N‐[ω‐(Purin‐6‐yl)aminoalkanoyl] Derivatives of Chiral Heterocyclic Amines as Promising Anti‐Herpesvirus Agents

Abstract

Novel conjugates of 2‐aminopurine and purine containing fragments of chiral heterocyclic amines attached at position 6 of purine core via a linker, fragment of omega‐amino acid, have been synthesized and evaluated in vitro for their anti‐herpetic activity in the Vero E6 cells; as a result, a new group of compounds possessing high inhibitory activity against herpes simplex virus type 1, including acyclovir‐resistant (TK–) strain has been revealed. The anti‐herpetic activity of the synthesized compounds is substantially dependent on the stereo configuration of the fragment of heterocyclic amine.

Synthesis of Pyrimidine Conjugates with 4-(6-Amino-hexanoyl)-7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine and Evaluation of Their Antiviral Activity

“…Compounds containing a linker fragment with n ≥ 5 are of the greatest interest in terms of anti-herpesvirus activity. The most active compound turned out to be a purine conjugate with (S)-7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine attached via a 6-aminohexanoyl residue (n = 5, compound (S)-1) [27][28][29].…”

“…We have demonstrated that it is the combination of difluorobenzoxazine and purine fragments in one molecule that leads to high anti-herpesvirus activity, including that against the acyclovir-resistant HSV-1 strain [27]. In recent years, our efforts have been focused on the search for efficient antiviral agents among purine and 2-aminopurine derivatives.…”

“…In recent years, our efforts have been focused on the search for efficient antiviral agents among purine and 2-aminopurine derivatives. For this purpose, we synthesized a number of conjugates of purine and 2-aminopurine with various N-heterocycles, including chiral ones, which are attached via a linker, the omega-aminocarboxylic acid NH(CH 2 ) n CO residue, to position 6 of the purine nucleus (Figure 2) [22][23][24][25][26][27][28][29][30][31]. During our investigations, we varied the structure of the heterocycle (including the configuration of the chiral center in the case of chiral compounds), the length of the polymethylene chain of the linker, and the substituent at the N 9 atom of purine.…”

“…Compounds containing a linker fragment with n ≥ 5 are of the greatest interest in terms of anti-herpesvirus activity. The most active compound turned out to be a purine conjugate with (S)-7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine attached via a 6-aminohexanoyl residue (n = 5, compound (S)-1) [27][28][29]. We have demonstrated that it is the combination of difluorobenzoxazine and purine fragments in one molecule that leads to high anti-herpesvirus activity, including that against the acyclovir-resistant HSV-1 strain [27].…”

Stereochemical aspects in the synthesis of novel N-(purin-6-yl)dipeptides as potential antimycobacterial agents

“…The synthesis of purine conjugates with natural amino acids is one of the promising directions in search for novel efficient therapeutic agents. These compounds are known to be highly active against herpes viruses (Beauchamp et al 1992 ; Krasnov et al 2019 ), HIV (McGuigan et al 2005 , 2006 ), hepatitis C (McGuigan et al 2010 ; Chang et al 2011 ; Al-Harbi and Abdel-Rahman 2012 ), and influenza viruses (Pautus et al 2013 ). It was also reported about purinyl amino acids exhibiting antitumor (Ward et al 1961 ), antimycobacterial (Voynikov et al 2014 ; Stavrakov et.…”