Hydroxyl-containing compounds

A method for inhibiting a cellular process or activity mediated by IL-12 signalling comprising the steps of:

• (a) contacting IL-12 responsive cells with a compound of the formula,
• (R)j-(CORE MOIETY),
• including resolved enantiomers, diastereomers, hydrates, salts, solvates and mixtures thereof, wherein j is an integer from one to three, the core moiety is a bicyclic ring structure having at least one heterocyclic ring that contains five to six ring atoms and up to two nitrogen heteroatoms, R is selected from the group consisting of hydrogen, halogen, hydroxyl, amino, substituted or unsubstituted benzyl, C1-6 alkyl or C1-6 alkenyl, and at least one R has the formula I:
• 68
• wherein n is an integer from 1 to 20, at least one of X or Y is —OH, another of X or Y, which is not —OH, being selected from H, CH3, CH3—CH2—CH3—(CH2)2—, or (CH3)2—CH2—, and each W1, W2, and W3 is independently selected from H, CH3, CH3—CH2—, CH3—(CH2)2—, or (CH3)2—CH2—, said X, Y, W1, W2 or W3 alkyl groups being unsubstituted or substituted by a hydroxyl, halo or dimethylamino group;
• and
• (b) determining that the response of the target cell is thereby modulated;

A method for treating a Th1 cell-mediated inflammatory response in a mammal in need of such treatment, the method comprising:

• administering to the mammal a therapeutically effective amount of a compound of the formula,
• (R)j-(CORE MOIETY),
• including resolved enantiomers, diastereomers, hydrates, salts, solvates and mixtures thereof, wherein j is an integer from one to three, the core moiety is a bicyclic ring structure having at least one heterocyclic ring that contains five to six ring atoms and up to two nitrogen heteroatoms, R is selected from the group consisting of hydrogen, halogen, hydroxyl, amino, substituted or unsubstituted benzyl, C1-6 alkyl or C1-6 alkenyl, and at least one R has the formula I:
• 70
• wherein n is an integer from 1 to 20, at least one of X or Y is —OH, another of X or Y, which is not —OH, being selected from H, CH3, CH3—CH2—CH3—(CH2)2—, or (CH3)2—CH2—, and each W1, W2, and W3 is independently selected from H, CH3, CH3—CH2—, CH3—(CH2)2—, or (CH3)2—CH2—, said X, Y, W1, W2 or W3 alkyl groups being unsubstituted or substituted by a hydroxyl, halo or dimethylamino group;
• and
• wherein said compound is capable of inhibiting an IL-12 mediated cellular process or activity, thereby inhibiting the inflammatory response.

The method of claim 21, wherein the disease or treatment-induced toxicity is selected from the group consisting of:

• tumor progression involving tumor stimulation of blood supply (angiogenesis) by production of FGF, VEGF or PDGF;
• tumor invasion and formation of metastases through adhesion molecule binding, expressed by vascular endothelial cells (VCAM and ICAM);
• tissue invasion through tumor metalloprotease production;
• autoimmune diseases caused by dysregulation of the T cell or B cell immune systems, treatable by suppression of the T cell or B cell responses;
• acute allergic reactions, mediated by pro-inflammatory cytokines including TNF and IL-1, or associated with enhanced localization of inflammatory cells and relase of inflammatory cytokines and metalloproteases;
• smooth muscle cell, endothelial cell, fibroblast and other cell type proliferation in response to growth factors, such as PDGF-AA, BB, FGF or EGF;
• activation of human immunodeficiency virus infection (AIDS and AIDS related complex);
• HIV-associated dementia;
• kidney mesangial cell proliferation in response to IL-1, MIP-1α, PDGF or FGF;
• inflammation;
• kidney glomerular or tubular toxicity in response to cyclosporin A or amphotericin B treatment;
• organ toxicity in response to a cytotoxic therapy;
• effects of non-alkylating anti-tumor agents;
• inflammation in response to inflammatory stimuli, characterized by production of metalloproteases or allergies due to degranulation of mast cells and basophils in response to IgE or RANTES;
• bone diseases caused by overproduction of osteoclast-activating factor (OAF) by osteoclasts;
• CNS diseases resulting from over-stimulation by pro-inflammatory neurotransmitters acetylcholine, serotonin, leuenkephalin or glutamate;
• acute inflammatory diseases such as septic shock, adult respiratory distress syndrome;
• multi-organ dysfunction associated with inflammatory cytokine cascade;
• and combinations thereof.