Reagent based DOS: a "Click, Click, Cyclize" strategy to probe chemical space.
The synthesis of small organic molecules as probes for discovering new therapeutic agents has been an important aspect of chemical-biology. Herein we report a reagent-based, diversity-oriented synthetic (DOS) strategy to probe chemical and biological space via a "Click, Click, Cyclize" protocol. In this DOS approach, three sulfonamide linchpins underwent cyclization protocols with a variety of reagents to yield a collection of structurally diverse S-heterocycles. In silico analysis is utilized to evaluate the diversity of the compound collection against chemical space (PC analysis), shape space (PMI) and polar surface area (PSA) calculations.
Rolfe
Alan
A
Department of Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, KS 66045-7582, USA.
Lushington
Gerald H
GH
Hanson
Paul R
PR
D003500:Cyclization; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D007202:Indicators and Reagents / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D013449:Sulfonamides / Q000737:chemistry*; D013499:Surface Properties
D006571:Heterocyclic Compounds; D007202:Indicators and Reagents; D013449:Sulfonamides
J Chem Inf Comput Sci. 2003 May-Jun;43(3):987-1003
12767158
Angew Chem Int Ed Engl. 2001 Jun 1;40(11):2004-2021
11433435
Nat Biotechnol. 1996 Nov;14(11):1516-8
9634812
Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):3-26
11259830
Science. 2000 Mar 17;287(5460):1964-9
10720315
Angew Chem Int Ed Engl. 2008;47(15):2808-12
18307176
Org Lett. 2009 Feb 5;11(3):531-4
19115841
Org Lett. 2008 Jun 5;10(11):2223-6
18447383
J Comb Chem. 2009 Jul-Aug;11(4):732-8
19505109
Angew Chem Int Ed Engl. 2008;47(1):48-56
18080276
J Med Chem. 1988 Dec;31(12):2235-46
2848124
J Med Chem. 2000 Feb 10;43(3):369-80
10669564
J Org Chem. 2008 Mar 7;73(5):1752-61
18266382
Org Biomol Chem. 2009 May 21;7(10):2053-62
19421442
European J Org Chem. 2008;(31):5254-5262
19603087
Tetrahedron. 2009 Jun 27;65(26):4992-5000
20161277
J Comb Chem. 2008 Nov-Dec;10(6):753-802
18991466
Curr Opin Chem Biol. 2003 Aug;7(4):511-5
12941427
J Comb Chem. 2007 Nov-Dec;9(6):855-902
17877417
J Med Chem. 1991 Apr;34(4):1356-62
2016710
Bioorg Med Chem Lett. 2007 Sep 1;17(17):4784-90
17616396
Chem Commun (Camb). 2006 Aug 21;(31):3296-8
16883415
Tetrahedron. 2009 Apr 18;65(16):3180-3188
20161276
Org Lett. 2008 Jul 17;10(14):2951-4
18553974
Nat Rev Drug Discov. 2002 Sep;1(9):727-30
12209152
J Med Chem. 2003 May 8;46(10):1811-23
12723945
Angew Chem Int Ed Engl. 2009;48(7):1194-6
19137520
Bioorg Med Chem. 1999 Dec;7(12):2811-22
10658585
J Am Chem Soc. 2001 Jul 11;123(27):6740-1
11439080
Tetrahedron Lett. 2009 Dec 16;50(50):6935-6937
20577568