- SUBSTITUTED 4-ARYL-1,4-DIHYDRO-1,6-NAPHTHYRIDINAMIDES AND USE THEREOF
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1,6-Naphthyridine or 8-azaquinazoline derivatives (I) are new. 1,6-Naphthyridine or 8-azaquinazoline derivatives of formula (I) are new. D : N or CR 4>; R 4> : H, F, CF 3 or 1-4C alkyl; Ar : 5-R 5>-6-R 6>-2-methyl-4-oxo-4H-1-benzopyran-8-yl; 3-R 6>-4-R 8>-1-naphthyl optionally substituted with 1-3 of R 7>; 7-R 6>-8-R 8>-5-quinolinyl optionally substituted with 1-2 of R 7>; or 2-R 9>-3-R 10>-4-R 8>-5-R 6>-phenyl; R 5> : H, F, Cl, CN, NO 2, CF 3 or 1-4C alkyl; R 6> : H or F; R 7> : halo, 1-4C alkyl, CF 3, 1-4C alkoxy or OCF 3; R 8> : CN or NO 2; R 9> : H or halo; optionally fluorinated 1-4C alkyl, 1-4C alkoxy, 1-4C alkylthio of di(1-4C alkyl)amino; or phenyl optionally substituted with halo, 1-4C alkyl or CF 3; R 10> : H, halo or 1-4C alkyl; R 1> : optionally fluorinated 1-4C alkyl; R 2> : 1-6C alkyl optionally substituted with 3-7C cycloalkyl or F; or SO 2R 11>; R 11> : 1-6C alkyl, CF 3 or 3-7C cycloalkyl; or phenyl or heteroaryl optionally substituted with 1-2 of halo, CN, 1-4C alkyl, CF 3, 1-4C alkoxy and/or OCF 3; R 3> : H, F, CF 3 or 1-4C alkyl. An independent claim is also included for a process for preparing (I). [Image] ACTIVITY : Hypotensive; Cardiant; Hepatotropic; Nephrotropic; Cerebroprotective. MECHANISM OF ACTION : Mineralocorticoid receptor (MR) antagonist. 4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2-methyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide had an IC 50 of 35 nM when tested on cells expressing a GAL4-MR chimera.
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- Efficient three-component synthesis of diversely substituted tetrahydro-1H-cyclopenta[c]quinolines
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The synthesis of highly functionalized substituted tetrahydro-1H-cyclopenta[c]quinoline (I) and its reduced derivatives hexahydro-1H-cyclopenta[c]quinolines (II) via Povarov reaction in high diastereoselectivity and high to moderate yields is described he
- Ni?o, Patricia,Caba, Marta,Aguilar, Nuria,Terricabras, Emma,Albericio, Fernando,Fernàndez, Joan-Carles
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p. 854 - 881
(2017/01/18)
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- MS565: A SPECT tracer for evaluating the brain penetration of BAF312 (siponimod)
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Abstract BAF312 (siponimod) is a sphingosine-1-phosphate (S1P) receptor modulator in clinical development for the treatment of multiple sclerosis, with faster organ/tissue distribution and elimination kinetics than its precursor FTY720 (fingolimod). Our a
- Briard, Emmanuelle,Rudolph, Bettina,Desrayaud, Sandrine,Krauser, Joel A.,Auberson, Yves P.
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p. 1008 - 1018
(2015/06/08)
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- SUBSTITUTED TRICYCLIC COMPOUNDS WITH ACTIVITY TOWARDS EP1 RECEPTORS
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The present invention belongs to the field of EP1 receptor ligands. More specifically it refers to compounds of general formula (I) having great affinity and selectivity for the EP1 receptor. The invention also refers to the process for their preparation, to their use as medicament for the treatment and/or prophylaxis of diseases or disorders mediated by the EP1 receptor as well as to pharmaceutical compositions comprising them.
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Page/Page column 52
(2013/10/22)
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- SUBSTITUTED-4-ARYL-1,4-DIHYDRO-1,6-NAPHTHYRIDINAMIDES AND USE THEREOF
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The present application relates to novel substituted 4-aryl-1,4-dihydro-1,6-naphthyridine-3-carboxamides, a process for their preparation, their use for the treatment and/or prophylaxis of diseases, and their use for the manufacture of medicaments for the treatment and/or prophylaxis of diseases, especially cardiovascular disorders.
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- SUBSTITUTED 4-ARYL-1,4-DIHYDRO-1,6-NAPHTHYRIDINES AND USE THEREOF
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The present application relates to novel substituted 4-aryl-1,4-dihydro-1,6-naphthyridines, a process for their preparation, their use for the treatment and/or prophylaxis of diseases, and their use for the manufacture of medicaments for the treatment and/or prophylaxis of diseases, especially cardiovascular disorders.
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Page/Page column 21
(2010/12/29)
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- Design and SAR of novel potassium channel openers targeted for urge urinary incontinence. 2. Selective and potent benzylamino cyclobutenediones
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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-benzonitrile 1 in the relaxation of precontracted rat detrusor strips can also be obtained with cyanobenzylamine derivative 4 (IC50 = 0.29 μM) (Figure 3). Addition of a 2-Cl substituted benzylamine moiety and changing the alkylamino substituent of 4 to a t-Bu amine gives 31 (IC50 = 0.14 μM) - a compound with similar in vitro potency as 4 as well as relaxant activity on bladder smooth muscle in vivo when administered orally (31, ED50 = 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 (IC50 = 0.10 μM) which shows excellent in vivo efficacy (ED50 = 0.6 mg/kg). Moreover, 60, 3-(2,4-dichloro-6-methyl-benzylamino)-4- (1,1-dimethylpropylamino)-cyclobut-3-ene-1,2-dione (WAY-151616), shows excellent tissue selectivity for bladder K channels over arterial tissue (60, MAP ED20 = 100 mg/kg; selectivity: MAP ED20/bladder ED50 = 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.
- Gilbert, Adam M.,Antane, Madelene M.,Argentieri, Thomas M.,Butera, John A.,Francisco, Gerardo D.,Freeden, Chris,Gundersen, Eric G.,Graceffa, Russell F.,Herbst, David,Hirth, Bradford H.,Lennox, Joseph R.,McFarlane, Geraldine,Norton, N. Wesley,Quagliato, Dominick,Sheldon, Jeffrey H.,Warga, Dawn,Wojdan, Alexandra,Woods, Morgan
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p. 1203 - 1214
(2007/10/03)
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