Category: 20776-50-5

Fioravanti, Rossella; Romanelli, Annalisa; Mautone, Nicola; Di Bello, Elisabetta; Rovere, Annarita; Corinti, Davide; Zwergel, Clemens; Valente, Sergio; Rotili, Dante; Botrugno, Oronza A.; Dessanti, Paola; Vultaggio, Stefania; Vianello, Paola; Cappa, Anna; Binda, Claudia; Mattevi, Andrea; Minucci, Saverio; Mercurio, Ciro; Varasi, Mario; Mai, Antonello published the artcile< Tranylcypromine-Based LSD1 Inhibitors: Structure-Activity Relationships, Antiproliferative Effects in Leukemia, and Gene Target Modulation>, Application In Synthesis of 20776-50-5, the main research area is tranyl cypromine derivative LSD1 inhibitor preparation cancer structure; antiproliferative activity; drug discovery; histone demethylases; lysine specific demethylase 1; structure-activity relationships.

Abstract: LSD1 is a lysine demethylase highly involved in initiation and development of cancer. To design highly effective covalent inhibitors, a strategy is to fill its large catalytic cleft by designing tranylcypromine (TCP) analogs decorated with long, hindered substituents. We prepared three series of TCP analogs, carrying aroyl- and arylacetylamino (1 a-h), Z-amino acylamino (2 a-o), or double-substituted benzamide (3 a-n) residues at the C4 or C3 position of the Ph ring. Further fragments obtained by chem. manipulation applied on the TCP scaffold (compounds 4 a-i) were also prepared When tested against LSD1, most of 1 and 3 exhibited IC50 values in the low nanomolar range, with 1 e and 3 a,d,f,g being also the most selective respect to monoamine oxidases. In MV4-11 AML and NB4 APL cells compounds 3 were the most potent, displaying up to sub-micromolar cell growth inhibition against both cell lines (3 a) or against NB4 cells (3 c). The most potent compounds in cellular assays were also able to induce the expression of LSD1 target genes, such as GFI-1b, ITGAM, and KCTD12, as functional read-out for LSD1 inhibition. Mouse and human intrinsic clearance data highlighted the high metabolic stability of compounds 3 a, 3 d and 3 g. Further studies will be performed on the new compounds 3 a and 3 c to assess their anticancer potential in different cancer contexts.

ChemMedChem published new progress about Antitumor agents. 20776-50-5 belongs to class bromides-buliding-blocks, and the molecular formula is C7H6BrNO2, Application In Synthesis of 20776-50-5.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Li, Peng; Liu, Ying; Yang, Hua; Liu, Hong-Min published the artcile< Design, synthesis, biological evaluation and structure-activity relationship study of quinazolin-4(3H)-one derivatives as novel USP7 inhibitors>, Name: 2-Amino-4-bromobenzoic acid, the main research area is piperidinylmethyl amino quinazolinone preparation USP7 inhibitor antitumor docking SAR; Gastric cancer; Inhibitors; Quinazolin-4(3H)-one; SAR; USP7; Ubiquitination.

The design, synthesis and biol. evaluation of novel I [R1 = pyrrolyl, Ph, pyridinyl, etc.] and II [R2 = Et, furanyl, dimethylaminomethylene, etc.;R3 = H, methyl] as potent USP7 inhibitors was reported. This results indicated that the compounds II [R2 = pyrrolidinylmethylene, dimethylaminomethylene;R3 = H, methyl] exhibited the greatest potency against the USP7 catalytic domain, with IC50 values of 4.86μM and 1.537μM, resp. Ub-AMC assays further confirmed IC50 values of 5.048μM and 0.595μM for II [R2 = pyrrolidinylmethylene, dimethylaminomethylene; R3 = H, methyl] resp. MTT assays indicated that gastric cancer MGC-803 cells were more sensitive to these compounds than BGC-823 cells. Flow cytometry anal. revealed that II [R2 = pyrrolidinylmethylene; R3 = H ] restricted cancer cell growth at the G0/G1 and S phases and inhibited the proliferation and clone formation of MGC-803 cells. Further biochem. experiments indicated that II [R2 = pyrrolidinylmethylene; R3 = H ] decreased the MDM2 protein level and increased the levels of the tumor suppressors p53 and p21 in a dose-dependent manner. Docking studies predicted that solvent exposure of the side chains of II [R2 = pyrrolidinylmethylene, dimethylaminomethylene; R3 = H, methyl] would uniquely form hydrogen bonds with Met407 of USP7. Addnl., II [R2 = pyrrolidinylmethylene; R3 = H ] exhibited a remarkable anticancer effect in a zebrafish gastric cancer MGC-803 cell model. Results demonstrated that I [R1 = pyrrolyl, Ph, pyridinyl, etc.] and II [R2 = Et, furanyl, dimethylaminomethylene etc.; R3 = H, methyl] were suitable as leads for the development of novel USP7 inhibitors and especially for anti-gastric cancer drugs.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 20776-50-5 belongs to class bromides-buliding-blocks, and the molecular formula is C7H6BrNO2, Name: 2-Amino-4-bromobenzoic acid.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Liu, Jingbo; Shi, Yabing; Tian, Zhicheng; Li, Fengyun; Hao, Zesheng; Wen, Wen; Zhang, Li; Wang, Yuanhong; Li, Yuxin; Fan, Zhijin published the artcile< Bioactivity-Guided Synthesis Accelerates the Discovery of Evodiamine Derivatives as Potent Insecticide Candidates>, HPLC of Formula: 20776-50-5, the main research area is evodiamine derivative preparation insecticide Mythimna Plutella Helicoverpa ryanodine receptor; evodiamine; insecticidal activity; insecticidal mechanism of action, molecular docking; structure−activity relationship.

Pests threaten worldwide food security by decreasing crop yields and damaging their quality. Natural product-based mol. design and structural optimization have been one of the most effective ways to innovate pesticides for integrated insect management. To continue our previous studies on the discovery of insecticidal lead, a series of evodiamine derivatives were designed, synthesized, and evaluated for their insecticidal activities. The bioassay results demonstrated that compounds (I) and (II) exhibited 90 and 80% insecticidal activities against Mythimna separata at 2.5 mg/L, resp., which were superior to evodiamine (10% at 10 mg/L), matrine (45% at 600 mg/L), and rotenone (30% at 200 mg/L). Compounds I, II and (III) showed 90% insecticidal activities against Plutella xylostella at 1.0 mg/L, far more potent than those of evodiamine, matrine, and rotenone. Compound I displayed 60% insecticidal activity against Helicoverpa armigera at 5.0 mg/L, while evodiamine, matrine, and rotenone showed very poor activities. The study on the insecticidal mechanism of action by a calcium imaging experiment indicated that the insect ryanodine receptors (RyRs) could be the potential target of I. Furthermore, the mol. docking indicated that I anchored in the binding site of the RyR of P. xylostella. The above results manifested the potential of evodiamine derivatives as potent insecticide candidates.

Journal of Agricultural and Food Chemistry published new progress about Helicoverpa armigera. 20776-50-5 belongs to class bromides-buliding-blocks, and the molecular formula is C7H6BrNO2, HPLC of Formula: 20776-50-5.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Akester, Jessica N.; Njaria, Paul; Nchinda, Aloysius; Le Manach, Claire; Myrick, Alissa; Singh, Vinayak; Lawrence, Nina; Njoroge, Mathew; Taylor, Dale; Moosa, Atica; Smith, Anthony J.; Brooks, Elizabeth J.; Lenaerts, Anne J.; Robertson, Gregory T.; Ioerger, Thomas R.; Mueller, Rudolf; Chibale, Kelly published the artcile< Synthesis, Structure-Activity Relationship, and Mechanistic Studies of Aminoquinazolinones Displaying Antimycobacterial Activity>, Safety of 2-Amino-4-bromobenzoic acid, the main research area is aminoquinazolinone preparation Mycobacterium tuberculosis pharmacokinetic SAR Suzuki antimycobacterial; 2-aminoquinazolinones; Mycobacterium tuberculosis; drug discovery; tuberculosis.

Phenotypic whole-cell screening against Mycobacterium tuberculosis (Mtb) in glycerol-alanine-salts supplemented with Tween 80 and iron (GASTE-Fe) media led to the identification of a 2-aminoquinazolinone hit compound, sulfone which was optimized for solubility by replacing the sulfone moiety with a sulfoxide I. The synthesis and structure-activity relationship (SAR) studies identified several compounds with potent antimycobacterial activity, which were metabolically stable and noncytotoxic. Compound I displayed favorable in vitro properties and was therefore selected for in vivo pharmacokinetic (PK) studies where it was found to be extensively metabolized to the sulfone. Both derivatives exhibited promising PK parameters; however, when I was evaluated for in vivo efficacy in an acute TB infection mouse model, it was found to be inactive. In order to understand the in vitro and in vivo discrepancy, compound I was subsequently retested in vitro using different Mtb strains cultured in different media. This revealed that activity was only observed in media containing glycerol and led to the hypothesis that glycerol was not used as a primary carbon source by Mtb in the mouse lungs, as has previously been observed Support for this hypothesis was provided by spontaneous-resistant mutant generation and whole genome sequencing studies, which revealed mutations mapping to glycerol metabolizing genes indicating that the 2-aminoquinazolinones kill Mtb in vitro via a glycerol-dependent mechanism of action.

ACS Infectious Diseases published new progress about Antimycobacterial agents. 20776-50-5 belongs to class bromides-buliding-blocks, and the molecular formula is C7H6BrNO2, Safety of 2-Amino-4-bromobenzoic acid.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Gui, Qing-Wen; Teng, Fan; Yang, Hao; Xun, Changping; Huang, Wen-Jie; Lu, Zi-Qin; Zhu, Meng-Xue; Ouyang, Wen-Tao; He, Wei-Min published the artcile< Visible-Light Photosynthesis of CHF2/CClF2/CBrF2-Substituted Ring-fused Quinazolinones in Dimethyl Carbonate>, Quality Control of 20776-50-5, the main research area is ring fused quinazolinone preparation; alkenyl quinazolinone visible light cascade difluoromethylation cyclization green chem; cascade radical reactions; difluoromethylation; dimethyl carbonate; metal-free; ring-fused quinazolinones.

With eco-friendly and sustainable CO2-derived di-Me carbonate as the sole solvent, the visible-light-induced cascade radical reactions have been established as a green and efficient tool for constructing various CHF2/CClF2/CBrF2-substituted ring-fused quinazolinones.

Chemistry – An Asian Journal published new progress about Cyclization. 20776-50-5 belongs to class bromides-buliding-blocks, and the molecular formula is C7H6BrNO2, Quality Control of 20776-50-5.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary