- Preparation method of tenuazonic Acid and derivative thereof
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The invention provides a preparation method of tenuazonic Acid and a derivative thereof. The synthesis route comprises the following steps: reacting malonic acid cycloisopropylidene ester with acyl chloride, then reacting with amino acid methyl ester hydr
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Paragraph 0062-0063
(2021/05/12)
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- Amic acid derivative as well as preparation method and application thereof
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The invention provides an amine acid derivative as well as a preparation method and application thereof. The amine acid derivative has the structure as follows. Herein, R is selected from methyl, methoxy and the like. R1 Selected from C1 - C4 a
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Paragraph 0117; 0146-0148
(2021/09/21)
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- 5 - N-propyl -4 -hydroxypyrrole -2 - ketone derivative as well as preparation method and application thereof
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5 - N-propyl -4 -hydroxypyrro -2 -one derivatives as well as a preparation method and application thereof are disclosed. The 5 -n-propyl -4 -hydroxypyrrole -2 - ketone derivative provided by the invention has a significant improvement in weeding activity
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Paragraph 0052-0054
(2021/11/03)
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- PANTETHEINE DERIVATIVES AND USES THEREOF
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The present disclosure relates to compounds of Formula (I), (II), or (II'): (I), (II), (II'), and pharmaceutically acceptable salts or solvates thereof. The present disclosure also relates to pharmaceutical compositions comprising the compounds and therapeutic and diagnostic uses of the compounds and pharmaceutical compositions.
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Paragraph 2121
(2020/06/19)
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- Quinolones modulate ghrelin receptor signaling: Potential for a novel small molecule scaffold in the treatment of cachexia
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Cachexia is a metabolic wasting disorder characterized by progressive weight loss, muscle atrophy, fatigue, weakness, and appetite loss. Cachexia is associated with almost all major chronic illnesses including cancer, heart failure, obstructive pulmonary disease, and kidney disease and significantly impedes treatment outcome and therapy tolerance, reducing physical function and increasing mortality. Current cachexia treatments are limited and new pharmacological strategies are needed. Agonists for the growth hormone secretagogue (GHS-R1a), or ghrelin receptor, prospectively regulate the central regulation of appetite and growth hormone secretion, and therefore have tremendous potential as cachexia therapeutics. Non-peptide GHS-R1a agonists are of particular interest, especially given the high gastrointestinal degradation of peptide-based structures, including that of the endogenous ligand, ghrelin, which has a half-life of only 30 min. However, few compounds have been reported in the literature as non-peptide GHS-R1a agonists. In this paper, we investigate the in vitro potential of quinolone compounds to modulate the GHS-R1a in both transfected human cells and mouse hypothalamic cells. These chemically synthesized compounds demonstrate a promising potential as GHS-R1a agonists, shown by an increased intracellular calcium influx. Further studies are now warranted to substantiate and exploit the potential of these novel quinolone-based compounds as orexigenic therapeutics in conditions of cachexia and other metabolic and eating disorders.
- Torres-Fuentes, Cristina,Pastor-Cavada, Elena,Cano, Rafael,Kandil, Dalia,Shanahan, Rachel,Juan, Rocio,Shaban, Hamdy,McGlacken, Gerard P.,Schellekens, Harri?t
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- Screening, synthesis, crystal structure, and molecular basis of 6-amino-4-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitriles as novel AKR1C3 inhibitors
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AKR1C3 is a promising therapeutic target for castration-resistant prostate cancer. Herein, an evaluation of in-house library discovered substituted pyranopyrazole as a novel scaffold for AKR1C3 inhibitors. Preliminary SAR exploration identified its derivative 19d as the most promising compound with an IC50 of 0.160 μM among the 23 synthesized molecules. Crystal structure studies revealed that the binding mode of the pyranopyrazole scaffold is different from the current inhibitors. Hydroxyl, methoxy and nitro group at the C4-phenyl substituent together anchor the inhibitor to the oxyanion site, while the core of the scaffold dramatically enlarges but partially occupies the SP pockets with abundant hydrogen bond interactions. Strikingly, the inhibitor undergoes a conformational change to fit AKR1C3 and its homologous protein AKR1C1. Our results suggested that conformational changes of the receptor and the inhibitor should both be considered during the rational design of selective AKR1C3 inhibitors. Detailed binding features obtained from molecular dynamics simulations helped to finally elucidate the molecular basis of 6-amino-4-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitriles as AKR1C3 inhibitors, which would facilitate the future rational inhibitor design and structural optimization.
- Zheng, Xuehua,Jiang, Zan,Li, Xiaolin,Zhang, Chen,Li, Zhe,Wu, Yinuo,Wang, Xinhua,Zhang, Chao,Luo, Hai-bin,Xu, Jun,Wu, Deyan
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supporting information
p. 5934 - 5943
(2018/11/23)
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- MELDRUM 'S ACID, BARBITURIC ACID AND PYRAZOLONE DERIVATIVES SUBSTITUTED WITH HYDROXYLAMINE AS HNO DONORS
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The disclosed subject matter provides certain N-substituted hydroxylamine derivative compounds, pharmaceutical compositions and kits comprising such compounds, and methods of using such compounds or pharmaceutical compositions. In particular, the disclosed subject matter provides methods of using such compounds or pharmaceutical compositions for treating, preventing, or delaying the onset and/or development of a disease or condition. In some embodiments, the disease or condition is selected from cardiovascular diseases, ischemia, reperfusion injury, cancerous disease, pulmonary hypertension and conditions responsive to nitroxyl therapy.
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Page/Page column 38; 39
(2013/05/09)
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- Employing modular polyketide synthase ketoreductases as biocatalysts in the preparative chemoenzymatic syntheses of diketide chiral building blocks
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Chiral building blocks are valuable intermediates in the syntheses of natural products and pharmaceuticals. A scalable chemoenzymatic route to chiral diketides has been developed that includes the general synthesis of α-substituted, β-ketoacyl N-acetylcysteamine thioesters followed by a biocatalytic cycle in which a glucose-fueled NADPH-regeneration system drives reductions catalyzed by isolated modular polyketide synthase (PKS) ketoreductases (KRs). To identify KRs that operate as active, stereospecific biocatalysts, 11 isolated KRs were incubated with 5 diketides and their products were analyzed by chiral chromatography. KRs that naturally reduce small polyketide intermediates were the most active and stereospecific toward the panel of diketides. Several biocatalytic reactions were scaled up to yield more than 100 mg of product. These syntheses demonstrate the ability of PKS enzymes to economically and greenly generate diverse chiral building blocks on a preparative scale.
- Piasecki, Shawn K.,Taylor, Clint A.,Detelich, Joshua F.,Liu, June,Zheng, Jianting,Komsoukaniants, Arkady,Siegel, Dionicio R.,Keatinge-Clay, Adrian T.
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experimental part
p. 1331 - 1340
(2012/02/01)
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- Facile and efficient aromatization of 1,4-dihydropyridines with M(NO 3)2·XH2O, TNCB, TBAP and HMTAI and preparation of deuterium labeled dehydronifedipine from nifedipine-d3
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The easy and efficient aromatization of various 1,4-dihydropyridines was investigated using various metal nitrates, trinitratocerium(IV) bromate (TNCB), and tetrabutyl ammonium periodate (TBAP) as oxidant in acetic acid at 100 °C, as well as hexamethylenetetramine-iodine (HMTAI) reflux in methanol. The efficient conversion of nifedipine-d3 to dehydronifedipine-d 3 as an internal standard can be used in the measurement of nifedipine concentration in a body.
- Shaikh, Ajam C.,Chen, Chinpiao
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supporting information; experimental part
p. 3664 - 3668
(2010/09/04)
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- Microwave assisted rapid and efficient synthesis of aryl methyl ketones and β-keto esters using Meldrum's acid
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Microwave mediated rapid and efficient synthesis of aryl methyl ketones and β-keto esters from acyl Meldrum's acid by hydrolysis and alcoholysis, respectively, has been reported.
- More,Mahulikar
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p. 823 - 825
(2007/10/03)
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- O-COORDINATED METAL CHELATES AND THEIR USE IN OPTICAL RECORDING MEDIA HAVING HIGH STORAGE CAPACITY
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The invention relates to novel o ptical recording materials that comprise specific and in some cases novel diketone enamines or metal chelates thereof and that have excellent recording and playback quality especially ata wavelength of 350-500 nm. The invention accordingly relates to an optical recording medium comprising a substrate, a recording layer and optionally a reflecting layer, wherein the recording layer comprises a compound of formula (I), wherein M is hydrogen, aluminium or, preferably, a transition metal, which may in addition be coordinated with one or more further ligands and/or, for balancing out an excess charge, where applicable, may have an electrostatic interaction with one or more further ions inside or outside the coordination sphere, but M in formulae (Ib) and (Ic) is not hydrogen, Q is C-H, N or C-R6, it being possible for the stereochernistry of the C=Q double bond to be either E or Z. For the exact definitions of R1 to R6 reference should be made to the description. Also claimed are the novel compounds, especially tetracoordinated chelates, and a process for the preparation thereof.
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Page/Page column 36
(2010/02/10)
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- Novel Synthetic Approach to 6,7-Dihydro-5H-imidazo[1,5-a]-pyrazin-8-ones
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(Matrix presented) A novel route to highly substituted chiral 6,7-dihydro-5H-imidazo[1,5-a]pyrazine-8-ones starting from Meldrum's acid is disclosed. The key features of the methodology are the incorporation of amino esters as a chiral pool and facile mil
- Gopalsamy, Ariamala,Shi, Mengxiao
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p. 3907 - 3909
(2007/10/03)
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- Synthesis of two optically active calcium channel antagonists labelled with carbon-11 for in vivo cardiac PET imaging
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(±)-S11568 (1, 3-ethyl-5-methyl-(±)-2-[(2-(2-aminoethoxy)ethoxy)methyl]-4-(2,3 -dichlorophenyl)-6-methyl-1,4-dihydropyridine-3,5- dicarboxylate), has an in vitro profile of high potency and of high selectivity for the low-voltage dependent L-type calcium channel. In in vitro binding studies, it displaced specifically bound (-)-[3H]PN 200-110 (isradipine (2), the reference molecule for in vitro studies) from cardiac and vascular smooth muscle preparations with potencies of 5.6 and 51 nM, respectively. It also appears as a pure pharmacological antagonist acting at a single channel L-type and free of any interaction at the benzothiazepine binding site such as amlodipine (3). Both enantiomers of S11568 have in vitro activities, the dextro isomer S12967 ((±)-1) being 6 to 18-fold less potent than the levo one S12968 ((-)-1). Two couples of optically active labelling precursors of S11568, ((-)-10/(+)-10 and (-)-14/(+)-14) have been synthesized using a modified Hantzsch's dihydropyridine synthesis. In both cases, the enantiomers were separated by preparative chiral HPLC. They both have been independently labelled with carbon-11, using [11C]diazomethane or [11C]iodomethane to give multimilliCurie quantities of (-)-1 (S12968) and (+)-1 (S12967) with high specific activities (500-1000 mCi/μmol, 18.5-37.0 GBq/μmol). Both enantiomers appear suitable for PET experiments: their myocardial concentration increases after a bolus injection to reach a maximum in 2 min and then remains on a plateau with a slight downslope while the blood concentration falls rapidly. Myocardial uptake was threefold higher than lung uptake, leading to a good contrast on PET images. The present preliminary biological results obtained in Beagle dogs showed that both enantiomers have similar myocardisk kinetics and in vivo affinity for the left ventricular myocardium.
- Dolle, Frederic,Hinnen, Francoise,Valette, Heric,Fuseau, Chantal,Duval, Raphael,Peglion, Jean-Louis,Crouzel, Christian
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p. 749 - 764
(2007/10/03)
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- 1,3-Oxazines and Related Compounds. XIII. Reaction of Acyl Meldrum's Acids with Schiff Bases Giving 2,3-Disubstituted 5-Acyl-3,4,5,6-tetrahydro-2H-1,3-oxazine-4,6-diones and 2,3,6-Trisubstituted 2,3-Dihydro-1,3-oxazin-4-ones
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The reaction of Schiff bases (2) with various acyl Meldrum's acids (1) were investigated.Refluxing of 1 and 2 in benzene caused an exchange reaction of the acetone moiety of 1 with the Schiff base moiety through the intermediate acylketenes 11 formed in s
- Yamamoto, Yutaka,Watanabe, Yukiyoshi,,Ohnishi, Shuhei
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p. 1860 - 1870
(2007/10/02)
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