)-3-ethoxy-3-(4-{[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]oxy}phenyl)propanoic acid, which was confirmed to have an enhancing effect on glucose-dependent insulin secretion after intravenous glucose injection in SD rats.
![(+)-(1S,3R)-3-[(9-Fluorenylmethoxycarbonyl)amino]cyclopentanecarboxylic acid](https://resource.bocsci.com/structure/220497-66-5.gif)
