The structure of 1-Phenyl-c-4-t-butyl-r-cyclohexylpiperidine hydrochloride 1 is shown by X-ray crystallography to have an axial t-butyl group. The conformational deformations. are smaller than expected except for the outward bending of the alkyl substituent with a concomittant flattening of the ...

A new procedure has been developed for removing the SiCl3 group from α-trichlorosilyl-substituted amines. In this procedure the trichlorosilyl substrate is treated first with amine hydrochloride in CH3CN, followed by hydrolysis with aqueous hydroxide. Using this sequence, amines corresponding t...

Two methods for the synthesis of the title compounds [3] are presented. The first, and less satisfactory, method uses the sulphide contraction, which involves salt formation between alkyl bromoacetates and N-arylpyrrolidine-2-thiones [2] followed by sulphur extrusion. By-products include N-arylp...

PMR spectra of carbonyl compounds 2a-k reveal significant variations in the population of E and Z isomers on changing the solvent from CDCl3 to DMSO-d6. In non-polar media, the intramolecular N-H…. O hydrogen bonded form is exclusively observed. In DMSO-d6, the alternative Z form is also popula...

Cyclooxygenase (COX) is a key rate-limiting enzyme for prostaglandin (PG) production cascades in the human body. The mechanisms of both the anti-inflammation effects and the side-effects of traditional COX inhibitors are associated with the existence of two COX isoforms. Thus while COX-1 is pred...

Dehydroacetic acid undergoes several kinds of reactions. Of these, ring transformations are having much more importance in organic synthesis. Most of the compounds formed by ring transformations of DHA are five-membered rings. When we see the mechanism of these transformations, we can observe th...

A series of N-fluoroalkyl-8-(6-methoxy-2-methylpyridin-3-yl)-2,7-dimethyl-N-alkylpyrazolo[1,5-a][1,3,5]triazin-4-amines were prepared and evaluated as potential CRF1R PET imaging agents. Optimization of their CRF1R binding potencies and octanol–phosphate buffer phase distribution coefficients r...

The addition of various amines to 5-chloro-1-pentenylphosphonate 4, prepared by zirconation or titanation of the corresponding alkynylphosphonates, has been used to produce novel substituted pyrrolidinyl-methylphosphonates 5 in 68–81% isolated yield.

Here we report the design and synthesis of spiro[pyrrolidine-3,3′-oxindole] derivatives representing a novel scaffold of 5-HT7 receptor ligands. The synthesized analogues were validated as low nanomolar ligands showing selectivity in a panel of related serotonin receptor subtypes including 5-HT...

Compound 5 (SCH772984) was identified as a potent inhibitor of ERK1/2 with excellent selectivity against a panel of kinases (0/231 kinases tested @ 100 nM) and good cell proliferation activity, but suffered from poor PK (rat AUC PK @10 mpk = 0 μM h; F% = 0) which precluded further development. ...

α-Glucosidase is considered as a therapeutic target for the treatment of type 2 diabetes mellitus (DM2). In current study, we synthesized pyrrolidine-2,5-dione (succinimide) and thiazolidine-2,4-dione derivatives and evaluated for their ability to inhibit α-Glucosidase. Pyrrolidine-2,5-dione d...

The increase of opportunistic fungal infections raises the need for design and synthesis of new antifungal agents. Taking into account that tetrazole derivatives exhibit antifungal activity, and some of them are in the phase of clinical trials, new tetrazole derivatives bearing pyrrolidine moiet...

A series of benzo[d]imidazol-2-yl)-1′-methyl-2-oxo-4′-phenylspiro[indoline-3,2′-pyrrolidine] and benzo[d]imidazol-2-yl)-2-oxo-7′-phenyl-3′,6′,7′,7a′-tetrahydro-1′H-spiro[indoline-3,5′-pyrrolo[1,2-c]thiazole] carbonitrile were synthesized via 1,3-dipolar cycloaddition (1,3-DC) reaction....

A novel and efficient synthetic approach to enantiopure 3-substituted pyrrolidine skeleton from readily available (S)-PMB glycidyl ether as a starting material and its application to the asymmetric synthesis of pyrrolidine core 1 of serotonin norepinephrine reuptake inhibitors (SNRIs) 2 and 3 ar...

We have synthesized a series of compounds based on a piperidyl benzimidazole carboxamide structure, and tested their PARP-1 inhibitory activity, as well as cellular inhibitory activity. Some of them show great potency as PARP-1 inhibitors and antitumor activity, which are valuable for further re...

The fluorinated piperidine iminosugars 2a-4a and their N-octyl and N-decyl derivatives 2b,c-4b,c were synthesized from d-mannose/d-xylose using nucleophilic fluorination as the key step. The conformation of iminosugars 2/3, either 2C5 or 5C2, was assigned based on the 1H NMR studies at different...

FT-IR spectrum of (2E)-3-(3-nitrophenyl)-1-[4-piperidin-1-yl]prop-2-en-1-one was recorded and analyzed. The vibrational wavenumbers were computed using HF and DFT quantum chemical calculations. The data obtained from wavenumber calculations are used to assign IR bands. Potential energy distribut...

This chapter describes methods of synthesis, pharmacological properties, and the use of derivatives of 2-substituted and 1,2-disubstituted piperidines such as methylphenidate, perhexiline, pipradrol, mefloquine, mepivacaine, ropivacaine, bupivacaine, levobupivacaine, flecainide, encainide, thior...

This chapter describes methods of synthesis, pharmacological properties, and the use of derivatives of 3-substituted and 1,3-disubstituted piperidines such as methixene, tipepidine, timepidium, tiagabine, piperidolate, mepenzolate, pipenzolate, benidipine, paroxetine, femoxetine, troxipide cytop...

Aroylhydrazones such as salicylaldehyde isonicotinoyl hydrazone (SIH) are tridentate iron chelators that may possess antioxidant and/or antineoplastic activities. Their main drawback, their low stability in plasma, has recently been partially overcome by exchanging the aldimine hydrogen for an u...