- A pyridine primary amine ruthenium complex, preparation method and its use
-
The invention relates to a pyridine primary amine ruthenium complex as well as a preparation method and application thereof. The pyridine primary amine ruthenium complex is excellent in anti-cancer activity in anti-cancer screening in vitro and especially has a good inhibition effect on the lung cancer and the human breast cancer, so that the pyridine primary amine ruthenium complex has huge development potential and application value in clinical treatment of tumor diseases.
- -
-
Paragraph 0065; 0066
(2017/04/03)
-
- N -pyridyl and pyrimidine benzamides as KCNQ2/Q3 potassium channel openers for the treatment of epilepsy
-
A series of N-pyridyl benzamide KCNQ2/Q3 potassium channel openers were identified and found to be active in animal models of epilepsy and pain. The best compound 12 [ICA-027243, N-(6-chloro-pyridin-3-yl)-3,4-difluoro-benzamide] has an EC50 of 0.38 μM and is selective for KCNQ2/Q3 channels. This compound was active in several rodent models of epilepsy and pain but upon repeated dosing had a number of unacceptable toxicities that prevented further development. On the basis of the structure-activity relationships developed around 12, a second compound, 51, [N-(2-chloro-pyrimidin-5-yl)-3,4-difluoro- benzamide, ICA-069673], was prepared and advanced into a phase 1 clinical study. Herein, we describe the structure-activity relationships that led to the identification of compound 12 and to the corresponding pyrimidine 51.
- Amato, George,Roeloffs, Rosemarie,Rigdon, Greg C.,Antonio, Brett,Mersch, Theresa,McNaughton-Smith, Grant,Wickenden, Alan D.,Fritch, Paul,Suto, Mark J.
-
scheme or table
p. 481 - 484
(2011/08/22)
-
- Structure-activity studies of novel cyanoguanidine ATP-sensitive potassium channel openers for the treatment of overactive bladder
-
A series of novel cyanoguanidine derivatives was designed and synthesized. Condensation of N-(1-benzotriazol-1-yl-2,2-dichloropropyl)-substituted benzamides with N-(substituted-pyridin-3-yl)-N′-cyanoguanidines furnished N-{2,2-dichloro-1-[N′-(substituted-pyridin-3-yl)-N′-cyanoguanidino] propyl}-substituted benzamide derivatives. These agents were glyburide-reversible potassium channel openers and hyperpolarized human bladder cells as assessed by the FLIPR membrane potential dye (KATP-FMP). These compounds were also potent full agonists in relaxing electrically stimulated pig bladder strips, an in vitro model of overactive bladder. The most active compound 9 was evaluated for in vivo efficacy and selectivity in a pig model of bladder instability. Preliminary pharmacokinetic studies in dog demonstrated excellent oral bioavailability and a t1/2 of 15 h. The synthesis, SAR studies, and biological properties of these agents are discussed.
- Perez-Medrano, Arturo,Brune, Michael E.,Buckner, Steven A.,Coghlan, Michael J.,Fey, Thomas A.,Gopalakrishnan, Murali,Gregg, Robert J.,Kort, Michael E.,Scott, Victoria E.,Sullivan, James P.,Whiteaker, Kristi L.,Carroll, William A.
-
p. 6265 - 6273
(2008/04/05)
-
- Syntheses and EGFR kinase inhibitory activity of 6-substituted-4-anilino [1,7] and [1,8] naphthyridine-3-carbonitriles
-
The syntheses and EGFR kinase inhibitory activity of a series of 6-substituted-4-anilino [1,7] and [1,8] naphthyridine-3-carbonitriles are described. Both reversible and irreversible binding inhibitors were prepared. These series were compared with each other and with the corresponding 4-anilinoquinoline-3-carbonitriles. Compounds having a 1,7-naphthyridine core structure can retain high potency while those with a 1,8-naphthyridine core are significantly less active. These results are consistent with molecular modeling observations.
- Wissner, Allan,Hamann, Philip R.,Nilakantan, Ramaswamy,Greenberger, Lee M.,Ye, Fei,Rapuano, Timothy A.,Loganzo, Frank
-
p. 1411 - 1416
(2007/10/03)
-
- SUBSTITUTED-3-CYANO-[1.7],[1.5], AND [1.8]-NAPHTHYRIDINE INHIBITORS OF TYROSINE KINASES
-
This invention provides compounds of formula (I) having structure (a) wherein A'' is a diavalent moiety selected from the group (a, b, c) which are useful as inhibitors of protein tyrosine kinase.
- -
-
-
- Process for preparing 4,6-disubstituted pyrido[3,4-d]pyrimidines
-
An improved process for the preparation of 4,6-disubstituted pyrido[3,4-d]pyrimidines is described where 5-amino-2-fluoropyridine is converted in seven operations to the desired products, as well as other valuable intermediates used in the process.
- -
-
-
- 3-Pyridyl enantiomers and their use as analgesics
-
The present invention relates to a method of controlling pain in mammals, including humans, comprising administering to a mammal or patient in need of treatment thereof selected compounds of formula I: STR1 or a pharmaceutically acceptable salt thereof. The invention further relates to selected (R) and (S) compounds of formula I above which are useful as analgesics as well as neuronal cell death preventors and anti-inflammatories.
- -
-
-
- Furopyridine, thienopyridine pyrrolopyridine useful in controlling chemical synaptic transmission
-
Novel heterocyclic ether compounds having the formula: STR1 wherein A, m, R, X, Y1, Y2 and Y3 are specifically defined, which are useful in selectively controlling chemical synaptic transmission; therapeutically-effective pharmaceutical compositions thereof; and use of said compositions to selectively control synaptic transmission in mammals.
- -
-
-
- Synthesis of 6-substituted pyrido[3,4-d]pyrimidin-4(3H)-ones via directed lithiation of 2-substituted 5-aminopyridine derivatives
-
Directed lithiation of Boc or pivaloyl derivatives of 2-substituted 5-aminopyridines with BuLi-TMEDA in diethyl ether at -10°C gave 4-lithio derivatives which were quenched with CO2 to give the analogous C-4 carboxylic acids. Hydrolysis of the protecting groups with either TFA or aqueous KOH gave 2-substituted 5-aminopyridine-4-carboxylic acids which were converted to 6-substituted pyrido[3,4-d]pyrimidin-4(3H)-ones by reaction with formamide or, more optimally, formamidine acetate. Boc protected aminopyridines provided the best overall results, with synthesis of these derivatives best achieved by direct reaction of the aminopyridine with di-tert-butyl dicarbonate in the absence of added base.
- Rewcastle, Gordon W.,Denny, William A.,Winters, R. Thomas,Colbry, Norman L.,Showalter, H. D. Hollis
-
p. 2221 - 2226
(2007/10/03)
-