Aachen smoking cessation and harm reduction (ASCHR) trial study protocol - scientific evaluation of a psychological-telemedical counseling concept for smoking cessation in patients with vascular diseases.

Background: Smoking is a major risk factor of cardiovascular diseases, notably peripheral arterial disease (PAD). Despite this link, research on smoking cessation interventions in PAD patients remains scarce and inconclusive regarding the efficacy of such interventions. Therefore, elucidating it is crucial and should address both individuals who smoke that are motivated to quit and individuals who smoke heavily lacking the motivation to quit.

Discovery of a Potent Analgesic NOP and Opioid Receptor Agonist: Cebranopadol.

In a previous communication, our efforts leading from 1 to the identification of spiro[cyclohexane-dihydropyrano[3,4-b]indole]-amine 2a as analgesic NOP and opioid receptor agonist were disclosed and their favorable in vitro and in vivo pharmacological properties revealed. We herein report our efforts to further optimize lead 2a, toward trans-6'-fluoro-4',9'-dihydro-N,N-dimethyl-4-phenyl-spiro[cyclohexane-1,1'(3'H)-pyrano[3,4-b]indol]-4-amine (cebranopadol, 3a), which is currently in clinical development for the treatment of severe chronic nociceptive and neuropathic pain.

Discovery of Spiro[cyclohexane-dihydropyrano[3,4-b]indole]-amines as Potent NOP and Opioid Receptor Agonists.

We report the discovery of spiro[cyclohexane-pyrano[3,4-b]indole]-amines, as functional nociceptin/orphanin FQ peptide (NOP) and opioid receptor agonists with strong efficacy in preclinical models of acute and neuropathic pain. Utilizing 4-(dimethylamino)-4-phenylcyclo-hexanone 1 and tryptophol in an oxa-Pictet-Spengler reaction led to the formation of spiroether 2, representing a novel NOP and opioid peptide receptor agonistic chemotype. This finding initially stems from the systematic derivatization of 1, which resulted in alcohols 3-5, ethers 6 and 7, amines 8-10, 22-24, and 26-28, amides 11 and 25, and urea 12, many with low nanomolar binding affinities at the NOP and mu opioid peptide (MOP) receptors.

From a simple liquid to a polymer melt: NMR relaxometry study of polybutadiene.

We utilize NMR field cycling relaxometry to study the crossover from glassy dynamics (t approximately > tau alpha) through Rouse to reptation behavior in a series of monodisperse polybutadienes with molecular weights M=355 to 817,000 g/mol. We separate characteristic polymer dynamics from the total spectrum dominated by glassy dynamics. The polymer dynamics show typical Rouse relaxation features that grow with M and saturate at high M.