5766-68-7Relevant academic research and scientific papers
Nickel(II), Copper(II), and Zinc(II) Complexes of Penta-azamacrocyclic Ligands. Crystal and Molecular Structure of 3,6,9,12-Tetramethyl-3,6,9,12,18-penta-azabicyclooctadeca-1(18),14,16-trienezinc(II) Perchlorate
Alcock, Nathaniel W.,Moore, Peter,Omar, Hadi A. A.,Reader, C. James
, p. 2643 - 2648 (1987)
The three related penta-azamacrocyclic ligands 6,9-dimethyl-2,13-dioxo-3,6,9,12,18-penta-azabicyclooctadeca-1(18),14,16-triene (L1), 6,9-dimethyl-3,6,9,12,18-penta-azabicyclooctadeca-1(18),14,16-triene (L2), and 3,6,9,12-tetramethyl-3,6,9,12,18-penta-azabicyclooctadeca-1(18),14,16-triene (L3), have been prepared.The complexes 2 (dmso = dimethyl sulfoxide; L = L2, M = Ni or Zn; L = L3, M = Ni) and 2 (L = L2, M = Cu; L = L3, M = Cu or Zn) have been isolated.The Ni2+ complexes are high-spin and six-co-ordinate, and the Cu2+ complexes five-co-ordinate. 13C N.m.r. spectroscopy shows 2)(dmso)>2 to be a 2:1 mixture of two species, one symmetric and the other asymmetric, whilst in 3)>2 only ca. 10 percent of the asymmetric species is present in nitromethane solution.X-Ray crystallography has been used to determine the structure of the symmetric isomer of 3)>2 /= 3.0> diffractometer collected reflections>; it reveals distorted trigonal-bipyramidal geometry about the zinc ion, and an approximate C2 rotation axis passing through the zinc and pyridine N atoms, and bisecting the macrocyclic C-C bond furthest removed from the pyridine ring .
Chromophore-modified bis-naphthalimides: Synthesis and antitumor activity of bis-dibenz[de,h]isoquinoline-1,3-diones
Bra?a,Castellano,Perron,Maher,Conlon,Bousquet,George,Qian,Robinson
, p. 449 - 454 (1997)
The bis-dibenz[de,h]isoquinoline-1,3-diones are a new series of antitumor agents that consist of two chromophores bridged by an alkylamino linker. In the present study we have explored the effect produced by the presence of two dibenz[de,h]isoquinoline-1,3-dione moieties with different polyamine chains on cellular cytotoxicity. Bis-dibenz[de,h]isoquinoline-1,3- diones with the bridge (CH2)2-NH-(CH2)(n)-NH-(CH2)2, where n = 2-5, showed optimum cytotoxicity with IC50's around 10 nM. Compound 16, which has the (CH2)2-NH-(CH2)3-NH-(CH2)2 bridge, altered DNA mobility and topoisomerase I and II activity at approximately 5 μM. When tested in vivo, compound 16 increased the median survival time of mice implanted with M5076 with an optimum %T/C of 154% and produced cures in 50% of mice implanted with Lox melanoma.
Synthesis and antitumor activity of some indeno[1,2-b]quinoline-based bis carboxamides
Deady, Leslie W.,Desneves, Jose,Kaye, Anthony J.,Finlay, Graeme J.,Baguley, Bruce C.,Denny, William A.
, p. 977 - 984 (2000)
A series of bis(11-oxo-11H-indeno[1,2-b]quinoline-6-carboxamides) linked through the 6-carboxamides were prepared by coupling the requisite acid imidazolides with various diamines. Compounds with mono-cationic linker chains were more potent cytotoxins than the corresponding monomer in a panel of rodent and human cell lines, while those with the dicationic linker chains (CH2)2NR(CH2)2NR(CH2)2 and (CH2)2NR(CH2)3NR(CH2)2 showed extraordinarily high potencies (for example, IC50s of 0.18-1.4 nM against human Jurkat leukemia; up to 1000-fold more potent than the parent monomer). As seen previously in the monomeric series, small, lipophilic 4-substituents significantly increased potency in cell culture. The dimeric compounds were all slightly to significantly more potent in the mutant JL(A) and JL(D) cell lines that under-express topo II, suggesting that this enzyme is not their primary target. An 11-imino-linked dimer was much less active, and an asymmetric indeno[1,2-b]quinoline-6-carboxamide/naphthalimide dimer was less active than the comparable symmetric bis(indeno[1,2-b]quinoline-6- carboxamide). Selected analogues were active against sub-cutaneously implanted colon 38 tumors in mice, giving growth delays comparable to that of the clinical topo I inhibitor irinotecan at up to 10-fold lower doses. These compounds form an interesting new class of putative topo I inhibitors. (C) 2000 Elsevier Science Ltd.
Rational design of an organocatalyst for peptide bond formation
Handoko,Satishkumar, Sakilam,Panigrahi, Nihar R.,Arora, Paramjit S.
supporting information, p. 15977 - 15985 (2019/10/11)
Amide bonds are ubiquitous in peptides, proteins, pharmaceuticals, and polymers. The formation of amide bonds is a straightforward process: amide bonds can be synthesized with relative ease because of the availability of efficient coupling agents. However, there is a substantive need for methods that do not require excess reagents. A catalyst that condenses amino acids could have an important impact by reducing the significant waste generated during peptide synthesis. We describe the rational design of a biomimetic catalyst that can efficiently couple amino acids featuring standard protecting groups. The catalyst design combines lessons learned from enzymes, peptide biosynthesis, and organocatalysts. Under optimized conditions, 5 mol % catalyst efficiently couples Fmoc amino acids without notable racemization. Importantly, we demonstrate that the catalyst is functional for the synthesis of oligopeptides on solid phase. This result is significant because it illustrates the potential of the catalyst to function on a substrate with a multitude of amide bonds, which may be expected to inhibit a hydrogen-bonding catalyst.
