The Synthesis of 1,3,5‐triazine Derivatives and JNJ7777120 Analogues with Histamine H 4 Receptor Affinity and Their Interaction with PTEN Promoter

The involvement of histamine and H 4 receptor (H 4 R) in cancer has been investigated recently using the H 4 R agonists and antagonists. The scope of the research project was synthesis and exploration of the consequences of a group of compounds with histamine H 4 receptor (H 4 R) affinity on the promoter of PTEN gene encoding the antitumor PTEN protein. The series of novel compounds based either on H 4 R antagonists JNJ 7777120 structure or 1,3,5‐triazine scaffold were synthesized, evaluated for histamine H 4 R affinity and used in this study. Compounds 5 and 7 belonging to the group of JNJ 7777120 analogues showed the highest interaction with the promoter of PTEN gene and weak affinity against H 4 R with K i value >100 μ m . These compounds showed no significant effect on neuroblastoma IMR ‐32 cells viability indicating no correlation between PTEN gene promoter affinity and antitumor activity. Compound 6 , another JNJ 7777120 analogue, showed the highest effect on IMR ‐32 viability with calculated IC 50 = 23.27 μ m . The 1,3,5‐triazine derivatives exhibited generally low or medium interaction with PTEN gene promoter. However, the 1,3,5‐triazine derivative 11 with the para ‐bromo substituent showed the highest affinity against H 4 R with K i value of 520 n m and may be considered as a new lead structure.