Tag: M.W=200-250

Buchieri, Maria V.; Cimino, Mena; Rebollo-Ramirez, Sonia; Beauvineau, Claire; Cascioferro, Alessandro; Favre-Rochex, Sandrine; Helynck, Olivier; Naud-Martin, Delphine; Larrouy-Maumus, Gerald; Munier-Lehmann, Helene; Gicquel, Brigitte published the artcile< Nitazoxanide Analogs Require Nitroreduction for Antimicrobial Activity in Mycobacterium smegmatis>, Safety of 2-(Trifluoromethoxy)benzoyl chloride, the main research area is nitazoxanide analog nitroredn antimicrobial Mycobacterium.

In this study, we aimed to decipher the natural resistance mechanisms of mycobacteria against novel compounds isolated by whole-cell-based high-throughput screening (HTS). We identified active compounds using Mycobacterium Aurum. Further analyses were performed to determine the resistance mechanism of M. smegmatis against one hit, 3-bromo-N-(5-nitrothiazol-2-yl)-4-propoxybenzamide (3), which turned out to be an analog of the drug nitazoxanide (1). We found that the repression of the gene nfnB coding for the nitroreductase NfnB was responsible for the natural resistance of M. smegmatis against 3. The overexpression of nfnB resulted in sensitivity of M. smegmatis to 3. This compound must be metabolized into hydroxylamine intermediate for exhibiting antibacterial activity. Thus, we describe, for the first time, the activity of a mycobacterial nitroreductase against 1 analogs, highlighting the differences in the metabolism of nitro compounds among mycobacterial species and emphasizing the potential of nitro drugs as antibacterials in various bacterial species.

Journal of Medicinal Chemistry published new progress about Antibiotic resistance. 162046-61-9 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H4ClF3O2, Safety of 2-(Trifluoromethoxy)benzoyl chloride.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Macdonald, Jonathan D.; Chacon Simon, Selena; Han, Changho; Wang, Feng; Shaw, J. Grace; Howes, Jennifer E.; Sai, Jiqing; Yuh, Joannes P.; Camper, Demarco; Alicie, Bethany M.; Alvarado, Joseph; Nikhar, Sameer; Payne, William; Aho, Erin R.; Bauer, Joshua A.; Zhao, Bin; Phan, Jason; Thomas, Lance R.; Rossanese, Olivia W.; Tansey, William P.; Waterson, Alex G.; Stauffer, Shaun R.; Fesik, Stephen W. published the artcile< Discovery and Optimization of Salicylic Acid-Derived Sulfonamide Inhibitors of the WD Repeat-Containing Protein 5-MYC Protein-Protein Interaction>, Recommanded Product: 5-Chloro-2-methoxybenzenesulfonyl chloride, the main research area is neoplasm WDR5 MYC protein interaction crystal structure.

The treatment of tumors driven by overexpression or amplification of MYC oncogenes remains a significant challenge in drug discovery. Here, we present a new strategy toward the inhibition of MYC via the disruption of the protein-protein interaction between MYC and its chromatin cofactor WD Repeat-Containing Protein 5. Blocking the association of these proteins is hypothesized to disrupt the localization of MYC to chromatin, thus disrupting the ability of MYC to sustain tumorigenesis. Utilizing a high-throughput screening campaign and subsequent structure-guided design, we identify small-mol. inhibitors of this interaction with potent in vitro binding affinity and report structurally related neg. controls that can be used to study the effect of this disruption. Our work suggests that disruption of this protein-protein interaction may provide a path toward an effective approach for the treatment of multiple tumors and anticipate that the mols. disclosed can be used as starting points for future efforts toward compounds with improved drug-like properties.

Journal of Medicinal Chemistry published new progress about Crystal structure. 22952-32-5 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H6Cl2O3S, Recommanded Product: 5-Chloro-2-methoxybenzenesulfonyl chloride.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Kong, Haiyan; Meng, Xianshe; Hou, Rui; Yang, Xiaoxiao; Han, Jihong; Xie, Zhouling; Duan, Yajun; Liao, Chenzhong published the artcile< Novel 1-(prop-2-yn-1-ylamino)-2,3-dihydro-1H-indene-4-thiol derivatives as potent selective human monoamine oxidase B inhibitors: Design, SAR development, and biological evaluation>, Formula: C8H8BrCl, the main research area is propynylamino dihydro indene thiol preparation hMAO B inhibitor; antiParkinson agent structure activity relationship; Fragment-based drug design; HMAO-B; Isoform selectivity; Structure activity relationship.

Successes have been achieved in developing human monoamine oxidase B (hMAO-B) inhibitors as anti-Parkinson’s disease (PD) drugs. However, low efficiency and unwanted side effects of the marketed hMAO-B inhibitors hamper their medical applications, therefore, novel potent selective hMAO-B inhibitors are still of great interest. Herein we report 1-(prop-2-yn-1-ylamino)-2,3-dihydro-1H-indene-4-thiol derivatives as hMAO-B inhibitors, which were designed by employing a fragment-based drug design strategy to link rasagiline to hydrophobic fragments. Among the synthesized 31 compounds, I and II demonstrated very encouraging hMAO-B inhibitory activities and selectivity over hMAO-A, better than rasagiline and safinamide. In vitro studies indicated that K8 and K24 are nontoxic to nervous tissue cells and they have considerable effects against ROS formation and potential neuroprotective activity. Further mice behavioral tests demonstrated these two compounds have good therapeutic effects on MPTP-induced PD model mice. All these experiment results suggest that compounds K8 and K24 can be promising candidates for further research for treatment of PD.

Bioorganic & Medicinal Chemistry Letters published new progress about Antiparkinsonian agents. 16799-05-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H8BrCl, Formula: C8H8BrCl.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Wu, Tian-bang; Xiang, Qiu-ping; Wang, Chao; Wu, Chun; Zhang, Cheng; Zhang, Mao-feng; Liu, Zhao-xuan; Zhang, Yan; Xiao, Lin-jiu; Xu, Yong published the artcile< Y06014 is a selective BET inhibitor for the treatment of prostate cancer>, Formula: C7H6Cl2O3S, the main research area is dimethylisoxazolyl benzoindolone preparation BET inhibitor SAR antitumor human docking; BRD4; Y06014; androgen receptor; bromodomain inhibitor; prostate cancer.

The design, synthesis and a structure-activity relationship study of 6-(3,5-dimethylisoxazol-4-yl)benzo[cd]indol-2(1H)-one derivative I [R = Et, PhSO2, PhCH2CH2CH2, etc.] as novel selective BET inhibitors was reported. One representative compound, compound I [R = Et], bound to BRD4(1) in the low micromolar range and demonstrated high selectivity for BRD4(1) over other non-BET bromodomain-containing proteins. This mol. also potently inhibited cell growth, colony formation and mRNA expression of AR-regulated genes in PC cell lines. The compound I [R = Et] also showed stronger activity than the second-generation antiandrogen enzalutamide. The compound I [R = Et] might serve as a new small mol. probe for further validation of BET as a mol. target for PC drug development.

Acta Pharmacologica Sinica published new progress about Antitumor agents. 22952-32-5 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H6Cl2O3S, Formula: C7H6Cl2O3S.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Li, Pei; Yin, Juan; Xu, Weiming; Wu, Jian; He, Ming; Hu, Deyu; Yang, Song; Song, Baoan published the artcile< Synthesis, Antibacterial Activities, and 3D-QSAR of Sulfone Derivatives Containing 1, 3, 4-Oxadiazole Moiety>, Computed Properties of 2905-54-6, the main research area is oxadiazole sulfone preparation antibacterial activity QSAR; 3D-QSAR; CoMFA; CoMSIA; antibacterial activities; sulfone derivatives; synthesis.

A series of sulfone derivatives containing 1, 3, 4-oxadiazole moiety were prepared and evaluated for their antibacterial activities by the turbidimeter test. Most compounds inhibited growth of Ralstonia solanacearum (R. solanacearum) from tomato and tobacco bacterial wilt with high potency, among which compounds I [X = H, F] exhibited the most potent inhibition against R. solanacearum from tomato and tobacco bacterial wilts with EC50 values of 19.77 and 8.29 μg/mL, resp. Our results also demonstrated that I [X = H, F] and a number of other compounds were more potent than com. bactericides Kocide 3000 and Thiodiazole Copper, which inhibited R. solanacearum from tomato bacterial wilt with EC50 values of 93.59 and 99.80 μg/mL and tobacco bacterial wilt with EC50 values of 45.91 and 216.70 μg/mL, resp. The structure-activity relationship (SAR) of compounds was studied using three-dimensional quant. structure-activity relationship (3D-QSAR) models created by comparative mol. field anal. (CoMFA) and comparative mol. similarity index anal. (CoMSIA) based on compound bioactivities against tomato and tobacco bacterial wilts. The 3D-QSAR models effectively predicted the correlation between inhibitory activity and steric-electrostatic properties of compounds

Chemical Biology & Drug Design published new progress about Agrochemicals. 2905-54-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H6Cl2O2, Computed Properties of 2905-54-6.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Verma, Krishan K.; Singh, Umesh K.; Jain, Jainendra published the artcile< Screening of Some Novel 4, 5 Disubstituted 1, 2, 4-Triazole-3-thiones for Anticonvulsant Activity>, Name: Methyl 2,3-dichlorobenzoate, the main research area is triazole thione anticonvulsant drug screening; GABA-AT; MES; Triazol-3-thiones; anticonvulsant activity; docking; scPTZ..

In the present study, we synthesized fifteen 4, 5-disubstituted 1, 2, 4-triazol- 3-thione derivatives and evaluated for anticonvulsant activity with neurotoxicity determination The synthesized compounds were characterized using FTIR, 1H-NMR and MS. The mol. docking study was also performed to study the interactions of compounds with LYS329 residue of gamma amino butyric acid aminotransferase (GABA-AT) using Autodock 4.2 software. The anticonvulsant activity was assessed by maximal electroshock (MES) test and s.c. pentylenetetrazol (scPTZ) tests. The neurotoxicity was assessed by rotarod ataxia test. In MES test, compounds 5a, 8a and 9a were found active at 100 mg/kg and five compounds were found active at 300 mg/kg dose after 1 h of administration. After 4 h of drug administration, only two compounds 8a and 9a exhibited protection at 100 mg/kg. In scPTZ test, three compounds 2a, 6a and 8a were found active at 100 mg/kg and 7a was active at 300 mg/kg after 1 h of test drug administration. Most of the compounds were found active in MES test with 8a and 9a being the most active among all. In docking study, 2a was found to be best compound based on the binding energy of -6.5 kcal/mol and estimated inhibition constant of 17.2μM. Majority of synthesized compounds were found active in MES test, whereas only few were found to possess anti scPTZ activity. Among all compounds, only 14a caused motor coordination impairment in rotarod ataxia test at 300 mg/kg 1 h duration.

Central Nervous System Agents in Medicinal Chemistry published new progress about Anticonvulsants. 2905-54-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H6Cl2O2, Name: Methyl 2,3-dichlorobenzoate.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics