Toshihiko Makino

The neuroprotective effect of a potent and selective inhibitor of type I NOS (L-MIN) in a rat model of focal cerebral ischaemia.

OUR newly synthesized δ-(S-methylisothioureidoJ-L-norvaline (L-MIN) was shown to have potent inhibitory effects on Ca2+-dependent and constitutively expressed neuronal nitric oxide synthase (type I NOS) when compared to other commonly recognized NOS inhibitors and produced an IC50 value of 5.7 nM. By contrast, this compound exhibited more than 40-fold weaker inhibitory effects on the other NOS isoforms. Administration of L-MIN (0.1, 0.3 and lmg kg-1, i.p.) to rats immediately after 2 h middle cerebral artery occlusion and 2 h reperfusion reduced infarct size in a dose-dependent manner. These results suggest that type I NOS activation has a crucial role in the pathogenic cellular mechanisms underlying cerebral ischaemia.

Benzopyran-4-carboxamide K+ channel openers

Abstract N -Substituted benzopyran-4-carboxamides 5 have been synthesized. Some of these compounds exhibited potent vasorelaxant activity.

Structure-activity relationships of 6-substituted benzopyran-4-carbothioamide potassium channel openers.

Abstract QSAR study of 6-substituted benzopyran-4-carbothioamides 1 showed that vasorelaxant activity is linearly correlated with the electronic parameter (σ m ) and parabolically correlated with steric ( L ) and hydrophobic (π) parameters of the 6-substituent.

Vasorelaxant activity of 2-fluoroalkyl-6-nitro-2H-1-benzopyran-4-carbothioamide and -carboxamide K+ channel openers

Abstract Synthesis and vasorelaxant activity of 2-fluoroalkyl-6-nitro-2 H -1-benzopyran-4-carbothioamides 4 and 6 and -carboxamides 5 and 7 are described. Potent smooth muscle relaxant activity was displayed by 6c .

Substituent effects of benzopyran-4-(N-cyano)-carboxamidine potassium channel openers for selectivity to guinea pig trachealis

Abstract 6-Substituted benzopyran-4-(N-cyano)amidines 1 and their analogs have been synthesized. Some of these compounds, 1a, 1e, and 1f exhibited selective activity for guinea pig trachealis.

Vasorelaxant activity of 2-substituted 6-nitro-2H-1-benzopyran-4-carbothioamide K+ channel openers

Abstract Synthesis and vasorelaxant activity of 2-substituted 6-nitro-2 H -1-benzopyran-4-carbothioamides 5 are described. Potent smooth muscle relaxant activity was displayed by 5c , 5h , and 5i .