- HETEROCYCLYLAMINO-SUBSTITUTED TRIAZOLES AS MODULATORS OF RHO-ASSOCIATED PROTEIN KINASE
-
This invention relates to novel compounds and pharmaceutical compositions comprising. Compounds of the invention useful as modulators of Rho-associated protein kinase (ROCK), for example ROCK1 and/or ROCK2 inhibitors. Methods of treatment employing the compounds are also contemplated by the present invention. The compounds of the invention are useful in treating ROCK mediated diseases.
- -
-
Page/Page column 185
(2019/08/12)
-
- Syntheses of 1-aryl-5-nitro-1h-indazoles and a general one-pot route to 1-aryl-1h-indazoles
-
An efficient route to substituted 1-aryl-1H-indazoles has been developed and optimized. The method involved the preparation of arylhydrazones from acetophenone or benzaldehyde substituted by fluorine at C2 and nitro at C5, followed by deprotonation and nucleophilic aromatic substitution (SNAr) ring closure in 45–90%. Modification of this procedure to a one-pot domino process was successful in the acetophenone series (73–96%), while the benzaldehyde series (63–73%) required a step-wise addition of reagents. A general one-pot protocol for 1-aryl-1H-indazole formation without the limiting substitution patterns required for the SNAr cyclization has also been achieved in 62–78% yields. A selection of 1-aryl-1H-indazoles was prepared in high yield by a procedure that requires only a single laboratory operation.
- Annor-Gyamfi, Joel K.,Gnanasekaran, Krishna Kumar,Bunce, Richard A.
-
-
- NOVEL SUBSTITUTED INDAZOLES, THE PREPARATION THEREOF AND USE OF SAME IN THERAPEUTICS
-
This disclosure relates to compounds of formula (I): wherein R1, R2, R3, R4, E, and n1 are as defined in the disclosure, to compositions containing them, to processes for preparing them, and the use t
- -
-
Page/Page column 23
(2010/12/29)
-
- Antifungal Triazole Derivatives
-
Disclosed herein are antifungal triazole derivatives or pharmaceutically acceptable salts thereof, a preparation method thereof, and a pharmaceutical composition comprising the same.
- -
-
Page/Page column 20-21
(2008/12/07)
-
- Design and synthesis of Rho kinase inhibitors (II)
-
In a previous study, we identified several structurally unrelated scaffolds of the Rho kinase inhibitor using pharmacophore information obtained from the results of a high-throughput screening and structural information from a homology model of Rho kinase. 1H-Indazole is one of the candidate scaffolds on which a new series of potent Rho kinase inhibitors could be developed. In this study, the detailed structure-activity relationship of 1H-indazole analogues was studied. During this study, we found that the cell-free enzyme inhibitory potential of Rho kinase inhibitors having the 1H-indazole scaffold did not necessarily correlate with their inhibitory potential toward the chemotaxis of cultured cells. The choice of the linker substructure was shown to be an important factor for the 1H-indazole analogues to inhibit the chemotaxis of cells. Optimization of the 1H-indazole inhibitors with respect to the in vitro inhibition of monocyte chemotaxis induced by MCP-1 was carried out. The inhibitory potential was improved both in the cell-free enzyme assay and in the chemotaxis assay.
- Iwakubo, Masayuki,Takami, Atsuya,Okada, Yuji,Kawata, Takehisa,Tagami, Yoshimichi,Ohashi, Hiroshi,Sato, Motoko,Sugiyama, Terumi,Fukushima, Kayoko,Iijima, Hiroshi
-
p. 350 - 364
(2008/02/04)
-
- ANTIFUNGAL TRIAZOLE DERIVATIVES
-
Disclosed herein are antifungal triazole derivatives or pharmaceutically acceptable salts thereof, a preparation method thereof, and a pharmaceutical composition comprising the same.
- -
-
Page/Page column 48-49
(2010/11/24)
-
- Rho-kinase inhibitors
-
Disclosed are compounds and derivatives thereof, their synthesis, and their use as Rho-kinase inhibitors. These compounds of the present invention are useful for inhibiting tumor growth, treating erectile dysfunction, and treating other indications mediated by Rho-kinase, e.g., coronary heart disease.
- -
-
Page/Page column 21
(2010/02/05)
-
- Design and synthesis of Rho kinase inhibitors (I)
-
Several structurally unrelated scaffolds of the Rho kinase inhibitor were designed using pharmacophore information obtained from the results of a high-throughput screening and structural information from a homology model of Rho kinase. A docking simulation using the ligand-binding pocket of the Rho kinase model helped to comprehensively understand and to predict the structure-activity relationship of the inhibitors. This understanding was useful for developing new Rho kinase inhibitors of higher potency and selectivity. We identified several potent platforms for developing the Rho kinase inhibitors, namely, pyridine, 1H-indazole, isoquinoline, and phthalimide.
- Takami, Atsuya,Iwakubo, Masayuki,Okada, Yuji,Kawata, Takehisa,Odai, Hideharu,Takahashi, Nobuaki,Shindo, Kazutoshi,Kimura, Kaname,Tagami, Yoshimichi,Miyake, Mika,Fukushima, Kayoko,Inagaki, Masaki,Amano, Mutsuki,Kaibuchi, Kozo,Iijima, Hiroshi
-
p. 2115 - 2137
(2007/10/03)
-
- Structure-Based Design, Synthesis, and Antimicrobial Activity of Indazole-Derived SAH/MTA Nucleosidase Inhibitors
-
The structure-based design, synthesis, and biological activity of a novel indazole-containing inhibitor series for S-adenosyl homocysteine/methylthioadenosine (SAH/MTA) nucleosidase are described. Use of 5-aminoindazole as the core scaffold provided a structure-guided series of low nanomolar inhibitors with broad-spectrum antimicrobial activity. The implementation of structure-based methodologies provided a 6000-fold increase in potency over a short timeline (several months) and an economy of synthesized compounds.
- Li, Xiaoming,Chu, Sam,Feher, Victoria A.,Khalili, Mitra,Nie, Zhe,Margosiak, Stephen,Nikulin, Victor,Levin, James,Sprankle, Kelly G.,Tedder, Martina E.,Almassy, Robert,Appelt, Krzysztof,Yager, Kraig M.
-
p. 5663 - 5673
(2007/10/03)
-