The Procter Gamble Company

Michael Philip Clark

Biswanath De

Matthew John Laufersweiler

Adam Golebiowski

Todd Andrew Brugel

Michael G Natchus

Mark Sabat

Jane Far-Jine Djung

Joshua Spector Tullis

John Charles Van Rens

Steven Karl Laughlin

Benjamin Eric Blass

Jennifer Anne Townes

Michael John Janusz

Roger Gunnard Bookland

Gregory Kent Bosch

Stephen Matthew Berberich

Cynthia Monesa Crago Clark

Robert Arthur Lyon

The present invention relates to 6,7-dihydro-5H-pyrazolo[1,2&#x3b1;]pyrazol-1-ones which inhibit the extracellular release of inflammatory cytokines, said cytokines responsible for one or more human or higher mammalian disease states. The present invention further relates to compositions comprising said 6,7-dihydro-5H-pyrazolo[1,2&#x3b1;]pyrazol-1-ones and methods for preventing, abating, or otherwise controlling enzymes which are understood to be the active components responsible for the herein described disease states.

Bicyclic pyrazolone cytokine inhibitors

The present invention relates to 1,1,3-tri-substituted ureas which inhibit the extracellular release of inflammatory cytokines, said cytokines responsible for one or more human or higher mammalian disease states. The present invention further relates to compositions comprising said 1,1,3-tri-substituted ureas which inhibit the extracellular release of inflammatory cytokines, and methods for preventing, abating, or otherwise controlling enzymes which are understood to be the active components responsible for the herein described disease states.

Tri-substituted ureas as cytokine inhibitors

The present invention relates to 2-(4-fluorophenyl)-3-(2-phenoxy-pyrimidin-4-yl)-6,7-dihydro-5H-pyrazolo-[1,2-a]pyrazol-1-one, including all enantiomeric and diasteriomeric forms and pharmaceutically acceptable salts thereof, having the formula: and pharmaceutical compositions thereof, and methods for controlling the level of one or more inflammation inducing cytokines selected from the group consisting of, interleukin-1 (IL-1), Tumor Necrosis Factor-&#x3b1; (TNF-&#x3b1;), interleukin-6 (IL-6), and interleukin-8 (IL-8), thereby controlling, mediating, or abating disease states affected by the level of extracellular inflammatory cytokines in humans.

6,7-Dihydro-5H-pyrazolo[1,2-a]pyrazol-1-ones which control inflammatory cytokines

The present invention relates to methods for treating diseases or disease states which are mediated or otherwise affected by the extracellular release of cytokines, said method comprising the step of administering to a human or higher mammal in need of treatment, one or more of the 6,7-dihydro-5H-pyrazolo[1,2a]pyrazol-1-ones of the present invention.

The present invention relates to 2,6,7-substituted pyrrolo[2,3-d]pyrimidines which inhibit the extracellular release of inflammatory cytokines, said cytokines responsible for one or more human or higher mammalian disease states. The present invention further relates to compositions comprising said 2,6,7-substituted pyrrolo[2,3-d]pyrimidines and methods for preventing, abating, or otherwise controlling enzymes which are understood to be the active components responsible for the herein described disease states.

Pyrrolo[2,3-d]pyrimidine cytokine inhibitors

The present invention relates to 2,8,9-substituted purines which inhibit the extracellular release of inflammatory cytokines, said cytokines responsible for one or more human or higher mammalian disease states. The present invention further relates to compositions comprising said 2,8,9-substituted purines and methods for preventing, abating, or otherwise controlling enzymes which are understood to be the active components responsible for the herein described disease states.

Purine cytokine inhibitors

The present invention relates to compound which are capable of preventing the extracellular release of inflammatory cytokines, said compounds, including all enantiomeric and diasteriomeric forms and pharmaceutically acceptable salts thereof, have the formula: wherein R comprises ethers or amines;

6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-ones which provide analgesia

The present invention relates to 2-(4-fluorophenyl)-3-(2-phenoxy-pyrimidin-4-yl)-6,7-dihydro-5H-pyrazolo-[1,2-a]pyrazol-1-one, including all enantiomeric and diasteriomeric forms and pharmaceutically acceptable salts thereof, having the formula:and pharmaceutical compositions thereof, and methods for controlling the level of one or more inflammation inducing cytokines selected from the group consisting of, interleukin-1 (IL-1), Tumor Necrosis Factor-&#x3b1;(TNF-&#x3b1;), interleukin-6 (IL-6), and interleukin-8 (IL-8), thereby controlling, mediating, or abating disease states affected by the level of extracellular inflammatory cytokines in humans.

6,7-dihydro-5H-pyrazolo[1,2a]pyrazol-1-ones which control inflammatory cytokines

Isoxazolone compounds having the generic structure:are used to treat disease associated with unwanted cytokine activity, including rheumatoid arthritis, osteoarthritis, diabetes, HIV/AIDS, inflammatory bowel disease, Crohn's disease, ulcerative colitis, congestive heart, hypertension, chronic obstructive pulmonary disease, septic shock syndrome, tuberculosis, adult respiratory distress, asthma, atherosclerosis, muscle degeneration, periodontal disease, cachexia, Reiter's syndrome, gout, acute synovitis, anorexia and bulimia nervosa fever, malaise, myalgia and headaches.

Isoxazolone compounds useful in treating diseases associated with unwanted cytokine activity

The present invention relates to compounds which are capable of preventing the extracellular release of inflammatory cytokines, said compounds, including all enantiomeric and diasteriomeric forms and pharmaceutically acceptable salts thereof, have the formula:wherein Ris substituted aryl; Ris substituted or unsubstituted aryl or heteroaryl.

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Maineville, OH, United States of America

Michael Philip Clark