21254-22-8Relevant articles and documents
Discovery of Novel Selective and Orally Bioavailable Phosphodiesterase-1 Inhibitors for the Efficient Treatment of Idiopathic Pulmonary Fibrosis
Wu, Yinuo,Tian, Yi-Jing,Le, Mei-Ling,Zhang, Si-Rui,Zhang, Chen,Huang, Meng-Xing,Jiang, Mei-Yan,Zhang, Bei,Luo, Hai-Bin
, p. 7867 - 7879 (2020)
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and devastating lung disease lacking effective therapy. To identify whether phosphodiesterase-1 (PDE1) inhibition could act as a novel target for the treatment of IPF, hit-to-lead structural optimizations were performed on the PDE9/PDE1 dual inhibitor (R)-C33, leading to compound 3m with an IC50 of 2.9 nM against PDE1C, excellent selectivity across PDE subfamilies, reasonable drug-like properties, and remarkable pharmacodynamic effects as an anti-IPF agent. Oral administration of compound 3m (10 mg/kg) exerted more significant anti-pulmonary fibrosis effects than pirfenidone (150 mg/kg) in a bleomycin-induced IPF rat model and prevented transforming growth factor-β-induced fibroblast-to-myofibroblast conversion in vitro, indicating that PDE1 inhibition could serve as a novel target for the efficient treatment of IPF.
PYRIMIDINE AMIDE COMPOUNDS AND USE THEREOF
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Page/Page column 22, (2021/04/30)
Disclosed are compounds of formula (I) below or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof: (I), in which each of variables each of variables R, R1, R2, X1, X2, X3 and n is defined herein. Also disclosed is a method for treating a cancer with a compound of formula (I) or a salt thereof and a pharmaceutical composition containing same.
COMPOUNDS HAVING PDE9A INHIBITORY ACTIVITY, AND PHARMACEUTICAL USES THEREOF
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Paragraph 0171-0172, (2021/10/15)
The present invention provides a compound having a specific chemical structure and having PDE9A inhibitory activity, or a pharmaceutically acceptable salt thereof. The present invention provides a composition containing the compound or a pharmaceutically acceptable salt thereof. The present invention provides a pharmaceutical use, for treating or preventing PDE9A-related diseases, of the compound according to the present invention, a salt thereof, and a composition containing the compound or salt. The present invention also provides a method for treating or preventing PDE9A-related diseases, the method comprising administering an effective amount of the compound according to the present invention, a salt thereof, or a composition containing the compound or salt to a subject in need of treatment.
COMPOUNDS HAVING PDE9A INHIBITORY ACTIVITY, AND PHARMACEUTICAL USES THEREOF
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Paragraph 0446-0450, (2021/10/15)
The present invention provides a compound having a specific chemical structure and having PDE9A inhibitory activity, or a pharmaceutically acceptable salt thereof. The present invention provides a composition containing the compound or a pharmaceutically acceptable salt thereof. The present invention provides a pharmaceutical use, for treating or preventing PDE9A-related diseases, of the compound according to the present invention, a salt thereof, and a composition containing the compound or salt. The present invention also provides a method for treating or preventing PDE9A-related diseases, the method comprising administering an effective amount of the compound according to the present invention, a salt thereof, or a composition containing the compound or salt to a subject in need of treatment.
Preparation method PDE9A inhibitor
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Paragraph 0056-0059, (2020/03/17)
The invention relates to a preparation method PDE9A of, inhibitor which takes 2, 4, 6 - tric- 5 5-pyrimidine formaldehyde as a starting material, in the presence of a base with a substituted hydrazine hydrochloride condensation ring, and then performing a hydrolysis reaction, and chiral amine reaction, recrystallization purification, to obtain 1,6 - disubstituted - 1111,5-dihydropyrazino [3,4] - pyrimidine - 2 2-one. easily realize industrial production, by a process with mild, process and a simple, process operation.
Substituted pyrazole[3,4-d]pyrimidine compound as well as preparation method and application thereof
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Paragraph 0058; 0061-0062, (2020/10/20)
The invention discloses a substituted pyrazole[3,4-d]pyrimidine compound as well as a preparation method and application thereof. The structure of the compound is shown as a formula (I) or a formula (II). The compound provided by the invention has a good inhibition effect on phosphodiesterase type I (PDE1), and can be used as a phosphodiesterase type I inhibitor; meanwhile, a medicine prepared from the compound has a relatively good curative effect on pulmonary arterial hypertension and idiopathic pulmonary fibrosis; therefore, the compound provided by the invention has important medicinal value and wide application prospect in preparing medicines for treating pulmonary arterial hypertension and idiopathic pulmonary fibrosis. In addition, the compound disclosed by the invention is novel instructure, simple in preparation method and suitable for large-scale industrial production and application.
Pyrazolpyrimidine derivative as well as preparation method and application thereof
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Paragraph 0021; 0023, (2019/09/17)
The invention discloses a pyrazol[3,4-d]pyrimidine derivative as well as a preparation method and an application thereof as an inhibitor of PDEIX (phosphodiesterase IX). The derivative as the inhibitor of the PDEIX has high activity, high selectivity and
SUBSTITUTED METHYL PYRAZOLOPYRIMIDINONE AND METHYL IMIDAZOPYRAZINONE COMPOUNDS AS PDE1 INHIBITORS
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Paragraph 0477, (2019/06/20)
A chemical entity of Formula (I) or Formula (II): wherein Ra, Rb, Re, and Rf have any of the values described herein, and compositions comprising such chemical entities; methods of making them; and their use in
A kind of N - substituted pyrazolo [3, 4 - d] pyrimidinone compound and use thereof
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Paragraph 0024; 0025; 0026, (2017/10/06)
The invention discloses an N-substituted pyrazolo[3,4-d]pyrimidinone compound shown in formula (I) and an application of the N-substituted pyrazolo[3,4-d]pyrimidinone compound as an inhibitor of phosphodiesterase IX (PDEIX). Formula (I) is shown in the sp
TRICYCLIC DERIVATIVE
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Paragraph 0179; 0182, (2016/04/20)
Disclosed are compounds useful as inhibitors of phosphodiesterase 1 (PDE1), compositions thereof, and methods of using the same.
