E. Marmo

N-acyl-N'-methyl-N-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl) benzamidines with hypotensive activity.

Lithium aluminium hydride reduction of N-phenoxycarbonyl-N,N-(1,3,3-trimethylbicyclo[2.2.1]-hept-2- yl)benzamidine (II), which afforded the N-acyl derivatives (III a-f) in good yields. Compounds (II) and (III) showed a moderate hypotensive activity in rats. Local anesthetic activity by infiltration in mice, effects on heart rate and antiarrhythmic activity in rats are also reported.

Reaction of Ketenes with N,N‐Disubstituted α‐Aminomethylene Ketones. Part 24. 2H‐Pyrano‐(3,2‐d)‐1‐benzoxepin Derivatives with Platelet Antiaggregating and Other Activities.

The synthesis of some N,N-disubstituted 4-amino-5,6-dihydro-3-phenyl-2H-pyrano[3,2-d]-1-benzoxepin-2 -ones by reaction of phenylchloroketene with a series of N,N-disubstituted (E)-4-aminomethylene-3,4-dihydro-1-benzoxepin-5(2H)-ones, followed by dehydrochlorination of the primary adducts with DBN, is described. Some of these compounds showed a platelet antiaggregating activity in vitro slightly superior to that of acetylsalicylic acid, as well as weak local anesthetic and antiinflammatory activities in mice and rats, respectively.

Reaction of Ketenes with N,N-Disubstituted α-Aminomethylene Ketones. Part 22. 2H,5H-(1)Benzothiopyrano(4,3-b)pyran Derivatives with Platelet Antiaggregating Activity.

The synthesis of some N,N-disubstituted 4-amino-3-phenyl-2H,5H-[1]benzothiopyrano [4,3-b]pyran-2-ones by reaction of phenylchloroketene with a series of N,N-disubstituted 3-aminomethylene-2,3-dihydro-4H-1-benzothiopyran-4-ones, followed by dehydrochlorination of the primary adducts with DBN, is described. Some of these compounds showed a strong platelet antiaggregating activity in vitro, superior to that of acetylsalicylic acid.

Influence of rat prenatal and postnatal exposure to a non-steroidal anti-inflammatory agent (flunoxaprofen) on cardiovascular function in the progeny

The present experiments evaluated in rats the effects of prenatal and postnatal exposure to a non-steroidal antiinflammatory agent, flunoxaprofen (5-10 and 20 mg/kg/day by the oral route), on cardiovascular function in the pups. In both conscious and anaesthetized rats pre- and postnatal flunoxaprofen exposure at the 30th and 60th day of age, significantly (P less than .05) induced a decrease of pressor response to carotid-sinus baroreceptor stimulation and to L-noradrenaline (0.1-1 and 5 micrograms/kg iv), and an increase of the hypotensive responses to L-isoprenaline (0.01-0.1 and 1 microgram/kg iv) and acetylcholine (0.01-0.1 and 1 microgram/kg iv). These effects were not observed in rats on the 90th day of age. Moreover, pre- and postnatal flunoxaprofen exposure did not modify systolic arterial blood pressure of plasma levels of catecholamines and acetylcholinesterases. Our results also show that in normotensive rats flunoxaprofen exposure during pregnancy did not affect the body weight, systolic or diastolic blood pressure or heart rate of pregnant rats. It did not affect the length of gestation, number of pups per litter or pup body weight. No macroscopic teratogenic effects were observed.

Esters of N-methyl-N-(2-hydroxyethyl or 3-hydroxypropyl)-1,3,3-trimethylbicyclo [2.2.1]heptan-2-endo-amine with hypotensive activity.

The synthesis of title compounds by reaction of fenchone nitrimine with 2-aminoethanol and 3-aminopropanol, followed by stereospecific NaBH4 reduction of the resulting imines, Eschweiler-Clarke reductive methylation and esterification with aliphatic and aromatic acyl chlorides is described. Some esters showed an appreciable hypotensive activity in rats. Effects on heart rate and antiarrhythmic activity in rats, as well as infiltration anesthesia in mice, are also reported.

Esters of N-(2-hydroxy-1,1-dimethylethyl)-1,7,7-trimethylbicyclo[2.2.1] heptan-2-exo-amine with hypotensive activity

The synthesis of title compounds by reaction of camphor nitrimine with 2-amino-2-methylpropanol, followed by NaBH4 reduction of the resulting imine to the aminoalcohol (III) and esterification of (III) with aliphatic and aromatic acyl chlorides in pyridine solution, is described. Phenyl carbamate (V) was also prepared by reaction of (III) with phenyl isocyanate. Some esters and (V) showed a moderate hypotensive activity in rats. Effects on heart rate and antiarrhythmic activity in rats, as well as infiltration anesthesia in mice, are also reported.

Amides of N-phenyl benzonorbornen-2-endo-amine with hypotensive and other activities.

The synthesis of two series of amides and glycinamides starting from N-phenyl benzonorbornen-2-endo-amine, prepared from benzonorbornen-2-one via sodium borohydride reduction of its N-phenyl imine, is described. Some amides showed a remarkable hypotensive activity in rats, whereas amides and glycinamides usually exhibited a moderate infiltration anesthesia in mice. Effects on heart rate in rats and antiarrhythmic activity in mice are also reported.

N-substituted 4,7,7-trimethyl-3-(1-piperidinyl)bicyclo-[2.2.1]hept-2-ene 2-carboxamides and 2-carbothioamides with hypotensive activity.

The synthesis of two series of N-substituted 4,7,7-trimethyl-3-(1-piperidinyl)bicyclo[2.2.1]hept-2-ene 2-carboxamides (I d-h) and 2-carbothioamides (I i-o), as well as of some N-aryl 4,7,7-trimethyl-3-(1-pyrrolidinyl)bicyclo[2.2.1]hept-2-ene 2-carboxamides (I a-c), by reaction of camphor piperidinoenamine and pyrrolidinoenamine with aryl isocyanates and isothiocyanates is described. On the whole compounds (I d-h) showed a weak hypotensive activity in rats.

Derivatives of 1,2,3,3-tetramethyl-2-azabicyclo[2.2.2]octan-5-trans-ol with antiarrhythmic and other activities. III.

The synthesis of a series of alkyl and aryl amides (IV) starting from 5-trans-(3-aminopropoxy)-N-benzyl-1,2,3,3-tetramethyl-2-azabicyclo [2.2.2] octane is described. Some of compounds (IV) showed a moderate hypotensive activity in rats and infiltration anesthesia in mice. Effects on heart rate in rats and antiarrhythmic activity in mice were practically absent.