RESUMO
An expert panel convened in 2005 by the College on Problems of Drug Dependence (CPDD) to consider strategies to reduce the risk of prescription medication abuse concluded that drug formulation plays a significant role in determining risk of abuse. Efforts on the part of the pharmaceutical industry to develop drugs that deter abuse have focused primarily on opioid formulations resistant to common forms of tampering, most notably crushing or dissolving the tablet to accelerate release. Several opioid formulations developed to be tamper resistant have been approved, but the US Food and Drug Administration has not approved explicit label claims of abuse deterrence and has stated that any such claim will require substantial postmarketing data. Drug development efforts in this area raise questions about the relative impact of abuse-deterrent formulations, not only on individuals who might abuse a medication, but also on patients who are compliant with therapy. This review discusses progress since the 2005 CPDD meeting with an emphasis on opioids. Articles cited in the review were identified via a PubMed search covering the period between January 1, 2000, and October 5, 2011. Scientific work presented by the authors and their colleagues at meetings held through May 2012 also was included. Published literature suggests that development of abuse-deterrent products will require broad public health support and continued encouragement from regulatory authorities so that such products will become the expected standard of care for certain drug classes.
Assuntos
Analgésicos Opioides , Química Farmacêutica/tendências , Composição de Medicamentos/tendências , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Analgésicos Opioides/síntese química , Analgésicos Opioides/normas , Química Farmacêutica/normas , Composição de Medicamentos/normas , Humanos , Medicamentos sob Prescrição/síntese química , Medicamentos sob Prescrição/normas , Pró-Fármacos/síntese química , Pró-Fármacos/normasRESUMO
A POCl(3)-mediated, direct amination reaction of heterocyclic amides/ureas with NH-heterocycles or N-substituted anilines is described. Compared to the existing methods, this operationally simple protocol provides unique reactivity and functional group compatibility because of the metal-free, acidic reaction conditions. The yields are generally excellent.
Assuntos
Amidas/química , Química Farmacêutica/métodos , Compostos Heterocíclicos/síntese química , Medicamentos sob Prescrição/síntese química , Ureia/química , Aminação , Compostos de Anilina/química , Anticolesterolemiantes/análise , Anticolesterolemiantes/química , Compostos Azabicíclicos/análise , Compostos Azabicíclicos/química , Benzamidas , Catálise , Cloridrato de Erlotinib , Zopiclona , Fluorbenzenos/análise , Fluorbenzenos/química , Compostos Heterocíclicos/análise , Humanos , Concentração de Íons de Hidrogênio , Hipnóticos e Sedativos/análise , Hipnóticos e Sedativos/química , Hipoglicemiantes/análise , Hipoglicemiantes/química , Mesilato de Imatinib , Estrutura Molecular , Compostos de Fósforo/química , Piperazinas/análise , Piperazinas/química , Medicamentos sob Prescrição/análise , Inibidores de Proteínas Quinases/análise , Inibidores de Proteínas Quinases/química , Pirimidinas/análise , Pirimidinas/química , Quinazolinas/análise , Quinazolinas/química , Rosiglitazona , Rosuvastatina Cálcica , Sulfonamidas/análise , Sulfonamidas/química , Tiazolidinedionas/análise , Tiazolidinedionas/química , Ureia/análogos & derivadosRESUMO
A Lewis base assisted Brønsted base catalysis (LBABB) strategy is applied for direct asymmetric vinylogous alkylation of allylic sulfones with Morita-Baylis-Hillman (MBH) carbonates, in which a strong Brønsted base, tert-butoxy anion, generated in situ from a tertiary amine catalyst and MBH carbonate, is crucial in activating unstabilized nucleophiles. The γ-regioselective alkylation products were obtained with good to excellent enantiomeric excess values when catalyzed by a modified cinchona alkaloid.