PATENT CLAIM ANALYSIS

Application Number: 16067158
Application Type: Utility
Filing Date: 2018-06
Publication Date: 2019-01
Patent Classification: ["514", "063000"]

Abstract:
The present invention discloses a nitrogen-containing fused heterocyclic compound, as well as a preparation method, intermediate, composition and application thereof. The nitrogen-containing fused heterocyclic compound of the present invention as represented by formula (I), as well as the pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, metabolite or drug precursor thereof, exhibit a high selectivity and a high inhibitory activity with respect to CDK4 and CDK6 at a molecular level, an excellent inhibitory activity with respect to breast cancer cells at a cellular level, and significant inhibition of tumor cell proliferation associated with cyclin-dependent kinase activity at an animal level. The invention also exhibits a good stability with respect to human or mouse liver microsomes without significant inhibition of metabolic enzymes, good in vivo absorption in mice and rats, a high bioavailability and good druggability.

Claim (Index 4):
The nitrogen-containing fused heterocyclic compound, the pharmaceutically acceptable salt, the enantiomer, the diastereomer, the tautomer, the solvate, the metabolite or the drug precursor thereof according to  claim 1 , wherein at least one of p and q is 1; preferably, when p and q are both 1, m is 0, 1 or 2, n is 0; or when p and q are both 1, n is 0, 1 or 2, m is 0; or when p is 0, q is 1, m and n are independently 0, 1 or 2; or, when p is 1, q is 0, m and n are independently 0, 1 or 2;\n and/or, halogen in R 1  is fluorine; and/or, substituted or unsubstituted C 1 -C 20  alkyl in R 1  is methyl or trifluoromethyl; and/or, substituted or unsubstituted C 1 -C 20  alkoxy in R 1  is methoxy; and/or, substituted or unsubstituted C 3 -C 12  cycloalkyl in R 1  is cyclopropyl; and/or, substituted or unsubstituted C 1 -C 20  alkyl in R 2  is methyl; and/or, substituted or unsubstituted C 1 -C 20  alkoxy in R 2  is methoxy; and/or, substituted or unsubstituted C 1 -C 20  alkylthio in R 2  is methylthio; and/or, substituted or unsubstituted C 3 -C 12  cycloalkyl in R 2  is cyclopropyl; and/or, substituted or unsubstituted C 1 -C 20  alkyl in R 3  is methyl, ethyl, isopropyl, tert-butyl, 1-ethylpropyl, 1-cyclopropylethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 1-methyl-2,2,2-trifluoroethyl or cyclopropylmethyl; and/or, substituted or unsubstituted C 3 -C 12  cycloalkyl in R 3  is 1-methylcyclopropyl, cyclopropyl, 3-oxocyclobutyl 3-hydroxycyclobutyl, 3-fluorocyclobutyl, 3,3-difluorocyclobutyl, cyclobutyl, cyclopentyl, cyclohexyl or and/or, substituted or unsubstituted C 1 -C 9  heterocycloalkyl in R 3  is 3-oxetanyl or 3-methyl-3-azacyclobutyl; and/or, when R 3  is substituted or unsubstituted C 1 -C 9  heterocycloalkyl, and the heteroatom is N, the N is substituted with C 1 -C 3  alkyl; and/or, when the \u201csubstituted\u201d in the \u201csubstituted or unsubstituted C 1 -C 20  alkyl\u201d, \u201csubstituted or unsubstituted C 2 -C 20  alkenyl\u201d, \u201csubstituted or unsubstituted C 2 -C 20  alkynyl\u201d, \u201csubstituted or unsubstituted C 1 -C 20  alkoxy\u201d, \u201csubstituted or unsubstituted C 1 -C 9  heterocycloalkyl\u201d, \u201csubstituted or unsubstituted C 3 -C 12  cycloalkyl\u201d and \u201csubstituted or unsubstituted C 1 -C 20  alkylthio\u201d in the definitions of R 1 , R 2  and R 3  refers to be independently substituted with halogen, the halogen is fluorine; and/or, when the \u201csubstituted\u201d in the \u201csubstituted or unsubstituted C 1 -C 20  alkyl\u201d, \u201csubstituted or unsubstituted C 2 -C 20  alkenyl\u201d, \u201csubstituted or unsubstituted C 2 -C 20  alkynyl\u201d, \u201csubstituted or unsubstituted C 1 -C 20  alkoxy\u201d, \u201csubstituted or unsubstituted C 1 -C 9  heterocycloalkyl\u201d, \u201csubstituted or unsubstituted C 3 -C 12  cycloalkyl\u201d and \u201csubstituted or unsubstituted C 1 -C 20  alkylthio\u201d in the definitions of R 1 , R 2  and R 3  refers to be independently substituted with C 1 -C 20  alkyl, the C 1 -C 20 alkyl is methyl; and/or, when the \u201csubstituted\u201d in the \u201csubstituted or unsubstituted C 1 -C 20  alkyl\u201d, \u201csubstituted or unsubstituted C 2 -C 20  alkenyl\u201d, \u201csubstituted or unsubstituted C 2 -C 20  alkynyl\u201d, \u201csubstituted or unsubstituted C 1 -C 20  alkoxy\u201d, \u201csubstituted or unsubstituted C 1 -C 9  heterocycloalkyl\u201d, \u201csubstituted or unsubstituted C 3 -C 12  cycloalkyl\u201d and \u201csubstituted or unsubstituted C 1 -C 20  alkylthio\u201d in the definitions of R 1 , R 2  and R 3  refers to be independently substituted with C 3 -C 12  cycloalkyl, the C 3 -C 12  cycloalkyl is cyclopropyl; and/or, halogen in R 4  is fluorine; and/or, C 1 -C 3  alkoxy in R 4  is methoxy; and/or, C 1 -C 6  alkyl in R 7  is methyl or ethyl; and/or, substituted or unsubstituted C 3 -C 8  cycloalkyl in R 7  is cyclobutyl, cyclopropyl or 4-methylcyclohexyl; and/or, substituted or unsubstituted C 1 -C 20  alkyl in R 5  is 2-methoxyethyl, 2-hydroxyethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, dimethylaminomethyl or 2-dimethylamino-ethyl; and/or, substituted or unsubstituted C 2 -C 20  alkynyl in R 5  is ethynyl, 2-butynyl or 2-propynyl; and/or, substituted or unsubstituted C 3 -C 12  cycloalkyl in R 5  is and/or, substituted or unsubstituted C 1 -C 9  heterocycloalkyl in R 5  is tetrahydrogenpyrrolyl, and/or, substituted or unsubstituted C 1 -C 20  alkyl in R 8  is dimethylaminomethyl; and/or, substituted or unsubstituted C 1 -C 9  heterocycloalkyl in R 8  is and/or, substituted or unsubstituted C 1 -C 20  alkoxy in R 8  is methoxy or ethoxy; and/or, substituted or unsubstituted C 1 -C 20  alkyl in R 9  is methyl, ethyl, isopropyl, aminomethyl, hydroxymethyl, hydroxyethyl, methylaminomethyl, dimethylaminomethyl, 2-dimethylamino-ethyl, or methoxymethyl;\n and/or, substituted or unsubstituted C 3 -C 12  cycloalkyl in R 9  is cyclobutyl, \n or 4-methylcyclohexyl;\n and/or, substituted or unsubstituted C 1 -C 20  alkoxy in R 9  is 2-dimethylamino-ethoxy; \n and/or, substituted or unsubstituted C 1 -C 9  heterocycloalkyl in R 9  is \n and/or, substituted or unsubstituted C 1 -C 20  alkyl in R 10a  and R 10b  is independently 2-dimethylamino-ethyl or 2-hydroxyethyl; and/or, substituted or unsubstituted C 1 -C 9  heterocycloalkyl in R 10a  and R 10b  is independently and/or, when the \u201csubstituted\u201d in the \u201csubstituted or unsubstituted C 1 -C 20  alkyl\u201d, \u201csubstituted or unsubstituted C 2 -C 20  alkenyl\u201d, \u201csubstituted or unsubstituted C 2 -C 20  alkynyl\u201d, \u201csubstituted or unsubstituted C 3 -C 12  cycloalkyl\u201d, \u201csubstituted or unsubstituted C 1 -C 9  heterocycloalkyl\u201d, \u201csubstituted or unsubstituted C 3 -C 12  aryl\u201d, \u201csubstituted or unsubstituted C 1 -C 9  heteroaryl\u201d, \u201csubstituted or unsubstituted C 1 -C 20  alkylthio\u201d and \u201csubstituted or unsubstituted C 1 -C 20  alkoxy\u201d in the definitions of R 5 , R 8 , R 9 , R 10a  and R 10b  refers to be independently substituted with C 1 -C 20  alkyl, the C 1 -C 20  alkyl is methyl or isopropyl; and/or, when the \u201csubstituted\u201d in the \u201csubstituted or unsubstituted C 1 -C 20  alkyl\u201d, \u201csubstituted or unsubstituted C 2 -C 20  alkenyl\u201d, \u201csubstituted or unsubstituted C 2 -C 20  alkynyl\u201d, \u201csubstituted or unsubstituted C 3 -C 12  cycloalkyl\u201d, \u201csubstituted or unsubstituted C 1 -C 9  heterocycloalkyl\u201d, \u201csubstituted or unsubstituted C 3 -C 12  aryl\u201d, \u201csubstituted or unsubstituted C 1 -C 9  heteroaryl\u201d, \u201csubstituted or unsubstituted C 1 -C 20  alkylthio\u201d and \u201csubstituted or unsubstituted C 1 -C 20  alkoxy\u201d in the definitions of R 5 , R 8 , R 9 , R 10a  and R 10b  refers to be independently substituted with C 2 -C 20  alkynyl, the C 2 -C 20  alkynyl is 2-propynyl; and/or, when the \u201csubstituted\u201d in the \u201csubstituted or unsubstituted C 1 -C 20  alkyl\u201d, \u201csubstituted or unsubstituted C 2 -C 20  alkenyl\u201d, \u201csubstituted or unsubstituted C 2 -C 20  alkynyl\u201d, \u201csubstituted or unsubstituted C 3 -C 12  cycloalkyl\u201d, \u201csubstituted or unsubstituted C 1 -C 9  heterocycloalkyl\u201d, \u201csubstituted or unsubstituted C 3 -C 12  aryl\u201d, \u201csubstituted or unsubstituted C 1 -C 9  heteroaryl\u201d, \u201csubstituted or unsubstituted C 1 -C 20  alkylthio\u201d and \u201csubstituted or unsubstituted C 1 -C 20  alkoxy\u201d in the definitions of R 5 , R 8 , R 9 , R 10a  and R 10b  refers to be independently substituted with halogen, the halogen is fluorine; and/or, when the \u201csubstituted\u201d in the \u201csubstituted or unsubstituted C 1 -C 20  alkyl\u201d, \u201csubstituted or unsubstituted C 2 -C 20  alkenyl\u201d, \u201csubstituted or unsubstituted C 2 -C 20  alkynyl\u201d, \u201csubstituted or unsubstituted C 3 -C 12  cycloalkyl\u201d, \u201csubstituted or unsubstituted C 1 -C 9  heterocycloalkyl\u201d, \u201csubstituted or unsubstituted C 3 -C 12  aryl\u201d, \u201csubstituted or unsubstituted C 1 -C 9  heteroaryl\u201d, \u201csubstituted or unsubstituted C 1 -C 20  alkylthio\u201d and \u201csubstituted or unsubstituted C 1 -C 20  alkoxy\u201d in the definitions of R 5 , R 8 , R 9 , R 10a  and R 10b  refers to be independently substituted with C 1 -C 20  silyl, the C 1 -C 20  silyl is trimethylsilyl; and/or, when the \u201csubstituted\u201d in the \u201csubstituted or unsubstituted C 1 -C 20  alkyl\u201d, \u201csubstituted or unsubstituted C 2 -C 20  alkenyl\u201d, \u201csubstituted or unsubstituted C 2 -C 20  alkynyl\u201d, \u201csubstituted or unsubstituted C 3 -C 12  cycloalkyl\u201d, \u201csubstituted or unsubstituted C 1 -C 9  heterocycloalkyl\u201d, \u201csubstituted or unsubstituted C 3 -C 12  aryl\u201d, \u201csubstituted or unsubstituted C 1 -C 9  heteroaryl\u201d, \u201csubstituted or unsubstituted C 1 -C 20  alkylthio\u201d and \u201csubstituted or unsubstituted C 1 -C 20  alkoxy\u201d in the definitions of R 5 , R 8 , R 9 , R 10a  and R 10b  refers to be independently substituted with substituted or unsubstituted C 1 -C 9  saturated or unsaturated heterocycloalkyl, the C 1 -C 9  unsaturated heterocycloalkyl is and/or, when the \u201csubstituted\u201d in the \u201csubstituted or unsubstituted C 1 -C 20  alkyl\u201d, \u201csubstituted or unsubstituted C 2 -C 20  alkenyl\u201d, \u201csubstituted or unsubstituted C 2 -C 20  alkynyl\u201d, \u201csubstituted or unsubstituted C 3 -C 12  cycloalkyl\u201d, \u201csubstituted or unsubstituted C 1 -C 9  heterocycloalkyl\u201d, \u201csubstituted or unsubstituted C 3 -C 12  aryl\u201d, \u201csubstituted or unsubstituted C 1 -C 9  heteroaryl\u201d, \u201csubstituted or unsubstituted C 1 -C 20  alkylthio\u201d and \u201csubstituted or unsubstituted C 1 -C 20  alkoxy\u201d in the definitions of R 5 , R 8 , R 9 , R 10a  and R 10b  refers to be independently substituted with substituted or unsubstituted C 1 -C 9  saturated or unsaturated heterocycloalkyl, the C 1 -C 9  saturated heterocycloalkyl is and/or, substituted or unsubstituted C 1 -C 20  alkyl in R 11a  and R 11b  is independently \u2014CF 3 , hydroxyethyl, 2-dimethylaminoethyl; and/or, substituted or unsubstituted C 2 -C 20  alkenyl in R 11a  and R 11b  is independently 2-propenyl; and/or, substituted or unsubstituted C 2 -C 20  alkynyl in R 11a  and R 11b  is independently 2-propynyl; and/or, substituted or unsubstituted C 1 -C 9  heterocycloalkyl in R 11a  and R 11b  is independently and/or, C 1 -C 6  alkyl in R cs  is methyl, ethyl, propyl or isopropyl; and/or, C 1 -C 6  alkyl in R hc  is methyl, ethyl or propyl; and/or, when the \u201csubstituted\u201d in the \u201csubstituted or unsubstituted C 1 -C 20  alkyl\u201d, \u201csubstituted or unsubstituted C 2 -C 20  alkenyl\u201d, \u201csubstituted or unsubstituted C 2 -C 20  alkynyl\u201d, \u201csubstituted or unsubstituted C 3 -C 12  cycloalkyl\u201d, \u201csubstituted or unsubstituted C 1 -C 9  heterocycloalkyl\u201d, \u201csubstituted or unsubstituted C 3 -C 12  aryl\u201d and \u201csubstituted or unsubstituted C 1 -C 9  heteroaryl\u201d in the definitions of R 11a  and R 11b  refers to be independently substituted with C 1 -C 20  silyl, the C 1 -C 20  silyl is trimethylsilyl; and/or, C 1 -C 20  alkoxy in R 12  is methoxy or ethoxy; and/or, \u201cC 1 -C 9  heterocycloalkyl which is optionally substituted with C 1 -C 20  alkyl\u201d in R 15 , R 16a  and R 16b  is and/or, \u201cC 1 -C 9  heterocycloalkyl which is optionally substituted with C 1 -C 20  alkyl\u201d in R 17  is and/or, C 3 -C 8  heteroaryl in R 20  is and/or, \u201cC 1 -C 9  heterocycloalkyl which is optionally substituted with C 1 -C 20  alkyl\u201d in R 24  is and/or, C 1 -C 20  alkoxy in R 25a  and R 25b  is independently ethoxy; and/or, \u201cC 1 -C 9  heterocycloalkyl which is optionally substituted with C 1 -C 20  alkyl\u201d in R 25a  and R 25b  is independently and/or, \u201cC 1 -C 9  heterocycloalkyl which is optionally substituted with C 1 -C 20  alkyl\u201d in R 27a  and R 27b  is independently and/or, substituted or unsubstituted C 1 -C 20  alkyl in R 27a  and R 27b  is independently methyl, ethyl or propyl; and/or, \u201cC 1 -C 9  heterocycloalkyl which is optionally substituted with C 1 -C 20  alkyl\u201d in R 29a  and R 29b  is independently

Metadata:
- Claim Count in Document: 1.0
- Percentile: 94.0
- Lexical Diversity: 1.8
- Patent Class: 514.0
- Transitional Phrase Type: none
- Component Type: 0
- Foreign Priority: True
- Related Applications: ['12723137', '14132877', '14883720', '10572958', '15612670']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.8206309734311897
- 35 USC 102 Novelty (BERT): 0.5358823544040685
- Combined Prediction Score: 0.7921561115284775
- Mean Citation Score: 369.647188
- Max Citation Score: 375.8492
- Similarity Product: 217.8596389393568

Labels:
- Claim Label 101: 1
- Claim Label 102: 0
- Claim Label 103: 1
- Claim Label 112: 0
- Combined Label: 0
- Label 101 Adjusted: 1

Dataset: test