US 12,404,277 B2
Substituted 4-phenylpiperidines, their preparation and use
Konstantin Petrukhin, New Windsor, NY (US); Graham Johnson, Sanbornton, NH (US); Rando Allikmets, Cornwall on Hudson, NY (US); Christopher Cioffi, Albany, NY (US); Emily Freeman, Albany, NY (US); Ping Chen, Albany, NY (US); Michael Conlon, Albany, NY (US); and Lei Zhu, Albany, NY (US)
Assigned to THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, New York, NY (US)
Filed by The Trustees of Columbia in the City of New York, New York, NY (US)
Filed on Dec. 19, 2022, as Appl. No. 18/068,005.
Application 18/068,005 is a continuation of application No. 17/099,231, filed on Nov. 16, 2020, granted, now 11,649,240.
Application 17/099,231 is a continuation of application No. 16/520,886, filed on Jul. 24, 2019, granted, now 10,913,746, issued on Feb. 9, 2021.
Application 16/520,886 is a continuation of application No. 16/058,299, filed on Aug. 8, 2018, granted, now 10,407,433, issued on Sep. 10, 2019.
Application 16/058,299 is a continuation of application No. 15/722,760, filed on Oct. 2, 2017, granted, now 10,072,016, issued on Sep. 11, 2018.
Application 15/722,760 is a continuation of application No. 15/254,966, filed on Sep. 1, 2016, granted, now 9,777,010, issued on Oct. 3, 2017.
Application 15/254,966 is a continuation of application No. 14/699,672, filed on Apr. 29, 2015, granted, now 9,434,727, issued on Sep. 6, 2016.
Claims priority of provisional application 61/986,578, filed on Apr. 30, 2014.
Prior Publication US 2023/0312585 A1, Oct. 5, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 471/04 (2006.01); C07D 487/04 (2006.01)
CPC C07D 487/04 (2013.01) [C07D 471/04 (2013.01)] 20 Claims
 
1. A method of inhibiting formation of a retinol binding protein 4 (RBP4)-retinol complex comprising contacting the RBP4 with a compound having the structure:

OG Complex Work Unit Chemistry
wherein
R1 is CF3, R2 is F, R3 is F, R4 is H, and R5 is H,
R1 is CF3, R2 is F, R3 is H, R4 is F, and R5 is H, or
R1 is CF3, R2 is F, R3 is H, R4 is H, and R5 is H;
R6 is H, OH, or halogen; and
B has the structure:

OG Complex Work Unit Chemistry
wherein
α, β, χ, and δ are each independently absent or present, and when present each is a bond;
X is C or N;
Z1 is N;
Z2 is N or NR7,
wherein R7 is H, C1-C4 alkyl, or oxetane; and
Q is a substituted or unsubstituted 5, 6, or 7 membered ring structure,
wherein
when R1 is CF3, R2 is F, R3 is H, R4 is H, and R5 is H,
B is other than

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof.