N-alkoxyamide conjugates as imaging agents

摘要

The present disclosure is directed to compounds, diagnostic agents, and related methods. In some cases, methods for treating patients are provided. More specifically, the disclosure provides compounds, diagnostic agents, and kits for detecting and/or imaging and/or monitoring elastin rich tissues. In addition, the disclosure provides methods of detecting and/or imaging and/or monitoring the presence of coronary plaque, carotid plaque, iliac/femoral plaque, aortic plaque, renal artery plaque, plaque of any arterial vessel, aneurism, vasculitis, other diseases of the arterial wall, and/or damage or structural changes in ligaments, uterus, lungs or skin, as indicated by changes in total vessel wall area, internal lumen size, and exterior arterial perimeter.

主权项

1. A compound of Formula (I),or a pharmaceutically acceptable salt thereof,wherein:
X is a heteroatom N, S, O, or P; R1 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, arylalkyl, alkylarylalkyl, alkoxyalkyl, heteroalkyl, and heterocyclylalkyl; R2 and R3 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, alkylaryl, alkylcarbonyl, aryl, arylalkyl, alkylarylalkyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, heteroalkyl, heterocyclyl, heterocyclylalkyl, and carbonyl; and R4 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, alkylaryl, alkylcarbonyl, aryl, arylalkyl, alkylarylalkyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, heteroalkyl, heterocyclyl, and heterocyclylalkyl, wherein each R1, R2, R3, and R4 is independently unsubstituted or substituted with one or more of the following: alkyl, alkenyl, alkynyl, cycloalkyl, alkylaryl, alkylcarbonyl, aryl, arylalkyl, alkylarylalkyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, heteroalkyl, heterocyclyl, heterocyclylalkyl, —NR19R20, —SH, —OH, —PR19R20, —P(O)R21R22, —CO2H, ═O, halo, trifluoromethyl, —CF2H, —CH2F, cyano, —CO2R24, —C(═O)R24, —C(═O)N(R24)2, —CHO, —CH2OR24, —OC(═O)R24, —OC(═O)R24, —OR24, —OC(═O)N(R24)2, —NR24C(═O)R24, —NR24CO(═O)R24, —NR24C(═O)N(R24)2, —NR24SO2N(R24)2, —NR24SO2R24, —SO3H, —SO2R24, —SR24, —S(═O)R24, —SO2N(R24)2, —N(R24)2, —NHC(═S)NHR24, ═NOR24, ═NO2, —C(═O)NHOR24, —C(═O)NHN(R24)2R24R24, —OCH2CO2H, 2-(1-morpholino)ethoxy, or a chelator moiety; or wherein at least one of R1, R2, R3, and R4 comprises the structure:wherein n is 0 or greater, m is 0 or greater, and Rc is a chelator moiety;
R19 and R20 are each independently selected from the group consisting of hydrogen, C1-10alkyl substituted with 0-3 R23, aryl substituted with 0-3 R23, C3-10cycloalkyl substituted with 0-3 R23, heterocyclyl-C1-10alkyl substituted with 0-3 R23, C6-10aryl-C1-10alkyl substituted with 0-3 R23, and heterocyclyl substituted with 0-3 R23; R21 and R22 are each independently selected from the group consisting of —OH, C1-10alkyl substituted with 0-3 R23, aryl substituted with 0-3 R23, C3-10cycloalkyl substituted with 0-3 R23, heterocyclyl-C1-10alkyl substituted with 0-3 R23, C6-10aryl-C1-10alkyl substituted with 0-3 R23, and heterocyclyl substituted with 0-3 R23; each R23 is independently selected from the group consisting of ═O, halo, trifluoromethyl, —CF2H, —CH2F, cyano, —CO2R24, —C(═O)R24, —C(═O)N(R24)2, —CHO, —CH2OR24, —OC(═O)R24, —OC(═O)R24, —OR24, —OC(═O)N(R24)2, —NR24C(═O)R24, —NR24CO(═O)R24, —NR24C(═O)N(R24)2, —NR24SO2N(R24)2, —NR24SO2R24, —SO3H, —SO2R24, —SR24, —S(═O)R24, —SO2N(R24)2, —N(R24)2, —NHC(═S)NHR24, ═NOR24, —NO2, —C(═O)NHOR24, —C(═O)NHN(R24)2, —OCH2CO2H, 2-(1-morpholino)ethoxy, C1-5alkyl, C2-4alkenyl, C2-4alkynyl, C3-6cycloalkyl, C3-6cycloalkylmethyl, C2-6alkoxyalkyl, aryl substituted with 0-2 R24, and heterocyclyl; each R24 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, alkylaryl, alkylcarbonyl, aryl, arylalkyl, alkylarylalkyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, heteroalkyl, heterocyclyl, heterocyclylalkyl, carbonyl, and a protecting group; and n′ is an integer from 1-3, wherein the compound comprises at least one chelator moiety, and wherein the chelator moiety comprises the structure:wherein:
each R′ is a group capable of coordinating a metal ion; and R″ is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, alkylaryl, alkylcarbonyl, aryl, arylalkyl, alkylarylalkyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, heteroalkyl, heterocyclyl, heterocyclylalkyl, or substituted derivatives thereof.