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Correction to “Discovery of SHP2-D26 as a First, Potent, and Effective PROTAC Degrader of SHP2 Protein”
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2020-12-23 , DOI: 10.1021/acs.jmedchem.0c02108 Mingliang Wang , Jianfeng Lu , Mi Wang , Chao-Yie Yang , Shaomeng Wang
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2020-12-23 , DOI: 10.1021/acs.jmedchem.0c02108 Mingliang Wang , Jianfeng Lu , Mi Wang , Chao-Yie Yang , Shaomeng Wang
Page 7510. SHP2-D26. The stereochemistry of SHP2-D26 in the TOC graphic was incorrect, and the correct TOC graphic is shown below. Similarly, the incorrect stereochemistry also appeared in the naming of the following compounds in the experimental part and the SMILE file in the Supporting Information. The correct compound names are shown below. N1-(3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)-N3-(4-(((S)-1-((2S,4R)-4-hydroxy-2-(((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-4-oxobutyl)malonamide (8). N1-(3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)-N3-(5-(((S)-1-((2S,4R)-4-hydroxy-2-(((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-5-oxopentyl)malonamide (9). N1-(3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)-N3-(6-(((S)-1-((2S,4R)-4-hydroxy-2-(((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-6-oxohexyl)malonamide (10). N1-(3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)-N3-(7-(((S)-1-((2S,4R)-4-hydroxy-2-(((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-7-oxoheptyl)malonamide (11). N1-(3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)-N3-(8-(((S)-1-((2S,4R)-4-hydroxy-2-(((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-8-oxooctyl)malonamide (12). N1-(3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)-N3-(9-(((S)-1-((2S,4R)-4-hydroxy-2-(((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-9-oxononyl)malonamide (13). N1-(3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)-N3-(10-(((S)-1-((2S,4R)-4-hydroxy-2-(((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-10-oxodecyl)malonamide (14). N1-(3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)-N3-(11-(((S)-1-((2S,4R)-4-hydroxy-2-(((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-11-oxoundecyl)malonamide (15). N1-(3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)-N3-(12-(((S)-1-((2S,4R)-4-hydroxy-2-(((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-12-oxododecyl)malonamide (16). N1-(3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)-N4-(11-(((S)-1-((2S,4R)-4-hydroxy-2-(((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-11-oxoundecyl)succinamide (17). N1-(3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)-N4-(12-(((S)-1-((2S,4R)-4-hydroxy-2-(((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-12-oxododecyl)succinamide (18). N1-(3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)-N5-(12-(((S)-1-((2S,4R)-4-hydroxy-2-(((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-12-oxododecyl)glutaramide (19). N1-(3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)-N4-((S)-13-((2S,4R)-4-hydroxy-2-(((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)carbamoyl)pyrrolidine-1-carbonyl)-14,14-dimethyl-11-oxo-3,6,9-trioxa-12-azapentadecyl)succinamide (20). N1-(3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)-N4-((S)-14-((2S,4R)-4-hydroxy-2-(((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)carbamoyl)pyrrolidine-1-carbonyl)-15,15-dimethyl-12-oxo-3,6,9-trioxa-13-azahexadecyl)succinamide (21). N1-(3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)-N4-((S)-17-((2S,4R)-4-hydroxy-2-(((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)carbamoyl)pyrrolidine-1-carbonyl)-18,18-dimethyl-15-oxo-3,6,9,12-tetraoxa-16-azanonadecyl)succinamide (22). (2S,4R)-1-((S)-2-(11-(4-(2-((3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)amino)-2-oxoethyl)piperazin-1-yl)undecanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide (23). (2S,4R)-1-((S)-2-(12-(4-(2-((3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)amino)-2-oxoethyl)piperazin-1-yl)dodecanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide (24). N1-(3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)-N16-((S)-1-((2S,4R)-4-hydroxy-2-(((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)hexadecanediamide (25). (2S,4R)-1-((S)-2-(9-(4-(4-((3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)amino)-4-oxobutanoyl)piperazin-1-yl)nonanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide (26). (2S,4R)-1-((S)-2-(10-(4-(4-((3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)amino)-4-oxobutanoyl)piperazin-1-yl)decanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide (27). N1-(3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)-N4-(4-((8-(((S)-1-((2S,4R)-4-hydroxy-2-(((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-8-oxooctyl)oxy)phenyl)succinamide (28). N1-(3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)-N4-(4-(4-(5-(((S)-1-((2S,4R)-4-hydroxy-2-(((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-5-oxopentyl)piperazin-1-yl)butyl)succinamide (29). (2S,4R)-1-((S)-2-(6-aminohexanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide hydrochloride (43d). (2S,4R)-1-((S)-2-(7-aminoheptanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide hydrochloride (43e). (2S,4R)-1-((S)-2-(8-aminooctanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide hydrochloride (43f). (2S,4R)-1-((S)-2-(9-aminononanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide hydrochloride (43g). (2S,4R)-1-((S)-2-(10-aminodecanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide hydrochloride (43h). (2S,4R)-1-((S)-2-(12-aminododecanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide hydrochloride (43j). (2S,4R)-1-((S)-14-amino-2-(tert-butyl)-4-oxo-6,9,12-trioxa-3-azatetradecanoyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide hydrochloride (48). (2S,4R)-1-((S)-1-amino-14-(tert-butyl)-12-oxo-3,6,9-trioxa-13-azapentadecan-15-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide hydrochloride (50a). (2S,4R)-1-((S)-1-amino-17-(tert-butyl)-15-oxo-3,6,9,12-tetraoxa-16-azaoctadecan-18-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide hydrochloride (50b). (2S,4R)-1-((S)-2-(9-(4l4-piperazin-1-yl)nonanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide hydrochloride (60a). (2S,4R)-1-((S)-2-(10-(4l4-piperazin-1-yl)decanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide hydrochloride (60b). (2S,4R)-1-((S)-2-(8-(4-aminophenoxy)octanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide hydrochloride (64). (2S,4R)-1-((S)-2-(5-(4-(4-aminobutyl)piperazin-1-yl)pentanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide hydrochloride (68). Page 7518. The structure of compound 28 in Scheme 6 should be corrected as shown below. The structures of compound 16 and compound 26 in the Supporting Information H NMR and C NMR data should be also correspondingly corrected as shown below. The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.jmedchem.0c02108.
中文翻译:
更正为“发现SHP2-D26作为SHP2蛋白的第一个有效的PROTAC降解剂”
第7510页。SHP2-D26。TOC图形中SHP2-D26的立体化学不正确,正确的TOC图形如下所示。同样,在实验部分中以下化合物的命名以及支持信息中的SMILE文件中,也出现了不正确的立体化学。正确的化合物名称如下所示。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫基)-2-氯苯基)-N3-(4-(((S) -1-((2 S,4 R)-4-羟基-2-(((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基) -3,3-二甲基-1-氧代丁烷-2-基)氨基)-4-氧代丁基)丙二酰胺(8)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫代)-2-氯苯基)-N3-(5-(((S) -1-((2 S,4 R)-4-羟基-2-((((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基)-3,3-二甲基-1-氧丁丁-2-基)氨基)-5-氧戊基)丙二酰胺(9)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫代)-2-氯苯基)-N3-(6-(((S) -1-((2 S,4 R)-4-羟基-2-(((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基) -3,3-二甲基-1-氧代丁烷-2-基)氨基)-6-氧己基)丙二酰胺(10)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫基)-2-氯苯基)-N3-(7-(((S) -1-((2 S,4 R)-4-羟基-2-(((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基) -3,3-二甲基-1-氧代丁烷-2-基)氨基)-7-氧庚基)丙二酰胺(11)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫基)-2-氯苯基)-N3-(8-(((S) -1-((2 S,4 R)-4-羟基-2-(((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基) -3,3-二甲基-1-氧代丁烷-2-基)氨基)-8-氧代辛基)丙二酰胺(12)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫基)-2-氯苯基)-N3-(9-(((S) -1-((2 S,4 R)-4-羟基-2-(((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基) -3,3-二甲基-1-氧代丁烷-2-基)氨基)-9-氧酮基)丙二酰胺(13)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫基)-2-氯苯基)-N3-(10-(((S) -1-((2 S,4 R)-4-羟基-2-((((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基)-3,3-二甲基-1-氧丁烷-2-基)氨基)-10-氧代十二烷基)丙二酰胺(14)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫代)-2-氯苯基)-N3-(11-(((S) -1-((2 S,4 R)-4-羟基-2-(((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基) -3,3-二甲基-1-氧代丁烷-2-基)氨基)-11-氧代十一烷基)丙二酰胺(15)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫基)-2-氯苯基)-N3-(12-(((S) -1-((2 S,4 R)-4-羟基-2-(((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基) -3,3-二甲基-1-氧丁烷-2-基)氨基)-12-氧十二烷基)丙二酰胺(16)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫基)-2-氯苯基)-N4-(11-(((S) -1-((2 S,4 R)-4-羟基-2-(((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基) -3,3-二甲基-1-氧代丁烷-2-基)氨基)-11-氧杂环丁烷基)琥珀酰胺(17)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫代)-2-氯苯基)-N4-(12-(((S) -1-((2 S,4 R)-4-羟基-2-(((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基) -3,3-二甲基-1-氧代丁烷-2-基)氨基)-12-氧十二烷基)琥珀酰胺(18)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫代)-2-氯苯基)-N5-(12-(((S) -1-((2 S,4 R)-4-羟基-2-((((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基)-3,3-二甲基-1-氧丁烷-2-基)氨基)-12-氧十二烷基)戊二酰胺(19)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫代)-2-氯苯基)-N4-(((S)-13-( (2 S,4 R)-4-羟基-2-((((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-羰基)-14,14 -二甲基-11-氧代-3,6,9-三氧杂-12-氮杂十五烷基)琥珀酰胺(20)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫代)-2-氯苯基)-N4-((S)-14-( (2 S,4 R)-4-羟基-2-((((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-羰基)-15,15 -二甲基-12-氧代-3,6,9-三氧杂-13-氮杂十六烷基)琥珀酰胺(21)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫代)-2-氯苯基)-N4-((S)-17-( (2 S,4 R)-4-羟基-2-((((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-羰基)-18,18 -二甲基-15-氧代-3,6,9,12-四氧杂-16-氮杂十二烷基)琥珀酰胺(22)。(2 S,4 R)-1-((S)-2-(11-(4-(2-((3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫代)-2-氯苯基)氨基)-2-氧乙基)哌嗪-1-基)十一烷酰胺基)-3,3-二甲基丁酰基)-4-羟基-N-((S)-1- (4-(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺(23)。(2 S,4 R)-1-((S)-2-(12-(4-(2-((3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫基)-2-氯苯基)氨基)-2-氧乙基)哌嗪-1-基)十二烷酰胺基)-3,3-二甲基丁酰基)-4-羟基-N-((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺(24)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫代)-2-氯苯基)-N16-((S)-1-( (2 S,4 R)-4-羟基-2-(((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基)-3,3 -二甲基-1-氧代丁烷-2-基)十六烷二酰胺(25)。(2 S,4 R)-1-((S)-2-(9-(4-(4-((3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫基)-2-氯苯基)氨基)-4-氧代丁酰基)哌嗪-1-基)壬酰胺基)-3,3-二甲基丁酰基)-4-羟基-N-((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺(26)。(2 S,4 R)-1-((S)-2-(10-(4-(4-((3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫代)-2-氯苯基)氨基)-4-氧代丁酰基)哌嗪-1-基)癸酰胺基)-3,3-二甲基丁酰基)-4-羟基-N-((S)-1- (4-(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺(27)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫代)-2-氯苯基)-N4-(4-((8-( ((S)-1-((2 S,4 R)-4-羟基-2-((((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基)-3,3-二甲基-1-氧丁烷-2-基)氨基)-8-氧代辛基)氧基)苯基)琥珀酰胺(28)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫基)-2-氯苯基)-N4-(4-(4-(5 -((((S)-1-((2 S,4 R)-4-羟基-2-(((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基)-3,3-二甲基-1-氧丁烷-2-基)氨基)-5-氧戊基)哌嗪-1-基)丁基)琥珀酰胺(29)。(2 S,4 R)-1-((S)-2-(6-氨基六氨基)-3,3-二甲基丁酰基)-4-羟基-N-((S)-1-(4-(4-甲基噻唑) -5-基)苯基)乙基)吡咯烷-2-羧酰胺盐酸盐(43d)。(2 S,4 R)-1-((S)-2-(7-氨基庚酰胺基)-3,3-二甲基丁酰基)-4-羟基-N-((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺盐酸盐(43e)。(2 S,4 R)-1-((S)-2-(8-氨基辛基氨基)-3,3-二甲基丁酰基)-4-羟基-N-((S)-1-(4-(4-甲基噻唑) -5-基)苯基)乙基)吡咯烷-2-羧酰胺盐酸盐(43f)。(2 S,4 R)-1-((S)-2-(9-氨基壬酰胺基)-3,3-二甲基丁酰基)-4-羟基-N-((S)-1-(4-(4-甲基噻唑) -5-基)苯基)乙基)吡咯烷-2-羧酰胺盐酸盐(43g)。(2 S,4 R)-1-((S)-2-(10-氨基十氨基)-3,3-二甲基丁酰基)-4-羟基-N-((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺盐酸盐(43h)。(2 S,4 R)-1-((S)-2-(12-氨基十二烷酰胺基)-3,3-二甲基丁酰基)-4-羟基-N-((S)-1-(4-(4-甲基噻唑) -5-基)苯基)乙基)吡咯烷-2-羧酰胺盐酸盐(43j)。(2 S,4 R)-1-((S)-14-氨基-2-(叔丁基)-4-氧代-6,9,12-三氧杂-3-azatetradecanoyl)-4-羟基-N- ((S)-1-(4-(4-(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺盐酸盐(48)。(2 S,4 R)-1-((S)-1-氨基-14-(叔-丁基)-12-氧代-3,6,9-三氧杂-13-氮杂十五烷-15-酰基)-4-羟基-N-((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺盐酸盐(50a)。(2 S,4 R)-1-((S)-1-氨基-17-(叔丁基)-15-氧代-3,6,9,12-四氧杂-16-氮杂十八烷-18-oyl)- 4-羟基-N-((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺盐酸盐(50b)。(2 S,4 R)-1-((S)-2-(9-(4l4-哌嗪-1-基)壬酰胺基)-3,3-二甲基丁酰基)-4-羟基-N-((S- 1-(4-(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺盐酸盐(60a)。(2 S,4 R)-1-((S)-2-(10-(4l4-哌嗪-1-基)癸酰胺基)-3,3-二甲基丁酰基)-4-羟基-N-((S)-1-(4-( 4-甲基噻唑-5-基)苯基)乙基吡咯烷-2-羧酰胺盐酸盐(60b)。(2 S,4 R)-1-((S)-2-(8-(4-氨基苯氧基)辛酰胺基)-3,3-二甲基丁酰基)-4-羟基-N-((S)-1-(4 -(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺盐酸盐(64)。(2 S,4 R)-1-((S)-2-(5-(4-(4-氨基丁基)哌嗪-1-基)戊酰胺)-3,3-二甲基丁酰基)-4-羟基-N- ((S)-1-(4-(4-(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺盐酸盐(68)。页面7518.化合物的结构28在方案6应该如下所示更正。支持信息H NMR和C NMR数据中化合物16和化合物26的结构也应进行相应校正,如下所示。可从https://pubs.acs.org/doi/10.1021/acs.jmedchem.0c02108免费获得支持信息。
更新日期:2021-01-14
- SMILE, molecule type, SHP2 allosteric inhibition, DC50 values (CSV)
- SMILE, molecule type, SHP2 allosteric inhibition, DC50 values (CSV)
中文翻译:
更正为“发现SHP2-D26作为SHP2蛋白的第一个有效的PROTAC降解剂”
第7510页。SHP2-D26。TOC图形中SHP2-D26的立体化学不正确,正确的TOC图形如下所示。同样,在实验部分中以下化合物的命名以及支持信息中的SMILE文件中,也出现了不正确的立体化学。正确的化合物名称如下所示。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫基)-2-氯苯基)-N3-(4-(((S) -1-((2 S,4 R)-4-羟基-2-(((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基) -3,3-二甲基-1-氧代丁烷-2-基)氨基)-4-氧代丁基)丙二酰胺(8)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫代)-2-氯苯基)-N3-(5-(((S) -1-((2 S,4 R)-4-羟基-2-((((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基)-3,3-二甲基-1-氧丁丁-2-基)氨基)-5-氧戊基)丙二酰胺(9)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫代)-2-氯苯基)-N3-(6-(((S) -1-((2 S,4 R)-4-羟基-2-(((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基) -3,3-二甲基-1-氧代丁烷-2-基)氨基)-6-氧己基)丙二酰胺(10)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫基)-2-氯苯基)-N3-(7-(((S) -1-((2 S,4 R)-4-羟基-2-(((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基) -3,3-二甲基-1-氧代丁烷-2-基)氨基)-7-氧庚基)丙二酰胺(11)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫基)-2-氯苯基)-N3-(8-(((S) -1-((2 S,4 R)-4-羟基-2-(((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基) -3,3-二甲基-1-氧代丁烷-2-基)氨基)-8-氧代辛基)丙二酰胺(12)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫基)-2-氯苯基)-N3-(9-(((S) -1-((2 S,4 R)-4-羟基-2-(((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基) -3,3-二甲基-1-氧代丁烷-2-基)氨基)-9-氧酮基)丙二酰胺(13)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫基)-2-氯苯基)-N3-(10-(((S) -1-((2 S,4 R)-4-羟基-2-((((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基)-3,3-二甲基-1-氧丁烷-2-基)氨基)-10-氧代十二烷基)丙二酰胺(14)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫代)-2-氯苯基)-N3-(11-(((S) -1-((2 S,4 R)-4-羟基-2-(((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基) -3,3-二甲基-1-氧代丁烷-2-基)氨基)-11-氧代十一烷基)丙二酰胺(15)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫基)-2-氯苯基)-N3-(12-(((S) -1-((2 S,4 R)-4-羟基-2-(((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基) -3,3-二甲基-1-氧丁烷-2-基)氨基)-12-氧十二烷基)丙二酰胺(16)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫基)-2-氯苯基)-N4-(11-(((S) -1-((2 S,4 R)-4-羟基-2-(((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基) -3,3-二甲基-1-氧代丁烷-2-基)氨基)-11-氧杂环丁烷基)琥珀酰胺(17)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫代)-2-氯苯基)-N4-(12-(((S) -1-((2 S,4 R)-4-羟基-2-(((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基) -3,3-二甲基-1-氧代丁烷-2-基)氨基)-12-氧十二烷基)琥珀酰胺(18)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫代)-2-氯苯基)-N5-(12-(((S) -1-((2 S,4 R)-4-羟基-2-((((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基)-3,3-二甲基-1-氧丁烷-2-基)氨基)-12-氧十二烷基)戊二酰胺(19)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫代)-2-氯苯基)-N4-(((S)-13-( (2 S,4 R)-4-羟基-2-((((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-羰基)-14,14 -二甲基-11-氧代-3,6,9-三氧杂-12-氮杂十五烷基)琥珀酰胺(20)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫代)-2-氯苯基)-N4-((S)-14-( (2 S,4 R)-4-羟基-2-((((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-羰基)-15,15 -二甲基-12-氧代-3,6,9-三氧杂-13-氮杂十六烷基)琥珀酰胺(21)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫代)-2-氯苯基)-N4-((S)-17-( (2 S,4 R)-4-羟基-2-((((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-羰基)-18,18 -二甲基-15-氧代-3,6,9,12-四氧杂-16-氮杂十二烷基)琥珀酰胺(22)。(2 S,4 R)-1-((S)-2-(11-(4-(2-((3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫代)-2-氯苯基)氨基)-2-氧乙基)哌嗪-1-基)十一烷酰胺基)-3,3-二甲基丁酰基)-4-羟基-N-((S)-1- (4-(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺(23)。(2 S,4 R)-1-((S)-2-(12-(4-(2-((3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫基)-2-氯苯基)氨基)-2-氧乙基)哌嗪-1-基)十二烷酰胺基)-3,3-二甲基丁酰基)-4-羟基-N-((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺(24)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫代)-2-氯苯基)-N16-((S)-1-( (2 S,4 R)-4-羟基-2-(((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基)-3,3 -二甲基-1-氧代丁烷-2-基)十六烷二酰胺(25)。(2 S,4 R)-1-((S)-2-(9-(4-(4-((3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫基)-2-氯苯基)氨基)-4-氧代丁酰基)哌嗪-1-基)壬酰胺基)-3,3-二甲基丁酰基)-4-羟基-N-((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺(26)。(2 S,4 R)-1-((S)-2-(10-(4-(4-((3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫代)-2-氯苯基)氨基)-4-氧代丁酰基)哌嗪-1-基)癸酰胺基)-3,3-二甲基丁酰基)-4-羟基-N-((S)-1- (4-(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺(27)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫代)-2-氯苯基)-N4-(4-((8-( ((S)-1-((2 S,4 R)-4-羟基-2-((((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基)-3,3-二甲基-1-氧丁烷-2-基)氨基)-8-氧代辛基)氧基)苯基)琥珀酰胺(28)。N1-(3-((3-氨基-5-(4-氨基-4-甲基哌啶-1-基)吡嗪-2-基)硫基)-2-氯苯基)-N4-(4-(4-(5 -((((S)-1-((2 S,4 R)-4-羟基-2-(((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)氨基甲酰基)吡咯烷-1-基)-3,3-二甲基-1-氧丁烷-2-基)氨基)-5-氧戊基)哌嗪-1-基)丁基)琥珀酰胺(29)。(2 S,4 R)-1-((S)-2-(6-氨基六氨基)-3,3-二甲基丁酰基)-4-羟基-N-((S)-1-(4-(4-甲基噻唑) -5-基)苯基)乙基)吡咯烷-2-羧酰胺盐酸盐(43d)。(2 S,4 R)-1-((S)-2-(7-氨基庚酰胺基)-3,3-二甲基丁酰基)-4-羟基-N-((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺盐酸盐(43e)。(2 S,4 R)-1-((S)-2-(8-氨基辛基氨基)-3,3-二甲基丁酰基)-4-羟基-N-((S)-1-(4-(4-甲基噻唑) -5-基)苯基)乙基)吡咯烷-2-羧酰胺盐酸盐(43f)。(2 S,4 R)-1-((S)-2-(9-氨基壬酰胺基)-3,3-二甲基丁酰基)-4-羟基-N-((S)-1-(4-(4-甲基噻唑) -5-基)苯基)乙基)吡咯烷-2-羧酰胺盐酸盐(43g)。(2 S,4 R)-1-((S)-2-(10-氨基十氨基)-3,3-二甲基丁酰基)-4-羟基-N-((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺盐酸盐(43h)。(2 S,4 R)-1-((S)-2-(12-氨基十二烷酰胺基)-3,3-二甲基丁酰基)-4-羟基-N-((S)-1-(4-(4-甲基噻唑) -5-基)苯基)乙基)吡咯烷-2-羧酰胺盐酸盐(43j)。(2 S,4 R)-1-((S)-14-氨基-2-(叔丁基)-4-氧代-6,9,12-三氧杂-3-azatetradecanoyl)-4-羟基-N- ((S)-1-(4-(4-(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺盐酸盐(48)。(2 S,4 R)-1-((S)-1-氨基-14-(叔-丁基)-12-氧代-3,6,9-三氧杂-13-氮杂十五烷-15-酰基)-4-羟基-N-((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺盐酸盐(50a)。(2 S,4 R)-1-((S)-1-氨基-17-(叔丁基)-15-氧代-3,6,9,12-四氧杂-16-氮杂十八烷-18-oyl)- 4-羟基-N-((S)-1-(4-(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺盐酸盐(50b)。(2 S,4 R)-1-((S)-2-(9-(4l4-哌嗪-1-基)壬酰胺基)-3,3-二甲基丁酰基)-4-羟基-N-((S- 1-(4-(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺盐酸盐(60a)。(2 S,4 R)-1-((S)-2-(10-(4l4-哌嗪-1-基)癸酰胺基)-3,3-二甲基丁酰基)-4-羟基-N-((S)-1-(4-( 4-甲基噻唑-5-基)苯基)乙基吡咯烷-2-羧酰胺盐酸盐(60b)。(2 S,4 R)-1-((S)-2-(8-(4-氨基苯氧基)辛酰胺基)-3,3-二甲基丁酰基)-4-羟基-N-((S)-1-(4 -(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺盐酸盐(64)。(2 S,4 R)-1-((S)-2-(5-(4-(4-氨基丁基)哌嗪-1-基)戊酰胺)-3,3-二甲基丁酰基)-4-羟基-N- ((S)-1-(4-(4-(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺盐酸盐(68)。页面7518.化合物的结构28在方案6应该如下所示更正。支持信息H NMR和C NMR数据中化合物16和化合物26的结构也应进行相应校正,如下所示。可从https://pubs.acs.org/doi/10.1021/acs.jmedchem.0c02108免费获得支持信息。
- SMILE,分子类型,SHP2变构抑制,DC50值(CSV)
- SMILE,分子类型,SHP2变构抑制,DC50值(CSV)