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 1):
A nitrogen-containing fused heterocyclic compound represented by formula I, a pharmaceutically acceptable salt, an enantiomer, a diastereomer, a tautomer thereof, a solvate, an metabolite or a drug precursor thereof; wherein, p and q are independently 0 or 1; m and n are independently 0, 1 or 2; X and Y are independently CH or N; the N atom in the cycle is oxidized or non-oxidized;\n R 1  is hydrogen, hydroxy, cyano, thio, substituted or unsubstituted C 2 -C 20  alkenyl, substituted or unsubstituted C 2 -C 20  alkynyl, halogen, substituted or unsubstituted C 1 -C 20  alkyl, C 1 -C 20  alkylthio, substituted or unsubstituted C 1 -C 20  alkoxy, substituted or unsubstituted C 3 -C 12  cycloalkyl, substituted or unsubstituted C 1 -C 9  heterocycloalkyl, or \u201cC 1 -C 20  alkyl mono-substituted, di-substituted or unsubstituted amino\u201d; wherein the two substituents in the \u201cC 1 -C 20  alkyl di-substituted amino\u201d are the same or different; \n R 2  is hydrogen, hydroxy, substituted or unsubstituted C 2 -C 20  alkenyl, substituted or unsubstituted C 2 -C 20  alkynyl, halogen, substituted or unsubstituted C 1 -C 20  alkyl, substituted or unsubstituted C 1 -C 20  alkoxy, substituted or unsubstituted C 1 -C 20  alkylthio, substituted or unsubstituted C 3 -C 12  cycloalkyl, cyano, \u201cC 1 -C 20  alkyl mono-substituted, di-substituted or unsubstituted amino\u201d or \n wherein two substituents in the \u201cC 1 -C 20  alkyl di-substituted amino\u201d are the same or different;\n R 3  is hydrogen, substituted or unsubstituted C 1 -C 20  alkyl, substituted or unsubstituted C 2 -C 20  alkenyl, substituted or unsubstituted C 2 -C 20  alkynyl, substituted or unsubstituted C 3 -C 12  cycloalkyl, or substituted or unsubstituted C 1 -C 9  heterocycloalkyl; wherein the \u201cheterocycloalkyl\u201d connects to another group via the carbon atom thereof, the heteroatom in the heterocycloalkyl is selected from the group consisting of O, N and S, the number of the heteroatom is 1 to 3; \n 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 the substituent selected from the group consisting of halogen, hydroxyl, oxo, thio, cyano, amino, nitro, C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, C 1 -C 20  alkoxy, C 1 -C 20  alkylthio, C 3 -C 12  cycloalkyl and \u201cC 1 -C 20  alkyl mono-substituted, di-substituted or unsubstituted amino\u201d; wherein two substituents in the \u201cC 1 -C 20  alkyl disubstituted amino\u201d are the same or different; when there are more than one substituents, the substituents are the same or different; \n R 4  is hydrogen, halogen, C 1 -C 6  alkyl, C 1 -C 3  alkoxy, cyano or \n R 7  contained in R 2  and R 4  is independently hydrogen, hydroxyl, C 1 -C 6  alkyl, substituted or unsubstituted C 3 -C 8  cycloalkyl, C 1 -C 6  alkoxy or \u201cC 1 -C 6  alkyl mono-substituted, di-substituted or unsubstituted amino\u201d; wherein the \u201csubstituted\u201d in the \u201csubstituted or unsubstituted C 3 -C 8  cycloalkyl\u201d refers to be substituted by C 1 -C 6  alkyl; two substituents in the \u201cC 1 -C 6  alkyl disubstituted amino\u201d are the same or different; at least one of R 1  and R 4  is halogen; R 5  is hydrogen, substituted or unsubstituted C 1 -C 20  alkyl, substituted or unsubstituted C 2 -C 20  alkenyl, substituted or unsubstituted C 2 -C 20  alkynyl, substituted or unsubstituted C 3 -C 12  cycloalkyl, substituted or unsubstituted C 1 -C 9  heterocycloalkyl, substituted or unsubstituted C 1 -C 9  heteroaryl, substituted or unsubstituted C 3 -C 12  aryl, wherein the \u201cC 1 -C 9  heterocycloalkyl\u201d connects to another group via the carbon atom thereof;\n in R 5 , each R 8  is independently hydroxyl, substituted or unsubstituted C 1 -C 20  alkyl, substituted or unsubstituted C 2 -C 20  alkenyl, substituted or unsubstituted C 2 -C 20  alkynyl, substituted or unsubstituted C 3 -C 12  cycloalkyl, substituted or unsubstituted C 1 -C 9  heteroaryl, substituted or unsubstituted C 3 -C 12  aryl, substituted or unsubstituted C 1 -C 9  heterocycloalkyl, substituted or unsubstituted C 1 -C 20  alkoxy or \n wherein the \u201cC 1 -C 9  heterocycloalkyl\u201d connects to another group via a carbon atom or a heteroatom thereof;\n in R 5 , each R 9  is independently hydrogen, hydroxyl, substituted or unsubstituted C 1 -C 20  alkyl, substituted or unsubstituted C 2 -C 20  alkenyl, substituted or unsubstituted C 2 -C 20  alkynyl, substituted or unsubstituted C 3 -C 12  cycloalkyl, substituted or unsubstituted C 1 -C 20  alkoxy, substituted or unsubstituted C 3 -C 12  aryl, substituted or unsubstituted C 1 -C 9  heteroaryl, or substituted or unsubstituted C 1 -C 9  heterocycloalkyl, or \n the \u201cC 1 -C 9  heterocycloalkyl\u201d connects to another group via a carbon atom or a heteroatom thereof;\n in R 8  and R 9 , each R 10a  and R 10b  is independently hydrogen, halogen, substituted or unsubstituted C 1 -C 20  alkyl, substituted or unsubstituted C 2 -C 20  alkenyl, substituted or unsubstituted C 2 -C 20  alkynyl, substituted or unsubstituted C 3 -C 12  cycloalkyl, substituted or unsubstituted C 1 -C 9  heteroaryl, substituted or unsubstituted C 3 -C 12  aryl, substituted or unsubstituted C 1 -C 9  heterocycloalkyl; wherein the \u201cC 1 -C 9  heterocycloalkyl\u201d connects to another group via a carbon atom or a heteroatom thereof; \n 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 definition of R 5 , R 8 , R 9 , R 10a  and R 10b  refers to be independently substituted with the substituent selected from the group consisting of \n C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, hydroxy, nitro, carboxyl, formyl, thio, trifluoromethyl, C 1 -C 20  silyl, halogen, cyano, C 1 -C 20  alkoxy, C 3 -C 12  cycloalkyl, substituted or unsubstituted C 1 -C 9  saturated or unsaturated heterocycloalkyl, thioureido, C 3 -C 12  aryl, C 1 -C 9  heteroaryl, \u2014SeR 19  and \u2014SF 5 , when there are more than one substituents, the substituents are the same or different; wherein the \u201csubstituted\u201d in the \u201csubstituted or unsubstituted C 1 -C 9  saturated or unsaturated heterocycloalkyl\u201d refers to be independently substituted with the substituent selected from the group consisting of methylene, oxo, thio, halogen, trifluoromethyl, hydroxy, \u2014PO(OH) 2 , \u2014PO(OR ps ) 2 , C 1 -C 20  alkyl which is optionally substituted with propynyl, C 1 -C 20  alkyl which is optionally substituted with ethynyl, C 1 -C 6  alkenyl, C 1 -C 20  alkynyl, \u2014B(OH) 2  and \u2014B(OR bs ) 2 , wherein R ps  and R bs  are independently C 1 -C 6  alkyl, when there are more than one substituents, the substituents are the same or different; the \u201cheterocycloalkyl\u201d connects to another group via a carbon atom or a heteroatom thereof; the N atom in is oxidized or non-oxidized;\n wherein R 11a  and R 11b  are independently hydrogen, halogen, substituted or unsubstituted C 1 -C 20  alkyl, substituted or unsubstituted C 2 -C 20  alkenyl, substituted or unsubstituted C 2 -C 20  alkynyl, substituted or unsubstituted C 3 -C 12  cycloalkyl, substituted or unsubstituted C 1 -C 9  heterocycloalkyl, guanidino, thioureido, substituted or unsubstituted C 3 -C 12  aryl, substituted or unsubstituted C 1 -C 9  heteroaryl \n \u2014SeR 26  or \u2014SF 5 ; wherein the \u201cheterocycloalkyl\u201d connects to another group via a carbon atom or a heteroatom thereof; or in R 11a  and R 11b  together with the N atom attached form wherein t and u are independently 1, 2 or 3, R c  is C(R cs ) 2 , NR cs , O, S, Si(R cs ) 2  or Se, each R cs  is independently H, C 1 -C 6  alkyl, or B(OH) 2 ; or, in R 11a  and R 11b  together with the N atom attached form wherein v and w are independently 1, 2 or 3, R cb  is CH or PH 2 , R cx  is CH 2 , O, S or \u2550N\u2014OH, R hc  is H or C 1 -C 6  alkyl; or in R 11a  and R 11b  together with the N atom attached form wherein v1 and w1 are independently 1, 2 or 3, R c1  and R c2  are independently O, NH or N\u2014CN;\n wherein 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 the substituent selected from the group consisting of C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, hydroxy, nitro, carboxyl, formyl, thio, C 1 -C 20  silyl, halogen, \n trifluoromethyl, cyano, C 1 -C 20  alkoxy, C 3 -C 12  cycloalkyl, C 1 -C 9  heterocycloalkyl, C 3 -C 12  aryl, C 1 -C 9  heteroaryl, and \u2014SF 5 , when there are more than one substituents, the substituents are the same or different; wherein the \u201cheterocycloalkyl\u201d connects to another group via a carbon atom or a heteroatom thereof;\n wherein each R 12  is independently hydrogen, halogen, C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, hydroxy, \u2014CF 3 , \u2014SF 5 , C 1 -C 20  alkoxy or \n wherein R 13  is hydrogen, C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, hydroxy, \u2014CF 3 , \u2014SF 5  or wherein each R 14  is independently halogen, C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, hydroxy, \u2014CF 3 , \u2014SF 5 , C 1 -C 20 alkoxy or wherein each R 15 , R 16a  and R 16b  is independently hydrogen, halogen, hydroxy, cyano, nitro, amino, formyl, C 1 -C 20  alkoxy, C 1 -C 20  alkylthio, C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, \u2014CF 3 , \u2014SF 5 , C 3 -C 12  cycloalkyl, or \u201cC 1 -C 9  heterocycloalkyl which is optionally substituted with C 1 -C 20  alkyl\u201d; wherein the \u201cC 1 -C 9  heterocycloalkyl\u201d connects to another group via a carbon atom or a heteroatom thereof;\n wherein R 17a  is independently hydrogen, halogen, hydroxy, cyano, nitro, amino, formyl, C 1 -C 20  alkoxy, C 1 -C 20  alkylthio, C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, \u2014CF 3 , \u2014SF 5 , \u2014SeR 26 , \n C 3 -C 12  cycloalkyl or \u201cC 1 -C 9  heterocycloalkyl which is optionally substituted with C 1 -C 20  alkyl\u201d, wherein the \u201cC 1 -C 9  heterocycloalkyl\u201d connects to another group via a carbon atom or a heteroatom thereof;\n wherein R 17b  is independently hydrogen, halogen, hydroxy, cyano, nitro, amino, formyl, C 1 -C 20  alkoxy, C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, \u2014CF 3 , \u2014SF 5 , \n \u2014OR 28 , C 3 -C 12  cycloalkyl or \u201cC 1 -C 9  heterocycloalkyl which is optionally substituted with C 1 -C 20  alkyl\u201d, wherein the \u201cC 1 -C 9  heterocycloalkyl\u201d connects to another group via a carbon atom or a heteroatom thereof;\n or, R 17a  and R 17b  together with the carbon atom, N atom attached form substituted or unsubstituted C 1 -C 9  heterocycloalkyl; wherein the \u201csubstituted\u201d in the \u201csubstituted or unsubstituted C 1 -C 9  heterocycloalkyl\u201d refers to be independently substituted with the substituent selected from the group consisting of C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, hydroxy, nitro, carboxyl, formyl, thio, C 1 -C 20  silyl, halogen, \n trifluoromethyl, cyano, C 1 -C 20  alkoxy, C 3 -C 12  cycloalkyl, C 1 -C 9  heterocycloalkyl, C 3 -C 12  aryl, C 1 -C 9  heteroaryl, \u2014SeR 26 , and \u2014SF 5 , when there are more than one substituents, the substituents are the same or different; wherein the \u201csubstituted or unsubstituted C 1 -C 9  heterocycloalkyl\u201d connects to another group via a carbon atom or a heteroatom thereof;\n wherein R 18a  and R 18b  are independently hydrogen, halogen, hydroxy, cyano, C 1 -C 20  alkoxy, C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, \u2014CF 3 , \u2014SF 5 , C 3 -C 12  cycloalkyl or \u201cC 1 -C 9  heterocycloalkyl which is optionally substituted with C 1 -C 20  alkyl\u201d; wherein the \u201cC 1 -C 9  heterocycloalkyl\u201d connects to another group via a carbon atom or a heteroatom thereof; \n or, R 18a  and R 18b  together with the heteroatom attached form substituted or unsubstituted C 1 -C 9  heterocycloalkyl; wherein the \u201csubstituted\u201d in the \u201csubstituted or unsubstituted C 1 -C 9  heterocycloalkyl\u201d refers to be independently substituted with the substituent selected from the group consisting of C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, hydroxy, nitro, carboxyl, formyl, thio, C 1 -C 20  silyl, halogen, \n trifluoromethyl, cyano, C 1 -C 20  alkoxy, C 3 -C 12  cycloalkyl, C 1 -C 9  heterocycloalkyl, C 3 -C 12  aryl, C 1 -C 9  heteroaryl, \u2014SeR 26 , and \u2014SF 5 , when there are more than one substituents, the substituents are the same or different; wherein the \u201cC 1 -C 9  heterocycloalkyl\u201d connects to another group via a carbon atom or a heteroatom thereof;\n wherein R 19  is C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, C 3 -C 12  cycloalkyl, C 1 -C 9  heterocycloalkyl, C 3 -C 12  aryl, C 1 -C 9  heteroaryl; \n wherein R 20  is independently hydrogen, halogen, C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 2 -C 20 alkynyl, hydroxy, \u2014CF 3 , \u2014SF 5 , C 3 -C 5  heteroaryl, C 1 -C 20  alkoxy or \n wherein R 21  is independently halogen, C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, hydroxy, \u2014CF 3 , \u2014SF 5 , C 1 -C 20  alkoxy or wherein R 22 , R 23a  and R 23b  are independently hydrogen, halogen, hydroxy, cyano, nitro, amino, formyl, C 1 -C 20  alkoxy, C 1 -C 20  alkylthio, C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, \u2014CF 3 , \u2014SF 5 , C 3 -C 12  cycloalkyl, or \u201cC 1 -C 9  heterocycloalkyl which is optionally substituted with C 1 -C 20  alkyl\u201d; wherein the \u201cC 1 -C 9  heterocycloalkyl\u201d connects to another group via a carbon atom or a heteroatom thereof;\n wherein R 24a  is independently hydrogen, halogen, hydroxy, cyano, nitro, amino, formyl, C 1 -C 20  alkoxy, C 1 -C 20  alkylthio, C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, \u2014CF 3 , \u2014SF 5 , \n \u2014SeR 31 , C 3 -C 12  cycloalkyl or \u201cC 1 -C 9  heterocycloalkyl which is optionally substituted with C 1 -C 20  alkyl\u201d; wherein the \u201cC 1 -C 9  heterocycloalkyl\u201d connects to another group via a carbon atom or a heteroatom thereof;\n wherein R 24b  is independently hydrogen, halogen, hydroxy, cyano, nitro, amino, formyl, C 1 -C 20  alkoxy, C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, \u2014CF 3 , \u2014SF 5 , \n \u2014OR 32 , C 3 -C 12  cycloalkyl or \u201cC 1 -C 9  heterocycloalkyl which is optionally substituted with C 1 -C 20  alkyl\u201d; wherein the \u201cC 1 -C 9  heterocycloalkyl\u201d connects to another group via a carbon atom or a heteroatom thereof;\n or, R 24a  and R 24b  together with the carbon atom, N atom attached form substituted or unsubstituted C 1 -C 9  heterocycloalkyl; wherein, the \u201csubstituted\u201d in the \u201csubstituted or unsubstituted C 1 -C 9  heterocycloalkyl\u201d refers to be independently substituted with the substituent selected from the group consisting of halogen, hydroxy, cyano, nitro, amino, formyl, carboxyl, thio, C 1 -C 20  silyl, C 1 -C 20  alkoxy, C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, \u2014CF 3 , \u2014SF 5 , \n \u2014OR 32 , C 3 -C 12  cycloalkyl, C 1 -C 9  heterocycloalkyl, C 3 -C 12  aryl, C 1 -C 9  heteroaryl, \u2014SeR 31 , \u201cC 1 -C 20  alkyl mono-substituted, di-substituted or unsubstituted amino\u201d and \u2014SF 5 , when there are more than one substituents, the substituents are the same or different; wherein the \u201csubstituted or unsubstituted C 1 -C 9  heterocycloalkyl\u201d connects to another group via a carbon atom or a heteroatom thereof;\n wherein R 25a  and R 25b  are independently hydrogen, halogen, hydroxy, cyano, C 1 -C 20  alkoxy, C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, \u2014CF 3 , \u2014SF 5 , C 3 -C 12  cycloalkyl or \u201cC 1 -C 9  heterocycloalkyl which is optionally substituted with C 1 -C 20  alkyl\u201d; wherein the \u201cC 1 -C 9  heterocycloalkyl\u201d connects to another group via a carbon atom or a heteroatom thereof; \n or, R 25a  and R 25b  together with the heteroatom attached form substituted or unsubstituted C 1 -C 9  heterocycloalkyl; wherein the \u201csubstituted\u201d in the \u201csubstituted or unsubstituted C 1 -C 9  heterocycloalkyl\u201d refers to be independently substituted with the substituent selected from the group consisting of halogen, hydroxy, cyano, nitro, amino, formyl, carboxyl, thio, C 1 -C 20  silyl, C 1 -C 20  alkoxy, C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, \u2014CF 3 , \u2014SF 5 , \n OR 32 , C 3 -C 12  cycloalkyl, C 1 -C 9  heterocycloalkyl, C 3 -C 12  aryl, C 1 -C 9  heteroaryl, \u2014SeR 31 , \u201cC 1 -C 20  alkyl mono-substituted, di-substituted or unsubstituted amino\u201d and \u2014SF 5 , when there are more than one substituents, the substituents are the same or different; wherein the \u201cC 1 -C 9  heterocycloalkyl\u201d connects to another group via a carbon atom or a heteroatom thereof;\n wherein R 26  is independently C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, C 3 -C 12  cycloalkyl, C 1 -C 9  heterocycloalkyl, C 3 -C 12  aryl or C 1 -C 9  heteroaryl; \n wherein R 27a  and R 27b  are independently hydrogen, halogen, hydroxy, cyano, formyl, C 1 -C 20  alkoxy, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, \u2014CF 3 , \u2014SF 5 , C 3 -C 12  cycloalkyl, substituted or unsubstituted C 1 -C 9  heterocycloalkyl, \n or substituted or unsubstituted C 1 -C 20  alkyl; wherein the \u201csubstituted\u201d in the \u201csubstituted or unsubstituted C 1 -C 20  alkyl\u201d and \u201csubstituted or unsubstituted C 1 -C 9  heterocycloalkyl\u201d refers to be independently substituted with the substituent selected from the group consisting of halogen, C 1 -C 20  alkoxy, C 1 -C 20  alkylthio and C 1 -C 20  silyl, when there are more than one substituents, the substituents are the same or different; wherein the \u201cC 1 -C 9  heterocycloalkyl\u201d connects to another group via a carbon atom or a heteroatom thereof;\n wherein R 28  is independently C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, or substituted or unsubstituted C 1 -C 20  silyl; wherein the substituent in the \u201csubstituted or unsubstituted C 1 -C 20  silyl\u201d is C 2 -C 20  alkenyl or C 2 -C 20  alkynyl; \n wherein R 29a  and R 29b  are independently hydrogen, halogen, hydroxy, cyano, formyl, C 1 -C 20  alkoxy, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, \u2014CF 3 , \u2014SF 5 , C 3 -C 12  cycloalkyl, substituted or unsubstituted C 1 -C 9  heterocycloalkyl, or substituted or unsubstituted C 1 -C 20  alkyl; wherein the \u201csubstituted\u201d in the \u201csubstituted or unsubstituted C 1 -C 20  alkyl\u201d and \u201csubstituted or unsubstituted C 1 -C 9  heterocycloalkyl\u201d refers to be independently substituted with the substituent selected from the group consisting of halogen, C 1 -C 20  alkoxy, C 1 -C 20  alkylthio and C 1 -C 20  sily, when there are more than one substituents, the substituents are the same or different; wherein the \u201cC 1 -C 9  heterocycloalkyl\u201d connects to another group via a carbon atom or a heteroatom thereof; \n wherein R 30  is independently hydrogen, hydroxy, C 1 -C 20  alkyl which is optionally substituted with halogen, or C 1 -C 20  alkyl mono-substituted, di-substituted or unsubstituted amino; \n wherein R 31  is independently hydrogen, cyano, nitro, hydroxy, C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, C 3 -C 12  cycloalkyl, C 1 -C 9  heterocycloalkyl, C 6 -C 12  aryl or C 1 -C 9  heteroaryl; \n wherein R 32  is independently C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, or substituted or unsubstituted C 1 -C 20  silyl; wherein the substituent in the \u201csubstituted or unsubstituted C 1 -C 20  silyl\u201d is C 2 -C 20  alkenyl or C 2 -C 20  alkynyl; \n wherein each of R 33a  and R 33b  is independently hydrogen, hydroxy, cyano, nitro, halogen, C 1 -C 20  alkyl, C 2 -C 20  alkenyl, C 2 -C 20  alkynyl, C 1 -C 20  alkoxy, C 3 -C 12  cycloalkyl, C 1 -C 9  heterocycloalkyl, C 6 -C 12  aryl or C 1 -C 9  heteroaryl; \n R 6a , R 6b , R 6c  and R 6d  are independently hydrogen, hydroxy, C 1 -C 20  alkyl, C 3 -C 12  cycloalkyl or C 3 -C 12  heterocycloalkyl, but R 6a  and R 6b  are not hydroxy at the same time, R 6c  and R 6d  are not hydroxyl at the same time; or R 6a  and R 6b  together with the carbon atom attached form carbonyl; or R 6c  and R 6d  together with the carbon atom attached form carbonyl; \n the number of the heteroatom in the \u201cheterocycloalkyl\u201d, \u201cheteroaryl\u201d is 1 to 7 selected from the group consisting of oxygen, nitrogen, phosphorus, sulfur, selenium, boron and silicon; \n and, compound I is not selected from the group consisting of

Metadata:
- Claim Count in Document: 1.0
- Percentile: 94.0
- Lexical Diversity: 1.8
- Patent Class: 514.0
- Transitional Phrase Type: closed
- Component Type: 1
- Foreign Priority: True
- Related Applications: ['12723137', '14132877', '14883720', '10572958', '15612670']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.8404364519290205
- 35 USC 102 Novelty (BERT): 0.5333212300275115
- Combined Prediction Score: 0.8097249297388696
- Mean Citation Score: 369.647188
- Max Citation Score: 375.8492
- Similarity Product: 251.8925172141552

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