This study is based on our attempts to further explore the structure-activity relationship (SAR) of VX-148 (3) in an attempt to identify inosine 5 0 -mono-phosphate dehydrogenase (IMPDH) inhibitors superior to mycophenolic acid. A five-point pharmacophore developed using structurally diverse, known IMPDH inhibitors guided further design of novel analogs of 3. Several conventional as well as novel medicinal chemistry strategies were tried. The combined structure-and ligand-based approaches culminated in a few analogs with either retained or slightly higher potency. The compounds which retained the potency were also checked for their ability to inhibit human peripheral blood mononuclear cells proliferation. This study illuminates the stringent structural requirements and strict SAR for IMPDH II inhibition.

New substituted thieno[3,2-c]pyridine derivatives 5 were synthesized by the reaction of 3-bromo-4-chlorothieno[3,2-c]pyridine 1 with cyclic amine 2, which further on Suzuki reaction with boronic acids 4 converted to corresponding 3-arylthieno[3,2-c]pyridine 5. Substituent R has predominant effect on fluorescence properties of thienopyridines. However, the electron donor amine at C has no effect on fluorescence properties of thienopyridines. Graphical Abstract New thieno[3,2-c]pyridine derivatives were synthesized from 3-bromo-4-chlorothieno[3,2-c]pyridine and cyclic amines, which by on Suzuki reaction with boronic acids converted to corresponding 3-arylthieno[3,2-c]pyridine. Substituent R3 has predominant effect on fluorescence properties of thienopyridines. However, the electron donor amine at C4 has no effect on fluorescence properties of thienopyridines.

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4-Hetero-1-yl-2-bromothieno[3,2-c]pyridines 3(a-d) were synthesized by the reaction of 2-bromo-4-chlorothieno[3,2-c]pyridine (1) and cyclic amine 2(a-d), which on Suzuki coupling with substituted boronic acids 4(a-f) exclusively converted to corresponding 4-hetero -1-yl-2-arylthieno[3,2-c]pyridine 5(a-x) in good yields. The effect of donor-acceptor substituent on absorption emission properties and fluorescent quantum yield of new thienopyridine derivatives 5(a-x) were studied.

The KF, sucrose (table sugar) exploited as quenching system in solution phase parallel synthesis. Excess of electrophiles were covalently trapped with hydroxyl functionality of sucrose and due to polar nature of sucrose derivative was solubilize in water. Potassium fluoride used to convert various excess electrophilic reagents such as acid chlorides, sulfonyl chlorides, isocyanates to corresponding fluorides, which are less susceptible for hydrolysis and subsequently sucrose traps these fluorides and dissolves them in water thus removing them from reaction mixture. Various excess electrophilic reagents such as acid chlorides, sulfonyl chlorides, and isocyanates were quenched successfully to give pure products in excellent yields.