Heterocyclic aromatic compounds useful as growth hormone secretagogues

A compound of the structure

• including pharmaceutically acceptable salts thereof, prodrug esters thereof, and all stereoisomers thereof,
• wherein R1 is alkyl, aryl, alkenyl, alkynyl, arylalkyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl, arylalkyloxyalkyl, aryloxyalkyl, heteroaryl, cycloalkylalkoxyalkyl, heteroarylalkyl, cycloheteroalkyl or cycloheteroalkylalkyl, and these groups may be optionally substituted by 1,2 or 3-substituents selected from halogen, —OR8, —OC(O)R8, alkyl, phenyl, phenoxy, halophenyl, —CF3, —OCF3, —N(R8a)C(O)(R8), or —N(R8)(R8a);
• R1a is H, alkyl, or cycloalkyl;
• Xa is heteroaryl, which is
• U is oxygen, sulfur, —NH—, or —N—R5b;
• R5 is H, alkyl, aryl, alkenyl, arylalkenyl, alkynyl, arylalkyl, arylalkynyl, cycloalkylalkyl, alkoxyalkyl, aryloxyalkyl, arylalkyloxyalkyl, heteroaryl, cycloalkylalkoxyalkyl, —SO2T1, —SO2N(T1a)T1, or heteroarylalkyl, and where alkyl, aryl, alkenyl, arylalkenyl, alkynyl, arylalkyl, arylalkynyl, cycloalkylalkyl, alkoxyalkyl, aryloxyalkyl, arylalkyloxyalkyl, heteroaryl, heteroaryloxyalkyl, cycloalkylalkoxyalkyl, or heteroarylalkyl may be independently optionally substituted with 1 to 3 J1;
• R5a and R5b are the same or different and are independently selected from H, alkyl, aryl, alkenyl, arylalkenyl, alkynyl, arylalkyl, arylalkynyl, cycloalkylalkyl, alkoxyalkyl, aryloxyalkyl, arylalkyloxyalkyl, heteroaryl, cycloalkylalkoxyalkyl, heteroarylalkyl, or J1, and where alkyl, aryl, alkenyl, arylalkenyl, alkynyl, arylalkyl, arylalkynyl, cycloalkylalkyl, alkoxyalkyl, aryloxyalkyl, arylalkyloxy-alkyl, heteroaryl, heteroaryloxyalkyl, cycloalkylalkoxy-alkyl, or heteroarylalkyl may be independently optionally substituted with 1 to 3 J1;
• Y is
• where x and y are independently 0 to 3 and z is 1 to 3;
• Xc is a bond, —N—R6a or —O—;
• R7 and R7a are the same or different and are independently selected from H, alkyl, —CF3, phenyl, aryl, arylalkyl, and cycloalkyl;
• or one or both of R7 and R7a can be independently joined to one or both of R9 and R10 groups (of Xb) to form an alkylene bridge of 1 to 5 carbon atoms;
• or R7 and R7a are joined together to form a ring of from 3-7 carbon atoms;
• R6, R6a, R6b, R6c, R8, R8a, R8b, R8c, R8d, R8e, R8f, R8g, R8h, R8i, R8k, R8l, and R8m are the same or different and are independently H, alkyl, cycloalkyl, alkenyl or aryl;
• R8j is H, alkyl, aryl, hydroxy or —OC(O)R8k;
• Xb is
• R9 and R10 are the same or different and are independently selected from H, alkyl, and substituted alkyl where the substituents may be 1 to 3 hydroxy, 1 to 3 C1-C10-alkanoyloxy, 1 to 3 C1-6 alkoxy, phenyl, phenoxy, C1-C6-alkoxycarbonyl;
• or R9 and R10 can together form —(CH2)tXd(CH2)u— where Xd is C(R8h)(R8j), —O— or —N(R6b), t and u are independently 1-3;
• R11 is H, C1-C6alkyl, —CF3, arylalkyl, or aryl, and with the alkyl and aryl groups being optionally substituted with 1 to 3 hydroxy, 1 to 3 C1-10alkanoyloxy, 1 to 3 C1-6 alkoxy, phenyl, phenoxy or C1-C6 alkoxycarbonyl;
• R12 and R13 are independently H, C1-C6alkyl, —CF3, aryl, or halogen, and with the alkyl and aryl groups being optionally substituted with 1 to 3 hydroxy, 1 to 3 C1-C10-alkanoyloxy, 1 to 3 C1-6 alkoxy, or C1-C6 alkoxycarbonyl;
• J1 is nitro, —(CH2)vN(T1a)C(O)T1, —(CH2)vCN, —(CH2)vN(T1a)C(O)OT1, —(CH2)vN(T1a)C(O)N(T1b)T1, —(CH2)vN(T1a)SO2T1, —(CH2)vC(O)N(T1a)T1, —(CH2)vC(O)OT1, —(CH2)vOC(O)OT1, —(CH2)vOC(O)T1, —(CH2)vOC(O)N(T1a)T1, —(CH2)vN(T1a)SO2N(T1b)T1, —(CH2)vOT1, —(CH2)vSO2T1, —(CH2)vSO2N(T1a)T1, —(CH2)vC(O)T1, —(CH2)vCH(OH)T1, cycloheteroalkyl or heteroaryl, with v being 0-5;
• T1, T1a and T1b are the same or different and are independently H, alkyl, alkenyl, alkynyl, lower alkythioalkyl, alkoxyalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloheteroalkyl, or cycloalkyl, each of which may be optionally substituted with 1, 2 or 3 substituents selected from halogen, hydroxyl, —NR8fC(O)NR8gR8i, —C(O)NR8fR8g, —NR8fC(O)R8g, —CN, —N(R8f)SO2R14, —OC(O)R8f, —SO2NR8fR8g, —SOR14, —SO2R14, alkoxy, —COOH, cycloheteroalkyl, or —C(O)OR14;
• or T1 and T1a or T1 and T1b can together form —(CH2)wXe(CH2)z— where Xe is —C(R8m)(R8l), —O—, —S—, —SO—, —SO2—, —NC(O)OR14a, —NC(O)NR14aR14b, —NC(O)R14a or —N(R6c) where w and z are each independently 1-3;
• with the proviso that T1 can not be hydrogen when it is connected to carbonyl or sulfur, as in —C(O)T1 or —SO2T1;
• R14, R14a, and R14b are independently C1-C6alkyl, heteroaryl, or aryl, each optionally substituted with —(CH2)sOH, with s being 0-5.