Design, synthesis, and toward a side-ring optimization of tricyclic thieno[2,3-d]pyrimidin-4(3H)-ones and their effect on melanin synthesis in murine B16 cells

Abstract

Herein, we report the synthesis of 48 novel 3-sulfonylamides containing a tricyclic thieno[2,3-d]pyrimidin-4(3H)-one moiety, and their influence on melanin synthesis in murine B16 cells. All target sulfonylamides were synthesized through key intermediate 3-nitro-thieno[2,3-d]pyrimidin-4(3H)-ones using three types of ipso-nitration reactions. In this case, we converted the pyrido[1,2-a]- fragment of the thieno[2,3-d]pyrimidine moiety to pyrrolo[1,2-a]- and azepino[1,2-a]- side-rings in order to evaluate the bioactivities of the synthesized derivatives for a structure activity-relationships point of view. The obtained results suggest that some of the selected compounds revealed a promising influence on melanin synthesis in murine B16 cells and may serve as lead compounds for further drug discovery and development.

Graphical Abstract

Keywords:

• Thieno[2,3-d]pyrimidin-4(3H)-ones
• sulfonylamides
• ipso-nitration
• melanin synthesis
• murine B16 cells

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was funded by grants from the Chinese Academy of Sciences President’s International Fellowship Initiative (Grant No. 2016PT014) and National Natural Science Foundation of China (NSFC) (Grant No. 21550110495).