PATENT CLAIM ANALYSIS

Application Number: 15982043
Application Type: Utility
Filing Date: 2018-05
Publication Date: 2018-09
Patent Classification: ["549", "406000"]

Abstract:
The present invention provides compounds of formula (I), their use as an inhibitor of a p53-MDM2 interaction as well as pharmaceutical compositions comprising said compounds: wherein n, m, p, s, t, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 20 , X, Y, Q and Z have defined meanings.

Claim (Index 1):
A compound of formula (I): including any stereochemically isomeric form thereof, wherein\n m is 0, 1 or 2 and when m is 0 then a direct bond is intended; \n n is 0, 1, 2 or 3 and when n is 0 then a direct bond is intended; \n p is 0 or 1 and when p is 0 then a direct bond is intended; \n s is 0 or 1 and when s is 0 then a direct bond is intended; \n t is 0 or 1 and when t is 0 then a direct bond is intended; \n X is C(\u2550O) or CHR 8 , wherein\n R 8  is selected from hydrogen; C 1-6 alkyl; C 3-7 cycloalkyl; \u2014C(\u2550O)\u2014NR 17 R 18 ; carboxyl; arylC 1-6 alkyloxycarbonyl; heteroaryl; heteroarylcarbonyl; heteroarylC 1-6 alkyloxycarbonyl; piperazinylcarbonyl; pyrrolidinyl; piperidinylcarbonyl; C 1-6 alkyloxycarbonyl; C 1-6 alkyl substituted with a substituent selected from hydroxy, amino, aryl and heteroaryl; C 3-7 cycloalkyl substituted with a substituent selected from hydroxy, amino, aryl and heteroaryl; piperazinylcarbonyl substituted with a substituent selected from hydroxy, hydroxyC 1-6 alkyl and hydroxyC 1-6 alkyloxyC 1-6 alkyl; pyrrolidinyl substituted with hydroxyC 1-6 alkyl; and piperidinylcarbonyl substituted with one or two substituents selected from hydroxy, C 1-6 alkyl, hydroxyC 1-6 alkyl, C 1-6 alkyloxyC 1-6 alkyl, C 1-6 alkyl(dihydroxy)C 1-6 alkyl and C 1-6 alkyloxy(hydroxy)C 1-6 alkyl; R 17  and R 18  are each independently selected from hydrogen, C 1-6 alkyl, di(C 1-6 alkyl)aminoC 1-6 alkyl, arylC 1-6 alkyl, C 1-6 alkyloxyC 1-6 alkyl, hydroxyC 1-6 alkyl, hydroxyC 1-6 alkyl(C 1-6 alkyl), or hydroxyC 1-6 alkyl(arylC 1-6 alkyl); \n \n is \u2014CR 9 \u2550C< and then the dotted line is a bond, \u2014C(\u2550O)\u2014CH<, \u2014C(\u2550O)\u2014N<, \u2014CHR 9 \u2014CH<, or \u2014CHR 9 \u2014N<, wherein each R 9  is independently hydrogen or C 1-6 alkyl, or wherein R 9  together with one of R 2  or R 20  form a direct bond; R 1  is hydrogen; aryl; heteroaryl; C 1-6 alkyloxycarbonyl; C 1-12 alkyl; or C 1-12 alkyl substituted with one or two substituents independently selected from hydroxy, aryl, heteroaryl, amino, C 1-6 alkyloxy, mono- or di(C 1-6 alkyl)amino, morpholinyl, piperidinyl, pyrrolidinyl, piperazinyl, C 1-6 alkylpiperazinyl, arylC 1-6 alkylpiperazinyl, heteroarylC 1-6 alkylpiperazinyl, C 3-7 cycloalkyl-piperazinyl and C 3-7 cycloalkylC 1-6 alkylpiperazinyl; R 2  and R 20  are each independently selected from halo, hydroxy, cyano, nitro, carboxyl; polyhaloC 1-6 alkyl, polyhaloC 1-6 alkyloxy; C 1-6 alkyl, C 3-7 cycloalkyl, C 2-6 alkenyl, aryl, heteroaryl, arylC 1-6 alkyl, heteroaryl-C 1-6 alkyl, C 3-7 cycloalkylC 1-6 alkyl, morpholinyl, piperidinyl, pyrrolidinyl, piperazinyl, C 1-6 alkyloxy, aryloxy, heteroaryloxy, C 1-6 alkylthio, arylthio, heteroarylthio, C 1-6 alkylcarbonyl, C 3-7 cycloalkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, C 1-6 alkyloxycarbonyl, C 3-7 cycloalkyloxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, C 1-6 alkylcarbonyloxy, C 3-7 cycloalkylcarbonyloxy, arylcarbonyloxy or heteroarylcarbonyloxy, any of said groups being optionally and independently substituted with one or more, preferably one or two, substituents selected from halo, hydroxy, cyano, nitro, carboxyl, amino, mono- or di(C 1-6 alkyl)amino, C 1-6 alkyl, polyhaloC 1-6 alkyl, aryl, heteroaryl, C 1-6 alkyloxy, C 1-6 alkylcarbonyl, C 1-6 alkyloxycarbonyl and C 1-6 alkylcarbonyloxy; and \u2014(CH 2 ) w \u2014(C(\u2550O)) y NR 21 R 22  wherein\n w is 0, 1, 2, 3, 4, 5 or 6 and when w is 0 then a direct bond is intended; \n y is 0 or 1 and when y is 0 then a direct bond is intended; \n R 21  and R 22  are each independently selected from hydrogen, C 1-6 alkyl, C 3-7 cycloalkyl, C 1-6 alkylcarbonyl and arylC 1-6 alkylcarbonyl, any of said groups being optionally and independently substituted with one or more, preferably one or two, substituents selected from halo, hydroxy, amino, mono- or di(C 1-6 alkyl)amino, C 1-6 alkyl, polyhaloC 1-6 alkyl, C 1-6 alkyloxy, aryl and heteroaryl; \n or R 21  and R 22  together with the nitrogen to which they are attached form morpholinyl, piperidinyl, pyrrolidinyl or piperazinyl, any of said groups being optionally and independently substituted with one or more, preferably one or two, substituents selected from C 1-6 alkyl, polyhaloC 1-6 alkyl, C 1-6 alkyloxy, C 3-7 cycloalkyl, C 3-7 cycloalkylC 1-6 alkyl, arylC 1-6 alkyl and heteroarylC 1-6 alkyl; \n or R 2  and R 20  together with the phenyl ring to which they are attached form a naphthalenyl group, optionally substituted with one or more, preferably one or two, substituents each independently selected from halo, hydroxy, amino, mono- or di(C 1-6 alkyl)amino, C 1-6 alkyl, polyhaloC 1-6 alkyl, C 1-6 alkyloxy, aryl and heteroaryl; or R 2  and R 20  together form a bivalent radical of the formula \u2014(CH 2 ) b \u2014 wherein b is 3, 4 or 5, optionally substituted with one or more, preferably one or two, substituents selected from halo, hydroxy, amino, mono- or di(C 1-6 alkyl)amino, C 1-6 alkyl, polyhaloC 1-6 alkyl,\n C 1-6 alkyloxy, aryl and heteroaryl; \n or one of R 2  or R 20  is as defined above and the other one of R 2  or R 20  together with R 9  form a direct bond; R 3  is hydrogen; C 1-6 alkyl; heteroaryl; C 3-7 cycloalkyl; C 1-6 alkyl substituted with a substituent selected from hydroxy, amino, aryl and heteroaryl; or C 3-7 cycloalkyl substituted with a substituent selected from hydroxy, amino, aryl and heteroaryl; R 4  and R 5  are each independently hydrogen, halo, C 1-6 alkyl, hydroxyC 1-6 alkyl, polyhalo-C 1-6 alkyl, cyano, cyanoC 1-6 alkyl, hydroxy, amino, C 2-6 alkenyl or C 1-6 alkyloxy; or R 4  and R 5  together form a bivalent radical selected from methylenedioxy or ethylenedioxy; R 6  is hydrogen, C 1-6 alkyloxycarbonyl, or C 1-6 alkyl; when p is 1 then R 7  is hydrogen, arylC 1-6 alkyl, hydroxy, or heteroarylC 1-6 alkyl; Z is a radical selected from wherein\n R 10  or R 11  are each independently selected from hydrogen, halo, hydroxy, amino, C 1-6 alkyl, nitro, polyhaloC 1-6 alkyl, cyano, cyanoC 1-6 alkyl, tetrazoloC 1-6 alkyl, aryl, heteroaryl, arylC 1-6 alkyl, heteroarylC 1-6 alkyl, aryl(hydroxy)C 1-6 alkyl, heteroaryl(hydroxy)C 1-6 alkyl, arylcarbonyl, heteroarylcarbonyl, C 1-6 alkylcarbonyl, arylC 1-6 alkylcarbonyl, heteroarylC 1-6 alkylcarbonyl, C 1-6 alkyloxy, C 3-7 cycloalkylcarbonyl, C 3-7 cycloalkyl(hydroxy)C 1-6 alkyl, arylC 1-6 alkyloxyC 1-6 alkyl, C 1-6 alkyloxyC 1-6 alkyloxyC 1-6 alkyl, C 1-6 alkylcarbonyloxyC 1-6 alkyl, C 1-6 alkyloxycarbonylC 1-6 alkyloxyC 1-6 alkyl, hydroxyC 1-6 alkyloxyC 1-6 alkyl, C 1-6 alkyloxycarbonylC 2-6 alkenyl, C 1-6 alkyloxyC 1-6 alkyl, C 1-6 alkyloxycarbonyl, C 1-6 alkylcarbonyloxy, aminocarbonyl, hydroxyC 1-6 alkyl, aminoC 1-6 alkyl, hydroxycarbonyl, hydroxycarbonylC 1-6 alkyl and \u2014(CH 2 ) v \u2014(C(\u2550O)) r \u2014(CHR 19 ) u \u2014NR 13 R 14 , wherein \n \u2003v is 0, 1, 2, 3, 4, 5, or 6 and when v is 0 then a direct bond is intended; \n \u2003r is 0 or 1 and when r is 0 then a direct bond is intended; \n \u2003u is 0, 1, 2, 3, 4, 5, or 6 and when u is 0 then a direct bond is intended; \n \u2003R 19  is hydrogen or C 1-6 alkyl; \n \u2003R 13  and R 14  are each independently selected from hydrogen; C 1-12 alkyl; C 1-6 alkylcarbonyl; C 1-6 alkylsulfonyl; arylC 1-6 alkylcarbonyl; C 3-7 cycloalkyl; C 3-7 cycloalkylcarbonyl; \u2014(CH 2 ) k \u2014NR 15 R 16 ; C 1-12 alkyl substituted with a substituent selected from hydroxy, hydroxycarbonyl, cyano, C 1-6 alkyloxycarbonyl, C 1-6 alkyloxy, aryl or heteroaryl; or C 3-7 cycloalkyl substituted with a substituent selected from hydroxy, C 1-6 alkyloxy, aryl, amino, arylC 1-6 alkyl, heteroaryl or heteroarylC 1-6 alkyl; or \n \u2003R 13  and R 14  together with the nitrogen to which they are attached form morpholinyl, piperidinyl, pyrrolidinyl, piperazinyl, or piperazinyl substituted with a substituent selected from C 1-6 alkyl, arylC 1-6 alkyl, arylC 1-6 alkyloxycarbonyl, heteroarylC 1-6 alkyl, C 3-7 cycloalkyl and C 3-7 cycloalkylC 1-6 alkyl; wherein \n \u2003k is 0, 1, 2, 3, 4, 5, or 6 and when k is 0 then a direct bond is intended; \n \u2003R 15  and R 16  are each independently selected from hydrogen; C 1-12 alkyl; arylC 1-6 alkyloxycarbonyl; C 3-7 cycloalkyl; C 1-12 alkyl substituted with a substituent selected from hydroxy, C 1-6 alkyloxy, aryl, and heteroaryl; and C 3-7 cycloalkyl substituted with a substituent selected from hydroxy, C 1-6 alkyloxy, aryl, arylC 1-6 alkyl, heteroaryl, and heteroarylC 1-6 alkyl; or \n \u2003R 15  and R 16  together with the nitrogen to which they are attached form morpholinyl, piperazinyl, or piperazinyl substituted with C 1-6 alkyloxycarbonyl; \n \u2003R 12  is hydrogen; C 1-6 alkyl; C 3-7 cycloalkyl; C 1-6 alkyl substituted with a substituent selected from hydroxy, amino, C 1-6 alkyloxy and aryl; or C 3-7 cycloalkyl substituted with a substituent selected from hydroxy, amino, aryl and C 1-6 alkyloxy; \n aryl is phenyl or naphthalenyl;\n each phenyl or naphthalenyl can optionally be substituted with one, two or three substituents each independently selected from halo, hydroxy, C 1-6 alkyl, amino, polyhaloC 1-6 alkyl and C 1-6 alkyloxy; and \n each phenyl or naphthalenyl can optionally be substituted with a bivalent radical selected from methylenedioxy and ethylenedioxy; \n heteroaryl is pyridinyl, indolyl, quinolinyl, imidazolyl, furanyl, thienyl, oxadiazolyl, tetrazolyl, benzofuranyl or tetrahydrofuranyl;\n each pyridinyl, indolyl, quinolinyl, imidazolyl, furanyl, thienyl, oxadiazolyl, tetrazolyl, benzofuranyl, or tetrahydrofuranyl can optionally be substituted with one, two or three substituents each independently selected from halo, hydroxy, C 1-6 alkyl, amino, polyhaloC 1-6 alkyl, aryl, arylC 1-6 alkyl or C 1-6 alkyloxy; or \n each pyridinyl, indolyl, quinolinyl, imidazolyl, furanyl, thienyl, benzofuranyl, or tetrahydrofuranyl can optionally be substituted with a bivalent radical selected from methylenedioxy or ethylenedioxy; \n an N-oxide form thereof, an addition salt thereof or a solvate thereof;\n provided that if \n is \u2014CR 9 \u2550C< or \u2014CHR 9 \u2014CH<, then Z is not (a-1), (a-2), (a-3), or (a-4).

Metadata:
- Claim Count in Document: 16.0
- Percentile: 93.0
- Lexical Diversity: 1.53061
- Patent Class: 549.0
- Transitional Phrase Type: none
- Component Type: 0
- Foreign Priority: True
- Related Applications: ['12678961', '12938633', '12678680', '11575552', '12293545']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.8180894263036784
- 35 USC 102 Novelty (BERT): 0.5922313001047345
- Combined Prediction Score: 0.795503613683784
- Mean Citation Score: 491.280192
- Max Citation Score: 504.37778
- Similarity Product: 463.2716554482638

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

Dataset: test