US 12,145,926 B2
Compounds and radioligands for targeting neurotensin receptor and uses thereof
Fa Liu, Watchung, NJ (US)
Assigned to Full-Life Technologies HK Limited, Admiralty (CN)
Filed by Full-Life Technologies HK Limited, Hong Kong (CN)
Filed on Mar. 13, 2024, as Appl. No. 18/604,397.
Application 18/604,397 is a continuation of application No. PCT/US2023/013314, filed on Feb. 17, 2023.
Claims priority of provisional application 63/311,621, filed on Feb. 18, 2022.
Prior Publication US 2024/0287046 A1, Aug. 29, 2024
Int. Cl. C07D 403/12 (2006.01); A61K 31/41 (2006.01); A61K 31/4155 (2006.01); A61K 51/04 (2006.01); A61P 35/00 (2006.01)
CPC C07D 403/12 (2013.01) [A61K 31/4155 (2013.01); A61K 51/0482 (2013.01); A61P 35/00 (2018.01)] 27 Claims
 
1. A compound of Formula I or a pharmaceutically acceptable salt or solvate thereof

OG Complex Work Unit Chemistry
wherein
R1 is selected from H, C1-6alkyl, C3-6cycloalkyl and C1-3alkyleneC3-6cycloalkyl, the latter three groups being optionally substituted with one or more halo;
R2 is selected from H, halo, NO2, C1-6alkyl, C3-8cycloalkyl and C1-3alkyleneC3-8cycloalkyl, the latter three groups being optionally substituted with one or more halo;
R3 is selected from 2-amino-2-adamantane carboxylic acid, cyclohexylglycine and 9-amino-bicyclo[3.3.1]nonane-9-carboxylic acid;
X is O;
L consists of 1 to 10 groups independently selected from C1-6alkyleneO, C1-6alkyleneNR7, C(O)C1-6alkyleneO and C(O)C1-6alkyleneNR7, wherein R7 is H or C1-4alkyl;
E is selected from the group selected from the group consisting of 1,4,7-triazacyclononane (TACN): 1,4,7-triazacyclononane-triacetic acid (NOTA); 1,4,7-triazacyclononane-N-succinic acid-N,N″-diacetic acid (NOTASA); 1,4,7-triazacyclononane-N-glutamic acid-N,N″-diacetic acid (NODAGA); 1,4,7-triazacyclononane-N,N′,N″-tris(methylenephosphonic) acid (NOTP); 1,4,7,10-tetraazacyclododecane ([12]aneN4) (cyclen); 1,4,7,10-tetraazacyclotridecane ([13]aneN4); 1.4.7.11-tetraazacyclotetradecane (iso-cyclam); 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA); 2-(1,4,7,10-tetraazacyclododecan-1-yl)acetate (DO1A); 2.2′-(1.4.7.10-tetraazacyclododecane-1,7-diyl) diacetic acid (DO2A); 2,2′,2″-(1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid (DO3A); 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(methanepnosphonic acid) (DOTP); 1,4,7,10-tetraazacyclododecane-1,7-di(methanephosphoriic acid) (DO2P); 1,4,7,10-tetraazacvclododecane-1,4,7-tri(methanephosphonic acid) (DO3P); 1,4,7,10-tetraazacvclo-decane-1-qlutamic acid-4,7,10-triacetic acid (DOTAGA); 1,4,7,10-tetraazacyclodecane-1-succinic acid-4,7,10-triacetic acid (DOTASA); 1,4,8,11-tetraazacvclotetradecane ([14]aneN4) (cyclam); 1,4,8,12-tetraazacyclopentadecane ([15]aneN4); 1,5,9,13-tetraazacyclohexadecane ([16]aneN4); 1,4-ethano-1,4,8,11-tetraazacyclo-tetradecane (et-cyclam); 1,4,8,11-tetraazacvclotetradecane-1,4,8,11-tetraacetic acid (TETA); 2-(1,4,8,11-tetraazacyclotetradecane-1-yl) acetic acid (TE1A); 2,2′-(1,4,8,11-tetraazacyclotetradecane-1,8-diyl) diacetic acid (TE2A); 4,11-bis(carboxy methyl)-1,4,8,11-tetraazabicyclo[6.6.2]-hexadecane (CB-TE2A); 3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane (Sar); 1,4,7,10-tetra-(2-carbamoyl-methyl)-cyclododecane (TCMC); N,N′-bis[(6-carboxy-2-pyridil)methyl]-4,13-diaza-18-crown-6 (macropa), phthalocyanines, and porphyrins.