373608-50-5Relevant articles and documents
CYCLIN-DEPENDENT KINASE INHIBITING COMPOUNDS FOR THE TREATMENT OF MEDICAL DISORDERS
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Page/Page column 172; 198, (2021/11/26)
This invention is in the area of cell cycle inhibiting compounds for the treatment of disorders involving abnormal cellular proliferation, and include selective CDK2 inhibitors for medical therapy and their pharmaceutically acceptable salts and compositions.
Discovery of Novel Apigenin-Piperazine Hybrids as Potent and Selective Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors for the Treatment of Cancer
Long, Huan,Hu, Xiaolong,Wang, Baolin,Wang, Quan,Wang, Rong,Liu, Shumeng,Xiong, Fei,Jiang, Zhenzhou,Zhang, Xiao-Qi,Ye, Wen-Cai,Wang, Hao
, p. 12089 - 12108 (2021/09/06)
Poly (ADP-ribose) polymerase-1 (PARP-1) is a potential target for the discovery of chemosensitizers and anticancer drugs. Amentoflavone (AMF) is reported to be a selective PARP-1 inhibitor. Here, structural modifications and trimming of AMF have led to a series of AMF derivatives (9a-h) and apigenin-piperazine/piperidine hybrids (14a-p, 15a-p, 17a-h, and 19a-f), respectively. Among these compounds, 15l exhibited a potent PARP-1 inhibitory effect (IC50 = 14.7 nM) and possessed high selectivity to PARP-1 over PARP-2 (61.2-fold). Molecular dynamics simulation and the cellular thermal shift assay revealed that 15l directly bound to the PARP-1 structure. In in vitro and in vivo studies, 15l showed a potent chemotherapy sensitizing effect against A549 cells and a selective cytotoxic effect toward SK-OV-3 cells through PARP-1 inhibition. 15l·2HCl also displayed good ADME characteristics, pharmacokinetic parameters, and a desirable safety margin. These findings demonstrated that 15l·2HCl may serve as a lead compound for chemosensitizers and the (BRCA-1)-deficient cancer therapy.
PYRIMIDINE-BASED ANTIPROLIFERATIVE AGENTS
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Page/Page column 172; 201; 203, (2018/02/28)
This invention is in the area of pyrimidine-based compounds for the treatment of disorders involving abnormal cellular proliferation, including but not limited to tumors and cancers.
Preparation method of Volasertib intermediate 1-cyclopropyl methyl piperazine
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Paragraph 0029; 0034, (2018/09/08)
The invention provides a preparation method of a Volasertib intermediate 1-cyclopropyl methyl piperazine. The preparation method comprises the following steps: S1, adding N-Boc-piperazine into an inert solvent and triethylamine or pyridine, dropwise adding cyclopropanecarbonyl chloride, adding water for extraction after the reaction ends, obtaining an organic phase, and concentrating the organic phase to remove an organic solvent to obtain a solid; S2, adding the solid obtained in S1 into an ether solvent, then adding sodium borohydride, dropwise adding boron trifluoride-diethyl ether for reaction, quenching the mixture, then extracting the mixture, and concentrating the mixture to remove an organic solvent to obtain a solid; S3, adding the solid obtained in S2 into an alcohol solvent, dropwise adding concentrated hydrochloric acid for reaction, alkalizing the mixture with sodium hydroxide or potassium hydroxide aqueous solution, and performing extraction and concentration in sequenceto obtain the compound 1-cyclopropyl methyl piperazine. The raw materials used in the preparation method are readily available, and the preparation method is low in cost, easy to operate, high in safety, high in product quality and yield, and convenient for large-scale production.
POLY (ADP-RIBOSE) POLYMERASE INHIBITOR
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Paragraph 0115; 0116, (2015/02/25)
Disclosed are a phthalic hydrazide (phthalazine ketone) compound, and a pharmaceutical composition comprising the same. As a DNA repair enzyme poly (ADP-ribozyme) polymerase inhibitor, the compound and the pharmaceutical composition can effectively treat diseases involving PARP enzymatic activity, including cancer, neural degenerative diseases, inflammation and the like.
POLY (ADP-RIBOSE) POLYMERASE INHIBITOR
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Paragraph 0089; 0090, (2014/11/13)
Disclosed are a phthalic hydrazide (phthalazine ketone) compound, and a pharmaceutical composition comprising the same. As a DNA repair enzyme poly (ADP-ribozyme) polymerase inhibitor, the compound and the pharmaceutical composition can effectively treat diseases involving PARP enzymatic activity, including cancer, neural degenerative diseases, inflammation and the like.
DIHYDROPTERIDINONE DERIVATIVES, PREPARATION PROCESS AND PHARMACEUTICAL USE THEREOF
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Page/Page column 68, (2012/08/08)
Dihydroperidinone derivatives, preparation process and pharmaceutical use thereof are disclosed. Specially, new dihydroperidinone derivatives represented by general formula (I), wherein each substituent of the general formula (I) is defined as in the description, their preparation process, pharmaceutical compositions comprising said derivatives and their use as therapeutical agents, especially as Plk kinase inhibitors are disclosed.
DIHYDROPTERIDINONE DERIVATIVES, PREPARATION PROCESS AND PHARMACEUTICAL USE THEREOF
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Page/Page column 69, (2012/07/28)
Dihydroperidinone derivatives, preparation process and pharmaceutical use thereof are disclosed. Specially, new dihydroperidinone derivatives represented by general formula (I), wherein each substituent of the general formula (I) is defined as in the description, their preparation process, pharmaceutical compositions comprising said derivatives and their use as therapeutical agents, especially as Plk kinase inhibitors are disclosed.
ACETYLENE DERIVATIVES AS STEAROYL COA DESATURASE INHIBITORS
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Page/Page column 58, (2008/12/05)
The present invention provides Stearoyl CoA Desaturase (SCD) inhibitors, hi particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders modulated by Stearoyl CoA Desaturase 1 (SCD 1) inhibitors. Also provided herein are processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders modulated by Stearoyl CoA Desaturase (SCD) inhibitors.
PHARMACEUTICAL COMPOUNDS
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Page/Page column 45-46, (2008/06/13)
Fused pyrimidines of formula (I); wherein A represents a thiophene or furan ring; n is 1 or 2; R1 is a group of formula (II); wherein m is 0 or 1; R30 is H or C1-C6 alkyl; R4 and R5 form, together with the N atom to which they are attached, a 5- or 6-membered saturated N-containing heterocyclic group which includes 0 or 1 additional heteroatoms selected from N, S and O, which may be fused to a benzene ring and which is unsubstituted or substituted; or one of R4 and R5 is alkyl and the other is a 5- or 6-membered saturated N-containing heterocyclic group as defined above or an alkyl group which is substituted by a 5- or 6-membered saturated N-containing heterocyclic group as defined above; R2 is selected from formula (a); wherein R6 and R7 form, together with the nitrogen atom to which they are attached, a morpholine, thiomorpholine, piperidine, piperazine, oxazepane or thiazepane group which is unsubstituted or substituted; and formula (b); wherein Y is a C2-C4 alkylene chain which contains, between constituent carbon atoms of the chain and/or at one or both ends of the chain, 1 or 2 heteroatoms selected from O, N and S, and which is unsubstituted or substituted; and R3 is an indazole group which is unsubstituted or substituted; and the pharmaceutically acceptable salt thereof have activity as inhibitors of P13K and may thus be used to treat diseases and disorders arising from abnormal cell growth, function or behaviour associated with P13 kinase such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine disorders and neurological disorders. Processes for synthesizing the compounds are also described.
