3535-24-8Relevant academic research and scientific papers
VU6010608, a Novel mGlu7 NAM from a Series of N-(2-(1H-1,2,4-Triazol-1-yl)-5-(trifluoromethoxy)phenyl)benzamides
Reed, Carson W.,McGowan, Kevin M.,Spearing, Paul K.,Stansley, Branden J.,Roenfanz, Hanna F.,Engers, Darren W.,Rodriguez, Alice L.,Engelberg, Eileen M.,Luscombe, Vincent B.,Loch, Matthew T.,Remke, Daniel H.,Rook, Jerri M.,Blobaum, Anna L.,Conn, P. Jeffrey,Niswender, Colleen M.,Lindsley, Craig W.
supporting information, p. 1326 - 1330 (2017/12/26)
Herein, we report the structure-activity relationships within a series of mGlu7 NAMs based on an N-(2-(1H-1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl)benzamide core with excellent CNS penetration (Kp 1.9-5.8 and Kp,uu 0.4-1.4). Analogues in this series displayed steep SAR. Of these, VU6010608 (11a) emerged with robust efficacy in blocking high frequency stimulated long-term potentiation in electrophysiology studies.
QUINAZOLINE DERIVATIVES AS RAF KINASE MODULATORS AND METHODS OF USE THEREOF
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Page/Page column 166, (2009/10/22)
Compounds according to formula (I), compositions and methods are provided for modulating the activity of RAF kinases, including BRAF kinase and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder mediated by RAF kinases. Formula (I): or a pharmaceutically acceptable salt, solvate, clathrate of hydrate thereof, wherein X is O or S(O)t; Ra is O or S.
USE OF CYANOQUINOLINES FOR TREATING OR INHIBITING COLONIC POLYPS
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, (2008/06/13)
This invention provides a method of treating or inhibiting colonic polyps which comprises providing a compound of formula (1); wherein R1, R2, R3, R4, X, Y, and n are defined hereinbefore, or a pharmaceutically acceptable salt thereof.
SUBSTITUTED 3-CYANOQUINOLINES AS PROTEIN TYROSINE KINASES INHIBITORS
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Page 63, (2010/02/04)
This invention provides compounds of formula (1) wherein R1, G1, G2, R4, Z, X and n are defined herein, or a pharmaceutically acceptable salt thereof, which are useful as antineoplastic agents and in the treatment of polycystic kidney disease.
SUBSTITUTED 3-CYANO QUINOLINES
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Page/Page column 68, (2008/06/13)
This invention provides compounds having formula (1), wherein: X is cycloalkyl which may be optionally substituted; or is a pyridinyl, pyrimidinyl, or phenyl ring; wherein the pyridinyl, pyrimidinyl, or phenyl ring may be optionally substituted; n is 0-1; Y is -NH-, -O-, -S-, or -NR-; R is alkyl of 1-6 carbon atoms; R1, R2, R3 and R4 are each, independently, hydrogen, halogen, alkyl, alkenyl, alkynyl, alkenyloxy, alkynyloxy, hydroxymethyl, halomethyl, alkanoyloxy, alkenoyloxy, alkynoyloxy, alkanoyloxymethyl, alkenoyloxymethyl, alkynoyloxymethyl, alkoxymethyl, alkoxy, alkylthio, alkylsulphinyl, alkylsulphonyl, alkylsulfonamido, alkenylsulfonamido, alkynylsulfonamido, hydroxy, trifluoromethyl, cyano, nitro, carboxy, carboalkoxy, carboalkyl, phenoxy, phenyl, thiophenoxy, benzyl, amino, hydroxyamino, alkoxyamino, alkylamino, dialkylamino, aminoalkyl, N-alkylaminoalkyl, N,N-dialkylaminoalkyl, phenylamino, benzylamino, formulae (a, b, c, d, e, f, g, h, i, j, k, l, m, n, o, p, q or r); R5 is alkyl which may be optionally substituted, or phenyl which may be optionally substituted; R6 is hydrogen, alkyl, or alkenyl; R7 is chloro or bromo; R8 is hydrogen, alkyl, aminoalkyl, N-alkylaminoalkyl, N,N-dialkylaminoalkyl, N-cycloalkylaminoalkyl, N-cycloalkyl-N-alkylaminoalkyl, N,N-dicycloalkylaminoalkyl, morpholino-N-alkyl, piperidino-N-alkyl, N-alkyl-piperidino-N-alkyl, azacycloalkyl-N-alkyl, hydroxyalkyl, alkoxyalkyl, carboxy, carboalkoxy, phenyl, carboalkyl +, chloro, fluoro, or bromo; Z is amino, hydroxy, alkoxy, alkylamino, dialkylamino, morpholino, piperazino, N-alkylpiperazino, or pyrrolidino; m = 1-4, q = 1-3, and p = 0-3; any of the substituents R1, R2, R3 or R4 that are located on contiguous carbon atoms can together be the divalent radical -O-C(R8)2-O-; or a pharmaceutically acceptable salt thereof with the proviso that when Y is -NH-, R1, R2, R3 and R4 are hydrogen, and n is O, X is not 2-methylphenyl, which are inhibitors of protein tyrosine kinase.
Anthranilic acid derivatives as inhibitors of the cGMP-phosphodiesterase
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, (2008/06/13)
Compounds of formula (I) STR1where R 1 is hydrogen; R 2 is nitro, cyano or halo(lower)alkyl; R 3 is phenyl substituted with one or more substituents selected from halogen, cyano and lower alkoxy; A is a lower alkylene group; R 4 is a group CR 6 R 7 R 8 wherein R 6 and R 7 form, together with the carbon atom to which they are attached a cycloalkyl group optionally substituted with hydroxy, lower alkoxy or a lower alkanoylamino; and R 8 is hydrogen; its prodrug and a salt thereof.
Method of treating or inhibiting colonic polyps
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, (2008/06/13)
This invention provides a method of treating or inhibiting colonic polyps which comprises providing a compound of formula 1 wherein:R1, R2, R3, R4, X, Y, and n are as defined hereinbefore, or a pharmaceutically acceptable salt thereof.
4-anilino-6,7-dialkoxyquinoline-3-carbonitrile inhibitors of epidermal growth factor receptor kinase and their bioisosteric relationship to the 4-anilino-6,7-dialkoxyquinazoline inhibitors
Wissner,Berger,Boschelli,Brawner Floyd Jr.,Greenberger,Gruber,Johnson,Mamuya,Nilakantan,Reich,Shen,Tsou,Upeslacis,Yu Fen Wang,Wu,Ye,Zhang
, p. 3244 - 3256 (2007/10/03)
The synthesis and SAR of a series of 4-anilino-6,7-dialkoxyquinoline-3-carbonitrile inhibitors of epidermal growth factor receptor (EGF-R) kinase are described. Condensation of 3,4-dialkoxyanilines with ethyl (ethoxymethylene)cyanoacetate followed by thermal cyclization gave, regiospecifically, 6,7-dialkoxy-4-oxo-1,4-dihydroquinoline-3-carbonitriles. Chlorination (POCl3) followed by the reaction with substituted anilines furnished the 4-anilino-6,7-dialkoxyquinoline-3-carbonitrile inhibitors of EGF-R kinase. An alternate synthesis of these compounds starts with a methyl 3,4-dialkoxybenzoate. Nitration followed by reduction (Fe, NH4Cl, MeOH-H2O) gave a methyl 2-amino-4,5-dialkoxybenzoate. Amidine formation using DMF-acetal followed by cyclization using LiCH2CN furnished a 6,7-dialkoxy-4-oxo-1,4-dihydroquinoline-3-carbonitrile, which was transformed as before. Compounds containing acid, ester, amide, carbinol, and aldehyde groups at the 3-position of the quinoline ring were also prepared for comparison, as were several 1-anilino-6,7-dimethoxyisoquinoline-4-carbonitriles. The compounds were evaluated for their ability to inhibit the autophosphorylation of the catalytic domain of EGF-R. The SAR of these inhibitors with respect to the nature of the 6,7-alkoxy groups, the aniline substituents, and the substituent at the 3-position was studied. The compounds were further evaluated for their ability to inhibit the growth of cell lines that overexpress EGF-R or HER-2. It was found that 4-anilinoquinoline-3-carbonitriles are effective inhibitors of EGF-R kinase with activity comparable to the 4-anilinoquinazoline-based inhibitors. A new homology model of EGF-R kinase was constructed based on the X-ray structures of Hck and FGF receptor-1 kinase. The model suggests that with the quinazoline-based inhibitors, the N3 atom is hydrogen-bonded to a water molecule which, in turn, interacts with Thr 830. It is proposed that the quinoline-3-carbonitriles bind in a similar manner where the water molecule is displaced by the cyano group which interacts with the same Thr residue.
