83004-27-7

Upstream product

• 383663-60-3 ethyl 3-(2-methyl-3-nitrophenyl)-3-hydroxypropionate 
• 124-63-0 methanesulfonyl chloride 
• 6674-22-2 1,8-diazabicyclo[5.4.0]undec-7-ene 
• 55289-35-5 2-bromo-6-nitrotoluene 
• 140-88-5 ethyl acrylate 
• 3740-52-1 2-(2-nitrophenyl)acetic acid 
• 1975-50-4 2-methyl-3-nitrobenzic acid 
• 39053-41-3 2-methyl-3-nitrobenzoyl chloride 

Downstream Products

• 383663-70-5 ethyl 3-(3-amino-2-methylphenyl)propionate hydrochloride 
• 757179-63-8 ethyl 3-(3-amino-2-methylphenyl)propanoate 

Relevant academic research and scientific papers

Discovery of the Soluble Guanylate Cyclase Activator Runcaciguat (BAY 1101042)

Herein we describe the discovery, mode of action, and preclinical characterization of the soluble guanylate cyclase (sGC) activator runcaciguat. The sGC enzyme, via the formation of cyclic guanosine monophoshphate, is a key regulator of body and tissue homeostasis. sGC activators with their unique mode of action are activating the oxidized and heme-free and therefore NO-unresponsive form of sGC, which is formed under oxidative stress. The first generation of sGC activators like cinaciguat or ataciguat exhibited limitations and were discontinued. We overcame limitations of first-generation sGC activators and identified a new chemical class via high-throughput screening. The investigation of the structure-activity relationship allowed to improve potency and multiple solubility, permeability, metabolism, and drug-drug interactions parameters. This program resulted in the discovery of the oral sGC activator runcaciguat (compound 45, BAY 1101042). Runcaciguat is currently investigated in clinical phase 2 studies for the treatment of patients with chronic kidney disease and nonproliferative diabetic retinopathy.

OXO-HETEROCYCLIC SUBSTITUTED CARBOXYLIC ACID DERIVATIVES AND THE USE THEREOF

The present application relates to novel carboxylic acid derivatives having an oxo-substituted azaheterocyclic partial structure, processes for their preparation, their use for the treatment and/or prophylaxis of diseases, and their use for producing medicaments for the treatment and/or prophylaxis of diseases, especially for the treatment and/or prevention of cardiovascular disorders.

SUBSTITUTED 3-PHENYLPROPIONIC ACIDS AND THE USE THEREOF

The present application relates to novel 3-phenylpropionic acid derivatives, to processes for their preparation, to their use for the treatment and/or prevention of diseases and to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of cardiovascular disorders.

Ligand-accelerated C-H activation reactions: Evidence for a switch of mechanism

Initial rate studies have revealed dramatic acceleration in aerobic Pd(II)-catalyzed C-H olefination reactions of phenylacetic acids when mono-N-protected amino acids are used as ligands. In light of these findings, systematic ligand tuning was undertaken, which has resulted in drastic improvements in substrate scope, reaction rate, and catalyst turnover. We present evidence from intermolecular competition studies and kinetic isotope effect experiments that implies that the observed rate increases are a result of acceleration in the C-H cleavage step. Furthermore, these studies suggest that the origin of this phenomenon is a change in the mechanism of C-H cleavage from electrophilic palladation to proton abstraction.

Benzoxazepinones and their use as squalene synthase inhibitors

There is disclosed a compound represented by the formula [I]: wherein R1 is optionally substituted 1-carboxyethyl group, optionally substituted alkyl-sulfonyl group, optionally substituted (carboxy-cycloalkyl)-alkyl group, -X1-X2-Ar-X3-X4-COOH (wherein X1 and X4 are a bond or alkylene group, X2 and X3 are a bond, -O-, -S-, Ar is divalent aromatic group etc.), R2 is alkyl group optionally substituted with alkanoyloxy group and/or hydroxy group, R3 is alkyl group, and W is halogen atom, etc., or a salt thereof. The compound has the cholesterol lowering activity and the triglyceride lowering activity and is useful for preventing and/or treating hyperlipidemia.

Process for the preparation of alkenylbenzenecarboxylic acid derivatives and alkenylnaphthalenecarboxylic acid derivatives

Compounds of the formula I STR1 in which p, m, Z, R, R' and Y are as defined in claim 1, can be obtained in a simple and economical manner by a novel process which comprises reacting a halide of the formula STR2 with the corresponding acrylic acid derivative, in the presence of a base and of certain palladium catalysts, such as palladium acetate. The compounds (I), and functional derivatives prepared therefrom, are useful for the preparation of photocrosslinkable polymers, which can in particular be employed as (so-called) photoresists.

THE PALLADIUM-CATALYSED ARYLATION OF ACTIVATED ALKENES WITH AROYL CHLORIDES

Aroyl chlorides react with activated alkenes in presence of a tertiary amine and a catalytic amount of palladium acetate to give arylated alkenes, specifically cinnamic acid derivatives and stilbenes.The reaction involves a highly efficient decarbonylation of the aroyl chloride.High yields can be obtained at low catalyst concentration by choice of an appropriate base.The reaction is not particularly sensitive to substituents in the aroyl chloride, although strongly electron-donating groups are advantagenous (yields up to 98percent).With monosubstituted alkenes E-isomers are formed with almost complete specificity.A mechanism for the reaction is proposed.