US 12,070,513 B2
PSMA-binding agents and uses thereof
Martin G. Pomper, Baltimore, MD (US); Ronnie Charles Mease, Fairfax, VA (US); and Ying Chen, Lutherville-Timonium, MD (US)
Assigned to THE JOHNS HOPKINS UNIVERSTY, Baltimore, MD (US)
Filed by The Johns Hopkins University, Baltimore, MD (US)
Filed on Apr. 22, 2021, as Appl. No. 17/237,850.
Application 17/237,850 is a division of application No. 16/674,089, filed on Nov. 5, 2019, abandoned.
Application 16/674,089 is a division of application No. 15/864,236, filed on Jan. 8, 2018, granted, now 10,500,292, issued on Dec. 10, 2019.
Application 15/864,236 is a division of application No. 14/987,032, filed on Jan. 4, 2016, granted, now 9,861,713, issued on Jan. 9, 2018.
Application 14/211,683 is a division of application No. 13/057,044, granted, now 8,778,305, issued on Jul. 15, 2014, previously published as PCT/US2009/052456, filed on Jul. 31, 2009.
Application 14/987,032 is a continuation of application No. 14/211,683, filed on Mar. 14, 2014, granted, now 9,226,981, issued on Jan. 5, 2016.
Claims priority of provisional application 61/085,462, filed on Aug. 1, 2008.
Claims priority of provisional application 61/111,791, filed on Nov. 6, 2008.
Prior Publication US 2022/0088229 A1, Mar. 24, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 51/04 (2006.01); A61K 9/127 (2006.01); C07C 275/16 (2006.01); C07C 275/18 (2006.01); C07D 213/16 (2006.01); C07D 213/61 (2006.01); C07D 213/74 (2006.01); C07D 213/82 (2006.01); C07F 7/22 (2006.01)
CPC A61K 51/0455 (2013.01) [A61K 9/127 (2013.01); A61K 51/0402 (2013.01); C07C 275/16 (2013.01); C07C 275/18 (2013.01); C07D 213/61 (2013.01); C07D 213/74 (2013.01); C07D 213/82 (2013.01); C07F 7/2208 (2013.01); C07B 2200/05 (2013.01); Y02P 20/55 (2015.11)] 23 Claims
 
1. A composition comprising a pharmaceutically acceptable carrier and a compound having the structure

OG Complex Work Unit Chemistry
wherein
Z is tetrazole or CO2Q; each Q is independently selected from hydrogen or a protecting group;
and wherein
m is 0, 1, 2, 3, 4, 5, or 6;
R is a pyridine ring selected from the group consisting of

OG Complex Work Unit Chemistry
wherein X is fluorine, iodine, a radioisotope of fluorine, a radioisotope of iodine, chlorine, bromine, a radioisotope of bromine, a radioisotope of astatine, NO2 NH2, N+(R2)3, Sn(R2)3, Si(R2)3, Hg(R2), B(OH)2, —NHNH2, —NHN═CHR3, —NHNH—CH2R3, n is 1, 2, 3, 4, or 5;
Y is O, S, N(R′), C(O), NR′C(O), C(O)N(R′), OC(O), C(O)(O), NR′C(O)NR′, NR′C(S)NR′, NR'S(O)2, S(CH2)p, NR′(CH2)p, O(CH2)p, OC(O)CHR8NHC(O), NHC(O) CHR8NHC(O), or a covalent bond; wherein p is 1, 2, or 3, R′is H or C1-C6 alkyl, and R8 is hydrogen, alkyl, aryl, or heteroaryl, each of which may be substituted;
R2 is a C1-C6 alkyl; and
R3 is alkyl, alkenyl, alkynyl, aryl, or heteroaryl each of which is substituted by fluorine, iodine, a radioisotope of fluorine, a radioisotope of iodine, chlorine, bromine, a radioisotope of bromine, or a radioisotope of astatine, NO2, NH2, N+(R2)3, Sn(R2)3, Si(R2)3, Hg(R2), or B(OH)2; OR
m is 0, 1, 2, 3, 4, 5, or 6;
Y is O, S, N(R′), C(O), NR′C(O), C(O)N(R′), OC(O), C(O)(O), NR′C(O)NR′, NR′C(S)NR′, NR′, NR'S(O)2, S(CH2)P, NR′—(CH2)P, O(CH2)P, OC(O)CHR8NHC(O), NHC(O) CHR8NHC(O), or a covalent bond; wherein p is 1, 2, or 3,R′ is H or C1-C6 alkyl, R8 is hydrogen, alkyl, aryl, or heteroaryl, each of which may be substituted;

OG Complex Work Unit Chemistry
R is
X′ is selected from the group consisting of NHNH2, —NHN═CHR3, —NHNH—CH2R3; R3 is alkyl, alkenyl, alkynyl, aryl, or heteroaryl each of which is substituted by fluorine, iodine, a radioisotope of fluorine, a radioisotope of iodine, chlorine, bromine, a radioisotope of bromine, or a radioisotope of astatine, NO2, NH2, N+(R2)3, Sn(R2)3, Si(R2)3, Hg(R2), or B(OH)2;
R2 is C1-C6 alkyl, n is 1, 2, 3, 4, or 5;
OR
m is 4,
Y is NR′, and
R is

OG Complex Work Unit Chemistry
wherein
G is O, NR′ or a covalent bond;
R′is H or C1-C6 alkyl; p is 1, 2, 3, or 4, and
R7 is selected from the group consisting of NH2, N═CHR3, NH—CH2R3, wherein R3 is alkyl, alkenyl, alkynyl, aryl, or heteroaryl each of which is substituted by fluorine, iodine, a radioisotope of fluorine, a radioisotope of iodine, chlorine, bromine, a radioisotope of bromine, or a radioisotope of astatine, NO2, NH2, N+(R2)3, Sn(R2)3, Si(R2)3, Hg(R2), or B(OH)2; and R2 is C1-C6 alkyl.