Inventi Rapid: Med Chem

Inventi:prmc/80362/24

Synthesis, Characterisation, Pharmacological Screening, In-Vitro Hydrolysis Studies and Computational ADME Studies of Potential Novel Prodrugs of N-(2,3-Xylyl Anthranillic Acid)

Present work involved synthesis and pharmacological screening of two series of analogs of N-(2,3-xylyl anthranillic acid), a potent non-steroidal anti-inflammatory drug (NSAID) with moderate analgesic activity but associated with gastrointestinal side effects. This was done with an objective of altering the carboxylic acid functional group of this NSAID which is believed to be involved in causing gastric damage by direct contact. The synthesized compounds were characterized using IR, 1H-NMR, ES-MS and elemental analysis. The prototypes of the title compounds were evaluated for analgesic and anti-inflammatory activity and exhibited pronounced analgesic and anti-inflammatory activity when compared with the standard drug N-(2, 3-xylylanthranillic acid). Compounds were found to be devoid of ulcerogenicity at the test dose level. Title compounds also presented significant values of ADME properties studied, obeying Lipinski Rule of five violations, good oral absorption and lipophilicity when subjected to in-silico ADME predictions using QikProp software (Schrödinger, Inc.). Hydrolysis studies revealed that the synthesized compounds were sufficiently stable at pH 1.2, indicating that no appreciable hydrolysis to the free acids might occur in the stomach. The amount of free drug released on hydrolysis in 80% human plasma (pH 7.4) was greater than that released in aqueous buffers, suggesting that the rate of hydrolysis of compounds in 80% human plasma was markedly accelerated compared with that in aqueous buffers....