Tetracyclic cyclic GMP-specific phosphodiesterase inhibitors, pr

Details Tetracyclic cyclic GMP-specific phosphodiesterase inhibitors, pr Tetracyclic cyclic GMP-specific phosphodiesterase inhibitors, pr

1998-09-16

2000-11-07

Cintins, Marianne M.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Heterocyclic carbon compounds containing a hetero ring...

514250, 514292, A61K 3150

Patent

active

061437468

ABSTRACT:
A compound of formula (I) and salts and solvates thereof, in which: R.sup.0 represents hydrogen, halogen, or C.sub.1-6 alkyl; R.sup.1 represents hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, haloC.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkylC.sub.1-3 alkyl, arylC.sub.1-3 alkyl, or heteroarylC.sub.1-3 alkyl; R.sup.2 represents an optionally substituted monocyclic aromatic ring selected from benzene, thiophene, furan, and pyridine, or an optionally substituted bicyclic ring (a) attached to the rest of the molecule via one of the benzene ring carbon atoms, and wherein the fused ring (A) is a 5- or 6-membered ring which may be saturated or partially or fully unsaturated, and comprises carbon atoms and optionally one or two heteroatoms selected from oxygen, sulphur, and nitrogen; and R.sup.3 represents hydrogen or C.sub.1-3 alkyl, or R.sup.1 and R.sup.3 together represent a 3- or 4-membered alkyl or alkenyl chain. A compound of formula (I) is a potent and selective inhibitor of cyclic guanosine 3',5'-monophosphate specific phosphodiesterase (cGMP specific PDE) having a utility in a variety of therapeutic areas where such inhibition is beneficial, including the treatment of cardiovascular disorders and erectile dysfunction.

REFERENCES:
patent: 3644384 (1972-02-01), Schulenberg
patent: 3717638 (1973-02-01), Schulenberg
patent: 3917599 (1975-11-01), Saxena et al.
patent: 4188390 (1980-02-01), Campbell
patent: 4686228 (1987-08-01), Campbell et al.
patent: 4801587 (1989-01-01), Voss et al.
patent: 5145852 (1992-09-01), Virag
patent: 5270323 (1993-12-01), Milne, Jr. et al.
patent: 5770606 (1998-06-01), El-Rashidy et al.
patent: 5859006 (1999-01-01), Daugan
patent: 5874437 (1999-02-01), Garvey et al.
A. Bowman et al., Br. J. Pharmac., (1984), 81, 665-674.
F. Trigo-Rocha et al., Am. J. Physiol., (Feb. 1993), 264, H419-H422.
J. Reiser et al., Br. J. Dis. Chest, (1986), 80, 157-163.
P. Bush et al., J. Urol., (Jun. 1992), 147, 1650-1655.
F. Holmquist et al., J. Urol. (Oct. 1993), 150, 1310-1315.
R. Rudd et al., Br. J. Dis. Chest, (1983), 77, 78-86.
E. McMahon et al., J. Pharmacol. Exp. Thera., (1989), 251, 1000-1005.
F. Holmquist et al., Acta Physiol. Scand., (1991), 143, 299-304.
G. Barbanti, Urol. Res., (1988), 16, 299-302.
L. Ignarro et al., Biochem. and Biophys. Res. Comm., (1990), 170(2), 843-850.
J. Krall et al., Bio. Reprod., (1988), 39, 913-922.
M. Wilkins et al., Proc. Natl. Acad. Sci., USA, (Aug. 1990), 87, 6465-6469.
M. Wilkins et al., J. Clin. Invest., (Apr. 1990), 85, 1274-1279.
J. Rajfer, N. Eng. J. Med., (Jan. 1992), 326(2), 90-94.
H. Knispel, Urol. Res., (1992), 20, 253-257.
G. Gwinup, Annals. of Internal Medicine, (Jul. 1988), 162-163.
A. Zorgniotti, J. Urol., (Apr. 1992), 147(4), 308A.
K. Azadzoi et al., J. Urol., (Nov. 1992), 148, 1587-1591.
K. Azadzoi et al., J. Urol., (Jan. 1992), 147, 220-225.
C. Sparwasser et al., J. Urol., (Dec. 1994), 152, 2159-2163.
T. Lue, "Campbell's Urology," 6th Ed., Chap. 16, P. Walsh et al., Eds., W.B. Saunders Co., 709-728 (1991).
N. Kim et al., J. Clin. Invest., (1991), 88, 112-118.
S. Francis et al., in J. Beavo et al. eds. "Cyclic Nucleotide PDEs," Ch. 5 (1990) 117-140.
R. Weishaar et al., J. Med. Chem., (1985), 28:5, 537-542.
H. Ahn et al., Biochem. Pharmacol., (1989), 39:19, 3331-3339.
C. Lugnier et al., Biochem. Pharmacol., (1986), 35:10, 1743-1751.
J. Doremieux et al., Ann. Urol. Paris, (1987), 21(6), 429-434.
D. Green et al., Geriatrics, (Jan. 1993), 48(1), 46-58.
M. Webster et al., Hematol. Oncol. Cl. of N. Am., (Feb. 1990), 4(1), 265-289.
F. Holmquist et al., Acta. Physiol. Scand., (1991), 141, 441-442.
J. Taher et al., J. Urol., (Apr. 1993), 149, 285A.
S. Uckert et al., J. Urol., 151 (5 Supp.), (1994), 495A.
W. Aronson et al., J. Urol., (1991), 145 (4 Supp.), 341A.
P. Bush et al., Fed. Am. Soc. Exp. Biol., (1991), 5(4), 175.
P. Bush et al., Fed. Am. Soc. Exp. Biol., (1992), 6(4), 2092.
W. Aronson et al., J. Urol., (1992), 147 (4 Supp.), 454A.
P. Bush et al., Circulation, (May 1993), 87 Supp. V, V-30-V-32.
R. Pickard et al., J. Urol., (May 1993) 149 (4 Supp.), 245A.
R. Pickard et al., Clin. Pharmacol., (Jan. 1993), 35(5), 536P-537P.
F. Trigo-Rocha et al., J. Urol., (Apr. 1993), 149, 872-877.
M. Krupp et al., J. Cardiovas. Pharmacol., (1989), 13 (Supp. 2), S11-S19.
"Physician' Desk Reference," (1992), 683,1099-1100, 1344, 1941-1943.
R. Morales et al., World J. Urol., (1990), 8, 80-83.
J. Cortijo, Br. J. Pharmacol., (Feb. 1993), 108(2), 562-568.
E. Kim et al., J. Urol., (1995), 153, 361-365.
S. Korenman et al., JAGS, (Apr. 1993), 41(4), 363-366.
K. Allenby et al., Angiology, (1991), 42, 418-420.
H. Hamilton et al., J. Med. Chem., (1987), 30, 91-96.
H. Padma-Nathan et al., Sem. in Urol., (Nov. 1986), vol. IV, No. 4, 236-238.
J. Beavo et al., TiPS, (Apr. 1990), 11, 150-155.
S. Korenman et al., Clin. Res., (1988), 36, 123A.
D. Halsted et al., J. Urol., (Jul. 1986), 136, 109-110.
W. Thompson, Pharmac. Ther., (1991), 51, 13-33.
M. Giembycz et al., Clin. and Exper. Allergy, (1992), 22, 337-344.
C. Nicholson et al., TIPS, (Jan. 1991), 12, 19-27.
J. LeBlanc et al., Eur. J. Cardiothorac Surg., (1993), 7, 211-215.
C. Stief et al., J. Urol., (Nov. 1992), 148, 1437-1440.
C. Stief et al., World J. Urol., (1991), 9, 237-239.
C. Clyne et al., Br. J. Surg., (Apr. 1987), 74, 246-248.
V. Mirone et al., Acta. Urol. Ltd., (1992), Suppl. 4, 11-12.
P. Bush, Ph.D. Thesis (1992), pp. 159-160.
T. Lincoln, Pharmac. Ther., (1989), 41, 479-502.
J. Heaton et al., Urology, (Feb. 1995), 45(2), 200-206.
Saxena et al., Journal of Medicinal Chemistry, vol. 16, No. 5, 560-564 (1973).
Ishida et al., Chem. Pharm. Bull., vol. 33, No. 8, 3237-3249 (1985).
Gillespie et al., Molecular Pharmacology, 36:773-781 (1989).
Brana et al., Synthetic Communications, 20(12), 1793-1820 (1990).
Dellouve-Courillon et al., Tetrahedron, 46, No. 9, 3245-3266 (1990).
Murray, DN&P 6(3), 150-156 (1993).
Zorgniotti et al. Int. J. Impotence Res., 6, 33-36 (1994).
Beyer et al., Phys. and Behav., (1981), 27, 731-733.
Pickard et al., Br. J. Pharmacol., (1991), 104 755-759.
Martinez-Pineiro et al., Eur. Urol., (1993), 24, 492-499.
Mirone et al., Br. J. Urol., (Mar., 1993), 71(3), 365.
Murray et al., Biochemical Soc. Trans., (1992), 20, 460-464.
Raeburn et al., Prog. Drug Res., (1993), 12-32.
Merkel, Cardio. Drug. Rev., (1993), 11(4), 501-515.
"Physicians' Desk Reference," (1992) 2207-2208.
Cimino et al., Biochem. Pharmacology, (1988), 37(14), 2739-2745.
Watanabe et al., Federation Proceedings, (1982), 41(7), 2292-2399.
Earl et al., Life Sciences, (1984), 35, 525-534.
Brindley, Brit. J. Phychiat., (1983), 143, 332-337.
Keogh, Aust. NZ. J. Med., (1989), 19, 108-112.
Funderbunk, New Engl. J. Med., (1974), 290, 630-631.
Beretta, Acta European Fertilitatis, (1986), 17, 43-45.
"Physicians' Desk Reference," (1992), 1778-1779.
Hess in "Prazosin: Evaluation of a New Antihypertensive Agent," D. Cotton ed., American Elsevier, NY, (1974), 3-15.
Dadkar et al., Ind. J. Exp. Biol., (1982), 20, 484-487.
D'Armiento et al., Eur. J. Pharmacol., (1980), 65, 234-247.
Bhalla et al., Brit. Med. J., (1979), 2, 1059.
Burke et al., Med. J. Aust., (1980), 382-383.
Segasouthy et al., Med. J. Malaysia, (1982), 37(4), 384.
Ylitalo et al., Acta Med. Scand., (1983), 213, 319-320.
Robbins et al., J. Urol., (1983), 130, 975.
Adams et al., J. Urol., (1984), 132, 1208.
Russell et al., Med. J. Aust., (1985), 143, 321.
Taher et al., Int. J. Impotence Res., Abstracts, Milan, Italy (Sep. 14-17, 1992).
Trigo-Rocha et al., Neurology and Urodynamics, 13, (1998) 71-80.

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