82378-91-4Relevant academic research and scientific papers
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.
Alleviating CYP and hERG liabilities by structure optimization of dihydrofuran-fused tricyclic benzo[d]imidazole series – Potent, selective and orally efficacious microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors: Part-2
Muthukaman, Nagarajan,Deshmukh, Sanjay,Tambe, Macchindra,Pisal, Dnyandeo,Tondlekar, Shital,Shaikh, Mahamadhanif,Sarode, Neelam,Kattige, Vidya G.,Sawant, Pooja,Pisat, Monali,Karande, Vikas,Honnegowda, Srinivasa,Kulkarni, Abhay,Behera, Dayanidhi,Jadhav, Satyawan B.,Sangana, Ramchandra R.,Gudi, Girish S.,Khairatkar-Joshi, Neelima,Gharat, Laxmikant A.
supporting information, p. 1211 - 1218 (2018/03/12)
In an effort to identify CYP and hERG clean mPGES-1 inhibitors from the dihydrofuran-fused tricyclic benzo[d]imidazole series lead 7, an extensive structure-activity relationship (SAR) studies were performed. Optimization of A, D and E-rings in 7 afforded many potent compounds with human whole blood potency in the range of 160–950 nM. Selected inhibitors 21d, 21j, 21m, 21n, 21p and 22b provided selectivity against COX-enzymes and mPGES-1 isoforms (mPGES-2 and cPGES) along with sufficient selectivity against prostanoid synthases. Most of the tested analogs demonstrated required metabolic stability in liver microsomes, low hERG and CYP liability. Oral pharmacokinetics and bioavailability of lead compounds 21j, 21m and 21p are discussed in multiple species like rat, guinea pig, dog, and cynomolgus monkey. Besides, these compounds revealed low to moderate activity against human pregnane X receptor (hPXR). The selected lead 21j further demonstrated in vivo efficacy in acute hyperalgesia (ED50: 39.6 mg/kg) and MIA-induced osteoarthritic pain models (ED50: 106 mg/kg).
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.
HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
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Paragraph 0235; 0339; 0340, (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.
4,5-Diamino-3-Halo-2-Hydroxybenzoic Acid Derivatives and Preparations Thereof
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Page/Page column 10; 11, (2012/05/04)
Disclosed are 4,5-diamino-3-halo-2-hydroxybenzoic acid derivatives and manufactures thereof. The 4,5-diamino-3-halo-2-hydroxybenzoic acid derivatives are presented by formula (I): wherein R1 group is H, CH3, or C2H5; R2 group is H, or Br; R3 group is CH3, or C3H7; and R4 group is H, or C(═NH)—NH2. 4,5-diamino-3-halo-2-hydroxybenzoic acid derivatives provided here were non-toxic to MDCK cells, particularly compounds 6a, 6b, 6c, 6e, 6f, 7a, 7b and 8 had better anti-H1N1 activity. In the future, these compounds can be used to focus on viral neuraminidases as targets to develop effective anti-influenza drugs.
