NOVELTY - Amide and thioamide derivatives (I) are new.
USE - (I) are useful in the treatment of cytokine mediated diseases particularly rheumatoid arthritis, osteoarthritis, Crohn's disease, ulcerative colitis, multiple sclerosis, Guillain-Barre syndrome, psoriasis, graft versus host disease, systemic lupus erythematosus, diabetes, toxic shock syndrome, osteoporosis, Alzheimer's disease, acute and chronic pain, contact dermatitis and atherosclerosis, and neutrophil-mediated diseases particularly stroke, myocardial infarction, thermal injury, adult respiratory distress syndrome, multiple organ injury secondary to trauma, acute glomerulonephritis, dermatoses with acute inflammatory components, acute purulent meningitis, hemodialysis, leukophoresis, granulocyte transfusion associated syndromes and necrotizing enterocolitis (claimed).
DETAILED DESCRIPTION - Amide and thioamide derivatives of formula (I) and their derivatives are new.
G1 = optionally substituted optionally unsaturated aromatic 6-10C carbocycle or nonaromatic 3-10C carbocycle; optionally substituted 6-14 membered mono-, bi- or tri-cyclic heteroaryl, 6-8 membered monocyclic heterocycle or 8-11 membered bicyclic heterocycle, each containing at least one O, N and/or S;
E1 = C (sic), O, NH or S;
A2 = optionally substituted phenyl, naphthyl, quinolinyl, isoquinolinyl, tetrahydronaphthyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, benzimidazolyl, benzofuranyl, dihydrobenzofuranyl, indolinyl, benzothienyl, dihydrobenzothienyl, indanyl, indenyl or indolyl;
W1 = O or S;
X1 = optionally substituted 5-8C cycloalkyl or cycloalkenyl, aryl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, pyridinyl, pyrimidinyl, pyridinonyl, dihydropyridinonyl, maleimidyl, dihydromaleimidyl, piperidinyl, benzimidazolyl, 3H-imidazo(4,5-b)pyridine, piperazinyl, pyridazinyl or pyrazinyl;
Y1 = bond or optionally substituted 1-4C optionally unsaturated C chain optionally partially or fully halogenated optionally having at least one methylene group replaced by O, NH or S(O)m;
Z1 = optionally substituted aryl or Het;
Het = pyridinyl, piperazinyl, pyrimidinyl, pyridazinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, furanyl, thienyl, pyranyl, tetrahydropyrimidonyl, cyclohexanonyl, cyclohexanolyl, 2-oxa- or 2-thia-5-aza-bicyclo(2.2.1)heptanyl, pentamethylene sulfidyl, pentamethylene sulfoxidyl, pentamethalene sulfonyl, tetramethylene sulfidyl, tetramethylene sulfoxidyl, tetramethylene sulfonyl, tetrahydropyranyl, tetrahydrofuranyl, 1,3-dioxolanonyl, 1,3-dioxanonyl, 1,4-dioxanyl, morpholino, thiomorpholino, thiomorpholino sulfoxidyl, thiomorpholino sulfonyl, piperidinyl, piperidinonyl, pyrrolidinyl or dioxolanyl; and
m = 0-2.
For the complete definitions, see 'Definition - Full Definitions'.
INDEPENDENT CLAIMS are also included for the following:
(1) 2 further similar compounds; and
(2) the preparation of the compounds.
