227328-16-7

Upstream product

• 2148-56-3 2-chloro-6-aminobenzoic acid 

Downstream Products

• 50460-70-3 2-amino-6-chloro-N-phenylbenzamide 
• 1616494-81-5 2-acetamido-6-chloro-N-methyl-N-phenylbenzamide 
• 1405392-50-8 2-amino-6-chloro-N-methyl-N-phenylbenzamide 
• 146516-21-4 6-chloro-3,4-dihydro-4-benzyl-1H-1,4-benzodiazepine-2,5-dione 

Relevant academic research and scientific papers

2-((3,5-Dinitrobenzyl)thio)quinazolinones: Potent Antimycobacterial Agents Activated by Deazaflavin (F420)-Dependent Nitroreductase (Ddn)

Swapping the substituents in positions 2 and 4 of the previously synthesized but yet undisclosed 5-cyano-4-(methylthio)-2-arylpyrimidin-6-ones 4, ring closure, and further optimization led to the identification of the potent antitubercular 2-thio-substituted quinazolinone 26. Structure-activity relationship (SAR) studies indicated a crucial role for both meta-nitro substituents for antitubercular activity, while the introduction of polar substituents on the quinazolinone core allowed reduction of bovine serum albumin (BSA) binding (63c, 63d). While most of the tested quinazolinones exhibited no cytotoxicity against MRC-5, the most potent compound 26 was found to be mutagenic via the Ames test. This analogue exhibited moderate inhibitory potency against Mycobacterium tuberculosis thymidylate kinase, the target of the 3-cyanopyridones that lies at the basis of the current analogues, indicating that the whole-cell antimycobacterial activity of the present S-substituted thioquinazolinones is likely due to modulation of alternative or additional targets. Diminished antimycobacterial activity was observed against mutants affected in cofactor F420 biosynthesis (fbiC), cofactor reduction (fgd), or deazaflavin-dependent nitroreductase activity (rv3547), indicating that reductive activation of the 3,5-dinitrobenzyl analogues is key to antimycobacterial activity.

NaNO2/I2 as an alternative reagent for the synthesis of 1,2,3-benzotriazin-4(3H)-ones from 2-aminobenzamides

An efficient transformation of 2-aminobenzamides to 1,2,3-benzotriazin-4(3H)-ones in the presence of sodium nitrite (NaNO2) and Iodine (I2) is described. The reaction is proposed to proceed via formation of nitrosyl halide that induces nitrosylation of the amino group of 2-aminobenzamide leading to diazotization followed by intramolecular cyclization.

Development of Quinazoline/Pyrimidine-2,4(1H,3H)-diones as Agonists of Cannabinoid Receptor Type 2

Starting from a prototypical structure 1, we describe our efforts to design and obtain novel quinazoline/pyrimidine-2,4(1H,3H)-diones with high CB2 agonist potency and selectivity as well as improved physicochemical characteristics, mainly hydrophilicity. The most potent and selective CB2 agonists, 8 and 36, in this series were also endowed with lower logP values than that of GW842166X and lead compound 1. These derivatives appear to be promising lead compounds for the development of future CB2 agonists.

Intramolecular metal-free oxidative aryl-aryl coupling: An unusual hypervalent-iodine-mediated rearrangement of 2-substituted n-phenylbenzamides

Hypervalent-iodine-mediated oxidative coupling of the two aryl groups in either 2-acylamino-N-phenyl-benzamides or 2-hydroxy-N-phenylbenzamides, with concomitant insertion of the ortho-substituted N or O atom into the tether, has been described for the first time. This unusual metal-free rearrangement reaction involves an oxidative C(sp2)?C(sp2) aryl-aryl bond formation, cleavage of a C(sp2)?C(O) bond, and a lactamization/lactonization. Furthermore, unsymmetrical diaryl compounds can be easily obtained by removing the tether within the cyclized product.

Synthesis and structure-activity relationships of 3,5-disubstituted 4,5- dihydro-6H-imidazo[1,5-a][1,4]benzodiazepin-6-ones at diazepam-sensitive and diazepam-insensitive benzodiazepine receptors

A series of imidazobenzodiazepin-6-ones possessing varying substituents at the 3- and 5-positions were synthesized and evaluated for their affinities at diazepam-sensitive (DS) and diazepam-insensitive (DI) benzodiazepine receptors (BzR) in rat cortical and cerebellar membranes. Replacement of an ester substituent at the 3-position with a carbamate, acetylamino, formylamino, isothiocyanato, 2-oxazolinyl, 2-benzoxazolyl, or p- tolylsulfonyl groups lead to >100-fold reductions in affinity at both DS and DI BzR. Replacement of a methyl group on the nitrogen at the 5-position with propyl, allyl, or phenethyl groups also led to significant reductions in affinity at both BzR isoforms. However, incorporation of a benzyl group yields ligands (11f,h,i and 14a-c) with moderate to high affinities at DS BzR, suggesting the presence of a hydrophobic pocket at the receptor site. Introduction of chlorine at the 7-position enhances ligand affinity at DS BzR while chlorine at the 8-position decreases affinity (IC50: 11f, 9.3 nM; 11h, 2.4 nM 11i, 37.8 nM). In contrast, chlorine substitution at the 7- as well as the 8-position increases affinity at DI BzR (K(i): 11f, 112 nM; 11h, 20.2 nM; 11i, 10.9 nM). Compound 11i is among the few described high affinity DI-site ligands with a selectivity comparable to that of Ro 15-4513. Despite their in vitro affinities, compounds 11f, 11h, and 11i exhibit low in vivo activities that may be attributable to unfavorable metabolic or pharmacokinetic properties.