Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 8 de 8
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
ACS Med Chem Lett ; 6(1): 31-6, 2015 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-25589926

RESUMO

A novel Type II kinase inhibitor chemotype has been identified for maternal embryonic leucine zipper kinase (MELK) using structure-based ligand design. The strategy involved structural characterization of an induced DFG-out pocket by protein-ligand X-ray crystallography and incorporation of a slender linkage capable of bypassing a large gate-keeper residue, thus enabling design of molecules accessing both hinge and induced pocket regions. Optimization of an initial hit led to the identification of a low-nanomolar, cell-penetrant Type II inhibitor suitable for use as a chemical probe for MELK.

2.
J Org Chem ; 77(1): 652-7, 2012 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-22106838

RESUMO

A five-step synthesis of the natural product angelicoin A using a late stage highly regioselective palladium(0)-catalyzed decarboxylative prenyl migration and aromatization sequence as the key step is reported. The method was extended with geranyl migration in eight-step total syntheses of hericenone J and hericenol A from geraniol.


Assuntos
Neopreno/química , Fenóis/química , Fenóis/síntese química , Terpenos/química , Terpenos/síntese química , Monoterpenos Acíclicos , Catálise , Estrutura Molecular , Paládio/química , Estereoisomerismo
3.
Org Lett ; 13(21): 5748-50, 2011 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-21936533

RESUMO

Five-step total syntheses of angelicoin A and B from 2,2,6-trimethyl-4-dioxinone are reported using late stage biomimetic aromatization reactions via diketo-dioxinones as intermediates. In addition, with angelicoin A, this aromatization was coupled with a palladium-catalyzed decarboxylative prenylation in a one-pot sequence as the key step.


Assuntos
Materiais Biomiméticos/síntese química , Cumarínicos/síntese química , Paládio/química , Catálise , Estrutura Molecular , Prenilação
4.
Bioorg Med Chem Lett ; 21(19): 5939-43, 2011 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-21885277

RESUMO

The discovery of a series of highly potent and novel TLR7 agonist interferon inducers is described. Structure-activity relationships are presented, along with pharmacokinetic studies of a lead molecule from this series of N9-pyridylmethyl-8-oxo-3-deazapurine analogues. A rationale for the very high potency observed is offered. An investigation of the clearance mechanism of this class of compounds in rat was carried out, resulting in aldehyde oxidase mediated oxidation being identified as a key component of the high clearance observed. A possible solution to this problem is discussed.


Assuntos
Antivirais/síntese química , Antivirais/farmacologia , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Interferons/agonistas , Receptor 7 Toll-Like/agonistas , Aldeído Oxidase/metabolismo , Animais , Antivirais/química , Antivirais/farmacocinética , Relação Dose-Resposta a Droga , Descoberta de Drogas , Avaliação Pré-Clínica de Medicamentos , Hepacivirus/fisiologia , Hepatite C/virologia , Humanos , Injeções Intravenosas , Indutores de Interferon/síntese química , Indutores de Interferon/química , Indutores de Interferon/farmacocinética , Indutores de Interferon/farmacologia , Microssomos Hepáticos/metabolismo , Terapia de Alvo Molecular , Peso Molecular , Purinas/síntese química , Purinas/metabolismo , Ratos , Solubilidade , Estereoisomerismo , Relação Estrutura-Atividade
6.
Org Lett ; 11(21): 4910-3, 2009 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-19799447

RESUMO

The total synthesis of aigialomycin D, without the need for phenol protection, was carried out using the C-acylation of a keto-dioxinone dianion, a cascade sequence consisting of ketene generation, alcohol trapping and aromatization, and ring-closing metathesis.


Assuntos
Macrolídeos/síntese química , Ciclização , Macrolídeos/química , Estrutura Molecular
8.
J Org Chem ; 73(24): 9692-7, 2008 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-18834181

RESUMO

The antifungal natural product citrafungin A was synthesized using, as key steps, an asymmetric aldol reaction of a chiral oxazolidinone, diastereoselective alkylation of a chiral 1,3-dioxolan-2-one, semihydrogenation of an enyne, and selective methyl ester deprotection.


Assuntos
Alcenos/síntese química , Antifúngicos/síntese química , Lactonas/síntese química , Aldeídos/química , Alquilação , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Estereoisomerismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...