4664-61-3

Upstream product

• 67-56-1 methanol 
• 6328-74-1 4-phenoxyphenylacetic acid 
• 108-86-1 bromobenzene 
• 14199-15-6 Methyl 4-hydroxyphenylacetate 
• 98-80-6 phenylboronic acid 

Downstream Products

• 467468-18-4 5-(4-phenoxyphenyl)-5-(piperazin-1-yl)pyrimidine-2,4,6 (1H,3H,5H)-trione 
• 467468-09-3 5-(4-(2(-2-hydroxyethoxy)ethyl)piperazin-1-yl)-5-(4-phenoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione 
• 1333167-64-8 5-(4-((tetrahydrofuran-2-yl)methyl)piperazin-1-yl)-5-(4-phenoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione 
• 1333167-65-9 5-(4-benzylpiperazin-1-yl)-5-(4-phenoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione 
• 1333167-66-0 5-(4-butylpiperazin-1-yl)-5-(4-phenoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione 
• 1333167-67-1 5-(4-acetylpiperazin-1-yl)-5-(4-phenoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione 
• 1333167-68-2 5-(4-methylpiperazin-1-yl)-5-(4-phenoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione 
• 1333167-69-3 5-(4-phenoxyphenyl)-5-(4-(cyclopropylmethyl)-1,4-diazepan-1-yl)pyrimidine-2,4,6(1H,3H,5H)-trione 
• 1333167-71-7 5-(4-acetyl-1,4-diazepan-1-yl)-5-(4-phenoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione 
• 1333167-70-6 5-(4-benzyl-1,4-diazepan-1-yl)-5-(4-phenoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione 
• 1333167-72-8 5-(4-methyl-1,4-diazepan-1-yl)-5-(4-phenoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione 
• 1333167-26-2 5-(1,4-diazepan-1-yl)-5-(4-phenoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione 
• 1333167-73-9 5-(4-(thiophene-2-carbonyl)piperazin-1-yl)-5-(4-phenoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione 
• 1333167-74-0 5-((4-(4-cyanobenzoyl))piperazin-1-yl)-5-(4-phenoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione 

Relevant academic research and scientific papers

Palladium-catalyzed intermolecular C-H silylation initiated by aminopalladation

A Pd(ii)-catalyzed intermolecular C-H silylation reaction initiated by aminopalladation has been developed. The C-H bonds were activated by an alkyl Pd(ii) species generated through aminopalladation and then disilylated with hexamethyldisilane to form disilylated indolines as the final products. The reaction provides a new method for the introduction of silyl groups into complex organic molecules.

Discovery and Evaluation of Pyrazolo[3,4-d]pyridazinone as a Potent and Orally Active Irreversible BTK Inhibitor

The identification and lead optimization of a series of pyrazolo[3,4-d]pyridazinone derivatives are described as a novel class of potent irreversible BTK inhibitors, resulting in the discovery of compound 8. Compound 8 exhibited high potency against BTK kinase and acceptable PK profile. Furthermore, compound 8 demonstrated significant in vivo efficacy in a mouse-collagen-induced arthritis (CIA) model.

1-(1-Arylethylpiperidin-4-yl)thymine analogs as antimycobacterial TMPK inhibitors

A series of Mycobacterium tuberculosis TMPK (MtbTMPK) inhibitors based on a reported compound 3 were synthesized and evaluated for their capacity to inhibit MtbTMPK catalytic activity and the growth of a virulent M. tuberculosis strain (H37Rv). Modifications of the scaffold of 3 failed to afford substantial improvements in MtbTMPK inhibitory activity and antimycobacterial activity. Optimization of the substitution pattern of the D ring of 3 resulted in compound 21j with improved MtbTMPK inhibitory potency (three-fold) and H37Rv growth inhibitory activity (two-fold). Moving the 3-chloro substituent of 21j to the para-position afforded isomer 21h, which, despite a 10-fold increase in IC50-value, displayed promising whole cell activity (minimum inhibitory concentration (MIC) = 12.5 μM).

Synthesis and structure activity relationships of cyanopyridone based anti-tuberculosis agents

Mycobacterium tuberculosis, the causative agent of tuberculosis, relies on thymidylate kinase (MtbTMPK) for the synthesis of thymidine triphosphates and thus also DNA synthesis. Therefore, this enzyme constitutes a potential Achilles heel of the pathogen. Based on a previously reported MtbTMPK 6-aryl-substituted pyridone inhibitor and guided by two co-crystal structures of MtbTMPK with pyridone- and thymine-based inhibitors, we report the synthesis of a series of aryl-shifted cyanopyridone analogues. These compounds generally lacked significant MtbTMPK inhibitory potency, but some analogues did exhibit promising antitubercular activity. Analogue 11i demonstrated a 10-fold increased antitubercular activity (MIC H37Rv, 1.2 μM) compared to literature compound 5. Many analogues with whole-cell antimycobacterial activity were devoid of significant cytotoxicity.

BTK INHIBITOR

Provided are a series of BTK inhibitors, and specifically disclosed are a compound, pharmaceutically acceptable salt thereof, tautomer thereof or prodrug thereof represented by formula (I), (II), (III) or (IV).

N-Substituted homopiperazine barbiturates as gelatinase inhibitors

Matrix metalloproteinases are implicated in a wide range of pathophysiological processes and potent selective inhibitors for these enzymes continue to be eagerly sought. 5,5-Disubstituted barbiturates hold promise as inhibitor types being stable in vivo and relatively selective for the gelatinases (MMP-2 and MMP-9). In this paper we describe the synthesis of 5-piperazine and -homopiperazine substituted barbiturates. The activity of these compounds as gelatinase inhibitors was evaluated using supernatants from 12-O-tetradecanoylphorbol-13-acetate (PMA)-stimulated HT-1080 cells as well as using recombinant human MMPs. N-Acyl homopiperazine compounds were found to be potent inhibitors of the gelatinases (range in nM) and generally more potent than the corresponding piperazine analogues. The panel of N-acyl homopiperazines was enlarged in order to exploit differences between the gelatinases at the S2′ site in order to design MMP-2- or MMP-9-selective inhibitors. Compounds in this group exhibited single digit nano-molar potency and some selectivity between the two enzymes. Representative potent compounds were effective inhibitors of cancer cell migration.

Novel benzimidazole derivatives as selective CB2 agonists

The preparation and evaluation of a novel class of CB2 agonists based on a benzimidazole moiety are reported. They showed binding affinities up to 1 nM towards the CB2 receptor with partial to full agonist potencies. They also demonstrated good to excellent selectivity (>1000-fold) over the CB1 receptor.

AGENT FOR CONTROLLING FUNCTION OF GPR34 RECEPTOR

The present invention provides a GPR receptor function regulator comprising the compound represented by the formula: [wherein ring A is an optionally substituted isocyclic or heterocyclic ring, P is a bond or spacer, ring D is an optionally substituted monocyclic aromatic ring which may be condensed with a 5-to 7-membered ring, V is a bond or the group represented by the formula -CR14=CR15 - or - N=CR16- (wherein R14, R15 and R16 each represents a hydrogen atom or optionally substituted hydrocarbon group), Q is a bond or spacer, and W is a carboxyl or a group biologically equivalent to a carboxyl] or its salt or a prodrug thereof

Inhibitors of the 11-beta-hydroxysteroid dehydrogenase type 1 enzyme

The present invention relates to compounds that are inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme. The present invention further relates to the use of inhibitors of 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme for the treatment of non-insulin dependent type 2 diabetes, insulin resistance, obesity, lipid disorders, metabolic syndrome and other diseases and conditions that are mediated by excessive glucocorticoid action.