2-Pyridinylpiperazine Carboxamide Class and Related TRPV1 Antagonists

Vanilloid Receptor TRPV1 in Drug Discovery: Targeting Pain and Other Pathological Disorders

Volumn , Issue , 2010, Pages 311-324

  Hawryluk, Natalie A ^a   Carruthers, Nicholas I ^a  

^a JOHNSON AND JOHNSON PHARMACEUTICAL RESEARCH AND DEVELOPMENT   (United States)

Author keywords

2 pyridinylpiperazine carboxamides one of the first classes of high affinity TRPV1 antagonists; 2 pyridinylpiperazine carboxamide CL; Progression of piperazine core structures to amino quinazolines

Indexed keywords

EID: 84889354272     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9780470588284.ch12     Document Type: Chapter

References (36)

1. Allison BD, Branstetter BJ, Breitenbucher JG, Hack MD, Hawryluk NA, Lebsack AD, McClure KJ, and Merit JE (2007) Preparation of 6,7,8,9 - tetrahydro - 5H - pyrimidoazepines as TRPV1 receptor modulators. WO Patent 2007109355 - A2.
2. Bakthavatchalam R (2002) Preparation of diarylpiperazines as capsaicin receptor ligands. WO Patent 008221 - A2.
3. Bakthavatchalam R, Blum CA, Brielmann H, Caldwell TM, Cortright DN, Hodgetts KJ, Peterson JM, and Zheng X (2006) Preparation of quinazolinamines and analogs as capsaicin receptor agonists. U.S. Patent 194805 - A1.
4. Bakthavatchalam R, Caldwell TM, Chenard BL, Hodgetts KJ, and Capitosti SM (2006) Preparation of substituted biaryl quinolin - 4 - ylamine analogues as capsaicin receptor modulators. WO Patent 042289 - A2.
5. Bakthavatchalam R, Chenard BL, Peterson JM, and Steenstra CK (2005) Preparation of arylalkylamino - substituted quinazolines as type VR1 capsaicin receptor modulators. WO Patent 087227 - A1.
6. Bakthavatchalam R, Blum CA, Brielmann H, Caldwell TM, Cortright DN, Hodgetts KJ, Peterson JM, and Zheng X (2005) Preparation of benzoimidazole, quinazoline and related N - based heterocyclic analogs as capsaicin receptor agonists. WO Patent 042498 - A2.
7. Bakthavatchalam R, Blum CA, and Chenard BL (2005) Substituted bicyclic quinazolin - 4 - ylamine derivatives as capsaicin receptor modulators. WO Patent 023807 - A2.
8. Bakthavatchalam R, Caldwell TM, Chenard BL, De Lombaert S, and Hodgetts KJ (2005) Preparation of substituted quinoline and naphthyridine amines as capsaicin receptor modulators. WO Patent 007652 - A2.
9. Bakthavatchalam R, Blum CA, Brielmann H, Caldwell TM, De Lombaert S, Hodgetts KJ, and Zheng X (2004) Preparation of carboxylic acid, phosphate, or phosphonate substituted (quinazolin - 4 - yl)amines as capsaicin receptor modulators. WO Patent 055004 - A1.
10. Bakthavatchalam R, Blum CA, Brielmann H, Caldwell TM, De Lombaert S, Hodgetts KJ, and Zheng X (2004) Preparation of (quinazolin - 4 - yl)amines as capsaicin receptor modulators. WO Patent 055003 - A1.
11. Bayliss T, Brown RE, Burkamp F, Jones AB, and Neduvelil JG (2005) E - Fluoro - 4 - (pyridin - 2 - yl) - piperidine - 1 - carboxamide derivatives and related compounds which modulate the function of the vanilloid - 1 receptor (VR1) for the treatment of pain. WO Patent 2005051390.
12. Behrendt HJ, Germann T, Gillen C, Hatt H, and Jostock R (2004) Characterization of the mouse cold - menthol receptor TRPM8 and vanilloid receptor type - 1 VR1 using a fluorometric imaging plate reader (FLIPR) assay. Br J Pharmacol 141: 737 - 745.
13. Bhattacharya A, Scott BP, Nasser N, Ao H, Maher MP, Dubin AE, Swanson DM, Shankley NP, Wickenden AD, and Chaplan SR (2007) Pharmacology and antitussive efficacy of 4 - (3 - trifluoromethyl - pyridin - 2 - yl) - piperazine - 1 - carboxylic acid (5 - trifluoromethyl - pyridin - 2 - yl) - amide (JNJ 17203212), a transient receptor potential vanilloid 1 antagonist in guinea pigs. J Pharm Exper Ther 323: 665 - 674.
14. Blum CA, Zheng X, Brielman H, Hodgetts KJ, Bakthavatchalam R, Chandrasekhar J, Krause JE, Cortright D, Matson D, Crandall M, Ngo CK, Fung L, Day M, Kershaw M, De Lombaert S, and Chenard BL (2008) Aminoquinazolines as TRPV1 antagonists: modulation of drug - like properties through the exploration of 2 - position substitution. Bioorg Med Chem Lett 18: 4573 - 4577.
15. Branstetter BJ, Breitenbucher JG, Lebsack AD, and Xiao W (2008) Preparation of thiazolopyrimidine derivatives as modulators of TRPV1. U.S. Patent 004253 - A1.
16. Brown BS, Keddy R, Zheng GZ, Schmidt RG, Koenig JR, McDonald HA, Bianchi BR, Honore P, Jarvis MF, Surowy CS, Polakowski JS, Marsh KC, Faltynek CR, and Lee CH (2008) Tetrahydropyridine - 4 - carboxamides as novel, potent transient receptor potential vanilloid 1 (TRPV1) antagonists. Bioorg Med Chem 16: 8516 - 8525.
17. Brown RE, Burkamp F, Doughty VA, Fletcher SR, Hollingworth GJ, Jones BA, and Sparey TJ (2004) Preparation of amino heterocycles as vanilloid receptor (VR1) modulators, in particular antagonists, for treating pain and/or inflammation. WO Patent 074290 - A1.
18. Caldwell TM, Chenard BL, and Hodgetts KJ (2006) Preparation of substituted pyridazinyl - and pyrimidinyl - quinolin - 4 - ylamine analogs for use in capsaicin VR1 receptor binding assays. WO Patent 081388 - A2.
19. Carruthers N (2005) Targeting the brain: successes and pitfalls. Annual One - Day Meeting on Medicinal Chemistry of SRC & KVCV, Namur, Belgium, November 25.
20. Carruthers NI, Shah CR, and Swanson DM (2005) Preparation of pyridyl piperazinyl ureas with VR1 antagonistic activity. WO Patent 014580 - A1.
21. Fletcher CR, McIver E, Lewis S, Burkamp F, Leech C, Mason G, Boyce S, Morrison D, Richards G, Sutton K, and Jones AB (2006) The search for novel TRPV1 - antagonists: from carboxamides to benzimidazoles and indazolones. Bioorg Med Chem Lett 16: 2872 - 2876.
22. Gharat LA and Szallasi A (2008) Advances in the design and therapeutic use of capsaicin receptor TRPV1 agonists and antagonists. Expert Opin Ther Pat 18: 159 - 209.
23. Ghilardi JR, Roehrich H, Lindsay TH, Sevcik MA, Schwei MJ, Kubota K, Halvorson KG, Poblete J, Chaplan SR, Dubin AE, Carruthers NI, Swanson D, Kuskowski M, Flores CM, Julius D, and Mantyh PW (2005) Selective blockade of the capsaicin receptor TRPV1 attenuates bone cancer pain. J Neurosci 25: 3126 - 3131.
24. Kelly MG, Janagani S, Wu G, Kincaid J, Lonergan D, Fang Y, and Wei ZL (2005) Preparation of bicycloheteroarylamines like 2,6 - naphthyridinamines and pyrido[3, 4 - d]pyrimidinamine as ion channel ligands and uses thereof. WO Patent 066171 - A1.
25. Kyle DJ and Sun Q (2003) Preparation of pyridin - 2 - ylpiperazine derivatives for treating pain. WO Patent 2003066595.
26. Lee CH, Brown BS, Keddy RG, Perner RJ, and Koenig JR (2006) Preparation of pyridopyrimidines as antagonists to the vanilloid receptor subtype 1 (VR1). U.S. Patent 062981 - A2.
27. Norman MH, Ognyanov VI, and Pettus LH (2005) Preparation of substituted quinazolines and pyridopyrimidines as vanilloid receptor ligands. U.S. Patent 165032 - A1.
28. Ognyanov VI, Balan C, Bannon AW, Bo Y, Dominguez C, Fotsch C, Gore VK, Klionsky L, Ma VV, Qian YX, Tamir R, Wang X, Xi N, Xu S, Zhu D, Gavva NR, Treanor JJ, and Norman MH (2006) Design of potent, orally available antagonists of the transient receptor potential vanilloid 1. Structure - activity relationships of 2 - piperazin - 1 - yl - 1H - benzimidazoles. J Med Chem 49: 3719 - 3742.
29. Pomonis JD, Harrison JE, Mark L, Bristol DR, Valenzano KJ, and Walker K (2003) N - (4 - Tertiarybutylphenyl) - 4 - (3 - chloropyridin - 2 - yl)tetrahydropyrazine - 1(2H) - carboxamide (BCTC), a novel, orally effective vanilloid receptor 1 antagonist with analgesic properties: II. in vivo characterization in rat models of inflammatory and neuropathic pain. J Pharm Exp Ther 306: 387 - 393.
30. Sun G and Wen X (2005) Heteroaryl - tetrahydropyridyl compounds useful for treating or preventing pain. WO Patent 2005009988.
31. Sun Q, Tafesse L, Islam K, Zhou X, Victory SF, Zhang C, Hachicha M, Schmid LA, Patel A, Rotshteyn Y, Valenzano KJ, and Kyle DJ (2003) 4 - (2 - pyridyl)piperazine - 1 - carboxamides: potent vanilloid receptor 1 antagonists. Bioorg Med Chem Lett 13: 3611 - 3616.
32. Sun Q, Wen X, and Zhou X (2005) Piperidine compounds and pharmaceutical compositions containing them. WO Patent 2005009987.
33. Swanson DM, Dubin AE, Shah C, Nasser N, Chang L, Dax SL, Jetter M, Breitenbucher JG, Liu C, Mazur C, Lord B, Gonzales L, Hoey K, Rizzolio M, Bogenstaetter M, Codd EE, Lee DH, Zhang SP, Chaplan SR, and Carruthers NI (2005) Identification and biological evaluation of 4 - (3 - trifluoromethylpyridin - 2 - yl)piperazine - 1 - carboxylic acid (5 - trifluoromethyl - pyridin - 2 - yl)amide, a high affinity TRPV1 (VR1) vanilloid receptor antagonist. J Med Chem 48: 1857 - 1872.
34. Tafesse L, Sun Q, Schmid L, Valenzano KJ, Rotshteyn Y, Su X, and Kyle DJ (2004) Synthesis and evaluation of pyridazinylpiperazines as vanilloid receptor 1 antagonists. Bioorg Med Chem Lett 14: 5513 - 5519.
35. Valenzano KJ, Grant ER, Wu G, Hachicha M, Schmid L, Tafesse L, Sun Q, Rotshteyn Y, Francis J, Limberis J, Malik S, Whittemore ER, and Hodges D (2003) N - (4 - Tertiarybutylphenyl) - 4 - (3 - chloropyridin - 2 - yl)tetrahydropyrazine - 1(2H) - carboxamide (BCTC), a novel, orally effective vanilloid receptor 1 antagonist with analgesic properties: I. in vitro characterization and pharmacokinetic properties. J Pharm Exp Ther 306: 377 - 386.
36. Zheng X, Hodgetts KJ, Brielmann H, Hutchison A, Burkamp F, Jones AB, Blurton P, Clarkson R, Chandrasekhar J, Bakthavatchalam R, De Lombaert S, Crandall M, Cortright D, and Blum CA (2006) From arylureas to biarylamides to aminoquinazolines: discovery of a novel, potent TRPV1 antagonist. Bioorg Med Chem Lett 16: 5217 - 5221.