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1.
Bioorg Med Chem Lett ; 30(21): 127574, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32980512

RESUMO

The NO-sGC-cGMP signaling pathway plays an important role in the cardiovascular system. Loss of nitric oxide tone or impaired signaling has been associated with cardiovascular diseases, such as hypertension, pulmonary hypertension and heart failure. Direct activation of sGC enzyme independent of NO represents a novel approach for modulating NO signaling with tremendous therapeutic potential. Herein, we describe the design of a structurally novel class of heme-dependent sGC stimulators containing the 3,3-dimethylpyrrolidin-2-one moiety which resulted in the identification of the potent, selective stimulator 30 (MK-2947) for the treatment of hypertension.


Assuntos
Anti-Hipertensivos/farmacologia , Descoberta de Drogas , Hipertensão/tratamento farmacológico , Guanilil Ciclase Solúvel/metabolismo , Anti-Hipertensivos/química , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
2.
Aust J Physiother ; 43(4): 235-242, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-11676693

RESUMO

A single case study was undertaken of a screen based keyboard operator with a subclinical work related neck and upper limb disorder. It was proposed that retraining the stabilisation capacity of the postural supporting muscles (deep cervical flexors and the lower scapular stabilisers) would relieve selected musculoskeletal structures of stress, making them less sensitive to physical tests. The study involved three four-week phases: pre-intervention, intervention and a post-intervention phase. The results showed that as the ability of the postural supporting muscles to hold a low level contraction improved, the mechanosensitivity of the structures tested was reduced. This points to the benefits of exercise to improve muscle stabilisation capacity in work injury prevention programs and warrants further study.

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