Synthesis and biological properties of 2-(4-chlorophenyl)-3-morpholin-4-yl-(4-alkoxyphenyl)alkanol hydrochlorides

New 2-(4-chlorophenyl)-3-morpholin-4-yl-1-(4-alkoxyphenyl)propan-1-ones were synthesized via aminomethylation of 2-(4-chlorophenyl)-1-(4-alkoxyphenyl)ethanones. Reduction of the former by lithium aluminum hydride produced 2-(4-chlorophenyl)-3-morpholin-4-yl-1-(4-alkoxyphenyl)propan-1-ols. Reaction of them with Grignard reagents gave 2-(4-chlorophenyl)-1-morpholin-4-yl-3-(4-alkoxyphenyl)alkan-3-ols. The synthesized compounds exhibited pronounced anticonvulsive and some peripheral n-cholinolytic activities while showing no antibacterial activity.     

Synthesis of 2-(4-substituted phenyl)-3-[4-substituted piperazino(piperidino)]propan-1-ol dihydrochlorides and their effects on adenosine deaminase activity

Aminomethylation of 4-substituted acetophenones yielded a series of β-amino-4-substituted propiophenones. Reduction of these with lithium alumohydride in dry ether produced 1-(4-substituted phenyl)-3-[4-substituted piperazino(piperidino)]propan-1-ols, which were then converted to the corresponding dihydrochlorides. The abilities of these compounds to inhibit adenosine deaminase, a key enzyme in purine metabolism in living organisms, were studied. Some of the compounds had quite marked inhibitory effects on the enzyme. The abilities of the compounds synthesized here to inhibit adenosine deaminase were found to depend on their structure. It is of note that virtually all the compounds inhibited the high molecular weight form of the enzyme to a significantly lesser extent than the low molecular weight form.     

Incidence of patent foramen ovale and migraine headache in adults with congenital heart disease with no known cardiac shunts

The purpose of this study was to understand why patients with adult congenital heart disease (CHD) but no obvious shunt have an increased frequency of migraine headaches (MH). CHD patients with no known cardiac shunts (CHD‐NKS), based on their echocardiographic or angiographic procedures, were tested for a right‐to‐left shunt using agitated saline contrast transcranial Doppler (TCD). Medical records of 2,920 patients from the UCLA Adult CHD Center were screened to participate in a study to evaluate the prevalence of MH in adults with CHD; 182 patients (6.23%) had CHD‐NKS; of these, 60 (30%) underwent a TCD; 23 (38%) tested positive and 37 (62%) tested negative for a right‐to‐left shunt (P = 0.01 compared with controls). The frequency of MH was 43% in CHD‐NKS compared with 11% in controls (P < 0.0001). TCD demonstrated right‐to‐left shunting in approximately 2/3 of patients with pulmonary stenosis, the Marfan syndrome and congenitally corrected transposition of great vessels, 1/4 of patients with bicuspid aortic valve, 1/5 of patients with mitral valve prolapse and all patients with Ebstein's anomaly. Approximately half of these experienced MH. Patients who had MH did not show a higher frequency of right‐to‐left shunt when compared with patients without MH (P = 0.57). In conclusion, CHD patients with conditions usually not associated with a shunt have a higher than expected prevalence of PFO which permits intermittent right‐to‐left shunting undetected by standard non‐contrast TTE and TEE; the increased prevalence of right‐to‐left shunting may partially explain the higher than expected frequency of migraines. © 2012 Wiley Periodicals, Inc.     

Synthesis and pharmacological activity of 1-(4-substituted phenyl)-1-alkyl(aryl)-3-piperidinopropanol hydrochlorides

Aminomethylation of substituted acetophenones with paraformaldehyde and piperidine hydrochloride yielded 4-substituted β-piperidinopropiophenones. Interaction of compounds I with the Grignard reagents in ether yielded 1-(4-substituted phenyl)-1-alkyl(aryl)-3-piperidinopropanols. The anti-inflammatory, analgesic, antipyretic, central m-cholinoblocking, and peripheral n-cholinoblocking actions of 1-(4-substituted phenyl)-1-alkyl(aryl)-3-piperidinopropanol hydrochlorides were studied. The study compounds were found to have marked central m-cholinoblocking and peripheral n-cholinoblocking activities. Only 1-(4-methoxyphenyl)-1-cyclohexyl-3-piperidinopropanol hydrochloride had anti-inflammatory activity.     

Involvement of dopamine D<Subscript>1</Subscript> and D<Subscript>2</Subscript> receptors in the rat nucleus accumbens in immunostimulation

Analysis of the nature of changes in the immune response in operated Wistar rats showed that electrolytic lesioning of the nucleus accumbens, the site of the greatest density of dopamine D₁ and D₂ receptors, led to suppression of the immune response in animals immunized with sheep erythrocytes. Administration of SKF 38393 (20 mg/kg) and quinpirol (1 mg/kg), selective agonists of dopamine D₁ and D₂ receptors respectively, to sham-operated rats induced significant increases in immune responses. However, no immunostimulation was seen on administration of the selective dopamine D₂ agonist quinpirol to animals with lesions to the nucleus accumbens as compared with controls. At the same time, treatment of animals with nucleus accumbens lesions using the dopamine D₁ receptor agonist SKF 38393 had no effect on the immune response as compared with that in sham-operated animals given the D₁ receptor agonist. These data provide evidence that dopamine D₂ receptors in the nucleus accumbens have a role in the mechanisms of immunostimulation, though D₂ receptors in other brain structures may also make some contribution to this process; D₁ receptors in the nucleus accumbens make no significant contribution to controlling the immune response. __________ Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 91, No. 11, pp. 1281–1287, November, 2005.