US 11,859,014 B2
Peptidomimetics for the treatment of Norovirus infection
Raymond F Schinazi, Miami, FL (US); Franck Amblard, Atlanta, GA (US); Ladislau Kovari, Detroit, MI (US); Peng Liu, Atlanta, GA (US); Shaoman Zhou, Atlanta, GA (US); Benjamin D Kuiper, Detroit, MI (US); and BRadley J Keusch, Detroit, MI (US)
Assigned to EMORY UNIVERSITY, Atlanta, GA (US)
Filed by EMORY UNIVERSITY, Atlanta, GA (US)
Filed on May 25, 2021, as Appl. No. 17/329,670.
Application 17/329,670 is a continuation of application No. 16/301,168, granted, now 11,021,513, previously published as PCT/US2017/032600, filed on May 15, 2017.
Claims priority of provisional application 62/335,962, filed on May 13, 2016.
Prior Publication US 2021/0395300 A1, Dec. 23, 2021
Int. Cl. C07K 5/06 (2006.01); C07K 5/065 (2006.01); A61P 31/14 (2006.01); A61K 38/05 (2006.01); A61K 45/06 (2006.01)
CPC C07K 5/06078 (2013.01) [A61K 38/05 (2013.01); A61K 45/06 (2013.01); A61P 31/14 (2018.01)] 16 Claims
 
1. A compound of the following formula:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
R5 is selected from the group consisting of

OG Complex Work Unit Chemistry
R2, R2′, R10, R10′, R11 and R11′ are, independently, hydrogen, CF3, C1-6 alkyl, C1-6 haloalkyl, or C2-6 alkenyl,
R12 and R12′ are, independently, C1-6 alkyl, C1-6 haloalkyl, or C2-6 alkenyl,
R12 and R12 can come together to form an optionally substituted C3-7 ring, optionally containing an N, O, or S;
R8 is, independently, optionally substituted C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, aryl, or arylalkyl;
m, n, p and r are independently 0, 1, 2, 3, 4 or 5;
q is 1, 2, 3, 4 or 5;
X is NH,
Y is independently Cl, F, I or Br,
R12 is hydrogen, CF3, CO2R′, S(O)2R′, S(O)2N(R′)2, P(O)(OR′)2, C2-6 alkenyl, C2-6 alkynyl, C3-6 alkoxyalkyl, C1-6 alkyl, arylalkoxycarbonyl, C1-6 haloalkyl, heterocyclylalkyl, or C1-6 hydroxy alkyl;
R6 and R6′ are, independently, hydrogen, halogen, CF3, hydroxy, N(R′)S(O)2R′, S(O)2R′, S(O)2N(R′)2, C1-6 alkoxy, C2-6 alkenyl, cyano, C2-6 alkynyl, C3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, C1-6 alkyl, arylalkoxycarbonyl, carboxy, C1-6 haloalkyl, heterocyclylalkyl, or C1-6 hydroxyalkyl,
or R6 and R6′, together with the carbon to which they are attached, form a carbonyl;
each R′ is, independently, H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, aryl, heteroaryl, alkylaryl, or arylalkyl,
the R′ groups, and other optionally substituted groups, can optionally be substituted with one or more substituents, which substituents are, independently, halo, C1-6 haloalkyl, C1-6 hydroxyalkyl, hydroxyl, carboxyl, acyl, aryl, acyloxy, amino, amido, carboxyl derivatives, alkylamino, dialkylamino, arylamino, alkoxy, alkoxyalkyl, aryloxy, nitro, cyano, sulfonic acid, thiol, imine, sulfonyl, sulfanyl, sulfinyl, sulfamonyl, ester, carboxylic acid, amide, phosphonyl, phosphinyl, phosphoryl, phosphine, thioester, thioether, acid halide, anhydride, oxime, hydrazine, carbamate, phosphonic acid, or phosphonate;
two R′ residing on the same carbon or nitrogen atom can come together to form a C3-6 ring optionally containing an N, O, or S;
R6 and R6 can come together to form an optionally substituted double bond, a C3-6 ring optionally containing an N, O, or S;
R7 and R7′ are, independently, hydrogen, CF3, N(R′)S(O)2R′, S(O)2R′, S(O)2N(R′)2, C1-6 alkoxy, C2-6 alkenyl, cyano, C2-6 alkynyl, C3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, C1-6 alkyl, arylalkoxycarbonyl, carboxy, C1-6 haloalkyl, heterocyclylalkyl, or C1-6 hydroxyalkyl;
R7 and R7′ can come together to form an optionally substituted double bond or a C3-6 ring optionally containing an N, O, or S;
R3 is arylalkyl or heteroarylalkyl,
R4 is optionally substituted C1-6 alkyl, C1-6 haloalkyl, C2-8 alkoxyalkyl, arylalkyl, heteroarylalkyl, or —CH2—R4′,
R4′ is a six-membered ring or a six-membered bridged or spiro-fused ring containing zero, one, or two heteroatoms, which are independently N, O, or S, a seven-membered bridged or spiro-fused ring containing zero, one, or two heteroatoms, which are, independently, N, O, or S, a five-membered ring containing zero, one, or two heteroatoms, which are, independently, N, O, or S; a four-membered ring containing zero, one, or two heteroatoms, which are, independently, N, O, or S, or a three membered ring; and
R1 is optionally substituted aryl, heteroaryl, aryloxy, heteroaryloxy, arylalkoxy, or heteroarylalkoxy.