30125-76-9Relevant academic research and scientific papers
Palladium-Catalyzed Cyclocarbonylation of Pyridinylated Vinylogous Amides and Ureas to Generate Ring-Fused Pyridopyrimidinones
Yan, Gang,Golden, Jennifer E.
, p. 4393 - 4396 (2018/08/09)
As part of a program aimed at generating new heterocyclic frameworks for medicinal chemistry exploration, an efficient approach to the assembly of novel ring-fused pyridopyrimidinones was undertaken. Specifically, a collection of 11H-pyrido[2,1-b]quinazoline-1,11(2H)-diones and 2,3-dihydropyrido[1,2-a]pyrrolo[3,4-d]pyrimidine-1,10-diones was generated via a palladium-catalyzed, pyridine-directed, cyclocarbonylation of 2-pyridyl-linked vinylogous amides and ureas in yields of up to 90%.
TARGETED COVALENT PROBES AND INHIBITORS OF PROTEINS CONTAINING REDOX-SENSITIVE CYSTEINES
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, (2014/06/24)
Covalent, irreversible small-molecule inhibitors that modify the sulfenyl form (i.e., sulfenic acid, RSOH and sulfenamide, RSNR'2) of therapeutically important proteins (particularly kinases and phosphatases) are disclosed, where the compositions include a compound having a substituted aryl or heterocyclic core structure that promotes binding interactions with a specific protein, and a nucleophilic reaction center (carbon, nitrogen, sulfur, or phosphorous) that is capable of forming a covalent bond with a sulfenic acid- or sulfenamide-modified cysteine residue in the protein. Methods for synthesizing these compounds are also disclosed, as well as methods of using them for determining the bioactivity of a chemical composition comprising an active compound toward a specific protein and for determining the potency of an inhibitor against a specific protein.
Simple route to azabicyclic peroxides from tetramic acid derivatives using manganese(III)-based molecular oxygen trapping reaction
Chowdhury, Firoz Alam,Nishino, Hiroshi,Kurosawa, Kazu
, p. 575 - 591 (2007/10/03)
A simple one-step synthesis of azabicyclic peroxides was achieved by the manganese(III)-mediated oxidative formal [2+2+2] cycloaddition. The reaction of alkenes (1) with pyrrolidinediones (2) was carried out with manganese(III) acetate in acetic acid at 2
Synthesis and protein kinase C inhibitory activities of acyclic balanol analogs that are highly selective for protein kinase C over protein kinase A
Defauw, Jean M.,Murphy, Marcia M.,Jagdmann Jr., G. Erik,Hu, Hong,Lampe, John W.,Hollinshead, Sean P.,Mitchell, Thomas J.,Crane, Heidi M.,Heerding, Julia M.,Mendoza, José S.,Davis, Jefferson E.,Darges, James W.,Hubbard, Frederick R.,Hall, Steven E.
, p. 5215 - 5227 (2007/10/03)
A series of balanol analogs in which the perhydroazepine ring and the p- hydroxybenzamide moiety were combined into an acyclic linked unit have been prepared and evaluated for their inhibitory properties against the serine/threonine kinase PKC. Several low-micromolar to lownanomolar inhibitors of the α, β'(I), β(II), γ, δ, ε, and η PKC isozymes were prepared. In general, these acyclic balanol analogs were found to be highly selective for PKC over the serine/threonine kinase PKA. The type and number of atoms linking the benzophenone ester to the p-hydroxyphenyl group necessary for optimal PKC inhibition were investigated. The most potent compounds contained a three-carbon linker in which the carboxamide moiety of balanol had been replaced by a methylene group. The effect of placing substituents on the three-carbon chain was also investigated. The preferred compounds contained either a 2-benzene-sulfonamido (6b) or a 1-methyl (21b) substituent. The preferred compounds 6b and 21b were tested against a panel of serine/threonine kinases and found to be highly selective for PKC. The more active enantiomer of 6b, (S)-12b, was 3-10-fold more active than the R- enantiomer against the PKC isozymes. The effect of making the analogs more rigid by making the three-carbon chain part of a five-membered ring, but with retention of the methylene replacement for the carboxamide moiety, led to potent PKC inhibitors including anti-substituted pyrrolidine analog 35b and the most potent PKC inhibitor in the series, anti-substituted cyclopentane analog 29b. The anti cyclopentane analog 29b was a low-micromolar inhibitor of the PMA-induced superoxide burst in neutrophils, and its carboxylic ester was a high-nanomolar inhibitor of neutrophils. Finally esterification of 21b, (S)-12b, and 35b turned these potent PKC inhibitors into low-micromolar inhibitors of neutrophils.
Potent and selective PKC inhibitory 5-membered ring analogs of balanol with replacement of the carboxamide moiety
Jagdmann Jr., G. Erik,Defauw, Jean M.,Lampe, John W.,Darges, James W.,Kalter, Kiyomi
, p. 1759 - 1764 (2007/10/03)
Balanol ((-)-1) is a potent protein kinase inhibitory natural product isolated from the fungus Verticillium balanoides. The lack of cellular activity and protein kinase C selectivity in balanol has prompted a search for analogs that incorporate these properties. This paper describes the synthesis and biological activity of such compounds with substitution similar to balanol, but with a single atom bridge in place of the carboxamide moiety.
3-(1,3-dithiol-2-ylidene)-2,4-dioxopyrrolidines, -piperidines, and -hexahydroazepines and use thereof against hepatic diseases
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, (2008/06/13)
Novel thioketene derivatives of the formula: STR1 wherein R1 is hydrogen atom, an alkyl group, a lower alkenyl group, a phenyl group or a group of the formula: --B--Y; Y is a nitrogen-containing monocyclic heterocyclic group or a substituted or unsubstituted phenyl group; B is a straight or branched lower alkylene group; R2 and R3 are both a lower alkyl group or are combined together to form a group of the formula: --CH2 CH2 -- or --CH=CH--; R4 is hydrogen atom, a lower alkyl group or a (lower alkoxy)carbonyl group; A is a group of the formula: --(CH2)n -- or --CH(COOR5)--; n is an integer of 0, 1 or 2 and R5 is a lower alkyl group, are disclosed. The compound (I) is useful as an agent for treating and protecting various liver diseases.
A NOVEL SYNTHETIC METHOD OF LACTAMS FROM 1,3-DIOXIN-4-ONES VIA INTRAMOLECULAR KETENE TRAPPING
Sato, Masayuki,Ogasawara, Hiromichi,Takayama, Kazuhisa,Kaneko, Chikara
, p. 2611 - 2614 (2007/10/02)
A novel route to four- and five-membered lactams from 1,3-dioxin-4-ones having an α-aminoalkyl side-chain at 5- or 6-position through cycloreversion to acylketenes followed by intramolecular ketene trapping by the amino function is described.
