Novel alkyl-1,4-butanediamine Pt(II) complexes having a seven-membered ring structure were synthesized and characterized by fast atom bombardment mass and infrared spectra and elemental analysis. Their antitumor activities in vivo toward lymphoid leukemia L1210 and Lewis lung carcinoma LL were studied in the case where the leaving group was either dichloride or cyclobutane-1,1-dicarboxylate. 1,4-Butanediamine Pt(II) complexes (seven-membered ring) showed higher antitumor activities than those of ethylenediamine Pt(II) (five-membered ring) and 1,3-propanediamine Pt(II) (six-membered ring) complexes toward L1210 for both leaving groups. Alkyl-1,4-butanediamine Pt(II) complexes showed high antitumor activities toward L1210, except for 1,1-dimethyl-1,4-butanediamine Pt(II) complexes. In particular, 2,2-dimethyl-1,4-butanediamine and 2,3-dimethyl-1,4-butanediamine Pt(II) complexes exhibited excellent antitumor activities with T/C% values higher than 300. None of the dichloro Pt(II) complexes showed antitumor activities toward LL, but the cyclobutane-1,1-dicarboxylato Pt(II) complexes, which were moderately active toward L1210 with T/C% values around 200, also showed high antitumor activities toward LL with T/C% values of more than 200. Alkyl-1,4-butanediamine Pt(II) complexes with a seven-membered ring structure were found to be stable and to have antitumor activities in vivo.
Factor analysis was applied to the data matrix of in vitro growth inhibitory activities of 52 platinum complexes against 9 tumor cell lines, L1210, P388, Lewis lung, AH66, AH66F, HeLa S3, KB, HT-1197 and HT-1376 cell lines. Three factors were obtained by the principal factor analysis method. After the varimax rotation of these three factors, tumor cell lines were classified into four groups according to their factor loadings. The platinum complexes were characterized by the factor scores. Cisplatin was situated in an extreme position as compared with the other platinum complexes. In vivo antitumor activities of the platinum complexes were tested against L1210 and LL murine tumor models. The in vivo activity against L1210 showed a negative correlation with that against LL. Factor 2 scores of the complexes obtained by factor analysis of in vitro antitumor activities showed a good correlation with these in vivo antitumor activities. Then, the structure-factor 2 score relationships among platinum complexes were analyzed by the Free-Wilson method. From this analysis, structure-activity relationships for carrier ligands and leaving groups are proposed. Factor analysis is suggested to be a useful method to establish an efficient screening system for platinum complexes.
The trapping of the cationic species, which was generated by the protonation of 1,3-bis(p-vinylphenyl)propane , was tried by using a number of olefins as nucleophiles. Among the olefins, styrene, p-methylstyrene, p-chlorostyrene, m-(trifluoromethyl)styrene, 2-phenylpropene, 1,1 -diphenylethylene, indene, 1,3-cyclohexadiene, trans-1,3-pentadiene, and St-C3-St itself were able to trap the cation to give cisand iraní-l-methyl-3-substituted[3.3]paracyclophanes (cis/trans ratio, 1.0-7.4) in 8-46% yields. 2-Phenylpropene gave the highest yield. Other a,w-bis(p-vinylphenyl)alkanes (St-C"-St, = 4-6) also afforded cis-and trans-1 -methyl-3-styryl [3 ,n]paracyclophanes ( = 4-6) in 43-61% yields in this cationic cyclocodimerization with styrene. From the consideration of the reaction mechanism, the propriety of olefins as a comonomer was clarified by using their ionization potentials and total delocalization energies, which were calculated for the face-to-face oriented benzyl cation-olefin pairs. Styrene derivatives and dienes of which ionization potentials lie in the range of 8.1 to 8.6 eV are concluded to be suitable for the comonomers.The methyl group of trans-1 -methyl-3-X-substituted[3.3]paracyclophane (X = methyl, styryl, a-methylstyryl, or indenyl) showed temperature-dependent NMR resonance, which indicates conformational inversion at the disubstituted linkage. The line-shape analyses showed that the relative bulkiness of the substituents to the methyl group increased in the order of styryl < a-methylstyryl « indenyl. Their activation free energies at 273 K were almost equal (11.5-11.9 kcal/mol), because of the compensative contribution of AH* and AS*. Especially the indenyl group substituted cyclophane showed remarkably small AH* and largely negative AS*. These temperature-dependent NMR spectra also gave definite evidence for the cis/trans structural assignments of isomers.Cationic cyclization, in which a carbocation intramolecularly reacts with unsaturation(s) to form a ring(s), is a general and useful method for the common-ring formation. Johnson's wellknown biomimetic synthesis1 of steroid skeletons from polyenes is one of the excellent and sophisticated applications of the method. However, carbocations are so labile in most organic solvents that the cationic C-C bond formations are often accompanied by several side reactions. Therefore, they are seldom used to make macrocyclic systems from open-chain starting materials that have
Die durch Protonierung der Bis‐ (p‐vinyl‐phenyl)‐alkane (I) gebildeten kationischen Spezies werden von Olefinen (II) bzw. (V) unter Bildung der Paracyclophane (III)+(IV) bzw. (VI) + (VII) abgefangen; die analog mit den Olefinen (VIII) bzw. (IX) gebildeten Primärprodukte können nicht getrennt werden; sie werden erst nach ihrer Hydrierung isoliert [→(X) + (XI); keine präparativen Angaben].
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.