1-Alkyl-3-amino-5-aryl-1H-[1,2,4]triazoles: novel synthesis via cyclization of N-acyl-S-methylisothioureas with alkylhydrazines and their potent corticotropin-releasing factor-1 (CRF(1)) receptor antagonist activities

Bioorg Med Chem Lett. 2001 Dec 17;11(24):3165-8. doi: 10.1016/s0960-894x(01)00657-6.


Cyclizations of alkylhydrazines with N-acyl-S-methylisothioureas, readily synthesized from acyl chlorides, sodium thioisocyanate, dialkylamines then methyl iodide in a one-pot reaction, gave 1-alkyl-3-dialkylamino-5-phenyltriazoles 7 as major products. The regioisomers were assigned through the use of NOE NMR experiments. While bearing a N-bis(cyclopropyl)methyl-N-propylamino group, this series of compounds shows very good binding affinity on the human CRF(1) receptor. Among them, 1-methyl-3-[N-bis(cyclopropyl)methyl-N-propylamino]-5-(2,4-dichlorophenyl)-1H-[1,2,4]triazole 7a had the best binding affinity for the CRF(1) receptor (K(i)=9 nM).

MeSH terms

  • Humans
  • Hydrazines / chemistry*
  • Magnetic Resonance Spectroscopy
  • Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors*
  • Thiourea / chemistry*
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry
  • Triazoles / pharmacology*


  • Hydrazines
  • Receptors, Corticotropin-Releasing Hormone
  • Triazoles
  • CRF receptor type 1
  • Thiourea