Cycloalkyl substituted imidazoles

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...

Patent

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

514825, 514866, 514903, 544316, A61K 31505, C07D40304

Patent

active

059290765

DESCRIPTION:

BRIEF SUMMARY
This invention relates to a novel group of imidazole compounds, processes for the preparation thereof, the use thereof in treating cytokine mediated diseases and pharmaceutical compositions for use in such therapy.


BACKGROUND OF THE INVENTION

Interleukin-1 (IL-1) and Tumor Necrosis Factor (TNF) are biological substances produced by a variety of cells, such as monocytes or macrophages. IL-1 has been demonstrated to mediate a variety of biological activities thought to be important in immunoregulation and other al., Rev. Infect. Disease, 6, 51 (1984)!. The myriad of known biological activities of IL-1 include the activation of T helper cells, induction of fever, stimulation of prostaglandin or collagenase production, neutrophil chemotaxis, induction of acute phase proteins and the suppression of plasma iron levels.
There are many disease states in which excessive or unregulated IL-1 production is implicated in exacerbating and/or causing the disease. These include rheumatoid arthritis, osteoarthritis, endotoxemia and/or toxic shock syndrome, other acute or chronic inflammatory disease states such as the inflammatory reaction induced by endotoxin or inflammatory bowel disease; tuberculosis, atherosclerosis, muscle degeneration, cachexia, psoriatic arthritis, Reiter's syndrome, rheumatoid arthritis, gout, traumatic arthritis, rubella arthritis, and acute synovitis. Recent evidence also links IL-1 activity to diabetes and pancreatic .beta. cells.
Dinarello, J. Clinical Immunology, 5 (5), 287-297 (1985), reviews the biological activities which have been attributed to IL-1. It should be noted that some of these effects have been described by others as indirect effects of IL-1.
Excessive or unregulated TNF production has been implicated in mediating or exacerbating a number of diseases including rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis, gouty arthritis and other arthritic conditions; sepsis, septic shock, endotoxic shock, gram negative sepsis, toxic shock syndrome, adult respiratory distress syndrome, cerebral malaria, chronic pulmonary inflammatory disease, silicosis, pulmonary sarcoisosis, bone resorption diseases, reperfusion injury, graft vs. host reaction, allograft rejections, fever and myalgias due to infection, such as influenza, cachexia secondary to infection or malignancy, cachexia, secondary to acquired immune deficiency syndrome (AIDS), AIDS, ARC (AIDS related complex), keloid formation, scar tissue formation, Crohn's disease, ulcerative colitis, or pyresis.
AIDS results from the infection of T lymphocytes with Human Immunodeficiency Virus (HIV). At least three types or strains of HIV have been identified, i.e., HIV-1, HIV-2 and HIV-3. As a consequence of HIV infection, T-cell mediated immunity is impaired and infected individuals manifest severe opportunistic infections and/or unusual neoplasms. HIV entry into the T lymphocyte requires T lymphocyte activation. Other viruses, such as HIV-1, HIV-2 infect T lymphocytes after T Cell activation and such virus protein expression and/or replication is mediated or maintained by such T cell activation. Once an activated T lymphocyte is infected with HIV, the T lymphocyte must continue to be maintained in an activated state to permit HIV gene expression and/or HIV replication. Monokines, specifically TNF, are implicated in activated T-cell mediated HIV protein expression and/or virus replication by playing a role in maintaining T lymphocyte activation. Therefore, interference with monokine activity such as by inhibition of monokine production, notably TNF, in an HIV-infected individual aids in limiting the maintenance of T cell activation, thereby reducing the progression of HIV infectivity to previously uninfected cells which results in a slowing or elimination of the progression of immune dysfunction caused by HIV infection. Monocytes, macrophages, and related cells, such as kupffer and glial cells, have also been implicated in maintenance of the HIV infection. These cells, like T-cells, are targets for viral replication and the level

REFERENCES:
patent: 2748119 (1956-05-01), Rorig
patent: 3557114 (1971-01-01), Bicking
patent: 3707475 (1972-12-01), Lombardino
patent: 3772441 (1973-11-01), Lombardino
patent: 3929807 (1975-12-01), Fitzi
patent: 3940486 (1976-02-01), Fitzi
patent: 4058614 (1977-11-01), Baldwin
patent: 4199592 (1980-04-01), Cherkofsky
patent: 4447431 (1984-05-01), Sallmann
patent: 4503065 (1985-03-01), Wilkerson
patent: 4565875 (1986-01-01), Cavender
patent: 4686231 (1987-08-01), Bender et al.
patent: 4822805 (1989-04-01), Tasasugi et al.
patent: 5593991 (1997-01-01), Adams et al.
patent: 5593992 (1997-01-01), Adams et al.
patent: 5656644 (1997-08-01), Adams et al.
patent: 5658903 (1997-08-01), Adams et al.
patent: 5663334 (1997-09-01), Adams et al.
patent: 5670527 (1997-09-01), Adams et al.
patent: 5686455 (1997-11-01), Adams et al.
patent: 5716955 (1998-02-01), Adams et al.
patent: 5739143 (1998-04-01), Adams et al.
patent: 5756499 (1998-05-01), Adams et al.
Dinarello et al., Rev.Infect.Disease, 6, p. 51 (1984).
Dinarello, J.Clin.Immun., 5(5), p. 287-297 (1985).
R.P.Soni, Aust.J.Chem., 35, p. 1493-6 (1982).
Poli et al., Proc.Nat'l Acad.Sci., 87, p. 782-784 (1990).
VanLeusen et al., J.O.C., 42, p. 1153 (1977).
Kumada et al., Tetrahedron Letters, 22, p. 5319 (1981).
Pridgen, J.Org.Chem., 47, p. 4319 (1982).
Stille, J.Amer.Chem.Soc., 109, p. 5478 (1978).
Fischer et al., Rec.Trav.Chim.Pays.Bas., 84, p. 439 (1965).
Snieckus, V., Tetrahedron Letters, 29, 2135 (1988).
Terashimia, M., Chem.Pharm.Bull., 11, p. 4755 (1985).
Thompson, W.J., et al., J.Org.Chem., 49, p. 5237 (1984).
Kawasaki et al., J. Bio. Chem., 272(30), pp. 18518-18521.
Uno, Bull. Chem. Soc. Japan., vol. 69, pp. 1763-1767 (1996).
Katrutzky, Synthesis, pp. 45-47 (1993).
Johnson, P.A., J.Chem.Soc., Perkin Trans., vol. 1, pp. 895-905 (1996).
Ishibashi, Chem. Pharm. Bull., 37(8), pp. 2214-2216 (1989).
Garigipati, R., Tetrahedron Letters, 31, p. 190 (1989).
Engel & Steglich, Liebigs Ann. Chem., 1916 (1978).
Strzybny et al., J. Org. Chem., 28, p. 3381 (1963).
Zavyalov, et al., Khim Farm Zh, 26(3), p. 88 (1992) (With Translation).
Colotta et al., J. Immunol., 132(2), p. 936 (1984).
Simon et al., J. Immunol. Methods, 84, p. 85 (1985).
Becker et al., J. Immunol., 147, p. 4307 (1991).
Gilbert, Synthesis, pp. 30-32 (1972).
Morton et al., Tetrahedron Letters, 4123 (1982).
Armarego, W. J. Chem. Soc., (JCSOA9) p. 561 (1962).

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

Cycloalkyl substituted imidazoles does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Cycloalkyl substituted imidazoles, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Cycloalkyl substituted imidazoles will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-878986

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.