New azole antifungals. 2. Synthesis and antifungal activity of heterocyclecarboxamide derivatives of 3-amino-2-aryl-1-azolyl-2-butanol

Journal of Medicinal Chemistry

Volumn 41, Issue 11, 1998, Pages 1855-1868

  Bartroli, Javier ^a   Turmo, Enric ^a   Algueró, Mònica ^a   Boncompte, Eulàlia ^a   Vericat, Maria L ^a   Conte, Lourdes ^a   Ramis, Joaquim ^a   Merlos, Manuel ^a   García Rafanell, Julián ^a   Forn, Javier ^a  

^a Research Center   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

2 (4 CYANOPHENYL) N [2 (2,4 DIFLUOROPHENYL) 2 HYDROXY 1 METHYL 3 (1H 1,2,4 TRIAZOL 1 YL)PROPYL] 4 METHYLTHIAZOLE 5 CARBOXAMIDE; 3 AMINO 2 ARYL 1 AZOLYL 2 BUTANOL; 6 (4 CHLOROPHENYL) 3 [2 (2,4 DIFLUOROPHENYL) 2 HYDROXY 1 METHYL 3 (1H 1,2,4 TRIAZOL 1 YL)PROPYL]THIENO [3,2 D]PYRIMIDIN 4 (3H) ONE; ANTIFUNGAL AGENT; PYRIMIDINE DERIVATIVE; PYRROLE DERIVATIVE; UNCLASSIFIED DRUG; UR 9908;

ANTIFUNGAL ACTIVITY; ARTICLE; ASPERGILLOSIS; CANDIDIASIS; DRUG ELIMINATION; DRUG STRUCTURE; DRUG SYNTHESIS; PLASMA HALF LIFE; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

EID: 15444341737     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm970726e     Document Type: Article

References (45)

1. For part I of this study, see: Bartroli, J.; Turmo, E.; Algueró, M.; Boncompte, E.; Vericat, M. L.; García-Rafanell, J.; Forn, J. Synthesis and Antifungal Activity of New Azole Derivatives Containing an N-Acylmorpholine Ring. J. Med. Chem. 1995, 38, 3918-3932.
2. Maggon, K. K.; Slee, A. M.; Demos, C. H. Development of Antifungal Agents by the Pharmaceutical Industry. Drugs Today 1991, 27, 317-330.
3. For an excellent update on current antifungal therapy, see: Turner, W. W.; Rodriguez, M. J. Recent Advances in the Medicinal Chemistry of Antifungal Agents. Curr. Pharm. Des. 1996, 2, 209-224.
4. (a) Johnson, E. M.; Warnock, D. W.; Luker, J.; Porter, S. R.; Scully, C. Emergence of Azole Drug Resistance in Candida Species from HIV-infected Patients receiving Prolonged Fluconazole Therapy for Oral Candidosis. J. Antimicrol. Chemother. 1995, 35, 103-114.
5. (b) Rex, J. H.; Rinaldi, M. G.; Pfaller, M. A. Resistance of Candida Species to Fluconazole (Minireview) Antimicrob. Agents Chemother. 1995, 39, 1-8; and references therein.
6. For a recent review on the newer triazole derivatives in the clinic, see: Fung, J. C.; Bonner, D. P. Recent Developments in Pradimycin-benanomycin and Triazole Antibiotics Exp. Opin. Invest. Drugs 1997, 6, 129-145.
7. For a recent review on SCH-56592, see: Drugs Future 1997, 22, 203-204.
8. For a recent review on voriconazole, see: Voriconazole (UK-109496). Drugs Future 1997, 22, 326-327.
9. (a) Itoh, K.; Okonogi, K.; Tasaka, A.; Hayashi, R.; Tamura, N.; Tsuchimori, N.; Kitazaki, T.; Matsushita, Y.; Obita, J. TAK-187, a New Antifungal Triazole: Synthesis and Antifungal Activity. 36nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 1996, New Orleans, LA.
10. (b) Tasaka, A.; Kitazaki, T.; Tamura, N.; Tsuchimori, N.; Matsushita, Y.; Hayashi, R.; Okonogi, K; Itoh, K. Optically Active Antifungal Azoles. VII. Synthesis and Antifungal Activity of Stereoisomers of 2-[(1R, 2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]- 4-(2,2,3,3-tetrafluoro-propoxy)phenyl]-3-(2H,4H)-1,2,4-triazolone (TAK-187). Chem. Pharm. Bull. 1997, 45, 321-326.
11. Eisai's compound ER-30346 has been licensed to Bristol-Myers Squibb. The new laboratory code for this compound is BMS-207,-147. For a recent review on this compound, see: Naito, T.; Hata, K; Tsuruoka, A. Drugs Future 1996, 21, 20-24.
12. (a) Konosu, T.; Tajima, Y.; Takeda, N.; Miyaoka, T.; Kasahara, M.; Yasuda, H.; Oida, S. Triazole Antifungals. II. Synthesis and Antifungal Activities of 3-Acyl-4-methyloxazolidine Derivatives. Chem. Pharm. Bull. 1990, 38, 2476-2486.
13. (b) Konosu, T.; Tajima, Y.; Takeda, N.; Miyaoka, T.; Kasahara, M.; Yasuda, H.; Oida, S. Triazole Antifungals. IV. Synthesis and Antifungal Activities of 3-Acylamino-2-aryl-2-butanol Derivatives. Chem. Pharm. Bull. 1991, 39, 2581-2589.
14. (a) Stevens, D. A.; Devine, M. J.; Martinez, M.; Aristizabal, B. In Vitro Antifungal Activity of Novel Azole Derivatives with a Morpholine Ring, UR-9746 and UR-9751; Comparison with Fluconazole. 35 Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 1995, San Francisco, CA.;
15. (b) Clemens, K. V.; Stevens, D. A. Efficacy of Two Novel Azole Derivatives Each Containing a Morpholine Ring, UR-9746 and UR-9751 against Systemic Murine Coccidioidomycosis. Antimicrob. Agents Chemother. 1997, 41, 200-203.
16. (c) Bornay-Llinares, F. J.; Torres-Rodriguez, J. M. Anticryptococcal Activity of a New Azole Derivative (UR-9746) in a Murine Model. 35 Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 1995, San Francisco, CA.
17. (d) Bornay-Llinares, F. J.; Mayol-Belda, M. S.; Onrubia-Pintado, J.; Torreg-Rodriguez, J. M. Murine Cryptococcosis. Tissular Damage Decreases after Treatment with UR-9746. 35 Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 1995, San Francisco, CA.
18. (e) Restrepo, M.; Najvar, L.; Barchiesi, F.; Graybill, J. R.; Treatment of Murine Cryptococcal Meningitis with UR-9751 and UR-9746. 35 Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 1995, San Francisco, CA.
19. (f) Bornay-Llinares, F. J.; Torres-Rodriguez, J. M. Anticryptococcal Activity of a New Azole Derivative (UR-9746) in a Murine Model. Preliminary Results. 2nd Meeting of the European Confederation of Medical Mycology (ECMM), April 1995, Brussels, Belgium,
20. (g) Improvisi, L.; García-Hermoso, D.; Provost, F.; Dromer, F.; Dupont, B. Evaluation of Two Novel Antifungal Agents, UR-9746 and UR-9751 in the Treatment of Experimental Murine Histoplasmosis. 35 Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 1995, San Francisco, CA.
21. (h) demons, K.; Stevens, D. A. Personal communication.
22. Loebenberg, D.; Cacciapuoti, A.; Parmegiani, R.; Moss, E. L., Jr.; Menzel, F., Jr.; Antonacci, B.; Norris, C.; Yarosh-Tomaine, T.; Hare, R. S.; Miller, G. H. In Vitro and in Vivo Activities of SCH 42427, the Active Enantiomer of the Antifungal Agent SCH 39304. Antimicrob. Agents Chemother. 1992, 36, 498-501.
23. Tasaka, A.; Tamura, N.; Matsushita, Y.; Teranishi, K.; Hayashi, R.; Okonogi, K.; Itoh, K. Optically Active Antifungal Azoles. I. Synthesis and Antifungal Activity of (2R,3R)-2-(2,4-Difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl)-2-butanol and Its Stereoisomers. Chem. Pharm. Bull. 1993, 41, 1035-1042.
24. Bartroli, J.; Turmo, E.; Belloc, J.; Forn, J. Aldol Condensation of Evans Chiral Enolates with Acetophenones. Its Application to the Stereo selective Synthesis of Homochiral Antifungal Agents. J. Org. Chem. 1995, 60, 3000-3012.
25. (a) Alberola, A.; Andrés, J. M.; González, A.; Pedrosa, R.; Prádanos, P. Regioselective Synthesis of 2-Functionalized Thiophenes by Condensation of α-Mercapto Compounds with β-Amino enone Derivatives. Chem. Commun. 1990, 20, 2337-2547.
26. (b) Hauptmann, S.; Weissenfels, M.; Scholz, M.; Werner, E.-M.; Köhler, H.-J.; Weisflog, J. Eine neue Synthese substitutierter Thiophene und Pyrrole. Tetrahedron Lett. 1968, 1317-1319.
27. (c) Hartmann, H. A Simple Method for the Synthesis of 5-Aryl-3-amino-2-alkoxycarbonylthiophenes. Synthesis 1984, 275-276.
28. Veronese, A. C.; Cavicchioni, G.; Servadio, G.; Vecchiati, G. Syntheses of 2-Arylimidazole Derivatives through Annelations Employing Benzylamines. J. Heterocycl. Chem. 1980, 17, 1723-1725.
29. (a) Menozzi, G.; Mosti, L.; Schenone, P. J. Reaction of 2-Dimethyalminomethylene-1,3-diones with Dinucleophiles. VI. Synthesis of Ethyl or Methyl 1,5-Disubstituted 1H-Pyrazole-4-carboxylates. Heterocycl. Chem. 1987, 24, 1669-1675.
30. (b) For the compounds with B = H, carbethoxymalonaldehyde was obtained according to Panizzi, L. Investigations of β-dialdehydes. I. Carbethoxymalonaldehyde. Gazz. Chim. Ital. 1946, 76, 56-65.
31. (c) Fabis, F.; Dallemagne, P.; Rault, S.; Robba, M. A New Efficient Synthesis of 3-Amino-1-phenylpyrrole. Org. Prep. Proceed. Int. 1995, 27, 236-239.
32. Schmidt, P.; Eichenberger, K.; Wilhelm, M.; Druey, J. Pyrazolopyrimidine. III. Paraxanthin-, Theobromin- und Theophyllin-Analoga der Pyrazolo[3, 4-d]pyrimidin-Reihe. Helv. Chim. Acta 1959, 1, 349-359.
33. Plouvier, B.; Bailly, C.; Houssin, R.; Hénichart, J.-P. Synthesis of Two New Thiazole-Containing Oligopeptides as Potential DNA Minor Groove Binding Analogs of Netropsin. Heterocycles 1991, 32, 693-701.
34. Clemence, F.; Le Martret, O.; Fournex, R.; Dagnaux, M.; Plassard, G. Synthèse et Propriétés Antilipolytiques et Hypotriglycéridémiantes d'Acides Thiazole-5-carboxyliques. Eur. J. Med. Chem. 1976, 11, 567-570.
35. Crooks, P. A.; Cynkowska, G.; Ashton, P.; Cynkowski, T. Unexpected Reaction in the Attempted Synthesis of a Drug-Amino Acid Ester Conjugate. Abstract 223. 209th ACS National Meeting, April 1995, Anaheim, CA.
36. Dost, J.; Heschel, M.; Stein, J. Zur Herstellung von 1,3,4-Oxadiazol-2-carbonsäurederivative. J. Prakt. Chem. 1985, 327, 109-116.
37. Diana, G. D.; Rudewicz, P.; Pevear, D. C.; Nitz, T.; Aldous, S.; Aldous, D. J.; Robinson, D. T. Draper, T.; Dutko, F. Picornavirus Inhibitors: Trifluoromethyl Substitution Provides a Global Protective Effect against Hepatic Metabolism. J. Med. Chem. 1995, 38, 1355-1371.
38. Shimizu, T.; Hayashi, Y.; Teramura, K. A New Synthetic Method for Alkyl Carbonocyanidate N-oxides. Bull. Chem. Soc. Jpn. 1985, 58, 2519-2522.
39. Howe, R. K.; Franz, J. E. Nitrile sulfides. Synthesis of 1,2,4-thiadiazoles. J. Org. Chem. 1974, 39, 962-964.
40. Clinical trials for this product and its racemate (Genaconazole, SCH-39304) have been terminated. For a recent review, see: Drugs Future 1992, 17, 1145-1146.
41. Klopman, G.; Ptchelinstev, D. Antifungal Triazole Alcohols: A Comparative Analysis of Structure-Activity, Structure-Teratogenity and Structure-Therapeutic Index Relationships using the Multiple Computer-Automated Structure Evaluation (Multi-CASE) Methodology. J. Comput.-Aided Mol. Des. 1993, 7, 349-362.
42. Voriconazole is known to induce its own methabolism following multiple dose administration in sensitive rodent species and hence shows little efficacy in murine models. Jezequel, S. G.; Clark, M.; Cole, S.; Evans, K. M.; Wastall, P. UK-109,496, A Novel, Wide-Spectrum Triazole Derivative for the Treatment of Fungal Infections: Pre-clinical Pharmacokinetics. 35 Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 1995, San Francisco, CA.
43. Richardson, K. Antifungal 1,3-Bis-triazolyl-2-propanol Derivative. U.S. Patent 4,404,216, 1983.
44. Abdel-Lateef, M.; Fath-Alla; Eckstein, Z. Nucleophilic Halogen Replacement of 2-Bromo-4-methyl-5-thiazolecarboxylic acid Derivatives and Their Anomalies. Rocz. Chem. 1972, 46, 1647-1658.
45. Field, L.; Clark, R. D. Methyl p-Tolyl Sulfone. Organic. Syntheses; Wiley: New York, 1963; Collect. Vol. IV, p 674.