Al technical title is built by PatSnap Al team. It summarizes the technical point description of the patent document.
A compound and solvate technology, applied in the field of 2,3-naphthyridine derivatives and their use as medicine, can solve problems such as energy depletion
Active Publication Date: 2013-01-30
NANJING SANHOME PHARMACEUTICAL CO LTD
View PDF8 Cites 37 Cited by
Summary
Abstract
Description
Claims
Application Information
AI Technical Summary
This helps you quickly interpret patents by identifying the three key elements:
Problems solved by technology
Method used
Benefits of technology
Problems solved by technology
However, this ribosylation process is based on the consumption of cellular energy. The activation of PARP-1 caused by an appropriate amount of DNA damage plays a role in repairing and restoring the cells; while a large amount of DNA damage causes the excessive activation of PARP, through this ribosylation can cause cellular NAD + and ATP energy depletion and death
Method used
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more
Image
Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
Click on the blue label to locate the original text in one second.
Reading with bidirectional positioning of images and text.
Smart Image
Examples
Experimental program
Comparison scheme
Effect test
Embodiment 1
[0183] Example 1: Preparation of 4-(3-(4-pyridineformylpiperazine-1-carbonyl)phenylamino)phthalazin-1(2H)-one (001)
[0184] Dissolve tert-butoxycarbonylpiperazine (4.28g, 0.023mol), triethylamine (6.98g, 0.069mol), m-aminobenzoic acid (7.01g, 0.023mol) in N,N-dimethylformamide ( 100ml), add benzotriazole-N,N,N',N'-tetramethyluronium hexafluorophosphate (8.72g, 0.023mol), stir at room temperature, add water to quench the reaction and precipitate The solid product was filtered and dried to give tert-butyl 4-(3-aminobenzoyl)piperazine-1-carboxylate.
[0185] Add trifluoroacetic acid (0.25ml) to a solution of triethylamine (0.3ml) in ethanol (50ml) in an ice bath (0°C), and add 4-(3-aminobenzoyl)piperene obtained in the previous step after 15 minutes tert-butyloxazine-1-carboxylate (1.65g, 0.0054mol) and 1,4-dichlorophthalazine (1.07g, 0.0054mol), heated to reflux, after the reaction (about 30min), add ethyl acetate (100ml ), washed with water (3*50ml), the organic phase was dr...
Embodiment 2
[0191]Example 2: Preparation of 4-(3-(4-(2-propylpentanoylpiperazine-1-carbonyl)phenylamino)phthalazin-1(2H)-one (003)
[0192] Preparation Method Reference Example 1: The target compound was obtained with a melting point of 204-205°C.
[0193] ESI-MS m / z: 475.7(m+H) + ， Calculated: 475.3.
[0194]
Embodiment 3
[0195] Example 3: Preparation of 4-(3-(4-(cyclopropylformyl)piperazine-1-carbonyl)phenylamino)phthalazin-1(2H)-one (007)
[0196] The preparation method refers to Example 1, and the melting point is >230°C.
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more
PUM
Property
Measurement
Unit
melting point
aaaaa
aaaaa
melting point
aaaaa
aaaaa
melting point
aaaaa
aaaaa
Login to view more
Abstract
The present invention provides novel phthalazinone compounds and isomer thereof, pharmaceutically acceptable salts, solvates, chemically protected forms, and prodrugs; which can be used as PARP inhibitor and pharmaceutical compositions containing the novel phthalazinone compounds; wherein A, R1 and X are defined as shown. The medicine is used for the treatment of: vascular diseases, neurotoxicity, or diseases improved through the inhibition of PARP activity; or used as adjuvants for the treatment of cancers, or used for enhancing the therapeutic effect of radiation or chemotherapeutic agents on tumor cells, wherein the cancers includes breast cancer, ovarian cancer, colon cancer, melanoma, lung cancer, gastrointestinal stromal tumor, brain cancer, cervical cancer, pancreatic cancer, prostate cancer, gastric cancer, chronic myeloid leukocytes hypercytosis, liver canser, lymphoma, peritoneal cancer, soft tissue sarcoma, neuroendocrine tumors, advanced solid tumors, and glioblastoma.
Description
technical field [0001] The present invention relates to a class of novel phthalazinone derivatives and pharmaceutical compositions containing such derivatives, mainly related to 2,3-phthalazinone derivatives and their application as medicine. In particular, the present invention relates to the use of these compounds for inhibiting the activity of poly(ADP-ribose) polymerase (also known as poly(ADP-ribose) synthase and poly ADP-ribosyltransferase, commonly referred to as PARP) . [0002] Background technique [0003] The mammalian enzyme PARP, a 113 kDa multi-domain protein, is involved in DNA damage signaling through its ability to recognize and rapidly bind DNA single- or double-strand breaks (D'Amours et al., Biochem. J. 342: 249 -268 (1999)). [0004] The polyadenosine diphosphate (ADP-ribose) ribose synthetase family now includes about 18 proteins, which are divided into 3 types. Type Ⅰ mainly exists in the nucleus, including PARP-1, PARP-2, PARP-3, etc.; Ⅱ Type III ...
Claims
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more
Application Information
Patent Timeline
Application Date:The date an application was filed.
Publication Date:The date a patent or application was officially published.
First Publication Date:The earliest publication date of a patent with the same application number.
Issue Date:Publication date of the patent grant document.
PCT Entry Date:The Entry date of PCT National Phase.
Estimated Expiry Date:The statutory expiry date of a patent right according to the Patent Law, and it is the longest term of protection that the patent right can achieve without the termination of the patent right due to other reasons(Term extension factor has been taken into account ).
Invalid Date:Actual expiry date is based on effective date or publication date of legal transaction data of invalid patent.
Login to view more