63875-01-4Relevant academic research and scientific papers
Design, Synthesis, and Evaluation of the Highly Selective and Potent G-Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure
Okawa, Tomohiro,Aramaki, Yoshio,Yamamoto, Mitsuo,Kobayashi, Toshitake,Fukumoto, Shoji,Toyoda, Yukio,Henta, Tsutomu,Hata, Akito,Ikeda, Shota,Kaneko, Manami,Hoffman, Isaac D.,Sang, Bi-Ching,Zou, Hua,Kawamoto, Tetsuji
, p. 6942 - 6990 (2017/09/07)
A novel class of therapeutic drug candidates for heart failure, highly potent and selective GRK2 inhibitors, exhibit potentiation of β-adrenergic signaling in vitro studies. Hydrazone derivative 5 and 1,2,4-triazole derivative 24a were identified as hit compounds by HTS. New scaffold generation and SAR studies of all parts resulted in a 4-methyl-1,2,4-triazole derivative with an N-benzylcarboxamide moiety with highly potent activity toward GRK2 and selectivity over other kinases. In terms of subtype selectivity, these compounds showed enough selectivity against GRK1, 5, 6, and 7 with almost equipotent inhibition to GRK3. Our medicinal chemistry efforts led to the discovery of 115h (GRK2 IC50 = 18 nM), which was obtained the cocrystal structure with human GRK2 and an inhibitor of GRK2 that potentiates β-adrenergic receptor (βAR)-mediated cAMP accumulation and prevents internalization of βARs in β2AR-expressing HEK293 cells treated with isoproterenol. Therefore, 115h appears to be a novel class of therapeutic for heart failure treatment.
Copper-catalyzed selective oxygenation of methyl and benzyl substituents in pyridine with O2
Abe, Tsukasa,Tanaka, Shinji,Ogawa, Atsuko,Tamura, Masanori,Sato, Kazuhiko,Itoh, Shinobu
supporting information, p. 348 - 350 (2017/02/23)
A selective oxygenation of picolines and their derivatives has been achieved by usingasimple copper salt as a catalyst and molecular oxygen as an oxidant, where the α-position of the alkyl substituent is selectively oxidized to give the corresponding aldehydes or ketones. Addition of a catalytic amount of water enhances the catalytic activity, which could be attributed to the role of the proton donor to activate the substrates.
AMINOPYRIMIDINE HETEROCYCLIC COMPOUND WITH ADENOSINE RECEPTOR ANTAGONISTIC ACTIVITY
-
Paragraph 000119; 000120; 000121, (2017/06/23)
Disclosed hereinis an aminopyrimidine heterocyclic compound with adenosine receptor antagonistic activity, comprising a compound of the general formula (I), or a pharmaceutically acceptable salt thereof. The aminopyrimidine heterocyclic compound with adenosine receptor antagonistic activitydisclosed herein can be used as an effective adenosine receptor antagonist, and can be used for the treatment or prevention of disorders caused by abnormal level of adenosine.
Anti-inflammatory agents
-
Page/Page column 145, (2016/02/05)
Disclosed are novel compounds that are useful in regulating the expression of interleukin-6 (IL-6) and/or vascular cell adhesion molecule-1 (VCAM-1), and their use in the treatment and/or prevention of cardiovascular and inflammatory diseases and related disease states, such as, for example, atherosclerosis, asthma, arthritis, cancer, multiple sclerosis, psoriasis, and inflammatory bowel diseases, and autoimmune disease(s). Also, disclosed are compositions comprising the novel compounds, as well as methods for their preparation.
FUSED MORPHOLINOPYRIMIDINES AND METHODS OF USE THEREOF
-
, (2015/10/05)
The present disclosure relates to Fused Morpholinopyrimidines, pharmaceutical compositions comprising an effective amount of a Fused Morpholinopyrimidine and methods for using a Fused Morpholinopyrimidine in the treatment of a neurodegenerative disease, comprising administering to a subject in need thereof an effective amount of a Fused Morpholinopyrimidine.
P2X4 RECEPTOR MODULATING COMPOUNDS AND METHODS OF USE THEREOF
-
Paragraph 00217, (2015/06/25)
Provided herein are P2X4 receptor modulating compounds, methods of their synthesis, pharmaceutical compositions comprising the compounds, and methods of their use. The compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, including but not limited to, chronic pain, neuropathy, inflammatory diseases and central nervous system disorders.
P2X4 RECEPTOR MODULATING COMPOUNDS
-
Paragraph 00243, (2015/06/25)
Provided herein are P2X4 receptor modulating compounds, methods of their synthesis, pharmaceutical compositions comprising the compounds, and methods of their use. The compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, including but not limited to, chronic pain, neuropathy, inflammatory diseases and central nervous system disorders.
BENZIMIDAZOLES AND RELATED ANALOGS AS SIRTUIN MODULATORS
-
Page/Page column 131-132, (2010/04/03)
Provided herein are sirtuin-modulating compounds of formula (II) The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.
COMPOUNDS AND METHODS FOR INHIBITION OF RENIN, AND INDICATIONS THEREFOR
-
Page/Page column 64, (2010/11/18)
Compounds active as inhibitors of renin are described, as well as methods of using such compounds to treat diseases and conditions associated with the renin-angiotensin system. Formula (I)
IMIDAZOPYRIDINE AND RELATED ANALOGS AS SIRTUIN MODULATORS
-
Page/Page column 98-99, (2009/12/27)
Provided herein are novel sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.
