- Site-Selective, Remote sp3 C?H Carboxylation Enabled by the Merger of Photoredox and Nickel Catalysis
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A photoinduced carboxylation of alkyl halides with CO2 at remote sp3 C?H sites enabled by the merger of photoredox and Ni catalysis is described. This protocol features a predictable reactivity and site selectivity that can be modulated by the ligand backbone. Preliminary studies reinforce a rationale based on a dynamic displacement of the catalyst throughout the alkyl side chain.
- Sahoo, Basudev,Bellotti, Peter,Juliá-Hernández, Francisco,Meng, Qing-Yuan,Crespi, Stefano,K?nig, Burkhard,Martin, Ruben
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p. 9001 - 9005
(2019/06/24)
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- Antileukotrienic phenethylamido derivatives of arylalkanoic acids in the treatment of ulcerative colitis
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A series of arylalkanoic acid derivatives bearing methyl(phenethyl)amino groups were prepared and their inhibition of LTB4 biosynthesis was evaluated. Regression analysis showed the slightly different parabolic dependences of this activity on lipophilicity of α-methyl and α-unsubstituted alkanoic acid derivatives. The relationship derived for α-unsubstituted alkanoic acids was extended by previously prepared group of similar derivatives of arylacetic acids without any change of regression coefficients and statistical criteria. It was concluded that the most active compounds belong to 2-arylpropanoic acid derivatives with lipophilicity close to log Popt (=6.97). But generally, the structural changes in the acidic part of compounds under study did not yield the substantial improvement of LTB4 biosynthesis inhibition in comparison with the previously prepared series of derivatives IV. The anti-inflammatory effect of the compounds under study was evaluated in three animal models of inflammation and their possible utilization in the treatment of ulcerative colitis (UC) was followed. From 12 evaluated compounds, 4 compounds are more active in UC inhibition than the standard sulfasalazine but it can be stated that the change of connecting chain between aromatic ring and carboxyl did not bring about the important improvement of this activity in comparison with previous derivatives of arylacetic acids. Possible relation between LTB4 biosynthesis inhibition and ulcerative colitis is seriously broken by the compound 8a with carbonyl as the additional functional group on the connecting chain between carboxyl and aromatic ring.
- Junek, Richard,Kverka, Miloslav,Jandera, Antonin,Panajotova, Vladimira,Satinsky, Dalibor,Machacek, Milos,Kuchar, Miroslav
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experimental part
p. 332 - 344
(2009/04/06)
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- Synthesis and immunosuppressive activity of new artemisinin derivatives. 1. [12(β or α)-dihydroartemisininoxy]phen(ox)yl aliphatic acids and esters
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A series of novel dihydroartemisinin derivatives were synthesized and evaluated on their immunosuppressive activity in the search for potential immunosuppressive agents with high efficacy and low toxicity. These compounds were assayed in their cytotoxicity of lymphocyte, inhibition activity on concanavalin A (ConA) induced T cell proliferation and lipopolysaccharide (LPS) induced B cell proliferation. Among them, 11b, 13b, 14d, 15b, 16, and 17 remarkably exhibited lower cytotoxicity and higher inhibition activity on the mitogen-induced T cell and B cell proliferation in comparison with artemisinin, artesunate, and artemether in vitro. More significantly, compound 11b displayed reduced cytotoxicity by over 100-fold compared with cyclosporin A (CsA) and comparable inhibition activity (SI = 848) on ConA-induced T cell proliferation to CsA (SI = 963) and more than 4000 times the inhibitory effect (SI = 28473) on LPS-induced B cell proliferation compared with CsA (SI = 7) in vitro. The in vivo experimental results showed that compound 16 could inhibit 2,4-dinitrofluorobenzene (DNFB)-induced delayed-type hypersensitivity (DTH) reaction and sheep red blood cell (SRBC) induced antibody production, respectively. The structure and activity relationships (SAR) of these compounds were also discussed.
- Yang, Zhong-Shun,Zhou, Wen-Liang,Sui, Yi,Wang, Jun-Xia,Wu, Jin-Ming,Zhou, Yu,Zhang, Yu,He, Pei-Lan,Han, Ji-Ye,Tang, Wei,Li, Ying,Zuo, Jian-Ping
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p. 4608 - 4617
(2007/10/03)
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- Process for producing an α-aromatic group substituted alkanoic acid derivative
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Compounds having anti-inflammatory and analgesic activity of the formula STR1 are produced from compounds having the formula STR2 by rearrangement in the presence of a base or an amide and (1) X S O X 1 or X S O 2 X 1 where X and X 1 are halogen or trifluoromethyl or (2) sulfur dioxide and halogen.
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- Process for the preparation of alpha-hydroxyaryl-alkanoic acids
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A process is described for the preparation of alpha-hydroxyl-alkanoic acids of formula STR1 which are known anti-inflammatory agents or intermediates for known pharmaceutical products. The process consists essentially in the rearrangement of phenolates of formula STR2 wherein Ar is an unsubstituted or substituted phenyl or naphthyl, in aqueous environment or in an organic medium, at temperatures comprised within the range of from 0° to 100° C. and within short times, followed by either acid or alkaline hydrolysis.
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- Process for preparing phenylalkanoic acids
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Hydroxyphenylacetic acids are formed from the corresponding benzaldehydes or alkyl phenyl ketones by reduction, cyanation and hydrolysis without isolation or purification of intermediate products.
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- METHOD FOR TREATMENT OR PROPHYLAXIS OF CARDIAC DISORDERS
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A method for the treatment of prophylaxis of cardiac disorders in a mammal, comprising administering to such mammal a short-acting β-blocking compound of the formula: STR1 wherein R may be lower alkyl, aryl, or aralkyl; n may be an integer from 0 to about 10; x may be an integer from 1 to 3; Ar may be substituted or unsubstituted aromatic; R. sub.1 may be lower alkyl, or aralkyl; and pharmaceutically accepted salts thereof. Novel compounds possessing short-acting β-adrenergic blocking activity are also disclosed.
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- THE SYNTHESIS OF ARYLPROPIONIC ACIDS AND THE QUANTITATIVE RELATIONSHIP BETWEEN THE STRUCTURE AND THE ACTIVATION OF FIBRINOLYSIS
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A number of substituted 2-arylpropionic (IV) and 3-arylpropionic (V) acids were prepared and their activity in the activation of fibrinolysis and the inhibition of heat denaturation of serum albumin was evaluated.The results were worked up using the method of regression analysis.From the regression equation obtained it may be considered that both activities are affected mainly by the lipophilicity of the aromatic substituents.The effect of branching in the connecting chain between the carboxyl group and the aromatic ring is negligible in both activities.Thelinear dependence of the fibrinolytic capacity on lipophilicity is in both series of acids, IV and V, characterized by a distinct decrease in activity, following the attainment of the optimum value of lipophilicity.In the series of cinnamic acids (VI) regression equations concerning the inhibition of the denaturation of serum albumin and the activation of fibrinolysis were also calculated, showing a linear dependence of these activities on the lipophilicity of the varying substituents R and X.Summary regression equations were derived for both activities in the whole set of acids I-VI.Both the inhibition of the denaturation of serum albumin , and the activation of fibrinolysis depends on the lipophilicity of the mentioned acids exclusively.The modification of the connecting chain between the carboxyl group and the aromatic ring affects both activities primarily by the corresponding change in lipophilicity.
- Kuchar, Miroslav,Brunova, Bohumila,Rejholec, Vaclav,Roubal, Zdenek,Nemecek, Oldrich
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p. 1173 - 1187
(2007/10/02)
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- Process for the production of 2-aryl-2H-benzotriazoles
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A process for the production of 2-aryl-2H-benzotriazoles comprises reducing and cyclizing the corresponding o-nitroazobenzenes with hydrogen at a temperature in the range of about 20° C. to about 100° C. and at a pressure in the range of about 15 psia (1 atmosphere) to about 1000 psia (66 atmospheres) in an alkaline medium at a pH over 10 in the presence of a nickel catalyst, preferably molybdenum-promoted Raney nickel. High yields of pure product are obtained directly with a concomitant reduction of undesired by-product and a reduction in effluent pollution problems.
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- Process for the production of 2-aryl-2H-benzotriazoles
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A process for the production of 2-aryl-2H-benzotriazoles comprises reducing and cyclizing the corresponding o-nitroazobenzenes with carbon monoxide at a temperature in the range of about 20° C. to about 150° C. and at a pressure in the range of about 15 psia (1 atmosphere) to about 1000 psia (66 atmospheres) in an alkaline medium at a pH over 10 in the presence of a copper-amine complex catalyst. High yields of pure product are obtained with a concomitant reduction of undesired by-products and a reduction in effluent pollution problems.
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- Process for the production of 2-aryl-2H-benzotriazoles
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An improved process for the production of 2-aryl-2H-benzotriazoles by the reduction of o-nitroazobenzene intermediates with zinc in alkaline medium comprises employing a ratio of moles of alkali to moles of o-nitroazobenzene intermediate in the range of 0.2-1.7/1 in the presence of less than 150 ppm of iron based on zinc used. The improved process results in higher yields of high purity products with a concomitant reduction in the amount of undesired cleavage amine by-products and a reduction in effluent pollution problems. The process is carried out in a polar/non-polar solvent mixture.
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