FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2002155454> ?p ?o ?g. }

• W2002155454 endingPage "1214" @default.
• W2002155454 startingPage "1203" @default.
• W2002155454 abstract "A novel series of benzylamine, potassium channel openers (KCOs) is presented as part of our program toward designing new, bladder-selective compounds for the treatment of urge urinary incontinence (UUI). We have found that the in vitro potency of (R)-4-[3,4-dioxo-2-(1,2, 2-trimethyl-propylamino)-cyclobut-1-enylamino]-3-ethyl-benzo nitrile 1 in the relaxation of precontracted rat detrusor strips can also be obtained with cyanobenzylamine derivative 4 (IC(50) = 0.29 microM) (Figure 3). Addition of a 2-Cl substituted benzylamine moiety and changing the alkylamino substituent of 4 to a t-Bu amine gives 31 (IC(50) = 0.14 microM)-a compound with similar in vitro potency as 4 as well as relaxant activity on bladder smooth muscle in vivo when administered orally (31, ED(50) = 3 mg/kg) in a rodent model of bladder instability. Further modifications, particularly the replacement of the t-Bu amino substituent with a tert-amylamine, gave a similarly active compound 60 (IC(50) = 0.10 microM) which shows excellent in vivo efficacy (ED(50) = 0.6 mg/kg). Moreover, 60, 3-(2,4-dichloro-6-methyl-benzylamino)-4-(1, 1-dimethyl-propylamino)-cyclobut-3-ene-1,2-dione (WAY-151616), shows excellent tissue selectivity for bladder K channels over arterial tissue (60, MAP ED(20) = 100 mg/kg; selectivity: MAP ED(20)/bladder ED(50) = 166). Other manipulations of the benzylamino cyclobutenediones, acylation of the benzylamine, conversion of the benzylamine substituent to a benzamide, homologation of the benzylamine to a phenethylamine, and incorporation of a methyl group at the benzyl carbon, all led to substantial loss of in vitro activity, although some in vivo activity was maintained in the acylated analogues. Compound 60 represents an attractive candidate for development in the treatment of UUI." @default.
• W2002155454 created "2016-06-24" @default.
• W2002155454 creator A5012005358 @default.
• W2002155454 creator A5013886924 @default.
• W2002155454 creator A5019770289 @default.
• W2002155454 creator A5020031770 @default.
• W2002155454 creator A5022941448 @default.
• W2002155454 creator A5023639409 @default.
• W2002155454 creator A5032527371 @default.
• W2002155454 creator A5037671307 @default.
• W2002155454 creator A5038094973 @default.
• W2002155454 creator A5038492719 @default.
• W2002155454 creator A5041675728 @default.
• W2002155454 creator A5052081278 @default.
• W2002155454 creator A5060722981 @default.
• W2002155454 creator A5065522366 @default.
• W2002155454 creator A5066442460 @default.
• W2002155454 creator A5072452112 @default.
• W2002155454 creator A5081128438 @default.
• W2002155454 creator A5088308010 @default.
• W2002155454 date "2000-03-01" @default.
• W2002155454 modified "2023-10-11" @default.
• W2002155454 title "Design and SAR of Novel Potassium Channel Openers Targeted for Urge Urinary Incontinence. 2. Selective and Potent Benzylamino Cyclobutenediones" @default.
• W2002155454 cites W1986430846 @default.
• W2002155454 cites W2026205238 @default.
• W2002155454 cites W2416432721 @default.
• W2002155454 doi "https://doi.org/10.1021/jm9905108" @default.
• W2002155454 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10737753" @default.
• W2002155454 hasPublicationYear "2000" @default.
• W2002155454 type Work @default.
• W2002155454 sameAs 2002155454 @default.
• W2002155454 citedByCount "49" @default.
• W2002155454 countsByYear W20021554542012 @default.
• W2002155454 countsByYear W20021554542013 @default.
• W2002155454 countsByYear W20021554542014 @default.
• W2002155454 countsByYear W20021554542015 @default.
• W2002155454 countsByYear W20021554542017 @default.
• W2002155454 countsByYear W20021554542018 @default.
• W2002155454 countsByYear W20021554542020 @default.
• W2002155454 countsByYear W20021554542021 @default.
• W2002155454 countsByYear W20021554542022 @default.
• W2002155454 crossrefType "journal-article" @default.
• W2002155454 hasAuthorship W2002155454A5012005358 @default.
• W2002155454 hasAuthorship W2002155454A5013886924 @default.
• W2002155454 hasAuthorship W2002155454A5019770289 @default.
• W2002155454 hasAuthorship W2002155454A5020031770 @default.
• W2002155454 hasAuthorship W2002155454A5022941448 @default.
• W2002155454 hasAuthorship W2002155454A5023639409 @default.
• W2002155454 hasAuthorship W2002155454A5032527371 @default.
• W2002155454 hasAuthorship W2002155454A5037671307 @default.
• W2002155454 hasAuthorship W2002155454A5038094973 @default.
• W2002155454 hasAuthorship W2002155454A5038492719 @default.
• W2002155454 hasAuthorship W2002155454A5041675728 @default.
• W2002155454 hasAuthorship W2002155454A5052081278 @default.
• W2002155454 hasAuthorship W2002155454A5060722981 @default.
• W2002155454 hasAuthorship W2002155454A5065522366 @default.
• W2002155454 hasAuthorship W2002155454A5066442460 @default.
• W2002155454 hasAuthorship W2002155454A5072452112 @default.
• W2002155454 hasAuthorship W2002155454A5081128438 @default.
• W2002155454 hasAuthorship W2002155454A5088308010 @default.
• W2002155454 hasConcept C114373084 @default.
• W2002155454 hasConcept C134018914 @default.
• W2002155454 hasConcept C150903083 @default.
• W2002155454 hasConcept C155647269 @default.
• W2002155454 hasConcept C185592680 @default.
• W2002155454 hasConcept C202751555 @default.
• W2002155454 hasConcept C207001950 @default.
• W2002155454 hasConcept C2776276205 @default.
• W2002155454 hasConcept C2778689049 @default.
• W2002155454 hasConcept C2780231548 @default.
• W2002155454 hasConcept C55493867 @default.
• W2002155454 hasConcept C71240020 @default.
• W2002155454 hasConcept C71924100 @default.
• W2002155454 hasConcept C83743174 @default.
• W2002155454 hasConcept C86803240 @default.
• W2002155454 hasConcept C98274493 @default.
• W2002155454 hasConceptScore W2002155454C114373084 @default.
• W2002155454 hasConceptScore W2002155454C134018914 @default.
• W2002155454 hasConceptScore W2002155454C150903083 @default.
• W2002155454 hasConceptScore W2002155454C155647269 @default.
• W2002155454 hasConceptScore W2002155454C185592680 @default.
• W2002155454 hasConceptScore W2002155454C202751555 @default.
• W2002155454 hasConceptScore W2002155454C207001950 @default.
• W2002155454 hasConceptScore W2002155454C2776276205 @default.
• W2002155454 hasConceptScore W2002155454C2778689049 @default.
• W2002155454 hasConceptScore W2002155454C2780231548 @default.
• W2002155454 hasConceptScore W2002155454C55493867 @default.
• W2002155454 hasConceptScore W2002155454C71240020 @default.
• W2002155454 hasConceptScore W2002155454C71924100 @default.
• W2002155454 hasConceptScore W2002155454C83743174 @default.
• W2002155454 hasConceptScore W2002155454C86803240 @default.
• W2002155454 hasConceptScore W2002155454C98274493 @default.
• W2002155454 hasIssue "6" @default.
• W2002155454 hasLocation W20021554541 @default.
• W2002155454 hasLocation W20021554542 @default.
• W2002155454 hasOpenAccess W2002155454 @default.
• W2002155454 hasPrimaryLocation W20021554541 @default.
• W2002155454 hasRelatedWork W1527559373 @default.

• next