Puentes, Cristian Ochoa and Hoecherl, Peter and Kuehnle, Matthias and Bauer, Stefanie and Buerger, Kira and Bernhardt, Guenther and Buschauer, Armin and Koenig, Burkhard (2011) Solid phase synthesis of tariquidar-related modulators of ABC transporters preferring breast cancer resistance protein (ABCG2). BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 21 (12). pp. 3654-3657. ISSN 0960-894X, 1464-3405
Full text not available from this repository. (Request a copy)Abstract
Aiming at structural optimization of potent and selective ABCG2 inhibitors, such as UR-ME22-1, from our laboratory, an efficient solid phase synthesis was developed to get convenient access to this class of compounds. 7-Carboxyisatoic anhydride was attached to Wang resin to give resin bound 2-aminoterephthalic acid. Acylation with quinoline-2- or -6-carbonyl chlorides, coupling with tetrahydroisoquinolinylethylphenylamine derivatives, cleavage of the carboxylic acids from solid support and treatment with trimethylsilydiazomethane gave the corresponding methyl esters. Among these esters highly potent and selective ABCG2 modulators were identified (inhibition of ABCB1 and ABCG2 determined in the calcein-AM and the Hoechst 33342 microplate assay, respectively). Interestingly, compounds bearing triethyleneglycol ether groups at the tetrahydroisoquinoline moiety (UR-COP77, UR-COP78) were comparable to UR-ME22-1 in potency but considerably more efficient (max inhibition 83% and 88% vs 60%, rel. to fumitremorgin c, 100%) These results support the hypothesis that solubility of the new ABCG2 modulators and of the reference compounds tariquidar and elacridar in aqueous media is the efficacy-limiting factor. (C) 2011 Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | P-GLYCOPROTEIN; POTENT INHIBITORS; DERIVATIVES; BCRP/ABCG2; MDR; Tariquidar; ABCB1; ABCG2; Hoechst 33342; Wang resin |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Alumni or Retired Professors > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer) Chemistry and Pharmacy > Institut für Organische Chemie > Lehrstuhl Prof. Dr. Burkhard König |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Jun 2020 06:35 |
| Last Modified: | 09 Jun 2020 06:35 |
| URI: | https://pred.uni-regensburg.de/id/eprint/20659 |
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