title: MCR synthesis of a tetracyclic tetrazole scaffold.
abstract: Scaffold diversity is key in the ongoing exercise of discovery of novel bioactive compounds using high throughput screening (HTS). Based on the Ugi tetrazole synthesis we have designed novel bi- and tri-cyclic scaffolds featuring interesting pharmacophore properties. The compounds of the scaffold (B) are synthesizable in large diversity and numbers in two steps using (hetero)phenylethylamines, HN3, oxo components and iscyanoacetaldehyde(dimethylacetale). The chemistry is amenable to parallel synthesis and is used to enhance and fill the screening decks of the European Lead factory (ELF). Here, we are reporting full experimental details, scope and limitations of the reaction, cheminformatic analysis and the 3D structures of selected compounds.
authors: Department of Drug Design, University of Groningen, A. Deusinglaan 1, Groningen 9700 AD, The Netherlands.
authors: Pravin
authors: P
authors: Patil
authors: Carmolex Inc., Pittsburgh, USA.
authors: Kareem
authors: K
authors: Khoury
authors: Technische Universität München, Germany.
authors: Eberhardt
authors: E
authors: Herdtweck
authors: Department of Drug Design, University of Groningen, A. Deusinglaan 1, Groningen 9700 AD, The Netherlands. Electronic address: a.s.s.domling@rug.nl.
authors: Alexander
authors: A
authors: Dömling
mesh_terms: D055808:Drug Discovery; D008958:Models, Molecular; D015394:Molecular Structure; D011083:Polycyclic Compounds / Q000138:chemical synthesis*; D013777:Tetrazoles / Q000138:chemical synthesis*
chemical_list: D011083:Polycyclic Compounds; D013777:Tetrazoles
keywords: Isocyanide; Parallel; Pictet–Spengler; Synthesis; Tetrazol; Ugi
references: Nature. 2011 Feb 10;470(7333):163-5
references: 21307913
references: J Org Chem. 2014 Sep 5;79(17):8481-5
references: 25140810
references: J Comb Chem. 2010 Jan-Feb;12(1):168-75
references: 19961214
references: J Chem Inf Model. 2014 Jun 23;54(6):1617-22
references: 24846291
references: Org Lett. 2014 Aug 1;16(15):4028-31
references: 25054213
references: Org Biomol Chem. 2013 Aug 7;11(29):4792-6
references: 23760036
references: ACS Comb Sci. 2014 Aug 11;16(8):393-6
references: 24983416
references: J Org Chem. 2011 Jan 21;76(2):637-44
references: 21190371
references: Chem Biol Drug Des. 2012 Apr;79(4):470-7
references: 22151001
references: Chem Rev. 2006 Jan;106(1):17-89
references: 16402771
references: ACS Comb Sci. 2012 Mar 12;14(3):160-3
references: 22330239
references: Nat Methods. 2012 Nov;9(11):1069-76
references: 23132118
references: Angew Chem Int Ed Engl. 2012 Oct 8;51(41):10280-3
references: 22968839
references: Nat Rev Drug Discov. 2013 Mar;12(3):173-5
references: 23449292
references: J Chem Inf Comput Sci. 2003 May-Jun;43(3):987-1003
references: 12767158
references: Chem Rev. 2012 Jun 13;112(6):3083-135
references: 22435608
references: J Org Chem. 2009 Sep 4;74(17):6895-8
references: 19663394
references: ACS Comb Sci. 2011 Mar 14;13(2):166-74
references: 21332123
references: J Med Chem. 2002 Jun 6;45(12):2615-23
references: 12036371
references: Nat Commun. 2010 Sep 21;1:80
references: 20865796
references: J Comput Aided Mol Des. 1995 Jun;9(3):251-68
references: 7561977
references: J Org Chem. 2014 Aug 15;79(16):7380-90
references: 25046801
references: Org Lett. 2012 Dec 7;14(23):5916-9
references: 23157402
references: PLoS One. 2012;7(3):e32839
references: 22427896
references: Chem Commun (Camb). 2010 Feb 7;46(5):770-2
references: 20087515
references: Chemistry. 2013 Jun 17;19(25):8048-52
references: 23649922
references: Org Lett. 2013 Feb 1;15(3):639-41
references: 23331054
references: Comb Chem High Throughput Screen. 2001 Feb;4(1):1-34
references: 11281825
references: Org Biomol Chem. 2013 Sep 28;11(36):6036-46
references: 23912086
references: Chemistry. 2010 Nov 2;16(41):12296-8
references: 20845417
references: Org Lett. 2003 Apr 3;5(7):1047-50
references: 12659570
references: Tetrahedron Lett. 2013 Aug 14;54(33):4467-4470
references: 23997316
references: Org Lett. 2014 Sep 5;16(17):4618-21
references: 25147957
references: Tetrahedron Lett. 2012 Mar 14;53(11):1313-1315
references: 22368307