38453-93-9

Upstream product

• 1007476-32-5 sodium ethyl acetylacetate enolate 
• 5469-26-1 1-Bromopinacolon 
• 13547-70-1 1-chloro-3,3-dimethyl-butan-2-one 
• 141-97-9 ethyl acetoacetate 
• 7307-04-2 acetylpinacolin 
• 92975-23-0 (Z)-2,2-Dimethyl-5-trimethylsilanyloxy-hex-4-en-3-one 

Downstream Products

• 38453-94-0 2-methyl-5-(tert-butyl)furan-3-carboxylic acid ethyl ester 
• 947397-71-9 C₂₂H₃₂FN₃O*ClH 
• 947397-78-6 C₂₃H₃₄FN₃O 

Relevant academic research and scientific papers

Synthesis and biological evaluation of 3-phenyl-3-aryl carboxamido propanoic acid derivatives as small molecule inhibitors of retinoic acid 4-hydroxylase (CYP26A1)

All-trans-retinoic acid (ATRA), the biologically active metabolite of vitamin A, is used medicinally for the treatment of hyperproliferative diseases and cancers. However, it is easily metabolized. In this study, the leading compound S8 was found based on virtual screening. To improve the activity of the leading compound S8, a series of novel S8 derivatives were designed, synthesized and evaluated for their in vitro biological activities. All of the prepared compounds showed that substituting the 5-chloro-3-methyl-1-phenyl-1H-pyrazole group for the 2-tertbutyl-5-methylfuran scaffold led to a clear increase in the biological activity. The most promising compound 32, with a CYP26A1 IC50 value of 1.36 μM (compared to liarozole (IC50 = 2.45 μM) and S8 (IC50 = 3.21 μM)) displayed strong inhibitory and differentiation activity against HL60 cells. In addition, the study focused on the effect of β-phenylalanine, which forms the coordination bond with the heme of CYP26A1. These studies suggest that the compound 32 can be used as an appropriate candidate for future development.

AROMATIC HETEROCYCLIC DERIVATIVE HAVING TRPV4-INHIBITING ACTIVITY

A compound having TRPV4 inhibitory activity or a pharmaceutically acceptable salt thereof is provided. The present invention is related to a compound represented by the formula (I). wherein R1a is substituted or unsubstituted alkyl or the like;

Further optimization of novel pyrrole 3-carboxamides for targeting serotonin 5-HT2A, 5-HT2C, and the serotonin transporter as a potential antidepressant

In the continuing search for novel compounds targeting serotonin 5-HT 2A, 5-HT2C, and serotonin transporter, new arylpiperazine-containing pyrrole 3-carboxamide derivatives were synthesized and evaluated. Based on the lead reported previously, structural modifications regarding N-(3-(4-(2,3-dichlorophenyl)piperazin-1-yl)propyl)-1,2-dimethyl-5- phenyl-1H-pyrrole-3-carboxamide 5, were accomplished for improvements in not only binding affinity against serotonin receptors and transporter, but also in hERG channel inhibition. Along the line, both the forced swimming tests and spontaneous locomotor activity tests were performed to distinguish between antidepressant activity and false positive results. As potential antidepressant agents, both 2,4-dimethyl-5-phenyl-1H-pyrrole-3-carboxamide and 5-tert-butyl-2-methyl-1H-pyrrole-3-carboxamide derivatives exhibited favorable in vitro and in vivo activities, warranting further investigation around these scaffolds.

PYRROLO- AND THIAZOLO-PYRIDINE COMPOUNDS, AND METHODS OF USE THEREOF

The present invention relates to novel compounds capable of modulating the stability and/or activity of hypoxia inducible factor (HIF).

PYRROLE DERIVATIVE OR SALT THEREOF

[Problem] To provide a compound which may be used for the prevention and/or treatment of diseases in which 5-HT2B receptor and 5-HT7 receptor are concerned, particularly for the treatment of irritable bowel syndrome (IBS). [Means for Resolution] It was found that a pyrrole derivative characterized by the possession of a guanidinocarbonyl group or amido group as a substituent group at the 3-position, or a pharmaceutically acceptable salt thereof, has a strong antagonism for both of the 5-HT2B receptor and 5-HT7 receptor. In addition, the compound of the present invention having the antagonistic activity for both of the receptors showed a good pharmacological action in comparison with the case in which an antagonist selective for either one of the receptors was used alone. Based on the above, the compound of the present invention is useful for the prevention and/or treatment of diseases in which 5-HT2B receptor and 5-HT7 receptor are concerned, particularly for the treatment of irritable bowel syndrome (IBS).

A Convenient Synthesis of 8-Substituted Indolizines as Precursors to 5-Substituted Cycl{3.2.2}azine Derivatives

The synthesis of 8-substituted indolizines is described via a two step process in which a 1,4-diketone, containing a tert-butyl group, is cyclocondensed with a trialkylsilyl protected pyrrole to provide 5,8-disubstituted indolizines in higher yields than the identical reaction with unprotected pyrrole. Cleavage of the tertbutyl group from the indolizine 5-position, by treatment with 85% phosphoric acid, provides 8-substituted indolizines in good yields. Treatment of 8-substituted indolizines with dimethyl acetylenedicarboxylate, in the presence of palladium-on-carbon, provides novel 5-substituted cycl{3.2.2} derivatives.

THE SYNTHESIS AND CHEMISTRY OF AZOLENINES. PART 18. PREPARATION OF 3-ETHOXYCARBONYL-3H-PYRROLES VIA THE PAAL-KNORR REACTION, AND SIGMATROPIC REARRANGEMENTS INVOLVING COMPETITIVE ESTER MIGRATIONS TO C-2, C-4 AND N.

3H-Pyrrole-3-carboxylic esters (4) have been prepared, in some cases together with isomers (5) and (6) having exocyclic double bonds, by cyclization of suitably substituted 2-ethoxycarbonyl-1,4-diketones (1) with liquid ammonia, followed by dehydration of the isolable 2-hydroxy-3,4-dihydro-2H-pyrrole intermediates (2) and (3) with aluminia in boiling solvents.Prolonged heating in toluene or p-xylene converts the 3H-pyrroles (4) quantitatively into isomeric 4-esters (11) and N-esters (13) of 1H-pyrroles via competitive sigmatropic rearrangements.Isolable intermediate 2H-pyrrole-2-carboxylic esters (12) are converted similarly into the same products, under the same conditions.Detection of 3H-pyrroles (4) as intermediates in the latter reaction demonstrates for the first time the reversibility of the thermal 2H-pyrrole to 3H-pyrrole interconversion.

CONVERSION OF 1,3-DICARBONYLS TO 1,4-DICARBONYLS

The cyclopropanation of β-trimethylsiloxy α,β-unsaturated esters and ketones, prepared from 1,3-dicarbonyl compounds, with carbenes followed by ring cleavage gave corresponding 1,4-dicarbonyl compounds in moderate yields.