Soluble epoxide hydrolase inhibitors: structural features, design strategies, and SAR insights

Several pathological disorders including inflammatory disorders, cardiovascular, metabolic and neurodegenerative disorders have increased at an alarming rate due to our lifestyle changes, pollution, diet and various other reasons. Different classes of Anti-inflammatory and Anti-cancer drugs must be designed and modified to counteract the rapid growth of inflammatory disorders. One such class of drugs is the Soluble Epoxide Hydrolase Inhibitor (sEHI) about which we have articulated in detail in this review work. Soluble Epoxide Hydrolase (sEH) is an enzyme which converts Epoxyeicosatrienoic acids (EET’s) into Dihydroxyeicosatrienoic acids (DHET’s) which are said to possess pro-inflammatory properties. The main aim of sEHI’s is to stop the conversion of EET’s into DHET’s thereby causing an increase in the level of EET’s which have anti-inflammatory properties. In this study, we have provided an insight into the structural and catalytic features of sEHI’s, their pharmacophores and design principles, their scaffold evolution including classes of sEHI’s like Ureas, Amides, Carbamates and other non-urea analogues. We have also discussed about the drug-likeness, ADMET and optimization challenges and lastly medicinal outlooks, future directives and the pre-clinical and clinical trials.