US 9,809,579 B2
Substituted 3-azabicyclo[3.1.0]hexanes as ketohexokinase inhibitors
Matthew Dowling, Old Lyme, CT (US); Dilinie Fernando, Niantic, CT (US); Kentaro Futatsugi, Quincy, MA (US); Kim Huard, Medford, MA (US); Thomas Victor Magee, Winchester, MA (US); Brian Raymer, Holliston, MA (US); Andre Shavnya, East Lyme, CT (US); Aaron Smith, North Providence, RI (US); Benjamin Thuma, Old Lyme, CT (US); Andy Tsai, Mystic, CT (US); and Meihua Tu, Acton, MA (US)
Assigned to Pfizer Inc., New York, NY (US)
Filed by Pfizer Inc., New York, NY (US)
Filed on Dec. 16, 2016, as Appl. No. 15/381,295.
Claims priority of provisional application 62/272,598, filed on Dec. 29, 2015.
Claims priority of provisional application 62/423,549, filed on Nov. 17, 2016.
Prior Publication US 2017/0183328 A1, Jun. 29, 2017
Int. Cl. C07D 401/14 (2006.01); C07D 403/14 (2006.01); C07D 403/04 (2006.01); C07D 401/04 (2006.01); A61K 31/403 (2006.01)
CPC C07D 403/14 (2013.01) [A61K 31/403 (2013.01); C07D 401/04 (2013.01); C07D 401/14 (2013.01); C07D 403/04 (2013.01)] 26 Claims
1. A compound of Formula I

OG Complex Work Unit Drawing
or a pharmaceutically salt thereof, wherein
Y is N or C—CN;
Z is N or CH;
X is N or CR3;
provided that at least one of Y, Z, or X is N;
R1 is C3-7cycloalkyl or a 4- to 7-membered heterocyclic moiety, wherein the heterocyclic moiety contains 1 to 2 atoms independently selected from nitrogen, oxygen and sulfur, and wherein the cycloalkyl or heterocyclic moiety has 0 to 3 substitutuents independently selected from —C1-3alkyl, and —OH, provided that there is no more than one —OH substituent; or
N(C1-3alkyl)2, NH(C1-3alkyl), or NH(C3-4cycloalkyl), wherein each C1-3alkyl is substituted with 0 to 1 OH;
R2 is -(L)m-CON(RN)2, -(L)m-SO2Rs, -L-(CH2)nSO2Rs, -L-(CH2)nCO2H, -L -(CH2)nC(O)Rc, -L-(CH2)nCONHSO2Rs, -L-(CH2)nSO2NHCORs, -L-(CH2)nSO2NHCONH2, or -L-(CH2)ntetrazol-5-yl;
m is 0 or 1;
n is 0 or 1;
RN is H or —C1-3alkyl;
Rs is H or —C1-3alkyl;
L is CH2, CHF, or CF2;
Rc is —C1-4alkyloxy, —C1-4alkyloxycarbonyloxy-C1-4alkyloxy, or —C1-4alkylcarbonyloxy-C1-4alkyloxy;
R3 is H, halogen, —CN, —C1-3alkyl, —OC1-3alkyl, —C1-3alkyl substituted with 1 to 3 halogen atoms, or —C3-4cycloalkyl; and
R4 is cyclopropyl, cyclobutyl, or —C1-3alkyl substituted with 0 to 5 halogen atoms as valency allows.