Verona Pharma Plc

Vernalis Limited

Rhinopharma Limited

David Jack

Alexander W Oxford

The present invention relates to derivatives of pyrimido[6,1-a]isoquinolin-4-one and their application as inhibitors of phosphodiesterase (PDE) isoenzymes. More particularly the invention relates to derivatives of pyrimido[6,1-a]isoquinolin-4-one and their use in medicine for example as bronchodilators with anti-inflammatory properties. 

Derivatives of pyrimido[6,1-A]isoquinolin-4-one

The invention provides compounds or salts thereof of the general formula (I): wherein each of Rand Rindependently represents a Calkyl or Cacyl group; X represents OCHor a group CRR; wherein each of Ror Rindependently represents a hydrogen atom or a Calkyl group; Rrepresents a hydrogen atom or a Calkyl, Calkenyl or Calkynyl group; Rrepresents a hydrogen atom or a Calkyl, Calkenyl, Calkynyl, amino, Calkylamino, di(C) alkylamino or Cacylamino group; each of Rand Rindependently represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, Calkyl, Calkenyl, Calkynyl, Cacyl, Calkylthio, Calkoxy, Ccycloalkyl; and Rrepresents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, Calkyl, Calkenyl, Calkynyl, Cacyl, Calkylthio, Calkoxy or Ccycloalkyl group. The compounds or salts thereof are useful for treatment of respiratory disorders such as asthma. Compounds of the invention have a longer duration of action than the known compound trequinsin (9,10-dimethoxy-3 methyl-2-mesitylimino-2, 3,6,7-tetrahydro-4H-pyrimido[6,1-a]isoquinolin-4-one).

Derivatives of pyrimido[6, 1-A]isoquinolin-4-one

Compounds of general formula (I) wherein each of Rand Rindependently represents a Calkyl or Cacyl group; Rrepresents a hydrogen atom or a Calkyl, Calkenyl or Calkynyl group; Rrepresents a hydrogen atom or a Calkyl, Calkenyl, Calkynyl, amino, Calkylamino, di(C)alkylamino or Cacylamino group, each of Rand Rindependently represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, Calkyl, Calkenyl, Calkynyl, Cacyl, Calkythio, Calkoxy, Ccycloalkyl; and Rrepresents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, Calkyl, Calkenyl, Calkynyl, Cacyl, Calkythio, Calkoxy or Ccycloalkyl group; X represents OCHor a group CRR, wherein each of Rand Rindependently represents a hydrogen atom or a Calkyl group; each of Rand Rindependently represents a hydrogen atom, a Calkyl, Ccycloalkyl or phenyl group; y represents an oxygen atom or a group CHNO, NCN, NH or NNO, n is an integer from 2 to 4; or a salt thereof; are useful for treatment of respiratory disorders such as asthma. Compounds of the invention have a longer duration of action than the known compound trequinsin (9,10-dimethoxy-3-methyl-2-mesitylimino-2,3,6,7-tetrahydro-4H-pyrimido[6,1-a]-isoquinolin-4-one) and do not have trequinsin's very bitter taste.

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Wheathampstead, United Kingdom

David Jack