Novel 2,2-dioxide-4,4-disubstituted-1,3-H-2,1,3-benzothiadiazines as non-nucleoside reverse transcriptase inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 10, Issue 2, 2000, Pages 193-195

  Corbett, Jeffrey W ^a   Gearhart, Lisa A ^a   Ko, Soo S ^a   Rodgers, James D ^a   Cordova, Beverly C ^a   Klabe, Ronald M ^a   Erickson Viitanen, Susan K ^a  

^a DUPONT COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BENZOTHIADIAZINE DERIVATIVE; DELAVIRDINE; EFAVIRENZ; NEVIRAPINE; RNA DIRECTED DNA POLYMERASE INHIBITOR;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ARTICLE; CHEMICAL STRUCTURE; DRUG POTENCY; DRUG SYNTHESIS; STRUCTURE ACTIVITY RELATION;

EID: 0034677061     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(99)00672-1     Document Type: Article

References (15)

1. Levy J.A. Microbiol. Rev. 57:1993;183.
2. Esnouf R., Ran J., Ross C., Jones Y., Stammers D., Stuart D. Nat. Struct. Biol. 2:1995;303.
3. Corbett J.W., Ko S.S., Rodgers J.D., Jeffrey S., Bacheler L.T., Klabe R.M., Diamond S., Lai C.-M., Rabel S.R., Saye J.A., Adams S.P., Trainor G.L., Anderson P.S., Erickson-Viitanen S.K. Antimicrob. Agents Chemother. 12:1999;2893.
4. Tucker, T. J.; Lyle, T. A.; Wiscount, C. M.; Britcher, S. F.; Young, S. D.; Sanders, W. M.; Lumma, W. C.; Goldman, M. E.; O'Brien, J. A.; Ball, R. G.; Homnick, C. F.; Schleif, W. A.; Emini, E. A.; Huff, J. R.; Anderson, P. S. J. Med. Chem. 1994, 37, 2437 and references contained therein.
5. Wright J.B. J. Org. Chem. 30:1965;3960.
6. The 2-amino-5-chlorobenzonitrile used in the preparation of the compounds described herein was obtained from Aldrich Chemical Company. However, there are currently no commercial sources for this chemical. A literature preparation of 2-amino-5-chlorobenzonitrile can be found in: Nickson, T. E.; Roche-Dolson, C. A. A. Synthesis 1985, 669.
7. 4, filtered, concentrated, and purified by flash chromatography.
8. All final products had satisfactory CHN analyses.
9. For the preparation of the ketone, see: Patel, M.; Ko, S. S.; McHugh, R. J.; Markwalder, J. A.; Srivastava, A. S.; Cordova, B. C.; Klabe, R. M.; Erickson-Viitanen, S. K.; Trainor, G. L.; Seitz, S. P. Bioorg. Med. Chem. Lett. 1999, 9, 2805.
10. 3, can be prepared by condensing sulfamide with an o-aminotrifluoromethyl ketone (as exhibited in Fig. 2). See ref 5 for an example of the condensation of sulfamide with an o-aminomethyl ketone to yield a 2,1,3-benzothiadiazine 2,2-dioxide.
11. All compounds were assayed for enzyme inhibitory activity according to the protocol described in ref 3.
12. All compounds were assayed for whole cell based antiviral activity according to the protocol described in: Bacheler, L. T.; Paul, M.; Jadhav, P. K.; Otto, M.; Stone, B.; Miller, J. Antiviral Chem. Chemother. 1994, 5, 111.
13. The biological results are reported as the results from a single assay.
14. The biological activity of the pure enantiomer of the structurally related 2(1H)-quinazolinone ring system is typically one-half that of the racemate. For examples of this phenomena, see ref 3.
15. Data shown represents the mean±standard deviation for 2-6 independent determinations.