TMCA　(3,4,5-trimethoxycinnamic　acid)　ester　and　amide　are　privileged　structural　scaffolds　in　drug　discovery　which　are　widely　distributed　in　natural　products　and　consequently　produced　diverse　therapeutically　relevant　pharmacological　functions.　Owing　to　the　potential　of　TMCA　ester　and　amide　analogues　as　therapeutic　agents,　researches　on　chemical　syntheses　and　modifications　have　been　carried　out　to　drug-like　candidates　with　broad　range　of　medicinal　properties　such　as　antitumor,　antiviral,　CNS　(central　nervous　system)　agents,　antimicrobial,　anti-inflammatory　and　hematologic　agents　for　a　long　time.　At　the　same　time,　SAR　(structure-activity　relationship)　studies　have　draw　greater　attention　among　medicinal　chemists,　and　many　of　the　lead　compounds　were　derived　for　various　disease　targets.　However,　there　is　an　urgent　need　for　the　medicinal　chemists　to　further　exploit　the　precursor　in　developing　chemical　entities　with　promising　bioactivity　and　druggability.　This　review　concisely　summarizes　the　synthesis　and　biological　activity　for　TMCA　ester　and　amide　analogues.　It　also　comprehensively　reveals　the　relationship　of　significant　biological　activities　along　with　SAR　studies.　(C)　2019　Elsevier　Masson　SAS.　All　rights　reserved.