Pyrroloquinolone PDE5 inhibitors with improved pharmaceutical profiles for clinical studies on erectile dysfunction

Journal of Medicinal Chemistry

Volumn 48, Issue 6, 2005, Pages 2126-2133

  Jiang, Weiqin ^a   Guan, Jihua ^a   Macielag, Mark J ^a   Zhang, Suying ^a   Qiu, Yuhong ^a   Kraft, Patricia ^a   Bhattacharjee, Sheela ^a   John, T Matthew ^a   Haynes Johnson, Donna ^a   Lundeen, Scott ^a   Sui, Zhihua ^a  

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

Author keywords

[No Author keywords available]

Indexed keywords

1,2,3,4 TETRAHYDRO 2 [5 (2 PYRIDINYL)PYRIMIDIN 2 YL] 3 (3,4 DIHYDROBENZOFURANYL) 9H PYRROLO[3,4 B]QUINOLIN 9 ONE; 2 [2,3']BIPYRIDINYL 6' YL 3 (2,3 DIHYDROBENZOFURAN 5 YL) 1,2,3,4 TETRAHYDROPYRROLO[3,4 B]QUINOLIN 9 ONE; 3 (2,3 DIHYDROBENZOFURAN 5 YL) 2 PYRIDIN 2 YL 1,2,3,4 TETRAHYDROPYRROLO QUINOLIN 9 ONE; CYCLODEXTRIN; METHYLCELLULOSE; PHOSPHODIESTERASE V INHIBITOR; PYRIMIDINYL PYRROLOQUINOLONE; SILDENAFIL; UNCLASSIFIED DRUG;

ANIMAL CELL; AQUEOUS SOLUTION; ARTICLE; CONTROLLED STUDY; DOG; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG POTENCY; DRUG SELECTIVITY; ERECTILE DYSFUNCTION; MALE; MOLECULAR WEIGHT; MONKEY; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION;

3',5'-CYCLIC-GMP PHOSPHODIESTERASE; ANIMALS; BIOLOGICAL AVAILABILITY; BLOOD PRESSURE; CELL LINE; CYCLIC GMP; DOGS; ELECTRIC STIMULATION; IMPOTENCE; MACACA MULATTA; MALE; PENIS; PYRROLES; QUINOLONES; RATS; RATS, SPRAGUE-DAWLEY; SOLUBILITY; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 20144367317     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0401098     Document Type: Article

References (26)

1. For MED, see: (a) Lue, T. F. Erectile Dysfunction. N. Engl. J. Med. 2000, 342, 1802-1818. (b) Feldman, H. A.; Goldstein, I.; Hatzichristou, D. G.; Krane, R. J.; McKinlay, J. B. Impotence and Its Medical and Physiological Correlates: Results of the Massachusetts Male Aging Study. J. Urol. 1994, 151, 54-56.
2. For MED, see: (a) Lue, T. F. Erectile Dysfunction. N. Engl. J. Med. 2000, 342, 1802-1818. (b) Feldman, H. A.; Goldstein, I.; Hatzichristou, D. G.; Krane, R. J.; McKinlay, J. B. Impotence and Its Medical and Physiological Correlates: Results of the Massachusetts Male Aging Study. J. Urol. 1994, 151, 54-56.
3. (a) Corbin, J. D.; Francis, S. H. Cyclic GMP Phosphodiesterase-5: Target of Sildenafil. J. Biol. Chem. 1999, 274, 13729-13732.
4. (b) Soderling, S. H.; Beavo, J. A. Regulation of cAMP and cGMP signaling: New phosphodiesterases and new functions. Curr. Opin. Cell Biol. 2000, 12, 174-179.
5. (c) Conti, M.; Jin, S.-L. C. The molecular Biology of Cyclic Nucleotide Phosphodiesterases. Prog. Nucleic Acid Res. Mol. Biol. 2001, 65, 1-52.
6. For Viagra (sildenafil), see: Brook, G. Sildenafil Citrate (Viagra). Drugs Today 2000, 36 (2-3), 125-134 and references therein.
7. For Cialis (tadalafil), see: (a) Sorbera, L A.; Martin, L.; Leeson, P. A.; Casraner, J.; IC-351, Treatment of Erectile Dysfunction. Treatment of Female Sexual Dysfunction, Phosphodiesterase 5 Inhibitor. Drugs Future 2001, 26 (1), 15-19 and references therein. For discovery of tadalafil, see: (b) Daugan, A.; Grondin, P.; Ruault, C.; Gouville, A.-C. L. M.; Coste, H.; Kirilovsky, J.; Hyafil, F.; Labaudiniere, R. The Discovery of Tadalafil: A Novel and Highly Selective PDE5 Inhibitor. 1: 5,6,11,11a-Tetrahydro-1H-imidazole[1′, 5′:1,6]pyrido[3,4-b]indole-1, 3(2H)-dione Analogues. J. Med. Chem. 2003, 46, 4525-4532. (c) Daugan, A.; Grondin, P.; Ruault, C.; Gouville, A.-C. L. M.; Coste, H.; Linget, J. M.; Kirilovsky, J.; Hyafil, F.; Labaudiniere, R. The Discovery of Tadalafil: A Novel and Highly Selective PDE5 Inhibitor. 2: 2,3,6,7,12,12a-hexahydropyrazino[1′,2′:1,6]pyrido[3,4-b]indole-1, 4-dione Analogues. J. Med. Chem. 2003, 46, 4533-4542.
8. For Cialis (tadalafil), see: (a) Sorbera, L A.; Martin, L.; Leeson, P. A.; Casraner, J.; IC-351, Treatment of Erectile Dysfunction. Treatment of Female Sexual Dysfunction, Phosphodiesterase 5 Inhibitor. Drugs Future 2001, 26 (1), 15-19 and references therein. For discovery of tadalafil, see: (b) Daugan, A.; Grondin, P.; Ruault, C.; Gouville, A.-C. L. M.; Coste, H.; Kirilovsky, J.; Hyafil, F.; Labaudiniere, R. The Discovery of Tadalafil: A Novel and Highly Selective PDE5 Inhibitor. 1: 5,6,11,11a-Tetrahydro-1H-imidazole[1′, 5′:1,6]pyrido[3,4-b]indole-1, 3(2H)-dione Analogues. J. Med. Chem. 2003, 46, 4525-4532. (c) Daugan, A.; Grondin, P.; Ruault, C.; Gouville, A.-C. L. M.; Coste, H.; Linget, J. M.; Kirilovsky, J.; Hyafil, F.; Labaudiniere, R. The Discovery of Tadalafil: A Novel and Highly Selective PDE5 Inhibitor. 2: 2,3,6,7,12,12a-hexahydropyrazino[1′,2′:1,6]pyrido[3,4-b]indole-1, 4-dione Analogues. J. Med. Chem. 2003, 46, 4533-4542.
9. For Cialis (tadalafil), see: (a) Sorbera, L A.; Martin, L.; Leeson, P. A.; Casraner, J.; IC-351, Treatment of Erectile Dysfunction. Treatment of Female Sexual Dysfunction, Phosphodiesterase 5 Inhibitor. Drugs Future 2001, 26 (1), 15-19 and references therein. For discovery of tadalafil, see: (b) Daugan, A.; Grondin, P.; Ruault, C.; Gouville, A.-C. L. M.; Coste, H.; Kirilovsky, J.; Hyafil, F.; Labaudiniere, R. The Discovery of Tadalafil: A Novel and Highly Selective PDE5 Inhibitor. 1: 5,6,11,11a-Tetrahydro-1H-imidazole[1′, 5′:1,6]pyrido[3,4-b]indole-1, 3(2H)-dione Analogues. J. Med. Chem. 2003, 46, 4525-4532. (c) Daugan, A.; Grondin, P.; Ruault, C.; Gouville, A.-C. L. M.; Coste, H.; Linget, J. M.; Kirilovsky, J.; Hyafil, F.; Labaudiniere, R. The Discovery of Tadalafil: A Novel and Highly Selective PDE5 Inhibitor. 2: 2,3,6,7,12,12a-hexahydropyrazino[1′,2′:1,6]pyrido[3,4-b]indole-1, 4-dione Analogues. J. Med. Chem. 2003, 46, 4533-4542.
10. For Levitra (vardenafil), see: Sorbera, L. A.; Martin, L.; Rabasseda, J.; Castaner, J.; Vardenafil, Treatment of Erectile Dysfunction, Phosphodiesterase 5 Inhibitor. Drugs Future 2001, 26 (2), 141-144 and references therein.
11. For comparison of the three launched PDE5 inhibitors, see: (a) Gresser, U.; Gleiter, C. H. Erectile Dysfunction: Comparison of Efficacy and Side Effects of the PDE-5 Inhibitors Sildenafil, Vardenafil and Tadalafil. Eur. J. Med. Res. 2002, 7, 435-466. (b) Sui, Z.; Phosphodiesterase-5 Inhibitors for Male Erectile Dysfunction. Expert Opin. Ther. Pat. 2003, 13 (9), 1373-1388.
12. For comparison of the three launched PDE5 inhibitors, see: (a) Gresser, U.; Gleiter, C. H. Erectile Dysfunction: Comparison of Efficacy and Side Effects of the PDE-5 Inhibitors Sildenafil, Vardenafil and Tadalafil. Eur. J. Med. Res. 2002, 7, 435-466. (b) Sui, Z.; Phosphodiesterase-5 Inhibitors for Male Erectile Dysfunction. Expert Opin. Ther. Pat. 2003, 13 (9), 1373-1388.
13. Fawcett, L.; Baxendale, R.; Stacey, P.; McGrouther, C.; Harrow, I.; Soderling, S.; Hetman, J.; Beavo, J. A.; Phillips, S. C.; Molecular cloning and characterization of a distinct human phosphodiesterase gene family: PDE11A. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 3702-07.
14. (a) Sui, Z.; Guan, J.; Macielag, M. J.; Jiang, W.; Zhang, S.; Qiu, Y.; Kraft, P., Bhattacharjee, S.; John, T. M.; Craig, E.; Haynes-Johnson, D.; Clancy, J. Pyrimidinyl Pyrroloquinolones as Highly Potent and Selective PDE5 Inhibitors for Treatment of Erectile Dysfunction. J. Med. Chem. 2002, 45, 4094-4096.
15. (b) Jiang, W.; Sui, Z.; Chen, X. Synthesis of Optically Pure Pyrroloquinolones via Pictet-Spengler and Winterfeldt Reactions. Tetrahedron Lett. 2002, 43 (49), 8941-8945.
16. (c) Qiu, Y.; Bhattacharjee, S.; Kraft, P.; John, T. M.; Craig, E.; Haynes-Johnson, D.; Guan, J.; Jiang, W.; Macielag, M.; Sui, Z.; Clancy, J.; Lundeen, S. Characterization of a novel phosphodiesterase type 5 inhibitor: JNJ-10258859. Eur. J. Pharm. 2003, 472 (1-2), 73-80.
17. (d) Lanter, J. C.; Walsh, S. P.; Sui, Z.; Macielag, M. J.; Jiang, W.; Fiordeliso, J. J.; Guan, J.; Qiu, Y.; Kraft, P.; Lombardi, E.; John, T. M.; Clancy, J. Structure-Activity Relationships of N-Acyl Pyrroloquinolone PDE-5 Inhibitors. J. Med. Chem. 2004, 47, 656-662.
18. (a) Winterfeldt, E. Chinolon-Derivate durch autoxidation. Liebigs Ann. Chem. 1971, 745, 23-30.
19. (b) Warneke, J.; Winterfeldt, E. Die autoxidative indol-chinolon- umwandlung eines camptothecin-modells. Chem. Ber. 1972, 105, 2120-2125.
20. (c) Boch, M.; Korth T.; Nelke, J. M.; Pike, D.; Radunz, H.; Winterfeldt, E.; Die biogenetisch orientierte totalsynthese von DL-Camptoyhecin und 7-chlor-camptothecin. Chem. Ber. 1972, 105, 2126-2142.
21. (d) Carniaux, J.-F.; Kan-Fan, C.; Royer, J.; Husson, H.-P. Synthesis of a Novel Fused Tricyclic Quinolone system via Oxidation of 1,2,3,4-Tetrahydro- β-Carbolines Tetrahedron Lett. 1997, 38, 2997-3000.
22. Pivsa-Art, S.; Sato, T.; Kawamura, Y.; Miura, M.; Nomura, M. Palladium-Catalyzed Arylation of Azolation of Azole Compounds with Aryl Halides in the Presence of Alkali Metal Carbonates and the Use of Copper Iodides in the Reaction. Bull. Chem. Soc. Jpn. 1998, 71, 467-73.
23. (a) Wolfe, J. P.; Buchwald, S. L.; Palladium-Catalyzed Amination of Aryl Iodides, J. Org. Chem. 1996, 61, 1133-35.
24. (b) Old, D. W.; Harris, M. C.; Buchwald, S. L.; Efficient Palladium-Catalyzed N-arylation of Indoles, Org. Lett. 2000, 2, 1403-1406.
25. (c) Wolfe, J. P.; Tomori, H.; Sadighi, J. P.; Yin, J.; Buchwald. S. L. Simple, Efficient Catalyst System for the Palladium-Catalyzed Amination of Aryl Chlorides, Bromides, and Triflates. J. Org. Chem. 2000, 65, 1158-74.
26. (d) Wolfe, J. P.; Buchwald, S. L. Scope and Limitations of the Pd/BINAP-Catalyzed Amination of Aryl Bromides. J. Org. Chem. 2000, 65, 1144-57.