50-86-2Relevant academic research and scientific papers
Mycobacterium tuberculosis arylamine N-acetyltransferase acetylates and thus inactivates para-aminosalicylic acid
Wang, Xude,Yang, Shanshan,Gu, Jing,Deng, Jiaoyu
, p. 7505 - 7508 (2016)
Mycobacterium tuberculosis arylamine N-acetyltransferase (TBNAT) is able to acetylate para-aminosalicylic acid (PAS) both in vitro and in vivo as determined by high-performance liquid chromatography (HPLC) and electrospray ionization-mass spectrometry (ESI-MS) techniques. The antituberculosis activity of the acetylated PAS is significantly reduced. As a result, overexpression of TBNAT in M. tuberculosis results in PAS resistance, as determined by MIC tests and drug exposure experiments. Taken together, our results suggest that TBNAT from M. tuberculosis is able to inactivate PAS by acetylating the compound.
A tautomeric ligand enables directed C-H hydroxylation with molecular oxygen
Li, Zhen,Wang, Zhen,Chekshin, Nikita,Qian, Shaoqun,Qiao, Jennifer X.,Cheng, Peter T.,Yeung, Kap-Sun,Ewing, William R.,Yu, Jin-Quan
, p. 1452 - 1457 (2021/06/30)
Hydroxylation of aryl carbon-hydrogen bonds with transition metal catalysts has proven challenging when oxygen is used as the oxidant. Here, we report a palladium complex bearing a bidentate pyridine/ pyridone ligand that efficiently catalyzes this reaction at ring positions adjacent to carboxylic acids. Infrared, x-ray, and computational analysis support a possible role of ligand tautomerization from monoanionic (L,X) to neutral (L,L) coordination in the catalytic cycle of aerobic carbon-hydrogen hydroxylation reaction. The conventional site selectivity dictated by heterocycles is overturned by this catalyst, thus allowing late-stage modification of compounds of pharmaceutical interest at previously inaccessible sites.
Aminobenzoic acid derivative and preparation method and application thereof
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Paragraph 0030-0031, (2020/12/30)
The invention relates to an aminobenzoic acid derivative and a preparation method and application thereof, and belongs to the field of medicinal chemistry, and the structural formula of the aminobenzoic acid derivative is shown in the specification, R is alkyl, substituted phenyl, heteroaromatic ring group or substituted styryl; R is alkyl; R is alkyl, substituted phenyl or benzyl; R is alkyl; R is guanidyl; and R is alkyl. The preparation method is simple and high in yield. Most compounds of the invention have good influenza virus neuraminidase inhibition activity.
Citric acid mosapride intermediate product and application
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Paragraph 0053; 0054; 0055, (2018/09/08)
The invention belongs to the field of medical chemistry synthesis, and provides a preparation method of citric acid mosapride intermediate product IV 4-[(4-fluorophenyl)methyl]-2-morpholinemethanaminesalt and citric acid mosapride. The 2-(4-fluorobenzoamido)ethanol and 1H-Isoindole-1,3(2H)-dione,2-(2-oxiranylmethyl) are taken as raw materials, and the intermediate product IV 4-[(4-fluorophenyl)methyl]-2-morpholinemethanamine salt is obtained after acid treating is conducted; the intermediate product IV and an intermediate V 2-oxethyl-4-acetamido-5-Chlorobenzoic acid ethyl ester compounds aretaken as raw materials, dichloromethane is taken as a solvent, and EDCI and DMAP are taken as catalysts to prepare mosapride salt; the mosapride salt is reacted with citric acid aqueous solution to prepare citric acid mosapride. The intermediate product has the advantages that products are high in yield, raw materials are easy to obtain, the production cost is low, and the intermediate product issuitable for industrialized production.
Design, synthesis, and pharmacological evaluation of fluorinated azoles as anti-tubercular agents
Gholap, Somnath,Tambe, Macchindra,Nawale, Laxman,Sarkar, Dhiman,Sangshetti, Jaiprakash,Damale, Manoj
, (2018/01/05)
Design, synthesis, and biological screening of 2,2-dimethyl-2,3-dihydrobenzofuran tethered 1,3,4-oxadiazole derivatives as anti-tubercular agents were described. The synthesis of the target compounds was conducted by a series of reaction schemes. All the synthesized compounds were characterized by IR, 1H NMR, 13C NMR, and mass spectrometry. The therapeutic potential of the synthesized compounds was confirmed by molecular docking studies. Among the synthesized compounds, 12a, 12c, 12d, 12e, 12g, and 12j were found to be more active against non-replicating than against replicating cultures of Mycobacterium tuberculosis H37Ra ex vivo and in vitro. These compounds exhibit minimum inhibitory concentration (MIC) values in the range of 2.31–23.91 μg/mL. The cytotoxicity study was conducted against the cell lines THP-1, A549 and PANC-1, and the compounds were observed to be non-toxic to host cells. Molecular docking was conducted with InhA (FabI/ENR) and suggested the antimycobacterial potential of the synthesized compounds. The investigation presented here was found to be adventitious for the development of new therapeutic agents against Mycobacterium infection.
Benzoic acid derivatives with trypanocidal activity: Enzymatic analysis and molecular docking studies toward trans-sialidase
Kashif, Muhammad,Moreno-Herrera, Antonio,Villalobos-Rocha, Juan Carlos,Nogueda-Torres, Benjamín,Pérez-Villanueva, Jaime,Rodríguez-Villar, Karen,Medina-Franco, José Luis,De Andrade, Peterson,Carvalho, Ivone,Rivera, Gildardo
, (2017/11/20)
Chagas, or American trypanosomiasis, remains an important public health problem in developing countries. In the last decade, trans-sialidase has become a pharmacological target for new anti-Chagas drugs. In this work, the aims were to design and find a new series of benzoic acid derivatives as trans-sialidase (TS) inhibitors and anti-trypanosomal agents. Three compounds (14, 18, and 19) sharing a para-aminobenzoic acid moiety showed more potent trypanocidal activity than the commercially available drugs nifurtimox and benznidazole in both strains: the lysis concentration of 50% of the population (LC50) was 0.15 μM on the NINOA strain, and LC50 0.22 μM on the INC-5 strain. Additionally, compound 18 showed a moderate inhibition (47%) on the trans-sialidase enzyme and a binding model similar to DANA (pattern A).
Discovery of furan and dihydrofuran-fused tricyclic benzo[d]imidazole derivatives as potent and orally efficacious microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors: Part-1
Muthukaman, Nagarajan,Tambe, Macchindra,Deshmukh, Sanjay,Pisal, Dnyandeo,Tondlekar, Shital,Shaikh, Mahamadhanif,Sarode, Neelam,Kattige, Vidya G.,Pisat, Monali,Sawant, Pooja,Honnegowda, Srinivasa,Karande, Vikas,Kulkarni, Abhay,Behera, Dayanidhi,Jadhav, Satyawan B.,Sangana, Ramchandra R.,Gudi, Girish S.,Khairatkar-Joshi, Neelima,Gharat, Laxmikant A.
, p. 5131 - 5138 (2017/11/20)
This letter describes the synthesis and biological evaluation of furan and dihydrofuran-fused tricyclic benzo[d]imidazole derivatives as novel mPGES-1 inhibitors, capable of inhibiting an increased PGE2 production in the disease state. Structure-activity optimization afforded many potent mPGES-1 inhibitors having 50 of 14.3 mg/kg in guinea pig.
Detection of Sulfatase Enzyme Activity with a CatalyCEST MRI Contrast Agent
Sinharay, Sanhita,Fernández-Cuervo, Gabriela,Acfalle, Jasmine P.,Pagel, Mark D.
, p. 6491 - 6495 (2016/05/02)
A chemical exchange saturation transfer (CEST) MRI contrast agent has been developed that detects sulfatase enzyme activity. The agent produces a CEST signal at δ=5.0 ppm before enzyme activity, and a second CEST signal appears at δ=9.0 ppm after the enzyme cleaves a sulfate group from the agent. The comparison of the two signals improved detection of sulfatase activity.
HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
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Paragraph 0235; 0337; 0338, (2014/05/20)
Disclosed herein are new heterocyclic compounds of Formula IIa: and compositions thereof, and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.
Tuning the solubility of hepta(p-benzamide)s via the monomer sequence
Seyler, Helga,Kilbinger, Andreas
supporting information, p. 753 - 756 (2013/03/13)
The automated synthesis of hepta(p-benzamide) heterosequences on solid support using a modified peptide synthesizer is reported. The oligomers are synthesized from 4-aminobenzoic acid and 4-amino-2-(hexyloxy)benzoic acid, the latter carrying a solubilizing hexyl side chain. It is known from previous studies that both the unsubstituted hepta(p-benzamide) and the fully hexyloxy-substituted hepta(p-benzamide) are insoluble in all common organic solvents. Heterosequences in which both types of monomers alternate are, however, soluble in polar organic solvents such as DMSO. The heterosequence heptamers behave as strong organogelators when DMSO solutions are left at room temperature for several hours. Transmission electron microscopic (TEM) investigations revealed that the gelation was due to the oligomers forming long entangled fibers via a non-covalent aggregation mechanism. We explain these phenomena by a heterosequence triggered switch of aggregation mechanism. The unsubstituted oligomers strongly aggregate via a directional hydrogen-bond driven mechanism which changes to a less directional π-interaction driven aggregation mechanism for the substituted oligomers. We hereby demonstrate that designed heterosequences in non-natural oligoamides can lead to materials with distinctly different conformations which directly affect the intermolecular interactions and their supramolecular organization.
