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1.
Expert Opin Emerg Drugs ; 29(2): 155-164, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38602142

RESUMO

INTRODUCTION: Chronic lower back pain is a leading cause of disability and healthcare spending worldwide. Discogenic pain, pain originating from the intervertebral disk, is a common etiology of chronic lower back pain. Currently, accepted treatments for chronic discogenic pain focus only on the management of symptoms, such as pain. There are no approved treatments that stop or reverse degenerating intervertebral discs. Biologic therapies promoting disc regeneration have been developed to expand treatment options. VIADISC™ NP, is a viable disc allograft supplementation that, in a recent trial, demonstrated a significant reduction in pain and increased function in patients suffering from symptomatic degenerative disc disease. AREAS COVERED: This manuscript summarizes the epidemiology and etiology of low back pain, the pathophysiology of degenerative disc disease, current treatments, and a need for newer therapies. The rationale behind intradiscal biologics for the treatment of symptomatic degenerative disc disease is also discussed. EXPERT OPINION: Characterization of the biology leading to disc degeneration has allowed for the development of intradiscal biologics. They may soon be capable of preventing and reversing disc degeneration. Clinical trials have shown promise, but further research into efficacy and safety is needed before these therapies are widely employed.


Assuntos
Dor Crônica , Degeneração do Disco Intervertebral , Dor Lombar , Humanos , Degeneração do Disco Intervertebral/fisiopatologia , Dor Lombar/etiologia , Dor Lombar/fisiopatologia , Dor Lombar/tratamento farmacológico , Dor Lombar/terapia , Dor Crônica/tratamento farmacológico , Dor Crônica/fisiopatologia , Dor Crônica/etiologia , Animais , Disco Intervertebral/fisiopatologia , Disco Intervertebral/patologia , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Produtos Biológicos/administração & dosagem , Desenvolvimento de Medicamentos
2.
Angew Chem Int Ed Engl ; 51(20): 4963-7, 2012 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-22489096

RESUMO

A cooperative catalysis approach for the enantioselective formal [3+2] addition of α,ß-unsaturated aldehydes to isatins has been developed. Homoenolate annulations of ß-aryl enals catalyzed by an N-heterocyclic carbene (NHC) require the addition of lithium chloride for high levels of enantioselectivity. This NHC-catalyzed annulation has been used for the total synthesis of maremycin B.


Assuntos
Indóis/síntese química , Lactonas/síntese química , Compostos de Espiro/síntese química , Catálise , Indóis/química , Lactonas/química , Ácidos de Lewis/química , Metano/análogos & derivados , Metano/química , Estrutura Molecular , Compostos de Espiro/química , Estereoisomerismo
3.
Org Lett ; 13(17): 4712-5, 2011 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-21834570

RESUMO

The formal synthesis of (+)-sorangicin A was completed by two independent routes. Both approaches feature a cross metathesis reaction to form the C29-C30 bond to arrive at the bicyclic ether/tetrahydropyran fragment. Formation of the C15-C16 olefin to unite the dihydropyran fragment with the rest of the molecule was achieved by either a cross metathesis reaction or a Julia-Kocienski olefination.


Assuntos
Aminoglicosídeos/síntese química , Aminoglicosídeos/química , Conformação Molecular , Estereoisomerismo
4.
Org Lett ; 12(19): 4416-9, 2010 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-20831229

RESUMO

The enantioselective total synthesis of spirofungins A (1) and B (2) is reported in 14 steps over the longest linear sequence. Key steps include the use of thiazolidinethione-mediated aldol reactions to assemble the major fragments and installation of the C1-C6 side chain using a cross metathesis reaction.


Assuntos
Piranos/síntese química , Compostos de Espiro/síntese química , Aldeídos/síntese química , Estrutura Molecular , Propanóis/síntese química , Estereoisomerismo
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