Non-peptide agonists and antagonists of adrenomedullin and gastrin releasing peptide

A complex, comprising:

• a compound of one of formula I, II, III′, IV-VIII, XII or XIII, in association with an adrenomedullin (AM) peptide, wherein formulas I, II, III′, IV-VIII, XII and XIII are:
• wherein:
• K is OR32, SR32, or NR33R34 where R32 is H or alkyl with four or fewer carbons, and R33 and R34 are the same or different and each is selected from H and lower alkyl;
• Ar is aryl, or aryl optionally substituted with one or more groups selected from —OH, —NH2, —SH, halogen and hydrocarbyl;
• n is an integer from 1-3;
• and
• R1, R2 and R3 are the same or different and is each selected from H, hydrocarbyl and a heterocyclic ring;
• or
• R1 and R2 together form a heterocyclic ring including the intervening nitrogen, and
• R3 is selected from H, alkyl, alkenyl, alkynyl, and a heterocyclic ring;
• or
• R1 is selected from H and hydrocarbyl and R2 and R3 together form a heterocyclic ring including the intervening nitrogen;
• wherein:
• R4 and R5 may be the same or different and each is an aryl group substituted with —C(O)K, and optionally further substituted with one or more groups selected from —OH, —NH2, —SH, halogen, hydrocarbyl and a heterocyclic ring, where K is as defined above;
• and
• m is an integer from 1-3;
• wherein:
• R7 is aryl optionally substituted with one or more groups selected from —OH, —NH2, —SH, halogen, a heterocyclic ring and hydrocarbyl;
• and
• R8 and R9 are the same or different and are each hydrocarbyl, optionally substituted with one or more halogens or lower alkyl groups, or
• R8 and R9 together form a heterocyclic ring having five, six or seven atoms, including the intervening nitrogen and optionally containing other heteroatoms, and also optionally substituted with one or more halogens or lower alkyl groups;
• wherein:
• K is as defined above;
• and
• R10 and R11 are the same or different and each is an aryl group, optionally substituted with a second aryl group that may be the same or different and the aryl groups may be substituted with one or more groups selected from —OH, —NH2, —SH, halogen, a heterocyclic ring and hydrocarbyl;
• wherein:
• p is an integer from 1-3;
• M1, M2, and M3 are the same or different and each is S or O;
• Z is S or P;
• R is hydrocarbyl or OR35, where R35 is H or hydrocarbyl;
• and
• R12 and R13 are the same or different and each is hydrocarbyl, a heterocyclic ring or lower alkyl, or R12 and R13 together form a ring;
• wherein:
• K is as defined above;
• r is and integer from 1-3;
• R14 and R15 are the same or different and each is aryl optionally substituted with one or more groups selected from —OH, —NH2, —SH, halogen, a heterocyclic ring and hydrocarbyl;
• and
• R16 and R17 are the same or different and each is hydrocarbyl or a heterocyclic ring;
• wherein:
• s is an integer from 1-10;
• R20, R21, R22 and R23 are the same or different and each is H, aryl, optionally substituted with one or more halogen or lower alkyl groups, hydrocarbyl and a heterocyclic ring;
• and
• R18, R19 are the same or different and each is aryl optionally substituted with one or more groups selected from —OH, —NH2, —SH, halogen and lower alkyl;
• wherein:
• t is an integer from 1-5;
• u is an integer from 1-2;
• and
• R24 is selected from H, a heterocyclic ring and hydrocarbyl, optionally substituted by halogen;
• and
• wherein:
• Q is selected from CH2, NH, S and O;
• and
• Z1 and Z3 are the same or different and selected from CH3, NH2, OH and SH,
• or tautomers thereof,
• or a pharmaceutically acceptable salt thereof.