BIOMAT Database Logo BIOMAT Database Logo

Structural development of 1H-pyrazolo-[3,4-b]pyridine-4-carboxylic acid derivatives as human peroxisome proliferator-activated receptor alpha (PPARα)-selective agonists. 2019

Hiroyuki Miyachi, and Tomohiro Yuzuriha, and Ryotaro Tabata, and Syohei Fukuda, and Kazuto Nunomura, and Bangzhong Lin, and Tadayuki Kobayashi, and Kenji Ishimoto, and Takefumi Doi, and Keisuke Tachibana
Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1, Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.

We previously reported that 1H-pyrazolo-[3,4-b]pyridine-4-carboxylic acid derivative 6 is an agonist of human peroxisome proliferator-activated receptor alpha (hPPARα). Here, we prepared a series of 1H-pyrazolo-[3,4-b]pyridine-4-carboxylic acid derivatives in order to examine the structure-activity relationships (SAR). SAR studies clearly indicated that the steric bulkiness of the substituent on 1H-pyrazolo-[3,4-b]pyridine ring, the position of the distal hydrophobic tail part, and the distance between the distal hydrophobic tail part and the acidic head part are critical for hPPARα agonistic activity. These SAR results are somewhat different from those reported for fibrate-class hPPARα agonists. A representative compound (10f) was as effective as fenofibrate in reducing the elevated plasma triglyceride levels in a high-fructose-fed rat model.

UI MeSH Term Description Entries
D011725 Pyridines Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular
D047493 PPAR alpha A nuclear transcription factor. Heterodimerization with RETINOID X RECEPTOR GAMMA is important to metabolism of LIPIDS. It is the target of FIBRATES to control HYPERLIPIDEMIAS. PPARalpha,Peroxisome Proliferator-Activated Receptor alpha,Peroxisome Proliferator Activated Receptor alpha

Related Publications

Hiroyuki Miyachi, and Tomohiro Yuzuriha, and Ryotaro Tabata, and Syohei Fukuda, and Kazuto Nunomura, and Bangzhong Lin, and Tadayuki Kobayashi, and Kenji Ishimoto, and Takefumi Doi, and Keisuke Tachibana
Discovery of a novel class of 1,3-dioxane-2-carboxylic acid derivatives as subtype-selective peroxisome proliferator-activated receptor alpha (PPARalpha) agonists.
March 2008, Bioorganic & medicinal chemistry letters,
Hiroyuki Miyachi, and Tomohiro Yuzuriha, and Ryotaro Tabata, and Syohei Fukuda, and Kazuto Nunomura, and Bangzhong Lin, and Tadayuki Kobayashi, and Kenji Ishimoto, and Takefumi Doi, and Keisuke Tachibana
Structure-activity relationship studies of non-carboxylic acid peroxisome proliferator-activated receptor α/δ (PPARα/δ) dual agonists.
November 2016, Bioorganic & medicinal chemistry,
Hiroyuki Miyachi, and Tomohiro Yuzuriha, and Ryotaro Tabata, and Syohei Fukuda, and Kazuto Nunomura, and Bangzhong Lin, and Tadayuki Kobayashi, and Kenji Ishimoto, and Takefumi Doi, and Keisuke Tachibana
Design and synthesis of substituted phenylpropanoic acid derivatives as human peroxisome proliferator-activated receptor alpha/delta dual agonists.
February 2006, Bioorganic & medicinal chemistry letters,
Hiroyuki Miyachi, and Tomohiro Yuzuriha, and Ryotaro Tabata, and Syohei Fukuda, and Kazuto Nunomura, and Bangzhong Lin, and Tadayuki Kobayashi, and Kenji Ishimoto, and Takefumi Doi, and Keisuke Tachibana
Discovery of Substituted 1H-Pyrazolo[3,4-b]pyridine Derivatives as Potent and Selective FGFR Kinase Inhibitors.
June 2016, ACS medicinal chemistry letters,
Hiroyuki Miyachi, and Tomohiro Yuzuriha, and Ryotaro Tabata, and Syohei Fukuda, and Kazuto Nunomura, and Bangzhong Lin, and Tadayuki Kobayashi, and Kenji Ishimoto, and Takefumi Doi, and Keisuke Tachibana
Novel peroxisome proliferator activated receptor-alpha agonists.
December 2007, The American journal of cardiology,
Hiroyuki Miyachi, and Tomohiro Yuzuriha, and Ryotaro Tabata, and Syohei Fukuda, and Kazuto Nunomura, and Bangzhong Lin, and Tadayuki Kobayashi, and Kenji Ishimoto, and Takefumi Doi, and Keisuke Tachibana
Structure-activity studies on 1,3-dioxane-2-carboxylic acid derivatives, a novel class of subtype-selective peroxisome proliferator-activated receptor alpha (PPARalpha) agonists.
January 2008, Bioorganic & medicinal chemistry,
Hiroyuki Miyachi, and Tomohiro Yuzuriha, and Ryotaro Tabata, and Syohei Fukuda, and Kazuto Nunomura, and Bangzhong Lin, and Tadayuki Kobayashi, and Kenji Ishimoto, and Takefumi Doi, and Keisuke Tachibana
Rhodanine derivatives as novel peroxisome proliferator-activated receptor gamma agonists.
December 2007, Acta pharmacologica Sinica,
Hiroyuki Miyachi, and Tomohiro Yuzuriha, and Ryotaro Tabata, and Syohei Fukuda, and Kazuto Nunomura, and Bangzhong Lin, and Tadayuki Kobayashi, and Kenji Ishimoto, and Takefumi Doi, and Keisuke Tachibana
Identification of 1H-pyrazolo[3,4-b]pyridine derivatives as potent ALK-L1196M inhibitors.
December 2019, Journal of enzyme inhibition and medicinal chemistry,
Hiroyuki Miyachi, and Tomohiro Yuzuriha, and Ryotaro Tabata, and Syohei Fukuda, and Kazuto Nunomura, and Bangzhong Lin, and Tadayuki Kobayashi, and Kenji Ishimoto, and Takefumi Doi, and Keisuke Tachibana
Design, synthesis, and evaluation of substituted phenylpropanoic acid derivatives as human peroxisome proliferator activated receptor activators. Discovery of potent and human peroxisome proliferator activated receptor alpha subtype-selective activators.
August 2003, Journal of medicinal chemistry,
Hiroyuki Miyachi, and Tomohiro Yuzuriha, and Ryotaro Tabata, and Syohei Fukuda, and Kazuto Nunomura, and Bangzhong Lin, and Tadayuki Kobayashi, and Kenji Ishimoto, and Takefumi Doi, and Keisuke Tachibana
Design and synthesis of 1H-pyrazolo[3,4-c]pyridine derivatives as a novel structural class of potent GPR119 agonists.
August 2016, Bioorganic & medicinal chemistry letters,
Copied contents to your clipboard!