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Org Lett ; 19(22): 6196-6199, 2017 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-29115835


Tetrachloro-N-hydroxyphthalimide tetramethyluronium hexafluorophosphate (CITU) is disclosed as a convenient and economical reagent for both acylation and decarboxylative cross-coupling chemistries. Within the former set of reactions, CITU displays reactivity similar to that of common coupling reagents, but with increased safety and reduced cost. Within the latter, increased yields, more rapid conversion, and a simplified procedure are possible across a range of reported decarboxylative transformations.

Peptídeos/química , Acilação , Indicadores e Reagentes , Estrutura Molecular
ACS Med Chem Lett ; 6(7): 770-5, 2015 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-26191364


A series of dimeric macrocyclic compounds were prepared and evaluated as antagonists for inhibitor of apoptosis proteins. The most potent analogue 11, which binds to XIAP and c-IAP proteins with high affinity and induces caspase-3 activation and ultimately cell apoptosis, inhibits growth of human melanoma and colorectal cell lines at low nanomolar concentrations. Furthermore, compound 11 demonstrated significant antitumor activity in the A875 human melanoma xenograft model at doses as low as 2 mg/kg on a q3d schedule.

Bioorg Med Chem Lett ; 20(2): 503-7, 2010 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-20015649


The design and synthesis of novel opiates are reported. Based on the message-address principle a novel class of 4,4- and 3,3-biaryl piperidines was designed and synthesized. Biological evaluation confirmed that these compounds exhibit high affinity and selectivity for the delta opioid receptor. Key structure-activity relationships that influence affinity, selectivity, functional activity and clearance are reported.

Ligantes , Piperidinas/química , Receptores Opioides delta/antagonistas & inibidores , Animais , Desenho de Drogas , Humanos , Microssomos Hepáticos/metabolismo , Piperidinas/síntese química , Piperidinas/farmacologia , Ligação Proteica , Ratos , Receptores Opioides delta/metabolismo , Receptores Opioides kappa/antagonistas & inibidores , Receptores Opioides kappa/metabolismo , Receptores Opioides mu/antagonistas & inibidores , Receptores Opioides mu/metabolismo , Relação Estrutura-Atividade
J Med Chem ; 50(2): 182-5, 2007 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-17228859


A papaverine based pharmacophore model for PDE10A inhibition was generated via SBDD and used to design a library of 4-amino-6,7-dimethoxyquinazolines. From this library emerged an aryl ether pyrrolidyl 6,7-dimethoxyquinazoline series that became the focal point for additional modeling, X-ray, and synthetic efforts toward increasing PDE10A inhibitory potency and selectivity versus PDE3A/B. These efforts culminated in the discovery of 29, a potent and selective brain penetrable inhibitor of PDE10A.

Inibidores de Fosfodiesterase/síntese química , Diester Fosfórico Hidrolases/metabolismo , Pirrolidinas/síntese química , Quinazolinas/síntese química , Animais , Corpo Estriado/metabolismo , Cristalografia por Raios X , GMP Cíclico/metabolismo , Camundongos , Modelos Moleculares , Inibidores de Fosfodiesterase/química , Inibidores de Fosfodiesterase/farmacologia , Diester Fosfórico Hidrolases/química , Pirrolidinas/química , Pirrolidinas/farmacologia , Quinazolinas/química , Quinazolinas/farmacologia , Relação Estrutura-Atividade