IKCa-Channel Blockers. Part 2. Discovery of Cyclohexadienes.

ChemInform ◽  
2005 ◽  
Vol 36 (20) ◽  
Author(s):  
Klaus Urbahns ◽  
Siegfried Goldmann ◽  
Jochen Krueger ◽  
Ervin Horvath ◽  
Joachim Schuhmacher ◽  
...  
Keyword(s):  
Channel Blockers ◽  
Ikca Channel

4-Phenyl-4H-pyrans as IKCa channel blockers

2003 ◽  
Vol 13 (16) ◽  
pp. 2637-2639 ◽  
Author(s):  
Klaus Urbahns ◽  
Ervin Horváth ◽  
Johannes-Peter Stasch ◽  
Frank Mauler
Keyword(s):  
Channel Blockers ◽  
Ikca Channel

4-Phenyl-4H-pyrans as IKCa Channel Blockers.

ChemInform ◽  
2003 ◽  
Vol 34 (50) ◽  
Author(s):  
Klaus Urbahns ◽  
Ervin Horvath ◽  
Johannes-Peter Stasch ◽  
Frank Mauler
Keyword(s):  
Channel Blockers ◽  
Ikca Channel

IKCa-channel blockers. Part 2: Discovery of cyclohexadienes

2005 ◽  
Vol 15 (2) ◽  
pp. 401-404 ◽  
Author(s):  
Klaus Urbahns ◽  
Siegfried Goldmann ◽  
Jochen Krüger ◽  
Ervin Horváth ◽  
Joachim Schuhmacher ◽  
...  
Keyword(s):  
Channel Blockers ◽  
Ikca Channel

Secondary medical prevention in patients with peripheral arterial disease - Prescriptions of vascular surgeons and medical doctors (angiologists) in a multidisciplinary vascular centre

VASA ◽  
2010 ◽  
Vol 39 (2) ◽  
pp. 145-152 ◽  
Author(s):  
Klein-Weigel ◽  
Gutsche-Petrak ◽  
Wolbergs ◽  
Köning ◽  
Flessenkamper
Keyword(s):  
Peripheral Arterial Disease ◽  
Oral Anticoagulants ◽  
Arterial Disease ◽  
Disease Stage ◽  
Channel Blockers ◽  
Medical Doctors ◽  
Vascular Surgeon ◽  
Medical Prevention ◽  
Number Of Patients ◽  
Peripheral Arterial

Background: We compared medical secondary prevention in patients with peripheral arterial disease stage II (Fontaine) located in the femoro-popliteal artery managed by vascular surgeons and medical doctors / angiologists in our multidisciplinary vascular center. Patients and methods: We retrospectively analyzed demission protocols of in-hospital treatments between 01.01.2007 and 20.06.2008. Results: We surveyed 264 patients (54.2 % women; mean age 67.52 ± 8.98 yrs), 179 (67.8 %) primarily treated by medical doctors / angiologists and 85 (32.2 %) primarily managed by vascular surgeons. Medical doctors / angiologists treated more women (n = 109) than men (n = 34), (p = 0.002) and documented smoking and diabetes mellitus more often (p < 0.001) than vascular surgeons. Besides, patients had similar cardiovascular risk profiles and concomitant diseases, vascular surgeons prescribed 5.47 ± 2.26 drugs, medical doctors / angiologists 6.37 ± 2.67 (p = 0.005). Overall, 239 (90.5 %) patients were on aspirin, 180 (68.2 %) on clopidogrel, and 18 (6.9 %) on oral anticoagulants. Significantly more patients treated by medical doctors / angiologists received clopidogrel (169 versus 11; p < 0.001), significantly more surgical patients received oral anticoagulants (11 versus 7; p = 0.016). The number of patients without prescriptions for any antithrombotic therapy was 6 (6.9 %) in patients treated by vascular surgeons and 0 (0 %) in patients managed by medical doctors / angiologists (p = 0.001). Prescription-rates of β-blockers, ACE-inhibitors, Angiotensin II-antangonists, calcium channel blockers, and diuretics were statistically not different between the two disciplines, but statins were prescribed significantly more often by medical doctors / angiologists (139 versus 49; p < 0001). With the exceptions of Clopidogrel (women > men) and diuretics (men > women) we observed no gender-specific prescriptions. Conclusions: We observed high prescriptions rates of secondary medical prevention in patients primarily treated by medical doctors / angiologists and vascular surgeons. We believe that this result is highly influenced by our multidisciplinary approach. Nevertheless, efforts have to be made to raise vascular surgeon’s awareness of statin use and complete prescription of antithrombotic and antiplatelet drugs.

An Anthrone-Based Kv7.2/7.3 Channel Blocker with Improved Properties for the Investigation of Psychiatric and Neurodegenerative Disorders

2019 ◽  
Author(s):  
Jacob Porter ◽  
Oscar Vivas-Rodriguez ◽  
C. David Weaver ◽  
Eamonn Dickson ◽  
Abdulmohsen Alsafran ◽  
...  
Keyword(s):  
Patch Clamp ◽  
Neurodegenerative Disorders ◽  
Channel Blocker ◽  
Optimal Combination ◽  
Channel Blockers ◽  
Enolate Alkylation ◽  
Cyp Inhibition ◽  
Alkylation Reactions ◽  
Metabolic Instability

A set of novel Kv7.2/7.3 (KCNQ2/3) channel blockers was synthesized to address several liabilities of the known compounds XE991 (metabolic instability and CYP inhibition) and the clinical compound DMP 543 (acid instability, insolubility, and lipophilicity). Using the anthrone scaffold of the prior channel blockers, alternative heteroarylmethyl substituents were installed via enolate alkylation reactions. Incorporation of a pyridazine and a fluorinated pyridine gave an analog (JDP-107) with an optimal combination of potency (IC<sub>50</sub>= 0.16 𝜇M in a Kv7.2 thallium flux assay), efficacy in a Kv7.2/7.3 patch clamp assay, and drug-like properties.

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