56681-66-4Relevant articles and documents
Ambroxol derivative, and preparation method, medicinal composition and application thereof
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Paragraph 0075; 0077-0080, (2019/12/29)
The invention relates to the field of medicinal chemistry, and concretely relates to an ambroxol derivative or pharmaceutically acceptable salts thereof, and a preparation method, a medicinal composition and a medical application thereof. The ambroxol derivative is a compound with a structure represented by formula I shown in the specification, and R in the formula I is defined in claims.
A Convergent Total Synthesis of the Biologically Active Benzofurans Ailanthoidol, Egonol and Homoegonol from Biomass-Derived Eugenol
Espinoza-Hicks, José C.,Zaragoza-Galán, Gerardo,Chávez-Flores, David,Ramos-Sánchez, Víctor H.,Tamariz, Joaquín,Camacho-Dávila, Alejandro A.
, p. 3493 - 3498 (2018/09/04)
An efficient, general synthetic protocol for the synthesis of the biologically active benzofurans ailanthoidol, egonol and homoegonol was developed. The key starting material, eugenol, is a naturally occurring and abundant precursor. The protocol, involving sequential acylation and intramolecular Wittig reaction, provides a convenient method for building the benzofuran moiety in good yield.
Synthesis of Two Natural Furan-Cyclized Diarylheptanoids via 2-Furaldehyde
Se?inti, Hatice,Se?en, Hasan
, p. 938 - 944 (2015/11/23)
Two natural diarylheptanoids, 2-benzyl-5-(2-phenylethyl)furan (1) and 2-methoxy-4-{[5-(2-phenylethyl)furan-2-yl]methyl}phenol (2), were synthesized starting from 2-furaldehyde. A Wittig reaction of 2-furaldehyde with benzyltriphenylphosphonium bromide followed by reduction of the alkene C=C bond with Mg gave 2-(2-phenylethyl)furan (5). Lithiation of 5 with BuLi at -78 followed by alkylation with benzyl bromide gave natural product 1. In another approach, Friedel-Crafts acylation of compound 5 with benzoyl chloride followed by deoxygenation of the C=O group afforded 1. The natural product 2 was also synthesized by acylation of 5 with 4-acetoxy-3-methoxybenzoyl chloride (16) followed by deoxygenation and deacetylation.
2-Diazo-1-(4-hydroxyphenyl)ethanone: A versatile photochemical and synthetic reagent
Senadheera, Sanjeewa N.,Evans, Anthony S.,Toscano, John P.,Givens, Richard S.
, p. 324 - 341 (2014/02/14)
α-Diazo arylketones are well-known substrates for Wolff rearrangement to phenylacetic acids through a ketene intermediate by either thermal or photochemical activation. Likewise, α-substituted p-hydroxyphenacyl (pHP) esters are substrates for photo-Favorskii rearrangements to phenylacetic acids by a different pathway that purportedly involves a cyclopropanone intermediate. In this paper, we show that the photolysis of a series of α-diazo-p- hydroxyacetophenones and p-hydroxyphenacyl (pHP) α-esters both generate the identical rearranged phenylacetates as major products. Since α-diazo-p-hydroxyacetophenone (1a, pHP N2) contains all the necessary functionalities for either Wolff or Favorskii rearrangement, we were prompted to probe this intriguing mechanistic dichotomy under conditions favorable to the photo-Favorskii rearrangement, i.e., photolysis in hydroxylic media. An investigation of the mechanism for conversion of 1a to p-hydroxyphenyl acetic acid (4a) using time-resolved infrared (TRIR) spectroscopy clearly demonstrates the formation of a ketene intermediate that is subsequently trapped by solvent or nucleophiles. The photoreaction of 1a is quenched by oxygen and sensitized by triplet sensitizers and the quantum yields for 1a-c range from 0.19 to a robust 0.25. The lifetime of the triplet, determined by Stern-Volmer quenching, is 31 ns with a rate for appearance of 4a of k = 7.1 × 10 6 s-1 in aq. acetonitrile (1:1 v:v). These studies establish that the primary rearrangement pathway for 1a involves ketene formation in accordance with the photo-Wolff rearrangement. Furthermore we have also demonstrated the synthetic utility of 1a as an esterification and etherification reagent with a variety of substituted α-diazo-p- hydroxyacetophenones, using them as synthons for efficiently coupling it to acids and phenols to produce pHP protect substrates. The Royal Society of Chemistry and Owner Societies.
Pharmacological validation of trypanosoma brucei phosphodiesterases B1 and B2 as druggable targets for African sleeping sickness
Bland, Nicholas D.,Wang, Cuihua,Tallman, Craig,Gustafson, Alden E.,Wang, Zhouxi,Ashton, Trent D.,Ochiana, Stefan O.,McAllister, Gregory,Cotter, Kristina,Fang, Anna P.,Gechijian, Lara,Garceau, Norman,Gangurde, Rajiv,Ortenberg, Ron,Ondrechen, Mary Jo,Campbell, Robert K.,Pollastri, Michael P.
experimental part, p. 8188 - 8194 (2012/01/13)
Neglected tropical disease drug discovery requires application of pragmatic and efficient methods for development of new therapeutic agents. In this report, we describe our target repurposing efforts for the essential phosphodiesterase (PDE) enzymes TbrPDEB1 and TbrPDEB2 of Trypanosoma brucei, the causative agent for human African trypanosomiasis (HAT). We describe protein expression and purification, assay development, and benchmark screening of a collection of 20 established human PDE inhibitors. We disclose that the human PDE4 inhibitor piclamilast, and some of its analogues, show modest inhibition of TbrPDEB1 and B2 and quickly kill the bloodstream form of the subspecies T. brucei brucei. We also report the development of a homology model of TbrPDEB1 that is useful for understanding the compound-enzyme interactions and for comparing the parasitic and human enzymes. Our profiling and early medicinal chemistry results strongly suggest that human PDE4 chemotypes represent a better starting point for optimization of TbrPDEB inhibitors than those that target any other human PDEs.
NEUROPROTECTIVE COMPOUNDS AND THEIR USE
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Page/Page column 26, (2010/11/17)
Apocynin derivative compounds, active pharmaceutical ingredients, dosage forms, and methods of use thereof as neuroprotectants in the brain of mammals.
Induction of adiponectin by natural and synthetic phenolamides in mouse and human preadipocytes and its enhancement by docosahexaenoic acid
Yamazaki, Yoshimitsu,Kawano, Yasuhiro,Uebayasi, Masami
, p. 290 - 300 (2008/09/16)
Adiponectin, the adipose-derived cytokine, plays an important role in preventing metabolic syndromes. To develop new adiponectin inducers, eight species of ferulic esters and amides, and five related compounds were synthesized and tested on the stimulation of adiponectin production in mouse 3T3-L1 and normal human preadipocytes. The ferulamides with an aromatic ring in the N-substituent are very active in inducing adiponectin as compared with the known active compounds, curcumin, [6]-gingerol, and capsaicin, and furthermore the activities of these ferulamides are remarkably stronger than those of the corresponding esters or the straight chain octylamide. The most active compound, N-(2-phenylethyl)ferulamide (7), was found to activate the PPAR (peroxisome proliferator-activated receptor) γ-RXR (retinoid X receptor) α heterodimeric complex in the PPRE (PPAR-responsive element)-driven luciferase reporter assay. The adiponectin production by 7 is synergistically enhanced by coaddition of a PPARγ-specific agonist, pioglitazone (PGZ), or another PPARγ agonist, docosahexaenoic acid (DHA), in cultured preadipocytes. The compound 7 alone did not show a statistically significant effect on the plasma adiponectin level in KK-Ay/Ta mice, while 1% 7 in the diets significantly lowered the blood glucose and triglyceride levels and 0.3% 7 mixed with DHA oil in the diets significantly increased the adiponectin level as compared with the control. These results suggest that the present ferulamides would be useful lead compounds in developing more potent agents for treatment of metabolic syndromes through promoting the endogenous adiponectin production, and that such an activity is possibly enhanced by the coadministration with DHA.
Compounds and compositons for treating C1s-mediated diseases and conditions
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, (2008/06/13)
Disclosed is a method for treating the symptoms of an acute or chronic disorder mediated by the classical pathway of the complement cascade, comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Formula I or a solvate, hydrate or pharmaceutically acceptable salt thereof; wherein R1, R2, R3, R4, X, Y and Z are defined in the specification.
Heteroaryl amidines, methylamidines and guanidines, preparation thereof, and use thereof as protease inhibitors
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, (2008/06/13)
The present invention is directed to compounds of Formula I: wherein X is O, S or NR7and R1-R7, Y and Z are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof. Also described are methods for preparing the compounds of Formula I. The novel compounds of the present invention are potent inhibitors of proteases, especially trypsin-like serine proteases, such as chymotrypsin, trypsin, plasmin and urokinase. Certain of the compounds exhibit direct, selective inhibition of urokinase, or are intermediates useful for forming compounds having such activity.
Synthesis and structure-activity relationship of diarylamide derivatives as selective inhibitors of the proliferation of human coronary artery smooth muscle cells
Gita, Haruhisa,Sobe, Yoshiaki,Akaku, Haruo,Ekine, Rena,Oto, Yuso,Isawa, Satoru,Hayashi, Hideya
, p. 549 - 551 (2007/10/03)
A series of diarylamide derivatives were synthesized and evaluated for their inhibitory activities against human coronary artery smooth muscle cells (SMCs) and human coronary artery endothelial cells (ECs). Compound 2w was superior to the lead compound, Tranilast, in terms of the potency of the activity and cell selectivity.
