5193-58-8

Upstream product

• 40807-61-2 4-hydroxy-4-phenylpiperidin 
• 193882-53-0 2-[3-(4-Hydroxy-4-phenyl-piperidin-1-yl)-propyl]-isoindole-1,3-dione 
• 5193-57-7 3-(4-hydroxy-4-phenylpiperidin-1-yl)propanenitrile 

Downstream Products

• 777841-86-8 3-(3,4-Difluoro-phenyl)-5-oxo-morpholine-4-carboxylic acid-{3-[4-hydroxy-4-phenyl-piperidin-1-yl]-propyl}amide 
• 56079-70-0 N-3-(4-hydroxy-4-phenyl-1-piperidyl)propyl urea 

Relevant academic research and scientific papers

MORPHOLINONE AND MORPHOLINE DERIVATIVES AND USES THEREOF

This invention is directed to morpholinone and morpholine derivatives which are selective antagonists for human α 1a receptors. This invention is also related to uses of these compounds for lowering intraocular pressure, inhibiting cholesterol synthesis, relaxing lower urinary tract tissue, the treatment of benign prostatic hyperplasia, impotency, cardiac arrhythmia, sympathetic mediated pain, migraine, and for the treatment of any disease where the antagonism of the α 1a receptor may be useful. The invention further provides a pharmaceutical composition comprising a therapeutically effective amount of the above-defined compounds and a pharmaceutically acceptable carrier.

Design and synthesis of novel α1a adrenoceptor-selective dihydropyridine antagonists for the treatment of benign prostatic hyperplasia

We report the synthesis and evaluation of novel ttia adrenoceptor subtype-selective antagonists. Systematic modification of the lipophilic 4,4-diphenylpiperidinyl moiety of the dihydropyridine derivatives 1 and 2 provided several highly selective and potent α1a antagonists. From this series, we identified the 4-(methoxycarbonyl)-4-phenylpiperidine analogue SNAP 5540 (-) [(-)-63] for further characterization. When examined in an isolated human prostate tissue assay, this compound was found to have a Ki of 2.8 nM, in agreement with the cloned human receptor binding data (Ki = 2.42 nM). Further evaluation of the compound in isolated dog prostate tissue showed a Ki of 3.6 nM and confirmed it to be a potent antagonist (Kb = 1.6 nM). In vivo, this compound effectively blocked the phenylephrine-stimulated increase in intraurethral pressure (IUP) in mongrel dogs, at doses which did not significantly affect the arterial pressure (diastolic blood pressure, DBF), with a DBF Kb/IUP-Kb ratio of 16. In addition, (-)-63 also showed greater than 40 000-fold selectivity over the rat L-type calcium channel and 200-fold selectivity over several G protein-coupled receptors, including histamine and serotonin subtypes. These findings prove that aia adrenoceptor-subtype selective antagonists such as (-)-63 may be developed as uroselective agents for an improved treatment of BPH over nonselective 0.1 antagonists such as prazosin and terazosin, with fewer side effects.

Synthesis and pharmacological activity of 2-(substituted phenyl)-3{2 or 3-[(4-substituted phenyl-4-hydroxy)piperidino]ethyl or propyl}-1,3- thiazolidin-4-ones

A series of aryl-hydroxy-piperidinoalkyl-thiazolidinones was synthesized and evaluated to inhibit castor oil-induced diarrhea in mice. The dose dependent antidiarrheal activity of the most active compound 2-(p- nitrophenyl)-3-[2-[(4-(p-chlorophenyl)-4-hydroxy)piperidino]ethyl]-1,3- thiazolidin-4-one (6) was counteracted by naloxone, resulting comparable with that of loperamide, a μ opiate agonist.

A structure-activity relationship study of novel phenylacetamides which are sodium channel blockers

A structure-activity relationship study of a series of novel Na+ channel blockers, structurally related to N-[3-(2,6-dimethyl-1-piperidinyl)propyl]- α-phenylbenzeneacetamide (1, PD85639) is described. The diphenylacetic acid portion of the molecule was left unchanged throughout the study, while structural features in the amine portion and the amide alkyl linkage of the molecule were modified. The compounds were tested for inhibition of veratridine-stimulated Na+ influx in CHO cells expressing type IIA Na+ channels. Several derivatives show a trend toward more potent Na+ channel blockade activity with increasing lipophilicity of the amine portion of the molecule. The presence of a phenyl ring near the amine increases inhibitory potency. A three-carbon spacer between the amide and amine is optimal, and a secondary amide linkage is preferred.