144243-26-5Relevant articles and documents
SUBSTITUTED 2, 4-DIAMINO-QUINOLINE DERIVATIVES FOR USE IN THE TREATMENT OF PROLIFERATIVE DISEASES
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Page/Page column 205; 206, (2017/12/13)
This application discloses compounds according to generic Formula (I): wherein all variables are defined as described herein which exhibit strong inhibition effects on various cancer cell lines. The compounds disclosed herein are useful for the treatment of proliferative diseases, including neoplastic diseases such as cancer and non- neoplastic disorders such as rheumatoid arthritis. Also disclosed are pharmaceutical compositions containing compounds of Formula (I) and at least one carrier, diluent or excipient and optionally one or more additional therapeutically active agents, including anticancer agents. This application also discloses methods for treating a proliferative disease, including neoplastic diseases such as cancer and non- neoplastic disorders such as rheumatoid arthritis.
Synthesis and Biological Evaluation of Conformationally Restricted 2-(1-Pyrrolidinyl)-N--N-methylethylenediamines as ? Receptor Ligands. 1. Pyrrolidine, Piperidine, Homopiperidine, and Tetrahydroisoquinoline Classes
Costa, Brian R. de,Dominguez, Celia,He, Xiao-shu,Williams, Wanda,Radesca, Lilian,Bowen, Wayne
, p. 4334 - 4343 (2007/10/02)
The synthesis and ? receptor affinity of a series of conformationally restricted derivatives of 2-(1-pyrrolidinyl)-N--N-methylethylenediamine (1) is described.The pyrrolidinyl (or N,N-dialkyl), ethylenediamine, N-alkyl, and phenylethyl portions of this ? receptor pharmacophore were restricted by its incorporation into 1,2-cyclohexanediamine-, pyrrolidine-, piperidine-, homopiperidine-, and tetrahydroisoquinoline-containing ligands.The ? receptor binding affinities of these compounds were determined using (+)-pentazocine in guinea pig brain homogenates.The synthesis of all but one class was achieved by acylation and alane reduction of the appropriate diamine precursors whose synthesis is also reported. ? receptor affinities ranged from 1.34 nM for 6,7-dichloro-2-tetrahydroisoquinoline (12) to 455 nM for (1R,2R)-trans-N--N-methyl-2-(1-pyrrolidinyl)cyclohexylamine .In this displacement assay, (+)-pentazocine exhibited a Ki of 3.1 nM while DTG and haloperidol showed Ki values of 27.7 and 3.7 nM, respectively.The conformationally free parent compound 1 exhibited a Ki value of 2.1 nM.Comparison of both the ? receptor affinities and nitrogen atom geometry of the compounds revealed that a gauche relation of the nitrogen atoms of cis-1,2-cyclohexanediamines is not imperative for high affinity as we had previously thought.It is highly likely that nitrogen lone pair orientations and steric factors on the aliphatic portions of these ligands play a major role in the ? receptor binding of this pharmacophore.
