288083-64-7Relevant academic research and scientific papers
Designing new analogs for streamlining the structure of cytotoxic lamellarin natural products
Tangdenpaisal, Kassrin,Worayuthakarn, Rattana,Karnkla, Supatra,Ploypradith, Poonsakdi,Intachote, Pakamas,Sengsai, Suchada,Saimanee, Busakorn,Ruchirawat, Somsak,Chittchang, Montakarn
, p. 925 - 937 (2015/03/31)
Despite the therapeutic potential of marine-derived lamellarin natural products, their preclinical development has been hampered by their lipophilic nature, causing very poor aqueous solubility. In order to develop more drug-like analogs, their structure was streamlined in this study from both the cytotoxic activity and lipophilicity standpoints. First, a modified total synthetic route was successfully devised to construct a library of 59 systematically designed lamellarin analogs, which were then subjected to cytotoxicity and log P determinations. Along with the 25 first-generation lamellarins previously synthesized in our laboratory, the structure-activity and structure-lipophilicity relationships were extensively evaluated. Our results clearly indicated the additional structural requirements around the lamellarin skeleton which, when combined with those reported previously, can provide invaluable guidance for further modifications to increase the aqueous solubility of these compounds.
Syntheses and antitumor targeting G1 phase of the cell cycle of benzoyldihydroisoquinolines and related 1-substituted isoquinolines
Bermejo, Almudena,Andreu, Inmaculada,Suvire, Fernando,Léonce, Stephane,Caignard, Daniel H.,Renard, Pierre,Pierré, Alain,Enriz, Ricardo D.,Cortes, Diego,Cabedo, Nuria
, p. 5058 - 5068 (2007/10/03)
A series of 1-substituted 3,4-dihydroisoquinolines were synthesized and tested in vitro against the leukemia L 1210 cell line to evaluate their ability to perturb the cell cycle by arresting cells in the G1 phase. 1-Benzoylimines, 1-phenylimines, and 1-alkylimines were synthesized. The most powerful cytotoxic derivatives, 1-benzoyl-3,4-dihydroisoquinolines (1-26), were obtained from amides I via 1-benzyl-3,4-dihydroisoquinoline in good yield by a direct selective oxidation of the benzylic carbon of the corresponding imines through 10% Pd/C in acetonitrile. SAR studies let us to identify the essential structural features for cytotoxic activity. The most bioactive compounds (with IC50 5μM) were BzDHIQ (13, 22, 21, 8, 9, 11, 1, 20, 6, and 19), and they are characterized by the following: (i) An α-ketoimine moiety is necessary for potent antiproliferative activity (1-phenyl- and 1-alkyl-3,4-dihydroisoquinoline derivatives, 34-40, are less active). (ii) An hydrophobic, benzyloxy, alkyloxy, or allyloxy group at the C-6 position seems to be relevant for cytotoxicity. (iii) Regarding the influence of the benzoylic moiety, both the unsubstituted (13, 8, 9, 11, 1, and 6) and the 3′-monosubstituted (22, 21, 20, and 19) compounds were more potent than compounds with other substitutions.
An efficient method for the preparation of antitumoral α-keto-imines benzyldihydroisoquinolines by selective benzylic oxidation with C/Pd in acetonitrile
Andreu, Inmaculada,Cabedo, Nuria,Atassi, Ghanem,Pierre, Alain,Caignard, Daniel H,Renard, Pierre,Cortes, Diego,Bermejo, Almudena
, p. 757 - 759 (2007/10/03)
A series of potent antitumor α-keto-imine BDHIQ derivatives were synthesized and assayed in vitro against L1210 leukemia cell line. A new and easy method for the direct formation of α-keto-imine from imine BDHIQ's was performed with 10% C/Pd in acetonitrile.
Preparation of dopaminergic N-alkyl-benzyltetrahydro-isoquinolines using a 'one-pot' procedure in acid medium
Andreu, Inmaculada,Cortes, Diego,Protais, Philippe,Cassels, Bruce K.,Chagraoui, Abdeslam,Cabedo, Nuria
, p. 889 - 895 (2007/10/03)
The preparation of N-methyl-BTHIQ (4) from N-phenylethyl-phenacetamide (1) by cyclization, reduction and N-alkylation in acid medium has been achieved in good yield in a 'one-pot' procedure. Acylation of imine (2) intermediate afforded the Z and E stereoselectivity in the enamide formation. 6-Hydroxy-BTHIQ (7) shows selectivity for D2 dopamine receptors, while its N-methylated homologue (8) displays higher affinities for both D1 and D2 receptor types, with an unexpected increase in D1 dopamine receptor affinity. (C) 2000 Elsevier Science Ltd.
