In　order　to　reduce　the　high　failure　rate　of　drug　development　caused　by　the　poor　drug-like　properties　of　candidate　compounds,　it　is　helpful　to　improving　the　limitation　of　the　descriptors　in　CoMFA　table.　By　calculating　the　descriptors　of　70　novobiocin　compounds,　6122　descriptors　of　per　compound　were　obtained,　while　only　4　critical　descriptors　after　screening　were　remained.　Then　by　adding　the　screened　descriptors　into　standard　CoMFA　models,　the　best　modified　model　was　obtained　by　adding　descriptor　POS_05_-O-　and　PSA　simultaneously.　The　modified　model　exhibit　satisfying　results　with　higher　Q2,　Rncv2,　Rpre2　than　that　of　the　standard　CoMFA.　Moreover,　the　contour　maps　suggest　the　improvement　for　compounds,　and　also　verifies　the　reliability　of　the　model.　By　analyzing　the　distribution　of　the　descriptor　POS_05_-O-　and　PSA　in　70　compounds,　the　results　show　that　there　are　20　compounds　containing　the　descriptor　POS_05_-O-　and　with　PSA　from　90　to　110,　which　is　90%　of　the　active　compounds.　This　indicates　that　the　two　descriptors　are　indeed　significant　for　improving　compounds　activities　and　bioavailability.　©　2017,　Editorial　Department　of　Journal　of　Beijing　University　of　Technology.　All　right　reserved.