US 7,320,994 B2
Triazole derivatives as tachykinin receptor antagonists
Albert Kudzovi Amegadzie, Indianapolis, Ind. (US); Kevin Matthew Gardinier, Indianapolis, Ind. (US); Erik James Hembre, Indianapolis, Ind. (US); Jian Eric Hong, Carmel, Ind. (US); Louis Nickolaus Jungheim, Indianapolis, Ind. (US); Brian Stephen Muehl, Greenwood, Ind. (US); David Michael Remick, Fishers, Ind. (US); Michael Alan Robertson, Indianapolis, Ind. (US); and Kenneth Allen Savin, Indianapolis, Ind. (US)
Assigned to Eli Lilly and Company, Indianapolis, Ind. (US)
Appl. No. 10/512,249
PCT Filed Apr. 22, 2003, PCT No. PCT/US03/10681
§ 371(c)(1), (2), (4) Date Oct. 20, 2004,
PCT Pub. No. WO03/091226, PCT Pub. Date Nov. 06, 2003.
Claims priority of provisional application 60/376121, filed on Apr. 26, 2002.
Prior Publication US 2005/0239786 A1, Oct. 27, 2005
Int. Cl. A61K 31/41 (2006.01); C07D 249/04 (2006.01)
U.S. Cl. 514—359  [548/255] 34 Claims
 
1. A compound of Formula I:

OG Complex Work Unit Drawing
wherein:
D is a C1-C3 alkane-diyl;
R1 is phenyl,
which is optionally substituted with one to three substitutents independently selected from the group consisting of halo, C1-C4 alkyl, C1-C4 alkoxy, cyano, difluoromethyl, trifluoromethyl, and trifluoromethoxy;
R4 is a radical selected from the group consisting of:

OG Complex Work Unit Drawing
wherein
-A1-A2-A3-A4-, together with the atoms to which they are attached, form an aromatic carbocyclic or heterocyclic ring in which each of A1, A2, A3, and A4 is independently —CR8— or nitrogen, wherein at least one of A1, A2, A3, and A4 must be —CR8—;
-G1-G2-G3-, together with the atoms to which they are attached, form an aromatic heterocyclic ring in which each of G1, G2, and G3 is independently —CR8—, nitrogen, oxygen, or sulfur, wherein only one of G1, G2, and G3 can be oxygen or sulfur;
-G4-G5-G6-, together with the atoms to which they are attached, form an aromatic heterocyclic ring in which each of G4, G5, and G6 is independently —CR8—, or nitrogen;
each R8 is independently selected from the group consisting of hydrogen, halo, C1-C4 alkyl, substituted C1-C4 alkyl, C3-C6 cycloalkyl, —NR12R13, trifluoromethyl, and trifluoromethoxy;
R12 and R13 are each independently hydrogen, C1-C4 alkyl, or —C(O)—CH3, or R12 and R13, together with the nitrogen to which they are attached, form a 4-7 membered ring;
Q1, Q2, Q5, and Q6 are each independently —CH—, or nitrogen;
Q3 and Q4 are each independently oxygen or nitrogen, wherein at least one of Q3 and Q4 must be nitrogen;
R6 is C1-C4 alkyl, C3-C6 cycloalkyl, phenyl, or pyridyl,
which phenyl or pyridyl is optionally substituted with one to three substituents independently selected from the group consisting of halo, cyano, C1-C4 alkyl, C1-C4 alkoxy, trifluoromethyl, trifluoromethoxy, morpholino, and —NR14R15;
R14 and R15 are each independently hydrogen or C1-C4 alkyl, or R14 and R15, together with the nitrogen to which they are attached, form a 4-7 membered ring;
X is a bond, C1-C3 alkane-diyl, —CH(OH)—, —C(O)—, —O—, —S(O)p—, or —C═N—OR9—;
p is 0, 1, or 2;
R9 is hydrogen, C1-C4 alkyl, or benzyl;
Y is a bond, C1-C3 alkane-diyl, or —C(O)—;
n is 0, 1, or 2;
each R7 is independently C1-C4 alkyl;
R5 is halo, trifluoromethyl, C1-C4 alkyl, C3-C6 cycloalkyl, furyl, thienyl, pyrrolyl, imidazolyl, —NR16R17, pyridyloxy, phenyl, phenoxy, phenylthio, anilino,
which phenyl, phenoxy, phenylthio, or anilino group may be optionally substituted on the phenyl ring with one or two substituents independently selected from the group consisting of halo, C1-C4 alkyl, C1-C4 alkoxy, and —S(O)q(C1-C4 alkyl),
or a radical selected from the group consisting of:

OG Complex Work Unit Drawing
wherein
W is a bond, —CH2—, —O—, —NR11—, or —S(O)q—;
q is 0, 1, or 2;
R11 is selected from the group consisting of hydrogen, C1-C4 alkyl, acetyl, phenyl, benzyl, and —S(O)2CH3;
Z1, Z2, and Z3 are each independently —CH— or nitrogen;
R16 and R17 are each independently C1-C4 alkyl;
or a pharmaceutically acceptable salt thereof.