Synthesis and antiviral activities of N-mono- and/or N,N'-di-carbamoyl and acyl derivatives of symmetrical diamines.

N-carbamoyl and N-acyl diamine derivatives were synthesized from symmetrical diamines by their addition to iso(thio)cyanates, cleavage reaction of acid anhydride, or N-acylation by acyl chloride. (1R,2R)-1,2-Diaminocyclohexane [(1R,2R)-1], meso-1,2-diaminocyclohexane (meso-1), (1R,2R)-1,2-diphenylethylenediamine [(1R,2R)-3], or meso-1,2-diphenylethylenediamine (meso-3) were used as the starting symmetrical diamines. The target compounds synthesized herein were evaluated for antiviral activity with herpes simplex virus type 1 (HSV-1). A few derivatives of 1,2-diaminocyclohexane [(1R,2R)-7aa and cis-7b] with adamantyl group(s) showed significant antiviral activity (EC(50)=16.0, 27.0 microg/ml).

[1]  B. Hammock,et al.  1,3-disubstituted ureas functionalized with ether groups are potent inhibitors of the soluble epoxide hydrolase with improved pharmacokinetic properties. , 2007, Journal of medicinal chemistry.

[2]  K. Yokomizo,et al.  N-monocarbamoyl derivatives of symmetrical diamines with antiviral activity. , 2007, Chemical & pharmaceutical bulletin.

[3]  M. Uyeda,et al.  N-long-chain monoacylated derivatives of 2,6-diaminopyridine with antiviral activity. , 2007, Chemical & pharmaceutical bulletin.

[4]  E. De Clercq,et al.  Synthesis, conformational characteristics and anti-influenza virus A activity of some 2-adamantylsubstituted azacycles. , 2006, Bioorganic chemistry.

[5]  I. S. Morozov,et al.  MOLECULAR-BIOLOGICAL PROBLEMS OF DRUG DESIGN AND MECHANISM OF DRUG ACTION ADAMANTANE DERIVATIVES : PHARMACOLOGICAL AND TOXICOLOGICAL PROPERTIES ( REVIEW ) , 2006 .

[6]  R. J. Herr,et al.  A Convenient Method for the Preparation of Primary and Symmetrical N,N′-Disubstituted Thioureas , 2000 .

[7]  M. Salakhov,et al.  Acylation of o‐Phenylenediamine with 4‐Cyclohexene‐1,2‐dicarboxylic Anhydride. , 2010 .

[8]  M. Haffey,et al.  Selective activity and cellular pharmacology of (1R-1 alpha,2 beta,3 alpha)-9-[2,3-bis(hydroxymethyl)cyclobutyl]guanine in herpesvirus-infected cells. , 1991, Molecular pharmacology.

[9]  S. A. Metwally,et al.  Pyrazine Heterocycles from 2,3‐Pyrazinedicarboxylic Anhydride , 1991 .

[10]  R. Schinazi,et al.  Effect of combinations of acyclovir with vidarabine or its 5'-monophosphate on herpes simplex viruses in cell culture and in mice , 1982, Antimicrobial Agents and Chemotherapy.

[11]  H. Stetter,et al.  Über Verbindungen mit Urotropin‐Struktur, XXIV1) Derivate des 1‐Amino‐adamantans , 1962 .