71570-28-0Relevant articles and documents
Decoupled Roles for the Atypical, Bifurcated Binding Pocket of the ybfF Hydrolase
Ellis, Elizabeth E.,Adkins, Chinessa T.,Galovska, Natalie M.,Lavis, Luke D.,Johnson, R. Jeremy
, p. 1134 - 1144 (2013/07/26)
Serine hydrolases have diverse intracellular substrates, biological functions, and structural plasticity, and are thus important for biocatalyst design. Amongst serine hydrolases, the recently described ybfF enzyme family are promising novel biocatalysts with an unusual bifurcated substrate-binding cleft and the ability to recognize commercially relevant substrates. We characterized in detail the substrate selectivity of a novel ybfF enzyme from Vibrio cholerae (Vc-ybfF) by using a 21-member library of fluorogenic ester substrates. We assigned the roles of the two substrate-binding clefts in controlling the substrate selectivity and folded stability of Vc-ybfF by comprehensive substitution analysis. The overall substrate preference of Vc-ybfF was for short polar chains, but it retained significant activity with a range of cyclic and extended esters. This broad substrate specificity combined with the substitutional analysis demonstrates that the larger binding cleft controls the substrate specificity of Vc-ybfF. Key selectivity residues (Tyr116, Arg120, Tyr209) are also located at the larger binding pocket and control the substrate specificity profile. In the structure of ybfF the narrower binding cleft contains water molecules prepositioned for hydrolysis, but based on substitution this cleft showed only minimal contribution to catalysis. Instead, the residues surrounding the narrow binding cleft and at the entrance to the binding pocket contributed significantly to the folded stability of Vc-ybfF. The relative contributions of each cleft of the binding pocket to the catalytic activity and folded stability of Vc-ybfF provide a valuable map for designing future biocatalysts based on the ybfF scaffold.
RODENTICIDAL NORBORMIDE ANALOGUES
-
Page/Page column 78, (2013/09/26)
The present invention relates to norbormide analogues having rodenticidal activity; rodenticidal compositions comprising the analogues; uses of the analogues as rodenticides; uses of the analogues in the manufacture of rodenticidal compositions; and methods for controlling rodents using the compositions.
Design and synthesis of prodrugs of the rat selective toxicant norbormide
Rennison, David,Laita, Olivia,Bova, Sergio,Cavalli, Maurizio,Hopkins, Brian,Linthicum, Darwin S.,Brimble, Margaret A.
supporting information; experimental part, p. 3997 - 4011 (2012/09/08)
Norbormide [5-(α-hydroxy-α-2-pyridylbenzyl)-7-(α-2- pyridylbenzylidene)-5-norbornene-2,3-dicarboximide] (NRB), an existing but infrequently used rodenticide, is known to be uniquely toxic to rats but relatively harmless to other rodents and mammals. However, one major drawback of NRB as a viable rodenticide relates to an evolutionary aversion developed by the rat leading to sub-lethal dosing due to either its unpleasant 'taste' or rapid onset of effects. A series of NRB prodrugs were prepared in an effort to 'mask' this acute response. Their synthesis and biological evaluation (in vitro vasoconstrictory activity, in vitro hydrolytic and enzymatic stability and lethality/palatability in vivo) is described. Compound 19 displayed the most promising profile with respect to a delay in the onset of symptoms and was subsequently demonstrated to be significantly more palatable to rats.
SUBSTITUTED METHYLFORMYL REAGENTS AND METHOD OF USING SAME TO MODIFY PHYSICOCHEMICAL AND/OR PHARMACOKINETIC PROPERTIES OF COMPOUNDS
-
Page/Page column 93-94, (2012/10/18)
The present invention relates to the synthesis and application of novel chiral/ achiral substituted methyl formyl reagents to modify pharmaceutical agents and/or biologically active substances to modify the physicochemical, biological and/or pharmacokinetic properties of the resulting compounds from the unmodified original agent.
A practical synthesis of chloromethyl esters from acid chlorides and trioxane or paraformaldehyde promoted by zirconium tetrachloride
Mudryk, Boguslaw,Rajaraman, Shanthi,Soundararajan, Nachimuthu
, p. 6317 - 6318 (2007/10/03)
A practical synthesis of chloromethyl esters from acid chlorides and trioxane or paraformaldehyde using zirconium tetrachloride as the Lewis acid has been demonstrated. The new procedure is highly chemoselective and applies to a variety of acid chlorides.
Synthesis of α-Haloalkyl Esters from α-Arylthioalkyl Esters
Benneche, Tore,Strande, Per,Wiggen, Unni
, p. 74 - 77 (2007/10/02)
α-Monohaloalkyl esters have been prepared under mild conditions in high yields by selective cleavage of the carbon-sulfur bond in α-phenylthioalkyl esters using sulfuryl chloride or bromine.The intermediate α-phenylthioalkyl esters have been prepared by alkylation of the corresponding carboxylic acids with readily accessible α-haloalkyl phenyl sulphides.
Soft drugs: III. A new class of anticholinergic agents
Bodor,Woods,Raper,et al.
, p. 474 - 480 (2007/10/02)
A new class of antimuscarinic drugs was designed and synthesized. The compounds are 'soft' quaternary ammonium esters in which there is only one carbon atom separating the ester oxygen and the quaternary head. The compounds are potent anticholinergics when derived from hindered 'umbrella' acids and cholinergics when derivatives of simple aliphatic acids. The more potent anticholinergics have up to 10 times higher acetylcholine antagonist activity than atropine, but they have a much shorter duration of action. The compounds cleave hydrolytically with simultaneous destruction of the quaternary head. The compounds are promising as selective, local agents, particularly as inhibitors of eccrine sweating.
Soft drugs. 2. Soft alkylating compounds as potential antitumor agents.
Bodor,Kaminski
, p. 566 - 569 (2007/10/02)
A class of soft alkylating compounds as potential anticancer agents was developed. The first examples include alpha-halo esters of various carboxylic acids. A new method for quantitative evaluation of the alkylating reactivity was developed, using a competitive alkylation reactivity was developed, using a competitive alkylation reaction, followed by NMR analysis of the reaction mixture. The method is sensitive and reproducible. One of the two selected soft alkylating agents, chloromethyl hexanoate, was found to have anticancer activity.
