- A tautomeric ligand enables directed C-H hydroxylation with molecular oxygen
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Hydroxylation of aryl carbon-hydrogen bonds with transition metal catalysts has proven challenging when oxygen is used as the oxidant. Here, we report a palladium complex bearing a bidentate pyridine/ pyridone ligand that efficiently catalyzes this reaction at ring positions adjacent to carboxylic acids. Infrared, x-ray, and computational analysis support a possible role of ligand tautomerization from monoanionic (L,X) to neutral (L,L) coordination in the catalytic cycle of aerobic carbon-hydrogen hydroxylation reaction. The conventional site selectivity dictated by heterocycles is overturned by this catalyst, thus allowing late-stage modification of compounds of pharmaceutical interest at previously inaccessible sites.
- Li, Zhen,Wang, Zhen,Chekshin, Nikita,Qian, Shaoqun,Qiao, Jennifer X.,Cheng, Peter T.,Yeung, Kap-Sun,Ewing, William R.,Yu, Jin-Quan
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p. 1452 - 1457
(2021/06/30)
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- CONDENSED AZAHETEROARYL COMPOUNDS HAVING ANTIBACTERIAL ACTIVITY AGAINST TUBERCULOSIS BACTERIA
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Present invention relates to novel compound of general formula (I), their enantiomers, their diastereomers, their pharmaceutically accepted salts, or pro-drugs thereof, which are useful for the treatment of bacterial infection. The compounds of general formula (I) exhibit DprE1 enzyme inhibitory activity.
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Page/Page column 32-33
(2020/01/08)
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- Aromatic heterocyclic derivatives as enzyme inhibitors
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The present invention discloses peptide aldehydes which are potent and specific inhibitors of thrombin, their pharmaceutically acceptable salts, pharmaceutically acceptable compositions thereof, and methods of using them as therapeutic agents for disease states in mammals characterized by abnormal thrombosis.
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Page column 50
(2010/02/04)
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- Aromatic heterocyclic derivatives as enzyme inhibitors
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The present invention discloses peptide aldehydes which are potent and specific inhibitors of thrombin, their pharmaceutically acceptable salts, pharmaceutically acceptable compositions thereof, and methods of using them as therapeutic agents for disease states in mammals characterized by abnormal thrombosis.
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- AROMATIC HETEROCYCLIC DERIVATIVES AS ENZYME INHIBITORS
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The present invention discloses peptide aldehydes which are potent and specific inhibitors of thrombin, their pharmaceutically acceptable salts, pharmaceutically acceptable compositions thereof, and methods of using them as therapeutic agents for disease states in mammals characterized by abnormal thrombosis.
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- AROMATIC HETEROCYCLIC DERIVATIVES AS ENZYME INHIBITORS
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The present invention discloses heterocyclic aromatic peptide aldehydes which have an oxopyrimidine or oxopyridine group and an argininal tail which are potent and specific inhibitors of thrombin, their pharmaceutically acceptable salts, pharmaceutically acceptable compositions thereof, and methods of using them as therapeutic agents for disease states in mammals characterized by abnormal thrombosis.
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- AROMATIC HETEROCYCLIC DERIVATIVES AS ENZYME INHIBITORS
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The present invention discloses peptide aldehydes which are potent and specific inhibitors of thrombin, their pharmaceutically acceptable salts, pharmaceutically acceptable compositions thereof, and methods of using them as therapeutic agents for disease states in mammals characterized by abnormal thrombosis.
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- Nonpeptidic inhibitors of human leukocyte elastase. 2. Design, synthesis, and in vitro activity of a series of 3-amino-6-arylopyridin-2-one trifluoromethyl ketones
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A series of potent nonpeptidic inhibitors of the enzyme human leukocyte elastase (HLE) is reported. These inhibitors contain a 3-amino-2-pyridone ring as a central template in which the pyridone carbonyl and 3-position NH group are thought to form important hydrogen bonding interactions with the Val-216 residue of HLE. Substitution of the 6-position of the pyridone ring by various alkyl and aryl groups was found to afford increases in the in vitro potency of these inhibitors. A 6-position phenyl group, compound 10f, was found to result in a large increase in binding affinity, which was not obtained when the phenyl group was placed in either the 4- or 5-position of the molecule. Compound 10f was found to have good selectivity for HLE over other proteolytic enzymes, with the exception of bovine pancreatic chymotrypsin (BPC). Substitution of the 6-phenyl group in these molecules was found to decrease binding affinity for BPC without adversely affecting affinity for HLE.
- Damewood Jr.,Edwards,Feeney,Gomes,Steelman,Tuthill,Williams,Warner,Woolson,Wolanin,Veale
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p. 3303 - 3312
(2007/10/02)
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- Functionalization of substituted 2(1H)- and 4(1H)-pyridones. III. The preparation of substituted 6-vinyl-1,2-dihydro-2-oxo- and 1,4-dihydro-4-oxo-3-pyridinecarboxylic acids through the chemistry of pyridone dianions
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The synthesis of various substituted 6-vinyl-1,2-dihydro-2-oxo-3-pyridinecarboxylic acids from the dianions of 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile and the corresponding 3-t-butyl ester is reported. The dianions were generated with LDA in THF at low temperature and reacted with various carbonyl substrates. Several conditions for the dehydration and hydrolysis of these adducts to the vinyl pyridone acids are discussed. Employing the conditions used for the 2-pyridone analogs, a series of substituted 6-vinyl-1,4-dihydro-4-oxo-3-pyridinecarboxylic acids was prepared through the new dianion of 1,4-dihydro-6-methyl-4-oxo-3-pyridinecarboxylic acid, t-butyl ester.
- DeJohn,Domagala,Kaltenbronn,Krolls
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p. 1295 - 1302
(2007/10/02)
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- Isothiazolopyridinones
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This invention relates to novel isothiazolopyridinones of the formula: SPC1 Wherein Y is hydrogen, (C1 --C12)alkyl, aralkyl of up to 11 carbon atoms, (C1 -C4)alkylcarbonyl, (C6 -C10)arylcarbonyl, aralkyl-carbonyl of up to 11 carbon atoms, (C2 -C3)hydroxyalkyl, a group of the formula: EQU1 wherein R4 is hydrogen, (C1 -C4)alkyl or phenyl and R5 and R6 are individually (C1 -C4)alkyl or taken together with the nitrogen atom to which they are attached, form a 5 or 6 membered azacyclic ring, which can include as additional hetero atoms, O, S or N or any combination of these wherein the total number of hetero atoms does not exceed 3; or a carbamoyl group of the formula: EQU2 wherein R7 is (C1 -C18)alkyl, (C6 -C10)aryl or aralkyl of up to 11 carbon atoms; R1 and R3 are individually hydrogen, (C1 -C4)alkyl, phenyl or benzyl; and R2 is hydrogen or (C1 -C4)alkyl; provided that at least one of R1, R2 and R3 is other than hydrogen; to agricultural compositions containing them, to processes for preparing them and to their utilization in controlling phytopathogenic fungi.
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