Synthesis of spiropiperidine lactam acetyl-CoA carboxylase inhibitors

Journal of Organic Chemistry

Volumn 77, Issue 22, 2012, Pages 10050-10057

  Huard, Kim ^a   Bagley, Scott W ^a   Menhaji Klotz, Elnaz ^a   Préville, Cathy ^a   Southers, James A ^a   Smith, Aaron C ^a   Edmonds, David J ^a   Lucas, John C ^a   Dunn, Matthew F ^a   Allanson, Nigel M ^b   Blaney, Emma L ^b   Garcia Irizarry, Carmen N ^a   Kohrt, Jeffrey T ^a   Griffith, David A ^a   Dow, Robert L ^a  

^a PFIZER INC   (United States)

^b CXR Biosciences Ltd   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYL-COA CARBOXYLASE; AMIDATION; BENZYLIC; CYCLIC CARBOXYLATES; FLOW CONDITION; PYRAZOLES; REGIO-SELECTIVE; SPIROPIPERIDINE; SYNTHETIC STRATEGIES;

CHEMISTRY; ORGANIC COMPOUNDS;

CARBOXYLATION;

( 3 BROMO 1 TERT BUTYL 1H PYRAZOL 4 YL)METHANOL; ( 5 BROMO 1 ISOPROPYL 1H PYRAZOL 4 YL)METHANOL; 1 ( 1H INDAZOL 5 CARBONYL) 1' ISOPROPYL 4',6' DIHYDROSPIRO[PIPERIDINE 4,5' PYRAZOLO[3,4 C]PYRIDIN] 7' (1'H) ONE; 1 TERT BUTYL 4 ETHYL 4 ( 1 (CARBONYL)PIPERIDIN 4 CARBPNYL)PIPERIDINE 1,4 DICARBOXYLIC ACID; 1 TERT BUTYL 4 ETHYL 4 (( 3 BROMO 1 TERT BUTYL 1H PYRAZOL 4 YL)METHYL)PIPERIDINE 1,4 DICARBOXYLIC ACID; 2' (TERT BUTYL) 1 ( 1H INDAZOL 5 CARBONYL) 4',6' DIHYDROSPIRO[PIPERIDINE 4,5' PYRAZOLO[3,4 C]PYRIDIN] 7' (2'H) ONE; 3 BROMO 1 TERT BUTYL 1H PYRAZOLE 4 CARBOXYLIC ACID; 3 BROMO 1 TERT BUTYL 4 (CHLOROMETHYL) 1H PYRAZOLE; 3 BROMO 1 TERT BUTYL 4 (IODOMETHYL) 1H PYRAZOLE; 4 (( 3 BROMO 1 TERT BUTYL 1H PYRAZOL 4 YL)METHYL) 1 (TERT BUTOXYCARBONYL)PIPERIDINE 4 CARBOXYLIC ACID; 4 (( 5 BROMO 1 ISOPROPYL 1H PYRAZOL 4 YL)METHYL) 1 (TERT BUTOXYCARBONYL)PIPERIDINE 4 CARBOXYLIC ACID; 5 BROMO 1 ISOPROPYL 4 (CHLOROPMETHYL) 1H PYRAZOLE; 5 BROMO 1 ISOPROPYL 4 (IODOMETHYL) 1H PYRAZOLE; ACETYL COENZYME A CARBOXYLASE INHIBITOR; AMINE; CARBOXYLIC ACID DERIVATIVE; ETHYL 3 BROMO 1H PYRAZOLE 4 CARBOXYLIC ACID; ETHYL 5 AMINO 1 ISOPROPYL 1H PYRAZOLE 4 CARBOXYLIC ACID; ETHYL 5 BROMO 1 ISOPROPYL 1H PYRAZOLE 4 CARBOXYLIC ACID; ISOCYANATE; LACTAM; LACTAM DERIVATIVE; LIGASE INHIBITOR; N 2 TERT BUTYLPYRAZOLE; PYRAZOLE; PYRAZOLE DERIVATIVE; PYRIDINE DERIVATIVE; TERT BUTYL 4 (( 3 BROMO 1 TERT BUTYL 1H PYRAZOL 4 YL)METHYL 4 ISOCYANATOPIPERIDINE 1 CARBOXYLIC ACID; TERT BUTYL 4 (( 3 BROMO 1 TERT BUTYL 1H PYRAZOL 4 YL)METHYL) 4 ISOCYANATOPIPERIDINE 1 CARBOXYLIC ACID; TERT BUTYL 4 (( 5 BROMO 1 ISOPROPYL 1H PYRAZOL 4 YL)METHYL) 4 ISOCYANATOPIPERIDINE 1 CARBOXYLIC ACID; UNCLASSIFIED DRUG;

ALKYLATION; AMIDATION; ARTICLE; COLUMN CHROMATOGRAPHY; CONTROLLED STUDY; CRYSTAL STRUCTURE; CURTIUS REARRANGEMENT; CYCLIZATION; DRUG POTENCY; DRUG SYNTHESIS; FLOW KINETICS; IC 50; IN VITRO STUDY; MOLECULAR STABILITY; STEREOCHEMISTRY;

ACETYL-COA CARBOXYLASE; ALKYLATION; CYCLIZATION; LACTAMS; MOLECULAR STRUCTURE; PIPERIDINES; PYRAZOLES; PYRIDONES; STEREOISOMERISM;

EID: 84869186272     PISSN: 00223263     EISSN: 15206904     Source Type: Journal    
DOI: 10.1021/jo3014808     Document Type: Article

References (21)

1. Savage, D. B.; Petersen, K. F.; Shulman, G. I. Physiol. Rev. 2007, 87, 507-520
2. Tong, L.; Harwood, H. J., Jr. J. Cell. Biochem. 2006, 99, 1476-1488
3. Freeman-Cook, K. D.; Amor, P.; Bader, S.; Buzon, L. M.; Coffey, S. B.; Corbett, J. W.; Dirico, K. J.; Doran, S. D.; Elliott, R. L.; Esler, W.; Guzman-Perez, A.; Henegar, K. E.; Houser, J. A.; Jones, C. S.; Limberakis, C.; Loomis, K.; McPherson, K.; Murdande, S.; Nelson, K. L.; Phillion, D.; Pierce, B. S.; Song, W.; Sugarman, E.; Tapley, S.; Tu, M.; Zhao, Z. J. Med. Chem. 2012, 55, 935-942
4. Bagley, S. W.; Southers, J. A.; Cabral, S.; Rose, C. R.; Bernhardson, D. J.; Edmonds, D. J.; Polivkova, J.; Yang, X.; Kung, D. W.; Griffith, D. A.; Bader, S. J. J. Org. Chem. 2012, 77, 1497-1506
5. Limberakis, C.; Li, J.; Balan, G.; Griffith, D. A.; Kung, D. W.; Rose, C.; Vrieze, D. Tetrahedron Lett. 2012, 53, 2543-2547
6. For examples of aminal ACC inhibitors, see: Anderson, R.; Breazeale, S.; Elich, T.; Lee, S.-F. Modulators of acetyl-coenzyme A carboxylase and methods of use thereof. US20100009982, 2010.
7. Jahangir; Fisher, L. E.; Clark, R. D.; Muchowski, J. M. J. Org. Chem. 1989, 54, 2992-2996
8. Stoyanova, M. P.; Angelova, S. E.; Petrov, P. Y.; Nikolova, R. P.; Shivachev, B. L. ARKIVOC 2010, ii, 303-314
9. Stanetty, P.; Sigl, B.; Schnurch, M.; Mihovilovic, M. D. Acta Chim. Slov. 2009, 56, 513-520
10. Kralj, A.; Wetzel, A.; Mahmoudian, S.; Stamminger, T.; Tschammer, N.; Heinrich, M. R. Bioorg. Med. Chem. Lett. 2011, 21, 5446-5450
11. Knapp, S.; Levorse, A. T. J. Org. Chem. 1988, 53, 4006-4014
12. Widenhoefer, R. A.; Han, X. Eur. J. Org. Chem. 2006, 2006, 4555-4563
13. Wardrop, D. J.; Bowen, E. G.; Forslund, R. E.; Sussman, A. D.; Weerasekera, S. L. J. Am. Chem. Soc. 2010, 132, 1188-1189
14. Hamzik, P. J.; Brubaker, J. D. Org. Lett. 2010, 12, 1116-1119
15. Quin, C.; Trnka, J.; Hay, A.; Murphy, M. P.; Hartley, R. C. Tetrahedron 2009, 65, 8154-8160
16. Moreau, A.; Couture, A.; Deniau, E.; Grandclaudon, P.; Lebrun, S. Org. Biomol. Chem. 2005, 3, 2305-2309
17. Gonzalez-Temprano, I.; Osante, I.; Lete, E.; Sotomayor, N. J. Org. Chem. 2004, 69, 3875-3885
18. Michelotti, E. L.; Kelly, M.; Moffett, K.; Nguyen, D. Preparation of urea derivatives as inhibitors of MAP kinases. WO10019930, 2010.
19. Baumann, M.; Baxendale, I. R.; Ley, S. V.; Nikbin, N.; Smith, C. D.; Tierney, J. P. Org. Biomol. Chem. 2008, 6, 1577-1586
20. Bagley, S. W.; Dow, R. L.; Griffith, D. A.; Smith, A. C. N1/N2-Lactam Acetyl-CoA Carboxylase Inhibitors. WO12056372, 2012.
21. Burgess, J. L.; Johnson, N.; Knight, S. D.; Lafrance, L.; Miller, W. H. Azaindazoles. WO12005805, 2012.