Nakajima, Yutaka;Aoyama, Naohiro;Takahashi, Fumie;Sasaki, Hiroshi;Hatanaka, Keiko;Moritomo, Ayako;Inami, Masamichi;Ito, Misato;Nakamura, Koji;Nakamori, Fumihiro;Inoue, Takayuki;Shirakami, Shohei published 《Design, synthesis, and evaluation of 4,6-diaminonicotinamide derivatives as novel and potent immunomodulators targeting JAK3》. The research results were published in《Bioorganic & Medicinal Chemistry》 in 2016.Category: amides-buliding-blocks The article conveys some information:
In organ transplantation, T cell-mediated immune responses play a key role in the rejection of allografts. Janus kinase 3 (JAK3) is specifically expressed in hematopoietic cells and associated with regulation of T cell development via interleukin-2 signaling pathway. Here, we designed novel 4,6-diaminonicotinamide derivatives as immunomodulators targeting JAK3 for prevention of transplant rejection. Our optimization of C4- and C6-substituents and docking calculations to JAK3 protein confirmed that the 4,6-diaminonicotinamide scaffold resulted in potent inhibition of JAK3. We also investigated avoidance of human ether-a-go-go related gene (hERG) inhibitory activity. Selected compound 28 in combination with tacrolimus prevented allograft rejection in a rat heterotopic cardiac transplantation model. To complete the study, the researchers used 6-Aminonicotinamide (cas: 329-89-5) .
6-Aminonicotinamide (cas:329-89-5)Category: amides-buliding-blocks is a well-established inhibitor of the NADP+-dependent enzyme, 6-phosphogluconate dehydrogenase (Ki = 0.46 μM). 6-Aminonicotinamide also reduces cardiovascular oxidative injury following ischemia/reperfusion.
Reference:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics