	US 7,553,973 B2
	Pharmaceutical compounds
Marc Blouin, St-Lazare-de-Vaudreuil (Canada); Erich L. Grimm, Baie d'Urfe (Canada); Yves Gareau, Notre-Dame-de L'ile-Perrot (Canada); Marc Gagnon, Montreal (Canada); Helene Juteau, Montreal (Canada); Sebastien Laliberte, Ile Perrot (Canada); Bruce MacKay, Dollard-des-Ormeaux (Canada); and Richard Friesen, Kirkland (Canada)
Assigned to Merck Frosst Canada Ltd., Quebec (Canada)
Filed on Mar. 21, 2006, as Appl. No. 11/385,615.
Claims priority of provisional application 60/664317, filed on Mar. 23, 2005.
Prior Publication US 2007/0149579 A1, Jun. 28, 2007
This patent is subject to a terminal disclaimer.
Int. Cl. A01N 43/82 (2006.01); C07D 285/08 (2006.01); C07D 271/06 (2006.01)

U.S. Cl. 548—128 [548/133; 514/361; 514/363]

19 Claims

1. A compound of structural Formula Ia

or a pharmaceutically acceptable salt or ester thereof wherein:

is selected from a single and a double bond;

“A” is selected from the group consisting of (a) phenyl, (b) —CH₂— phenyl, and (c) naphthalenyl;

and wherein A is optionally mono- or di-substituted with a substituent independently selected at each occurrence from the group consisting of (i) —F (ii) —Cl, (iii) —C_1-3alkyl optionally substituted with one or more of halo, (iv) —OC_1-3alkyl optionally substituted with one or more of halo, (v) —OC_3-6cycloalkyl, (vi) —CH₂OH, (vii) —COOR¹, (viii) —CN and (ix) —NR¹⁰R¹¹;

X is selected from —O— and —S—;

Y is selected from —NR⁶—CHR⁷and —NR⁸—C(O)— wherein the nitrogen in Y is linked to the 5-membered heterocyclic moiety of Formula Ia and the carbon in Y is linked to the bicyclic heterocyclic moiety of Formula Ia;

R¹is selected from the group consisting of —H, —C_1-6alkyl and —C_3-6cycloalkyl;

R²is selected from the group consisting of —H, —OH, —F, —C_1-3alkyl, —OC_1-3alkyl and —OC(O)—C_1-3alkyl;

R³is selected from the group consisting of —H, —C_1-6alkyl, —C_1-6alkyl substituted with one or more of fluoro, —C_1-6alkyl substituted with R⁹, —C_2-6alkenyl, —C_3-6cycloalkyl, —C_5-7cycloalkenyl and -Z;

R⁴is selected from the group consisting of —H, —C_1-6alkyl, —C_1-6alkyl substituted with one or more of fluoro, —C_1-6alkyl substituted with R⁹, —C_2-6alkenyl, —C_3-6cycloalkyl, —C_5-7cycloalkenyl and -Z;

or R³and R⁴together represent oxo;

or R³and R⁴are joined together with the carbon to which they are attached to form a ring selected from the group consisting of a —C_3-6cycloalkyl ring and a —C_5-7cycloalkenyl ring, provided that when R³and R⁴are joined together with the carbon to which they are attached to form a —C_5-7cycloalkenyl ring, there is no double bond at the C-1 position in the ring;

or R², R³and R⁴are joined together with the carbon to which they are attached to form a cycloalkenyl ring selected from:

R⁵is absent or is a substituent selected from the group consisting of —C_1-6alkyl, —C_3-6cycloalkyl and halo;

R⁶is selected from the group consisting of (a) —H, (b) —C_1-4alkyl, (c) —C(O)C_1-4alkyl, and (d) —C(O)phenyl optionally substituted with —C_1-4alkyl;

R⁷is selected from the group consisting of (a) —H, (b) —C_1-4alkyl, (c) —C_3-6cycloalkyl, and (d) phenyl optionally mono- or di-substituted with a substituent independently selected at each occurrence from the group consisting of —C_1-4alkyl, —F and —Cl;

R⁸is selected from the group consisting of —H and —C_1-4alkyl;

R⁹is selected from the group consisting of —COOR¹, —C(O)H, —CN, CR¹R¹OH, —OR¹, —S—C_1-6alkyl and —S—C_3-6cycloalkyl;

R¹⁰is selected from the group consisting of —H, —C_1-6alkyl, —C_3-6cycloalkyl and —COOR¹;

R¹¹is selected from the group consisting of —H, —C_1-6alkyl and —C_3-6cycloalkyl; and

Z is selected from the group consisting of phenyl, —CH₂— phenyl and —CH₂-dioxolanyl,

and wherein Z is optionally mono- or di-subsituted with a substituent independently selected at each occurrence from the group consisting of (i) —F, (ii) —Cl, (iii) —C_1-3alkyl optionally substituted with one or more of halo, (iv) —OC_1-3alkyl optionally substituted with one or more of halo, (v) —OC_3-6cycloalkyl, (vi) —CH₂OH, (vii) —COOR¹, (viii) —CN and (ix) —NR¹⁰R¹¹.