- Discovery of zoniporide: A potent and selective sodium-hydrogen exchanger type 1 (NHE-1) inhibitor with high aqueous solubility
-
Zoniporide (CP-597,396) is a potent and selective inhibitor of NHE-1, which exhibits high aqueous solubility and acceptable pharmacokinetics for intravenous administration. The discovery, synthesis, activities, and rat and dog pharmacokinetics of this compound are presented. The potency and selectivity of zoniporide may be due to the conformation that the molecule adopts due to the presence of a cyclopropyl and a 5-quinolinyl substituent on the central pyrazole ring of the molecule.
- Guzman-Perez, Angel,Wester, Ronald T.,Allen, Mary C.,Brown, Janice A.,Buchholz, Allan R.,Cook, Ewell R.,Day, Wesley W.,Hamanaka, Ernest S.,Kennedy, Scott P.,Knight, Delvin R.,Kowalczyk, Paul J.,Marala, Ravi B.,Mularski, Christian J.,Novomisle, William A.,Ruggeri, Roger B.,Tracey,Hill, Roger J.
-
-
Read Online
- AZA-ARYL 1H-PYRAZOL-1-YL BENZENE SULFONAMIDES
-
Compounds are provided that act as potent antagonists of the CCR(9) receptor for treating Sjogren's syndrome. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions.
- -
-
Paragraph 0133; 0134
(2018/02/28)
-
- CALPAIN MODULATORS AND THERAPEUTIC USES THEREOF
-
Disclosed herein are small molecule calpain modulator compositions, pharmaceutical compositions, the use and preparation thereof.
- -
-
Paragraph 0684
(2018/04/17)
-
- PYRAZOLE DERIVATIVES AS MALT1 INHIBITORS
-
Disclosed are compounds, compositions and methods for treating of diseases, syndromes, conditions, and disorders that are affected by the modulation of MALT1. Such compounds are represented by Formula (I) as follows: wherein R1, R2, R3, R4, R5, R6, R5, G1, and G2 are defined herein.
- -
-
Paragraph 1149; 1150
(2018/07/05)
-
- AZA-ARYL 1H-PYRAZOL-1-YL BENZENE SULFONAMIDES
-
Compounds are provided that act as potent antagonists of the CCR(9) receptor. Animal testing demonstrates that these compounds are useful for treating inflammation, a hallmark disease for CCR(9). The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR(9)-mediated diseases, and as controls in assays for the identification of CCR(9) antagonists.
- -
-
Paragraph 0136; 0137
(2013/09/12)
-
- Study of synthesis of some pyrroloquinolines, pyrroloisoquinolines, pyridocarbazoles and their derivatives
-
The new isomers of pyrroloquinolines, pyrroloisoquinolines and pyridocarbazoles have been synthesized from the hydrazone of methylisopropylketone, 2-methylcyclohexanone, 5 and 8-quinolylhydrazine and 5-isoquinolylhydrazine by ring closure in AcOH at reflux in excellent yields. The methiodide of pyrroloisoquinoline and pyridocarbazole were reduced with NaBH4 at room temperature to produce corresponding hexahydropyrroloisoquinoline and decahydropyridoisoquinoline in good yields.
- Fathalipour, Soghra,Shahrokhnia, Nazila,Afghan, Arash,Baradarani, Mehdi M.
-
experimental part
p. 5808 - 5814
(2010/12/24)
-
- Ligand-Receptor Interactions via Hydrogen-Bond Formation. Synthesis and Pharmacological Evaluation of Pyrrolo and Pyrido Analogues of the Cardiotonic Agent 7-Hydroxycyclindole
-
The syntheses of N,N-dimethyl-6,7,8,9-tetrahydro-3H,10H-pyrrolocarbazol-7-amine (8), N,N-dimethyl-7,8,9,10-tetrahydro-11H-pyridocarbazol-8-amine (9a), and the N,N,11-trimethyl analogue (9b) are described.The in vitro inotropic activity of these compounds, as well as the known cardiotonics amrinone and 7-hydroxycyclindole (7), was investigated.Compound 8, a pyrrolo analogue of 7, was devoid of inotropic activity, while the pyrido analogues 9 were equiactive to 7 and amrinone.These results suggest that the hydroxyl group of 7 functions as an H-bondacceptor, rather than a donor, and that on interaction of 7, and the pyrido analogues 9, with a common receptor, an orbital occupied by one of the oxygen lone pair electrons of 7 must assume the same orientation as the orbital occupied by the pyridine nitrogen lone pair.
- Dionne, Gervais,Humber, Leslie G.,Asselin, Andre,McQuillan, Juanita,Treasurywala, Adi M.
-
p. 1452 - 1457
(2007/10/02)
-