Heteroaryl alkylamide derivatives useful as bradykinin receptor modulators

A method of treating a disorder modulated by the bradykinin receptor in a subject in need thereof selected from pain, inflammatory joint disease, inflammatory bowel disease, allergy, asthma, rhinitis, brain edema, brain trauma, tissue injury, septic shock, acute pancreatitis, post-operative pain, migraine and hypertension comprising administering to the subject a compound of Formula (I):

• wherein:
• A is
• Y is one to three substituents independently selected from the group consisting of halogen and C1-8alkyl;
• L is selected from the group consisting of:
• in which R5 is selected from the group consisting of hydrogen, C1-8alkyl, C2-8alkenyl and aryl(C1-8)alkyl wherein aryl is optionally substituted with one or more substituents independently selected from the group consisting of C1-8alkyl, C1-8alkoxy, [(C1-8)alkyl]2N—, halogen, and cyano;
• M is selected from the group consisting of C1-8alkylene and C2-8alkenylene;
• Z is selected from the group consisting of thienylene, (N—R6)pyrrolylene or pyridinylene, each optionally substituted with one or two C1-4alkyl substituents;
• provided that when Z is pyridinylene, then L can only be
• R6 is independently selected from the group consisting of C1-8alkyl, C2-8alkenyl, C3-8cycloalkyl(C1-8)alkyl and aryl(C1-8)alkyl wherein aryl is optionally substituted with one or more substituents independently selected from the group consisting of C1-8alkyl, C1-8alkoxy, [(C1-8)alkyl]2N—, halogen, and cyano;
• D is selected from the group consisting of —C(O)—, —NH—C(O)—, and phenylene;
• R1 is selected from the group C1-8alkyl, C2-8alkenyl, C1-8alkoxy, cyano, [(C1-8)alkyl]2aminoaryl, aryl(C1-8)alkyl, aryl(C1-8)alkenyl, C3-8cycloalkyl, (C1-8)alkylamino(C1-8)alkyl, [(C1-8)alkyl]2amino(C1-8)alkyl, (R7)aryl, (R8)heteroaryl, (R9)heteroaryl(C1-8)alkyl, (R10)heterocyclyl(C1-6)alkyl and [(R11)heteroaryl][(C1-8)alkyl]amino(C1-8)alkyl;
• R7 is one or two substituents independently selected from the group consisting of hydrogen, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl, aryl(C1-8)alkyl, C1-8alkoxy, aryloxy, aryl(C1-8)alkoxy, C1-8alkylthio, trifluoro(C1-8)alkyl, trifluoro(C1-8)alkoxy, heterocyclyl(C1-8)alkyl, methylenedioxy, amino, —NH(C1-8)alkyl, —N[(C1-8)alkyl]2, —NH(aryl), —N(aryl)2, —NH(C1-8)alkylaryl, —N[(C1-8)alkylaryl]2, —CO2(C1-8)alkyl, —CO2(aryl), —C(O)NH2, —C(O)NH(C1-8)alkyl, —C(O)N[(C1-8)alkyl]2, —NHC(O)(C1-8)alkyl, (C1-8alkyl)2—N—(C1-8)alkyl, S(O)(C1-8)alkyl, —SO2(C1-8)alkyl, —SO2NH2, —SO2NH(C1-8)alkyl, —SO2N[(C1-8)alkyl]2, —C(O)(C1-8)alkyl, —C(O)aryl, —C(O)(C1-8)alkylaryl, halogen, hydroxy, cyano, nitro, phenyl, a 5-membered monocyclic aromatic ring containing one O, S, or N atom and up to three additional N atoms, a 6-membered monocyclic aromatic ring containing at least one N atom and up to two additional N atoms, and a partially saturated or unsaturated 5- or 6-membered monocyclic ring having one O, S or N atom which optionally contains up to one additional O, S or N atom;
• R8 is one or two substituents independently selected from the group consisting of hydrogen, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl, aryl(C1-8)alkyl, C1-8alkoxy, aryloxy, aryl(C1-8)alkoxy, C1-8alkylthio, trifluoro(C1-8)alkyl, trifluoro(C1-8)alkoxy, heterocyclyl(C1-6)alkyl amino, —NH(C1-8)alkyl, —N[(C1-8)alkyl]2, —NH(aryl), —N(aryl)2, —NH(C1-8)alkylaryl, —N[(C1-8)alkylaryl]2, —CO2(C1-8)alkyl, —CO2(aryl), —C(O)NH2, —C(O)NH(C1-8)alkyl, —C(O)N[(C1-8)alkyl]2, —NHC(O)(C1-8)alkyl, (C1-8alkyl)2—N—(C1-8)alkyl, S(O)(C1-8)alkyl, —SO2(C1-8)alkyl, —SO2NH2, —SO2NH(C1-8)alkyl, —SO2N[(C1-8)alkyl]2, —C(O)(C1-8)alkyl, —C(O)aryl, —C(O)(C1-8)alkylaryl, halogen, hydroxy, cyano, nitro, phenyl, a 5-membered monocyclic aromatic ring containing one O, S, or N atom and up to three additional N atoms, a 6-membered monocyclic aromatic ring containing at least one N atom and up to two additional N atoms, and a partially saturated or unsaturated 5- or 6-membered monocyclic ring having one O, S or N atom which optionally contains up to one additional O, S or N atom;
• R9 is one or two substituents independently selected from the group consisting of hydrogen, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl, aryl(C1-8)alkyl, C1-8alkoxy, aryloxy, aryl(C1-8)alkoxy, C1-8alkylthio, trifluoro(C1-8)alkyl, trifluoro(C1-4)alkoxy, heterocyclyl(C1-6)alkyl amino, —NH(C1-8)alkyl, —N[(C1-8)alkyl]2, —NH(aryl), —N(aryl)2, —NH(C1-8)alkylaryl, —N[(C1-8)alkylaryl]2, —CO2(C1-8)alkyl, —CO2(aryl), —C(O)NH2, —C(O)NH(C1-8)alkyl, —C(O)N[(C1-8)alkyl]2, —NHC(O)(C1-8)alkyl, (C1-8alkyl)2—N—(C1-8)alkyl, S(O)(C1-8)alkyl, —SO2(C1-8)alkyl, —SO2NH2, —SO2NH(C1-8)alkyl, —SO2N [(C1-8)alkyl]2, —C(O)(C1-8)alkyl, —C(O)aryl, —C(O)(C1-8)alkylaryl, halogen, hydroxy, cyano, nitro, phenyl, a 5-membered monocyclic aromatic ring containing one O, S, or N atom and up to three additional N atoms, a 6-membered monocyclic aromatic ring containing at least one N atom and up to two additional N atoms, and a partially saturated or unsaturated 5- or 6-membered monocyclic ring having one O, S or N atom which optionally contains up to one additional O, S or N atom;
• R10 is one or two subsbtuents independently selected from the group consisting of C1-8alkyl, phenyl, aryl(C1-6)alkyl, a 5-membered monocyclic aromatic ring containing one O, S, or N atom and up to three additional N atoms, a 6-membered monocyclic aromatic ring containing at least one N atom and up to two additional N atoms, and a partially saturated or unsaturated 5- or 6-membered monocyclic ring having one O, S or N atom which optionally contains up to one additional O, S or N atom;
• R11 is one or two substituents independently selected from the group consisting of hydrogen, C1-8alkyl, C2-8alkenyl, C2-4alkynyl, C3-8cycloalkyl, aryl(C1-8)alkyl, C1-8alkoxy, aryloxy, aryl(C1-8)alkoxy, C1-8alkylthio, trifluoro(C1-6)alkyl, trifluoro(C1-8)alkoxy, heterocyclyl(C1-8)alkyl amino, —NH(C1-8)alkyl, —N[(C1-8)alkyl]2, —NH(aryl), —N(aryl)2, —NH(C1-8)alkylaryl, —N[(C1-8)alkylaryl]2, —CO2(C1-8)alkyl, —CO2(aryl), —C(O)NH2, —C(O)NH(C1-8)alkyl, —C(O)N[(C1-8)alkyl]2, —NHC(O)(C1-8)alkyl, (C1-8alkyl)2—N—(C1-8)alkyl, S(O)(C1-8)alkyl, —SO2(C1-8)alkyl, —SO2NH2, —SO2NH(C1-8)alkyl, —SO2N[(C1-8)alkyl]2, —C(O)(C1-8)alkyl, —C(O)aryl, —C(O)(C1-8)alkylaryl, halogen, hydroxy, cyano, nitro, phenyl, a 5-membered monocyclic aromatic ring containing one O, S, or N atom and up to three additional N atoms, a 6-membered monocyclic aromatic ring containing at least one N atom and up to two additional N atoms, and a partially saturated or unsaturated 5- or 6-membered monocycdic ring having one O, S or N atom which optionally contains up to one additional O, S or N atom;
• and pharmaceutically acceptable enantiomers, diastereomers and salts thereof.