Synthetic methodology utilized to prepare substituted imidazole p38 MAP kinase inhibitors

Current Opinion in Drug Discovery and Development

Volumn 6, Issue 6, 2003, Pages 945-965

  Murry, Jerry A ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Imidazole; p38 kinase; Thiazole

Indexed keywords

2 CHLORO 4 CYANOPYRIDINE; 4 (4 FLUOROPHENYL) 2 (4 HYDROXYPHENYL) 5 (4 PYRIDYL)IMIDAZOLE; 4 (4 FLUOROPHENYL) 2 (5 METHYL 5 MORPHOLINOCARBONYL 1,3 DIOXAN 2 YL) 5 (4 PYRIDINYL)IMIDAZOLE; 4 [4 (4 FLUOROPHENYL) 1 (3 PHENYLPROPYL) 5 (4 PYRIDINYL) 1H IMIDAZOL 2 YL] 3 BUTYN 1 OL; AMMONIUM ACETATE; BENZOIN; HETEROCYCLIC COMPOUND; IMIDAZOLE DERIVATIVE; IMINE; ISONIPECOTIC ACID; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; PYRIDINE DERIVATIVE; TOLUENESULFONIC ACID DERIVATIVE; UNCLASSIFIED DRUG;

CYCLIZATION; CYCLOADDITION; DRUG STRUCTURE; DRUG SYNTHESIS; POLYMERIZATION; REACTION ANALYSIS; REACTION OPTIMIZATION; REVIEW; RING CLOSING METATHESIS; STEREOCHEMISTRY; STRUCTURE ANALYSIS;

CHEMISTRY, PHARMACEUTICAL; ENZYME INHIBITORS; IMIDAZOLES; MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES;

EID: 0346458782     PISSN: 13676733     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (53)

1. Jackson PF, Bullington JL: Pyridinylimidazole based p38 MAP kinase inhibitors. Curr Top Med Chem (2002) 2(9):1011-1020. A thorough review of the medicinal chemistry, SAR and biological activity of various analogs.
2. Adams JL, Gallagher TF, Boehm JC, Kassis S, Gorycki PD, Gum RJ, Webb EF, Sorenson ME, Smietana JM, Garigipati RS, Hall RF et al: p38 MAP kinase inhibitors: Progress, pitfalls and possibilities. Special Publication Royal Society of Chemistry (2001) 264:163-173. An interesting review of p38 as an evolving medicinal chemistry program.
3. Adams JL, Badger AM, Kumar S, Lee JC: p38 MAP kinase: Molecular target for the inhibition of pro-inflammatory cytokines. Prog Med Chem (2001) 38:1-60.
4. Lee JC, Kumar S, Griswold DC, Underwood DC, Votta BJ, Adams JL: Inhibition of p38 MAP kinase as a therapeutic target strategy. Immunopharmacology (2000) 47(2-3):185-201.
5. Choy EH, Panayi GS: Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med (2001) 344(12):907-916. A recent review on the treatment of inflammation by controlling cytokine pathways.
6. Walz DT, DiMartino MJ, Misher A: Adjuvant-induced arthritis in rats. II. Drug effects on physiologic, biochemical and immunologic parameters. J Pharmacol Exp Ther (1971) 178(1):223-231.
7. Lee JC, Laydon JT, McDonnell PC, Gallagher TF, Kumar S, Green D, McNulty D, Blumenthal MJ, Heys JR, Landvatter SW, Stricler JE et al: A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature (1994) 372(6508):739-746.
8. Han J, Lee JD, Bibbs L, Ulevtich RJ: A MAP kinase targeted by endotoxin and hyperosmolarlty in mammalian cells. Science (1994) 265(5173):808-811.
9. Gupta RR, Kumar M, Gupta V (Eds): Heterocyclic Chemistry II, Five Membered Heterocycles. Springer, Berlin, Germany (1999).
10. Murry JA, Frantz DE, Soheili A, Tillyer R, Grabowski EJ, Reider PJ: Synthesis of α-amido ketones via organic catalysis: Thiazolium-catalyzed cross-coupling of aldehydes with acylimines. J Am Chem Soc (2001) 123(39):9696-9697.
11. Murry JA, Frantz DE, Frey L, Soheili A, Marcantonio K, Tillyer R, Grabowski EJ, Reider PJ: A practical synthesis of tetrasubstituted imidazole p38 MAP kinase inhibitors: A new method for the synthesis of α-amidoketones. In: Symposium Series No. 870/Chemical Process Research: The Role of Synthesis in Drug Development. Abdel-Magid A, Ragan J (Eds), American Chemical Society Publications, USA (2003): in print.
12. Lantos I, Bender PE, Razgaitis KA, Sutton BM, DiMartino MJ, Griswold DE, Walz DT: Antiinflammatory activity of 5,6-diaryl-2,3-dihydroimidazole[2,1-b]thiazoles. Isomeric 4-pyridyl and 4-substituted phenyl derivatives. J Med Chem (1984) 27(1):72-75.
13. Gallagher TF, Fier-Thompson SM, Garigipati RS, Sorenson M, Smietana JM, Lee D, Bender PE, Lee JC, Laydon JT, Griswold DE, Chabot-Fletcher MC et al: 2,4,5-Triarylimidizaole inhibitors of IL-1 biosynthesis. Bioorg Med Chem Lett (1995) 5(11):1171-1176.
14. Boehm JC, Smietana JM, Sorenson ME, Garigipati RS, Gallagher TF, Sheldrake PL, Bradbeer J, Badger AM, Laydon JT, Lee JC, Hillegass LM et al: 1-Substituted 4-aryl-5-pyridinylimidazoles: A new class of cytokine suppressive drugs with low 5-lipoxygenase and cyclooxygenase inhibitory potency. J Med Chem (1996) 39(20):3929-3937.
15. Adams JL, Boehm JC, Kassis S, Gorycki PD, Webb EF, Hall R, Sorenson M, Lee JC, Ayrton A, Griswold DE, Gallagher TF: Pyrimidinylimidazole inhibitors of CSBP/p38 kinase demonstrating decreased inhibition of hepatic cytochrome P450 enzymes. Bioorg Med Chem Lett (1998) 8(22):3111-3116.
16. Boehm JC, Bower MJ, Gallagher TF, Kassis S, Johnson SR, Adams JL: Phenoxypyrimidine inhibitors of p38 α kinase: Synthesis and statistical evaluation of the p38 inhibitory potencies of a series of 1-(piperidin-4-yl)-4-(4-fluorophenyl)-5-(2-phenoxypyrimidin-4-yl) imidazoles. Bioorg Med Chem Lett (2001) 11(9):1123-1126.
17. van Leusen AM, Wildeman J, Oldenziel OH: Chemistry of sulfonylmethyl isocyanides. 12. Base-induced cycloaddition of sulfonylmethyl isocyanides to carbon-nitrogen double bonds. Synthesis of 1,5-disubstituted and 1,4,5-trisubstituted imidazoles from aldimines and imidoyl chlorides. J Org Chem (1977) 42(7):1153-1159.
18. Sisko J, Kassick AJ, Mellinger M, Filan JJ, Allen A, Olsen M: An investigation of imidazole and oxazole syntheses using aryl-substituted TOSMIC reagents. J Org Chem (2000) 65(5):1516-1524.
19. Sisko J: A one-pot synthesis of 1-(2,2,6,6-tetramethyl-4-piperidinyl)-4-(4-fluorophenyl) -5-(2-amino-4-pyrimidinyl)-imidazole: A potent inhibitor of p38 MAP kinase. J Org Chem (1998) 63(13):4529-4531.
20. Sisko J, Mellinger M, Sheldrake PW, Baine NH: An efficient method for the synthesis of substituted TOSMIC precursors. Tetrahedron Lett (1996) 37(45):8113-8116. A detailed description of a new synthetic technology.
21. Olinjsma T, Engberts JB, Strating J: The preparation of tosyl-amides. Recl Trav Chim Pay B (1972) 91:209.
22. Sasaki H, Nakagawa H, Khuhara M, Kitigawa T: Efficient preparation of tosyl amides. Chem Lett (1988) 7:1531-1534.
23. van Leusen AM, Boerma GJ, Helmholdt RB, Siderius H, Straiting J: Chemistry of sulfonylmethylisocyanides. Simple synthetic approaches to a new versatile chemical building block. Tetrahedron Lett (1972) 13(23):2367-2368.
24. Hundschied RJ, Tandon VK, Rouwette PH, van Leusen AM: Synthesis of chiral sulfonylmethyl isocyanides, and comparison of their propensities in asymmetric induction reactions with acetophenones. Tetrahedron (1987) 43(21):5073-5088.
25. Liverton NL, Butcher JW, Claiborne CF, Claremon DA, Libby, BE, Nguyen KT, Pitzenberger SM, Selnick HG, Smith GR, Tebben A, Vacca JP et al: Design and synthesis of potent, selective and orally bioavailable tetrasubstituted imidazole inhibitors of p38 mitogen-activated protein kinase. J Med Chem (1999) 42(12):2180-2190
26. Claiborne CF, Liverton NJ, Nguyen KT: An efficient synthesis of tetrasubstituted imidazoles from N-(2-oxo)-amides. Tetrahedron Lett (1998) 39(49):8939-8942.
27. Wadsworth SA, Cavender DE, Beers SA, Lalan P, Schafer PH, Malloy EA, Wu W, Fahmy B, Olini GC, Davis JE, Pellegrino-Gensy JL et al: RWJ 67657, a potent orally active inhibitor of p38 mitogen activated protein kinase. J Pharmacol Exp Ther (1999) 291(2):680-687. A detailed description of the Merck medicinal chemistry program, and the discovery of some highly potent and selective imidazole-based inhibitors.
28. Fijen JW, Zijlstra JG, De Boer P, Spanjersberg R, Cohen Tervaert JW, Van Der Werf TS, Ligtenberg JJ, Tulleken JE: Suppression of the clinical and cytokine response to endotoxin by RWJ-67657, a p38 mitogen-activated protein-kinase inhibitor, in healthy human volunteers. Clin Exp Immunol (2001) 124 (1):16-20.
29. McLay IM, Halley F, Souness JE, McKenna J, Benning V, Birrell M, Burton B, Belvisi M, Collis A, Constan A, Foster M et al: The discovery of RPR 200765A, a p38 MAP kinase inhibitor displaying a good oral anti-arthritic efficacy. Bioorg Med Chem (2001) 9(2):537-554.
30. Revesz L, Di Padova FE, Buhl T, Feifel R, Gram H, Hiestand P, Manning U, Zimmerlin AG: SAR of 4-hydroxypiperidine and hydroxyalkyl substituted heterocycles as novel p38 MAP kinase inhibitors. Bioorg Med Chem Lett (2000) 10(11):1261-1264.
31. Harris MC, Huang X, Buchwald SL: Improved functional group compatibility in the palladium-catalyzed synthesis of aryl amines. Org Lett (2002) 4(17):2885-2888.
32. Frey L, Marcantonio K, Frantz DE, Murry JA, Tillyer RD, Grabowski EJ, Reider PJ: Practical routes toward the synthesis of 2-halo- and 2-alkylamino-4-pyridinecarboxaldehydes. Tetrahedron Lett (2001) 42(39):6815-6818.
33. Hansen HJ, Heimgertner H: Nitrile ylides. In: 1,3-Dipolar Cycloaddition Chemistry. A Padwa (Ed), John Wiley and Sons, New York, NY, USA (1984);Volume 1:83-168.
34. Padwa A, Carlsen PH: Photochemical transformations of small ring heterocycles. 81. Carbenic reactions of nitrile ylides. An example of a stepwise 1,3-dipolar cycloaddition. J Am Chem Soc (1977) 99(5)1514-1523.
35. Padwa A, Kamigata N: Photochemical transformations of small ring heterocyclic compounds. 82. Intramolecular dipolar cycloaddition reactions of unsaturated 2H-azirines. J Am Chem Soc (1977) 99(6):1871-1880.
36. Huisgen R, Stangl H, Sturm HJ, Wagenhofer H: Angew Chem Int Ed (1962) 1(1):50-51.
37. Bunge K, Huisgen R, Raab R, Sturm HJ: Dipolar cycloaddition of nitrilium ylides. Chem Ber (1972) 105():1307-1323.
38. Lee A, Huang L, Ellman JA: General solid-phase method for the preparation of mechanism-based cysteine protease inhibitors. J Am Chem Soc (1999) 121(43):9907-9914.
39. Rano TA, Timkey T, Peterson EP, Rotonda J, Nicholson DW, Becker JW, Chapman KT, Thornberry NA: A combinatorial approach for determining protease specificities: Application to interieukin-1α converting enzyme (ICE). Chem Biol (1997) 4(2):149-155.
40. Marquis RW, Ru Y, Yamashita DS, Oh HJ, Yen J, Thompson SK, Carr TJ, Levy MA, Tomaszek TA, Ijames CF, Smith WW et al: Potent dipeptidylketone inhibitors of the cysteine protease cathepsin K. Bioorg Med Chem (1999) 7(4):581-588.
41. Yamashita DS, Smith WW, Zhao B: Structure and design of potent and selective cathepsin K inhibitors. J Am Chem Soc (1997) 119(46):11351-11352.
42. Hassner A, Rai KM: The benzoin condensation. Comp Org Syn (1991) 1(1):541-577.
43. Breslow R: On the mechanism of thiamine action. IV. Evidence from studies on model systems. J Am Chem Soc (1958) 80(14):3719-3726.
44. Breslow R, Schmuck C: The mechanism of thiazolium catalysis. Tetrahedron Lett (1996) 37(45):8241-8242.
45. 2SO: Evidence for initial formation of 2-(α-hydroxybenzyl)-thiazolium by nucleophilic addition and for dramatic solvent effects on benzoin formation. J Org Chem (1994) 59(25):7714-7722.
46. Stetter H, Kuhlman H: Thiazolium catalyzed addition of aldehydes to enoates. Chem Ber (1976) (109):2890-2896.
47. Stetter H, Kuhlman H: Addition von Aldehyden an aktivierte Doppelbindungen; VII. Eine neue Einfache von cis-Jasmon und Dihydrojasmon. Synthesis (1975) (6):379-380.
48. Stetter H: Recent thiazolium catalyzed processes. Angew Chem Int Ed (1976) 15(8):639-712.
49. Kinoshita H, Hayashi Y, Murata Y, Inomata K: Thiazolium catalyzed coupling of aldehydes. Chem Lett (1993):1437-1440.
50. Castells J, Lopez-Calahora F, Bassedas M, Urios P: A new thiazolium salt-catalyzed synthesis of α-aminoketones from aldehydes and iminium salts. Synthesis (1988) (4):314-315.
51. Katritzky AR, Cheng D, Musgrave RP: α-Amino ketone synthesis from aldehydes and N-(α-dialkylaminoalkyl)benzotriazoles. Heterocycles (1996) 42(1):273-280.
52. El Du PONT DE NEMOURS & Co (Cherkofsky SC, Sharpe TR): Anti-inflammatory 4,5-diarly-2-(substituted-thio)imidazoles and their corresponding sulfoxides and sulfones. US-04190666 (1980).
53. CIBA-GEIGY CORP (Fitzi K): Imidazole derivatives in the treatment of pain. US-03940486 (1974).