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2 189 392

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C1

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IPC

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Application

2001101366/13, 2001-01-16

(24)

Start date

2001-01-16

(22)

Actual filing date

2001-01-16

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Published

2002-09-20

(72)

Inventor

Khropov Ju.V.Pjatakova N.V.Gavrilova S.A.Busygina O.G.Krasnoperov R.A.Medvedeva N.A.Severina I.S.

(73)

Holder

Biologicheskij Fakul'Tet Moskovskogo Gosudarstvennogo Universiteta Im. M.V. Lomonosova

INHIBITOR OF NO-DEPENDENT ACTIVATION OF SOLUBLE FORM OF GUANYLATE CYCLASE Russian patent published in 2002 - IPC

Abstract RU 2189392 C1

FIELD: organic chemistry, biochemistry, enzymology. SUBSTANCE: invention relates to the use of the known substituted N-(2-aminobenzyl)-cyclohexylamines of the general formula (I) where R is Cl or Br; R1 is H or OH and their pharmacologically acceptable salts as an inhibitor of NO-dependent activation of a soluble form of guanylate cyclase. Substituted N-(2-aminobenzyl)-cyclohexylamines of the designated formula (I) in the range of concentrations 1-100 mcM show the inhibitory effect on NO-dependent activation of partially purified soluble guanylate cyclase from human platelets and rat lung induced by sodium nitroprusside. The concentrations of ambroxol (R is Br and R1 is OH, trans-isomer, hydrochloride) when activating effect of sodium nitroprusside is decreased by 50% (IC50) are 3.9 and 2.1 mcM, respectively. Compounds of the general formula (I) under conditions in vivo prevent decrease of arterial pressure value in keep awaking rats caused by excessive formation of NO and by activation of soluble guanylate cyclase induced by sodium nitroprusside as an exogenous donor of nitrogen oxide. Infusion of ambroxol at the rate 14 mcl/min in the dose 2.8 x 10-7 mole/kg for 35 min causes the decrease of hypotensive effect of sodium nitroprusside in the doses 1-3 mcg/kg by 2.5-3 times but shows insignificant effect on heart beat frequency. Invention can be used in biochemistry for investigation of regulatory effects of nitrogen oxide and mechanism of effect of soluble guanylate cyclase and in pharmacology for treatment of diseases associated with the enhanced formation of nitrogen oxide and cyclic guanosine-3',5'-cyclophosphate (cGMP). EFFECT: valuable medicinal and pharmacological properties of inhibitor. 3 cl, 6 dwg

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RU 2 189 392 C1

Authors

Khropov Ju.V.

Pjatakova N.V.

Gavrilova S.A.

Busygina O.G.

Krasnoperov R.A.

Medvedeva N.A.

Severina I.S.

Dates

2002-09-20—Published

2001-01-16—Filed

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