US Patent No. 9,809,579

SUBSTITUTED 3-AZABICYCLO[3.1.0]HEXANES AS KETOHEXOKINASE INHIBITORS


Patent No. 9,809,579
Issue Date November 07, 2017
Title Substituted 3-azabicyclo[3.1.0]hexanes As Ketohexokinase Inhibitors
Inventorship 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)
Meihua Tu, Acton, MA (US)
Assignee Pfizer Inc., New York, NY (US)

Claim of US Patent No. 9,809,579

1. A compound of Formula I

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.