Patent IL-156465-A (IL)
Title: Growth hormone secretagogues for use in the treatment of sleep disorders
IPC: A61P43/00
Filed: 1998-06-05
Abstract: A compound of the formula or the stereoisomeric mixtures, diastereomerically enriched, diastereomerically pure, enantiomerically enriched or enantiomerically pure isomers, or the pharmaceutically acceptable salts and prodrugs thereof, wherein e is 0 or 1; n and w are each independently 0, 1 or 2; provided that w and n cannot both be 0 at the same; Y is oxygen or sulfur; 2024 ז' באב התשס" ד - July 25, 2004 where the alkyl and cycloalkyl groups in the definition of R1 are optionally substituted with (C1-C4) alkyl, hydroxyl, (C1-C4) alkoxy, carboxyl, -CONH2, -S(O)m(C1-C6) alkyl, -CO2(C1-C4) alkyl ester, 1H-tetrazol-5-yl or 1, 2 or 3 fluoro; Y1 is O, S(O)m -C(O)NX6-, -CH=CH-, -C:C-, -N(X6)C(O)-, -C(O)NX6-, -C(O)O-, -OC(O)N(X6)- or -OC(O)-; q is 0, 1, 2, 3 or 4; t is 0, 1, 2 or 3; said (CH2)q group and (CH2)t group may each be optionally substituted with hydroxyl, (C1-C4) alkoxy, carboxyl, -CONH2, -S(O)m(C1-C6) alkyl, -CO2(C1-C4) alkyl ester, 1H-tetrazol-5-yl, 1, 2 or 3 fluoro, or 1 or 2 (C1-C4) alkyl; R2 is hydrogen, (C1-C8) alkyl, -(C0-C3) alkylene-(C3-C8) cycloalkyl, -(C1-C4) alkylene-A1 or A1; where the alkyl groups and the cycloalkyl groups in the definition of R2 are optionally substituted with hydroxyl, -C(O)X6, -C(O)N(X6)(X6), -N(X6)(X6), -S(O)m(C1-C6) alkyl, -C(O)A1, -C(O)(X6), CF3, CN or 1, 2 or 3 halogen; R3 and A1, (C1-C10) alkyl, -(C1-C6) alkylene-A1, -(C1-C6) alkylene- (C3-C7) 2025 ז' באב התשס" ד - July 25, 2004 cycloalkyl, -(C1-C5) alkylene-X1-(C1-C5) alkyl, -((C1-C5) alkylene-X1- (C0-C5) alkylene-A1 or -(C1-C5) alkylene-X1-(C1-C5) alkylene-(C3-C7) cycloalkyl; where the alkylene groups in the definition of R3 are optionally substituted with -S(O)m(C1-C6) alkyl, -C(O)OX1, 1, 2, 3, 4 or 5 halogens, or 1, 2 or 3 OX3; X1 is O, S(O)m, -N(X2)C(O)-, -C(O) N(X2)-, -OC(O)-, -C(O)O-, -XC2=CX2-, -N(X2)C(O)O-, OC(O)N(X2)- or -C:C-; R4 is hydrogen, (C1-C6) alkyl or (C3-C7) cycloalkyl, or R4 is taken together with R3 and the carbon atom to which they are attached and form (C5-C7) cycloalkyl, (C5-C7) cycloalkenyl, a partially saturated or fully saturated 4- to 8-membered ring having 1 to 4 heteroatoms independently selected from the group consisting of oxygen, sulfur and nitrogen, or is a bicyclic ring system consisting of a partially saturated or fully saturated 5- or 6-membered ring, fused to a partially saturated, fully unsaturated or fully saturated 5- or 6-membered ring, optionallly having 1 to 4 heteroatoms independently selected from the group consisting of nitrogen, sulfur and oxygen; X4 is hydrogen or (C1-C6) alkyl or X4 is taken together with R4 and the nitrogen atom to which X4 is attached and the carbon atom to which R4 is attached and form a five to seven membered ring; R6 is a bond or is where a and b are independently 0, 1, 2 or 3; X5 and X5a are each independently selected from the group consisting of hydrogen, trifluoromethyl, A1 and optionally substituted (C1-C6) alkyl; the optionally substituted (C1-C6) alkyl in the definition of X5 and X5a is optionally substituted with a substituent selected from the group consisting of A1, OX2, -S(O)m(C1-C6) alkyl, -C(O)OX2, (C3-C7) cycloalkyl, -N(X2)(X2) and -C(O)N(X2)(X2); or the carbon bearing X5 or X5a forms one or two alkylene bridges with the nitrogen atom bearing R7 and R8 wherein each alkylene bridge contains 1 to 5 carbon atoms, provided that when one alkylene bridge is formed then X5 or X5a but not both may be on the carbon atom and R7 or R8 but not both may be on the nitrogen atom and further provided that when two alkylene bridges are formed then X5 and X5a cannot be on the carbon atom and R7 and R8 cannot be on the nitrogen atom; or X5 is taken together with X5a and the carbon atom to which they are attached and form a partially saturated or fully saturated 3- to 7-membered ring, or a partially saturated or fully saturated 4- to 8-membered ring having 1 to 4 heteroatoms independently selected from the group con