NOVEL UREA AND THIOUREA DERIVATIVES

摘要

The present application discloses compounds of formula (I) wherein X is ═O, ═S, ═NH, ═NOH and ═NO-Me; A is —C(═O)—, —S(═O)2—, —C(═S)— and P(═O)(R5)—; B is, —O—, —(CH2)3-6—, and O—(CH2)2-5—; D is, —O—, —CR7R8— and —NR9; m is 0-12, n is 0-12, m+n is 1-20; p is 0-4; R1 is opt.sub. heteroaryl; and pharmaceutically acceptable salts thereof, and prodrugs thereof. The application also discloses the compound for use as a medicament for the treatment of a disease or a condition caused by an elevated level of nicotinamide phosphoribosyltransferase (NAMPRT), e.g. inflammatory and tissue repair disorders; dermatosis; autoimmune diseases, Alzheimers disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, ataxia telengiectasia.

主权项

1. A compound of the formula (I) wherein X is selected from ═O, ═S, ═NH, ═NOH and ═NO-Me; A is selected from —C(═O)—, —S(═O)2—, —C(═S)— and —P(═O)(R5)—, wherein R5 is selected from C1-6-alkyl, C1-6-alkoxy and hydroxy; B is selected from a single bond, —(CH2)3-6—, —O—, and —O—(CH2)2-5—; D is selected from a single bond, —O—, —CR7R8— and —NR9, wherein R7, R8 and R9 are independently selected from hydrogen, optionally substituted C1-12-alkyl, optionally substituted C1-12-alkenyl, optionally substituted aryl, optionally substituted heterocyclyl, and optionally substituted heteroaryl; m is an integer of 0-12 and n is an integer of 0-12, wherein the sum m+n is 1-20; p is an integer of 0-4; R1 is selected from optionally substituted heteroaryl; R2 is selected from hydrogen, optionally substituted C1-12-alkyl, optionally substituted C3-12-cycloalkyl, —[CH2CH2O]1-10-(optionally substituted C1-6-alkyl), optionally substituted C1-12-alkenyl, optionally substituted aryl, optionally substituted heterocyclyl, and optionally substituted heteroaryl; and R3 is selected from optionally substituted C1-12-alkyl, optionally substituted C3-12-cycloalkyl, —[CH2CH2O]1-10-(optionally substituted C1-6-alkyl), optionally substituted C1-12-alkenyl, optionally substituted aryl, optionally substituted heterocyclyl, and optionally substituted heteroaryl; or R2 and R3 together with the intervening atoms (i.e. —N—B—) form an optionally substituted N-containing heterocyclic or heteroaromatic ring; each of R4 and R4* is independently selected from hydrogen, optionally substituted C1-12-alkyl and optionally substituted C1-12-alkenyl; with the provisos that R1 is not optionally substituted thiazol-2-yl when p is 0; and with the proviso that the compound is not phenyl-NH—C(═O)—(CH2)5—NH—C(═S)—NH-(4-pyridyl); and pharmaceutically acceptable salts thereof, and prodrugs thereof.