PDE IV inhibitors: "bis-compounds"

Details PDE IV inhibitors: "bis-compounds" PDE IV inhibitors: "bis-compounds"

1996-09-16

1998-04-28

Berch, Mark L.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

514266, 544276, 544277, 544253, 544280, 546112, 546113, 546183, C07D51900, A61K 3152, A61K 31505, A61K 3144

Patent

active

057444730

ABSTRACT:
Novel compounds which are effective PDE IV inhibitors are disclosed. The compounds possess improved PDE IV inhibition as compared to theophylline or rolipram, with improved selectivity with regard to, e.g., PDE V inhibition. Also provided is a process of making compounds of Formula I. Compounds of the present invention are represented by Formula I: ##STR1## its pharmaceutically acceptable salts, hydrochloride salts, or prodrug forms thereof, wherein:

REFERENCES:
patent: 2691654 (1954-10-01), Hitchings
patent: 2844577 (1958-07-01), Acker
patent: 2903455 (1959-09-01), Strong et al.
patent: 2956998 (1960-10-01), Baizer
patent: 2957875 (1960-10-01), Lyttle et al.
patent: 2966488 (1960-12-01), Shive et al.
patent: 3135753 (1964-06-01), Hitchings
patent: 3136771 (1964-06-01), Liechti et al.
patent: 3215696 (1965-11-01), Denayer
patent: 3225046 (1965-12-01), Zwahlen
patent: 3262929 (1966-07-01), Okubu et al.
patent: 3494919 (1970-02-01), Collins et al.
patent: 3541100 (1970-11-01), Ramirez et al.
patent: 3574218 (1971-04-01), Hideg et al.
patent: 3636039 (1972-01-01), Gruenman et al.
patent: 3674781 (1972-07-01), Schinzel et al.
patent: 3706834 (1972-12-01), Scheilenbaum et al.
patent: 3923833 (1975-12-01), Gruenmann et al.
patent: 3962452 (1976-06-01), Evans et al.
patent: 4025636 (1977-05-01), Dunwell et al.
patent: 4025637 (1977-05-01), Dunwell et al.
patent: 4167628 (1979-09-01), Kormany
patent: 4308278 (1981-12-01), Schneider et al.
patent: 4361699 (1982-11-01), Rasmusson et al.
patent: 4416892 (1983-11-01), Dawson
patent: 4652654 (1987-03-01), Verga et al.
patent: 4684656 (1987-08-01), Atwal
patent: 4710503 (1987-12-01), Hofer
patent: 4803216 (1989-02-01), Appleton et al.
patent: 4831152 (1989-05-01), Itoh et al.
patent: 4868183 (1989-09-01), Kanai et al.
patent: 4925847 (1990-05-01), Hofer
patent: 5047411 (1991-09-01), Takasugi et al.
patent: 5068236 (1991-11-01), Suzuki et al.
patent: 5117830 (1992-06-01), McAfee et al.
patent: 5190942 (1993-03-01), Poss
patent: 5206255 (1993-04-01), Ubsawa et al.
patent: 5264589 (1993-11-01), Corey
patent: 5322847 (1994-06-01), Marfat et al.
patent: 5496853 (1996-03-01), Shiota et al.
Leonard, J.A.C.S. 95, 4010 (1973).
Ronald E. Weishaar, et al., Subclasses of Cyclic GMP-Specific phosphodiesterase and their role in regulating the effects of atrial natriuretic factor, Dept. Of Pharmacology, Park-Davis Pharmaceutical Research Division, Warner-Lambert Co. Hypertension, vol. 15, No. 5, May 1990.
"Differential modulation of tissue function and therapeutic potential selective inhibitors of cyclic nucleotide phosphodiesterase isoenzymes", C. David Nicholson, R.A. John Chaliss and Mohammed Shahid, 1991, Elsevier Science Publishers Ltd. (UK), TIPS 12:19-27.
"Phosphodiesterase inhibitors: new opportunities for the treatment of asthma", Theodore J. Torphy, Bradley J. Undem, Thorax 1991; 46:512-523.
"Novel phosphodiesterase inhibitors for the therapy of asthma", Theodore J. Torphy, George P. Livi and Siegried B. Christensen, DN&P 6(4), May 1993 pp. 203-214.
"Assay of cyclic nucleotide phosphodiesterase and resolution of multiple molecular forms of the enzyme", W. Joseph Thompson, Wesley L. Terasaki, Paul M. Epstein, Samuel J. Strada, Advances in Cyclic Nucleotide Research, vol. 10, 1979, pp. 69-92.
"Identification, characterization and functional role of phosphodiesterase isozymes in human airway smooth muscle", Theodore J. Torphy, Bradley J. Undem, Lenora B. Cieslinski, Mark A. Luttmann, Martin L. Reeves and Douglas W.P. Hay, The Journal of Pharmacology and Experimental Therapeutics, 1993, vol. 265, No. 3, 1213-1223.
"The PDE IV family of calcium-independent phosphodiesterase enzymes", John A. Lowe III and John B. Cheng, Drugs of the Future, 1992, 17(9):799-807.
"Could isoenzyme-selective phosphodiesterase inhibitors render bronchodilator therapy redundant in the treatment of bronchial asthma?", Mark A. Giembycz, Biochemical Pharmacology, 1992, vol. 43, No. 10 pp. 2041-2051.
"Differential pharmacologic sensitivity of cyclic nucleotide phosphodiesterase isozymes from cardiac muscle, arterial and airway smooth muscle", Paul J. Silver, Linda T. Hamel, Mark H. Perrone, Ross G. Bently, Cynthia R. Bushover and Dale B. Evans, European Journal of Pharmacology, 150 (1988) 85-94, Elsevier.
"The pharmacology and therapeutic use of theophylline", Miles Weinberger, M.D., The Journal of Allergy and Clinical Immunology, vol. 73, No. 5, part 1, 525-544.
"Structure-Activity Relationships in a Series of 6-Thioxanthines with Bronchodilator and Coronary Dilator Properties", A.K. Armitrage, Janet Boswood and B.J. Large, Brit. J. Pharma. 1961, 17:196-207.
"The Synthesis of Some 6 Thioxanthines", K.R.H. Wooldrige and R. Slack, J. Chem. Soc. 1962, Annex IV:1863-1868.
Enoki et al Chemical Abstracts, vol. 85, No. 1 (Jul. 9, 1976) 5692s.
Enoki et al Chemical Abstracts, vol. 84, No. 25 (Jun. 21, 1976) 180299v.
Aida et al Chemical Abstracts, vol. 86, No. 7 (Feb. 14, 1977) 43746r.
Isomura et al., "Studies on the synthesis and anti-inflammatory activity of 2,6-Di-tert-butylphenols with a heterocyclic group at the 4-position.I", vol. 31, No. 9, pp. 3168-3178 (1983).
Chemical Abstracts 103:37354, 1985 (Nagarajan).
Chemical Abstracts 116:255335, 1992 (Bender).
Itaya, Tetrahedron Letters, vol. 23, No. 21 (1982), pp. 2203-2204.
Reitz, Journal of Organic Chemistry, vol. 55, No. 22 (Oct. 26, 1990), pp. 5761-5766.
Chemical Abstracts 88:51054, 1977 (Ninomiya).
Kazimier Czvil et al Chemical Abstracts, vol. 82 (19) May 12, 1975, Abstract #12358x.
Chemical Abstracts 114:246982, 1990 (Naruto).
"Controlled Interaction between Nucleic Acid Bases. Intramolecular Stacking Interactions between Two Adenine Rings", Nelson J. Leonard, et al.; Journal of the American Chemical Society, 95:12, Jun. 13, 1973, pp. 4010-4016.
Chemical Abstracts 92:6207, 1977 (Pirisino).
Ronald E. Weishaar, et al., Multiple molecular forms of cyclic nucleotide phosphodiesterase in cardiac and smooth muscle and in platelets, Biochemical Pharmacology, vol. 35, No. 5., pp. 787-800, 1986.
G.T. Rogers and T.L.V. Ulbricht, "Synthesis of 3-Methylisoguanine (6-amino-3-methylpurin-2(3H)-one)", J. Chem. Soc. (C), pp. 2364-2366 (1971).
Chemical Absracts 116:173873 (1979) Girshovich.
J. A. Montgomery, et al., "Synthesis of Potential Anticancer Agents. XIX. 2-Substituted N.sup.6 -Alkyladenines" (1959) J.A.C.S. vol. 81, pp. 3963-3967.
Chemical Abstracts 53:6243 (1957) Elion.
T. Fuji, et al. "3-Substituted Adenines. In Vitro Enzyme Inhibition and Antiviral Activity", Am. Chem. Soc., vol. 22, No. 2, pp. 126-129.

Affiliated with

Also associated with

Rating

PDE IV inhibitors: "bis-compounds" does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with PDE IV inhibitors: "bis-compounds", we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and PDE IV inhibitors: "bis-compounds" will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1532160