Optimized synthesis and indium complex formation with the bifunctional chelator NODIA-Me

Abstract

Multi-step synthetic route provides the ligand NODIA-Me in high yield. Radiolabeling with [111In]InCl3 yields stable complexes in high radiochemical purity and yield.

New Triazacycloalkane Derivatives as Cytotoxic Agents for CLL Treatment: From Proof of Concept to the Targeting Biomolecule

“…NMR spectra were recorded at the "Service commun" of the University of Brest. 1 H and 13 C NMR spectra were recorded using Brucker DRX 500 (500 MHz), Bruker Avance 500 (500 MHz), Bruker Avance 400 (400 MHz), or Bruker AMX-3 300 (300 MHz) spectrometers at 298 K. High-resolution mass spectrometry (HRMS) analyses were realized on an HRMS Q-Tof MaXis (sources ESI, APCI, APPI, nano-ESI) (at the Institute of Organic and Analytic Chemistry�ICOA in Orleáns). Numbering of compounds ( 6)−( 11) and 6′-SL-no3py are given in the ESI.…”

“…1 H NMR (500 MHz, CDCl 3 , 298 K) δ (ppm): 8.48 (s, 2H, H31), 8.39 (d, J = 4.9 Hz, 1H, H19), 7.62 (t, J = 7.1 Hz, 2H, H29), 7.50 (d, J = 7.7 Hz, 3H, H20, H28), 7.12 (m, 3H, H18, H30), 5.61 (d, J H1−H2 = 5.0 Hz, 1H, H1), 5.45 (s, 1H, H3), 5.41 (d, J H3′−H4′ = 2.6 Hz, 1H, H4′), 5.33−5.27 (m, 1H, H8″), 5.24 (d, J = 9.2 Hz, 1H, H7″), 5.11 (dd, J H2′−H1′ = 8.2 Hz, J H2′−H3′ = 10.2 Hz, 1H, H2′), 5.01 (dd, J H3′−H4′ = 3.3 Hz, J H2′−H3′ = 10.4 Hz, 1H, H3′), 4.84 (ddd, J H3″eq−H4″ = 4.7 Hz, J H3″ax−H4″ = 12.0 Hz, 1H, H4″), 4.66 (d, J H1′−H2′ = 7.9 Hz, 1H, H1′), 4.28 (dd, J = 2.0, 12.2 Hz, 1H, H9″a), 4.25 (m, 2H, H2, H6a), 4.14−3.84 (m, 11 H, H6b, H6″, H9″b, H5′, H5″, H22, H26), 3.81−3.79 (m, 1H, H5), 3.79 (s, 3H, COOCH 3 ), 3.72 (d, J H4−H5 = 9.9 Hz, 1H, H4), 3.64 (dd, J H5′−H6′a = 6 Hz, J H6′a−H6′b = 10.8 Hz, 1H, H6′a), 3.52 (m, 2H, H9), 3.38 (m, 3H, H10, H6′b), 2.93 (br s, 12H, H23, H24, H25), 2.53−2.43 (m, 3H, H3″a, H14), 2.33 (m, 2H, H12), 2.15 (s, 3H, CH 3 OAc), 2.11 (s, 3H, CH 3 OAc), 2.07 (s, 9H, CH 3 OAc), 2.02 (s, 3H, CH 3 OAc), 2.00 (s, 3H, CH 3 OAc), 1.98 (s, 3H, CH 3 OAc), 1.92 (m, 5H, CH 3 OAc +H13), 1.85 (m, 4H, CH 3 NHAc + H3″ax), 1.66 (s, 3H, H8). 13 C NMR (125 MHz, CDCl 3 , 298 K) some signals are missing δ (ppm): 172.1 (C11), 170.8, 170.6, 170.5, 170.4, 170.2, 170.0, 169.7, 169.6, 169.5, 168.9 (Cq OAc), 167.7 (C1″), 2 * 148.9 (C31, C19), 136.5 (C29), 125.4, 124.7, 123.5 (C18, C20, C28, C30), 121.4 (C7), 102.0 (C1′), 99.1 (C2″), 96.8 (C1), 79.3 (C16), 76.9 (C4), 73.2 (C2), 72.4 (C6″), 71.6 (C5′), 70.9 (C3′), 70.4 (C3), 68.9 (C2′), 68.6 (C4″), 67.9 (C8″), 67.2, 67.0, 66.9 (C5, C4′, C7″), 63.3 (C6), 62.7, 62.5, 62.4 (C6′, C9″, C9), 52.8 (COOCH 3 ), 49.3 (C5″), 39.2 (C10), 37.7 (C3″), 34.9 (C12), 24.0 (C13), 23 Synthesis of 6′-SL-no3py. To a solution of compound (11) (30 mg, 19 μmol) in CH 3 OH (1 mL) was added a 0.4 M solution of NaOCH 3 in MeOH (20 μL), and the reaction mixture was stirred at room temperature for 17 h before addition of K 2 CO 3 (6 mg, 43 μmol, 2.3 equiv).…”

“…H NMR (300 MHz, CDCl 3 , 298 K) δ (ppm): 8.54 (d, 1H, 3 J = 5 Hz, CH ar ), 7.47 (s, 1H, CH ar ), 7.29 (d, 1H, 3 J = 5 Hz, CH ar ), 5.32 (s, 2H, CH 2 OMs), 3.69 (s, 3H, CH 3 ester), 3.12 (s, 3H, CH 3 SO 2 ), 2.47−2.56 (m, 4H, CH 2 ), 1.95 (qt, 2H, 3 J = 6 Hz, CH 2 ) 13. C NMR (75 MHz, CDCl 3 , 298 K) δ CN was added dropwise over a period of 15 min.…”

Proof-of-Concept Study of the NOTI Chelating Platform: Preclinical Evaluation of 64Cu-Labeled Mono- and Trimeric c(RGDfK) Conjugates

“…Chemicals and solvents were purchased from Sigma-Aldrich and TCI Europe, and used as received. The bifunctional chelator NODIA-Me 3 was prepared as previously described [28,29]. The peptide c(RGDfK) 7 was purchased from ABX (Radeberg, Germany (30 g) cartridge.…”

Synthetic Approaches to the Bifunctional Chelators for Radio­nuclides Based On Pyridine-Containing Azacrown Compounds

“…The choice of BFC is therefore governed by the thermodynamic and kinetic stability of the radiometal complexes. 6,[11][12][13][14] Fast room temperature radiolabeling becomes an important property when working with BFCconjugates of heat sensitive molecules such as antibodies and their derivatives, or when working with short half-life isotopes such as 212/213 Bi, 68 Ga, 44 Sc, and 62 Cu. [15][16][17][18][19][20]…”