89809-67-6Relevant academic research and scientific papers
Facile construction of 4H-chromenes via Michael addition of phenols to benzylidene oxobutanoates and their successful conversion into pyranocoumarins
Priyanka,Sharma, Rajesh K.,Butcher, Ray J.,Katiyar, Diksha
supporting information, p. 2347 - 2351 (2018/05/24)
An efficient and simple approach for the synthesis of functionalized 4H-chromenes has been developed via acid catalyzed Michael addition of phenols to benzylidene oxobutanoates. Preliminary mechanistic studies were conducted, suggesting that intermediate
Potent and Selective Human Neutrophil Elastase Inhibitors with Novel Equatorial Ring Topology: In vivo Efficacy of the Polar Pyrimidopyridazine BAY-8040 in a Pulmonary Arterial Hypertension Rat Model
Von Nussbaum, Franz,Li, Volkhart M.,Meibom, Daniel,Anlauf, Sonja,Bechem, Martin,Delbeck, Martina,Gerisch, Michael,Harrenga, Axel,Karthaus, Dagmar,Lang, Dieter,Lustig, Klemens,Mittendorf, Joachim,Sch?fer, Martina,Sch?fer, Stefan,Schamberger, Jens
supporting information, p. 199 - 206 (2016/01/30)
Human neutrophil elastase (HNE) is a key driver of inflammation in many cardiopulmonary and systemic inflammatory and autoimmune conditions. Overshooting high HNE activity is the consequence of a disrupted protease-antiprotease balance. Accordingly, there has been an intensive search for potent and selective HNE inhibitors with suitable pharmacokinetics that would allowing oral administration in patients. Based on the chemical probe BAY-678 and the clinical candidate BAY 85-8501 we explored further ring topologies along the equator of the parent pyrimidinone lead series. Novel ring systems were annulated in the east, yielding imidazolo-, triazolo-, and tetrazolopyrimidines in order to ensure additional inhibitor-HNE contacts beyond the S1 and the S2 pocket of HNE. The western annulation of pyridazines led to the polar pyrimidopyridazine BAY-8040, which combines excellent potency and selectivity with a promising pharmacokinetic profile. In vivo efficacy with regard to decreasing cardiac remodeling and amelioration of cardiac function was shown in a monocrotaline-induced rat model for pulmonary arterial hypertension. This demonstrated in vivo proof of concept in animals. Exploring new rings! Human neutrophil elastase (HNE) is a driver of inflammation in pulmonary arterial hypertension (PAH). Herein we describe the discovery of BAY-8040, a small-molecule inhibitor with nanomolar potency and good pharmacokinetics. BAY-8040 shows in vivo efficacy in a PAH rat model, thereby demonstrating proof of concept in animals.
A simple method for the preparation of functionalized trisubstituted alkenes and α,β,γ,δ-unsaturated carbonyl compounds by using natural amino acid l-tryptophan
Hu, Ying,He, Yan-Hong,Guan, Zhi
scheme or table, p. 656 - 659 (2010/11/05)
Primary natural amino acid l-tryptophan was used, for the first time, as a catalyst in Knoevenagel condensations of aliphatic, aromatic, hetero-aromatic and α,β-unsaturated aldehydes with less reactive acetylacetone and ethyl acetoacetate. The reactions were carried out at room temperature and gave good yields. It is a convenient entry for preparation of functionalized trisubstituted alkenes and α,β,γ,δ-unsaturated carbonyl compounds.
Domino imino-aldol-aza-Michael reaction: One-pot diastereo- and enantioselective synthesis of piperidines
Ghorai, Manas K.,Halder, Sandipan,Das, Raj Kumar
supporting information; experimental part, p. 7061 - 7072 (2010/12/25)
Addition of α-arylmethylidene- or α-alkylidene-β-keto ester enolate to N-activated aldimines via the imino aldol pathway followed by intramolecular aza-Michael reaction in a domino fashion has been developed, and a highly diastereoselective route to subst
Magnesium perchlorate as efficient Lewis acid for the Knoevenagel condensation between β-diketones and aldehydes
Bartoli, Giuseppe,Bosco, Marcella,Carlone, Armando,Dalpozzo, Renato,Galzerano, Patrizia,Melchiorre, Paolo,Sambri, Letizia
, p. 2555 - 2557 (2008/09/21)
A new protocol for the Knoevenagel condensation between β-diketones and aliphatic and aromatic aldehydes promoted by Mg(ClO4)2 under mild conditions is reported.
Synthesis, structure, and electrochemical characteristics of 4-aryl-2-carbamoylmethylthio-5-ethoxycarbonyl-1,4-dihydropyridine-3-carboxylic acid nitriles
Baumane,Krauze,Belyakov,Sile,Chernova,Griga,Duburs,Stradins
, p. 362 - 373 (2007/10/03)
We have obtained 4-aryl-2-carbamoylmethylthio-5-ethoxycarbonyl-1,4- dihydropyridine-3-carboxylic acid nitriles by S-alkylation of the corresponding 2-thioxo-1,2,3,4-tetrahydropyridine-3-carboxylic acid nitrile by iodoacetamide or one-pot multicomponent synthesis methods: condensation of 2-arylidene-acetoacetic acid ethyl ester, 2-cyanothioacetamide, piperidine, and iodoacetamide; acetoacetic acid ethyl ester, 3-aryl-2-cyanothioacrylamide, piperidine, and iodoacetamide; acetoacetic acid ethyl ester, an aromatic aldehyde, 2-cyanothioacetamide, piperidine, and iodoacetamide. We have carried out a comparative analysis of the capability of 2-alkylthio-4-aryl-5- ethoxycarbonyl-1,4-dihydropyridine-3-carboxylic acid nitriles for electrochemical oxidation as a function of the electronic properties of the aryl substituent in the 4 position of the heterocycle and the 2-alkylthio substituent. X-ray diffraction data indicate the existence of a hydrogen bond between the C=O of the 2-carbamoylmethylthio substituent and the NH of the hydrogenated heterocycle, which explains the more facile oxidation of the studied compounds compared with 2-methylthio-substituted 1,4-dihydropyridines.
DIHYDROPYRIDINONE DERIVATIVES
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Page 67-68, (2010/02/06)
The invention relates to novel dihydropyridinone derivatives, processes for their preparation, and their use in medicaments, especially for the treatment of chronic obstructive pulmonary diseases, acute coronary syndrome, acute myocardial infarction and heart failure development.
Studies on cerebral protective agents. I. Novel 4-arylpyrimidine derivatives with anti-anoxic and anti-lipid peroxidation activities
Kuno,Sugiyama,Katsuta,Kamitani,Takasugi
, p. 1452 - 1461 (2007/10/02)
Novel 4-arylpyrimidine derivatives were synthesized by the oxidation of 4-aryl-1,4-dihydropyrimidines, and their effects on anti-anoxic (AA) activity in mice and anti-lipid peroxidation (ALP) activity in rat brain mitochondria were investigated. Among these compounds, ethyl 6-methyl-2-phenyl-4-(4-pyridyl)-5-pyrimidinecarboxylate (4b) has AA activity (10mg/kg, i.p.) and ethyl 6-methyl-4-(3-nitrophenyl)-2-phenyl-5-pyrimidinecarboxylate (4f) has ALP activity (73% inhibition at 10-5 g/ml). The latter compound (100mg/kg, i.p.) was also effective on arachidonate-induced cerebral edema in rats with comparable potency to that of vitamin E.
SYNTHESIS OF HETEROCYCLIC COMPOUNDS. XXXVI. PREPARATION OF ALKYL SUBSTITUTED PYRANCARBONITRLES.
Soto, Jose L.,Seoane, Carlos,Martin, Nazario,Quinteiro, Margarita
, p. 1 - 6 (2007/10/02)
The cyclization of the ketonitriles obtained from the reaction of suitably substituted propenones with propanedinitrile leads to alkyl substituted 4H-pyrans.Some of the starting propenones had to be prepared by base promoted opening of an isoxazole ring in the presence of an aldehyde.An exception to the general synthesis is also reported.
