76311-94-9

Upstream product

• 124-38-9 carbon dioxide 
• 5326-87-4 N-(phenyl)bromoacetamide 
• 587-65-5 N-chloroacetyl-aniline 
• 74-88-4 methyl iodide 
• 59-88-1 phenylhydrazine hydrochloride 
• 105-34-0 methyl 2-cyanoacetate 
• 67-56-1 methanol 
• 15580-32-2 malonanilic acid 
• 114-83-0 1-acetyl-2-phenylhydrazine 
• 62-53-3 aniline 
• 7341-97-1 N-phenyl propynamide 
• 146722-47-6 3-iodo-N-phenylpropiolamide 
• 124-41-4 sodium methylate 
• 109-77-3 malononitrile 

Downstream Products

• 76311-77-8 5-Oxo-1-phenyl-pyrrolidine-2,4-dicarboxylic acid 2-ethyl ester 4-methyl ester 
• 76311-82-5 2,6-Dioxo-1-phenyl-hexahydro-furo[3,4-b]pyrrole-3-carboxylic acid methyl ester 
• 15775-59-4 N¹-hydroxy-N³-phenylmalonamide 
• 14438-90-5 N-phenylpropanediamide 
• 852619-54-6 N-phenyl-N'-(2-tritylsulfanyl-ethyl)-malonamide 
• 15580-32-2 malonanilic acid 
• 80420-99-1 3-Anilino-2-(phenylcarbamoyl)propensaeure-methylester 
• 76311-80-3 3-Methyl-5-oxo-1-phenyl-pyrrolidine-2,4-dicarboxylic acid dimethyl ester 

Relevant academic research and scientific papers

Phosphonate as a Stable Zinc-Binding Group for “Pathoblocker” Inhibitors of Clostridial Collagenase H (ColH)

Microbial infections are a significant threat to public health, and resistance is on the rise, so new antibiotics with novel modes of action are urgently needed. The extracellular zinc metalloprotease collagenase H (ColH) from Clostridium histolyticum is a virulence factor that catalyses tissue damage, leading to improved host invasion and colonisation. Besides the major role of ColH in pathogenicity, its extracellular localisation makes it a highly attractive target for the development of new antivirulence agents. Previously, we had found that a highly selective and potent thiol prodrug (with a hydrolytically cleavable thiocarbamate unit) provided efficient ColH inhibition. We now report the synthesis and biological evaluation of a range of zinc-binding group (ZBG) variants of this thiol-derived inhibitor, with the mercapto unit being replaced by other zinc ligands. Among these, an analogue with a phosphonate motif as ZBG showed promising activity against ColH, an improved selectivity profile, and significantly higher stability than the thiol reference compound, thus making it an attractive candidate for future drug development.

COMPOUND USED AS AUTOPHAGY REGULATOR, AND PREPARATION METHOD THEREFOR AND USES THEREOF

It is related to compounds used as autophagy modulators and a method for preparing and using the same, specifically providing a compound of general formula (I), or pharmaceutically acceptable salts thereof, which is a type of autophagy modulators, particularly mammalian ATG8 homologues modulators.

Iodine-mediated aryl transfer reaction from arylhydrazine hydrochlorides to nitriles

An iodine-promoted, metal-, base-, and solvent-free cross-coupling reaction was developed for the synthesis of various useful secondary amides via an aryl N-addition reaction of aryl groups to cyano groups. This aryl transfer reaction proceeds with arylhydrazine hydrochlorides serving as the aryl donors. A labelling experiment shows that the N atom in the product comes from the cyano group of the nitriles, which are low in cost. A plausible radical-driven mechanism is also proposed.

Palladium-Catalyzed [3 + 2]-C-C/N-C Bond-Forming Annulation

The synthesis of bi- and tricyclic structures incorporating pyrrolidone rings is disclosed, starting from resonance-stabilized acetamides and cyclic α,β-unsaturated-γ-oxycarbonyl derivatives. This process involves an intermolecular Tsuji-Trost allylation/intramolecular nitrogen 1,4-addition sequence. Crucial for the success of this bis-nucleophile/bis-electrophile [3 + 2] annulation is its well-defined step chronology in combination with the total chemoselectivity of the former step. When the newly formed annulation product carries a properly located o-haloaryl moiety at the nitrogen substituent, a further intramolecular keto α-arylation can join the cascade, thereby forming two new cycles and three new bonds in the same synthetic operation.

Controlling Plasma Stability of Hydroxamic Acids: A MedChem Toolbox

Hydroxamic acids are outstanding zinc chelating groups that can be used to design potent and selective metalloenzyme inhibitors in various therapeutic areas. Some hydroxamic acids display a high plasma clearance resulting in poor in vivo activity, though they may be very potent compounds in vitro. We designed a 57-member library of hydroxamic acids to explore the structure-plasma stability relationships in these series and to identify which enzyme(s) and which pharmacophores are critical for plasma stability. Arylesterases and carboxylesterases were identified as the main metabolic enzymes for hydroxamic acids. Finally, we suggest structural features to be introduced or removed to improve stability. This work thus provides the first medicinal chemistry toolbox (experimental procedures and structural guidance) to assess and control the plasma stability of hydroxamic acids and realize their full potential as in vivo pharmacological probes and therapeutic agents. This study is particularly relevant to preclinical development as it allows obtaining compounds equally stable in human and rodent models.

Hypervalent Iodine(III)-Promoted Phenyl Transfer Reaction from Phenyl Hydrazides to Nitriles

A useful transformation of nitriles to N-phenyl amides has been achieved through a novel intermolecular phenyl transfer reaction from phenyl hydrazides and N-addition to nitriles in the presence of PIFA under mild and solvent-free conditions. This cross-coupling reaction includes the oxidative cleavage of sp2 C-N bonds of phenyl hydrazides to form a phenyl radical and the subsequent N-addition to cyanos to form new sp2 C-N bonds and provides efficient access to various N-phenyl amides in moderate to good yields under mild reaction conditions.

Diels-Alder Reactions of α-Amido Acrylates with N-Cbz-1,2-dihydropyridine and Cyclopentadiene

Thermal Diels-Alder reactions of α-amido acrylates with N-Cbz-1,2-dihydropyridine and cyclopentadiene have been explored to investigate the factors influencing the endo/exo selectivity. For the dihydropyridine, steric factors allowed the diastereoselectivity to be modulated to favor either endo- or exo-ester adducts. For cyclopentadiene, the endo-ester adducts were favored regardless of steric perturbation, although catalysis by bulky Lewis acids increased the proportion of exo-ester adducts in some cases. These Lewis acids were incompatible with the dihydropyridine diene as they induced its decomposition.

Compound of bisamide structure and preparing method and application thereof

The invention discloses a compound of a bisamide structure in the technical field of agricultural chemistry and a preparing method and application thereof. The preparing method includes the steps that monomethyl malonate acyl chloride is used as a raw material and reacts with arylamine in anhydrous dichloromethane to obtain an intermediate product III; the intermediate product III reacts with lithium hydroxide and then reacts with oxalyl chloride in tetrahydrofuran to obtain an intermediate product IV; 2,6-dimethylaniline is used as a raw material and reacts with 2-methyl bromopropionate to obtain an intermediate product VI; finally the intermediate product IV and the intermediate product VI react in a methylbenzene solution to obtain the compound of the bisamide structure shown in the final product I. The compound and a preparation have good bactericidal activity, have a good growth inhibiting function on phytophthora capsici, alternaria solani, rhizoctonia solani, cotton rhizoctonia solani, phytophthora infestans, and botrytis cinerea and have high pesticide research value.

Palladium-catalyzed alcoholysis of 3-iodopropynamides: Selective synthesis of carbamoylacetates

A novel and selective method for the synthesis of carbamoylacetates via the alcoholysis of 3-iodopropynamides has been developed. 3-Iodopropynamides react with alcohols in the presence of palladium(II) acetate and DABCO to afford the corresponding carbamoylacetates in moderate to good yields.

A facile and efficient synthesis of fully substituted pyridin-2(1H)-ones from α-oxoketene-S,S-acetals

A facile and efficient synthesis of fully substituted pyridin-2(1H)-ones has been developed by the reaction of readily available α-oxoketene-S,S- acetals with malononitrile in the presence of sodium methoxide in methanol under reflux.