Patent ES-2862469-T3 (ES)
Title: Moduladores de proteólisis a base de imidas y métodos de uso asociados
Inventor: CREWS CRAIG
IPC: C07D495/14
Filed: 2016-06-03
Granted: 2021-10-07
Abstract: Un compuesto seleccionado entre el grupo que consiste en: 2-[(9R)-7-(4-clorofenil)-4,5,13-trimetil-3-tia-1,8,11,12-tetraazatriciclo[8.3.0.02,6]-trideca-2(6),4,7,10,12-pentaen-9- il]-N-[4-({1-[2-(2,6-dioxopiperidin-3-il)-1-oxo-2,3-dihidro-1H-isoindol-4-il]-4,7,10-trioxa-1-azadodecan-12- il}oxi)fenil]acetamida; 2-[(9S)-7-(4-clorofenil)-4,5,13-trimetil-3-tia-1,8,11,12-tetraazatriciclo[8.3.0.02,6]-trideca-2(6),4,7,10,12-pentaen-9- il]-N-[(1S)-1-(4-{5-[2-(2-{[2-(2,6-dioxopiperidin-3-il)-1,3-dioxo-2,3-dihidro-1H-isoindol-4- il]amino}etoxi)etoxi]pirimidin-2-il}fenil)etil]-acetamida; 2-[(9S)-7-(4-clorofenil)-4,5,13-trimetil-3-tia-1,8,11,12-tetraazatriciclo[8.3.0.02,6]-trideca-2(6),4,7,10,12-pentaen-9- il]-N-{2-[2-(2-{[2-(2,6-dioxopiperidin-3-il)-1,3-dioxo-2,3-dihidro-1H-isoindol-4-il]amino}etoxi)etoxi]etil}acetamida; 2-[(9S)-7-(4-clorofenil)-4,5,13-trimetil-3-tia-1,8,11,12-tetraazatriciclo[8.3.0.02,6]tri-deca-2(6),4,7,10,12-pentaen-9- il]-N-[(1R)-1-{4-[2-(2-{[2-(2,6-dioxopiperidin-3-il)-1-oxo-2,3-dihidro-1H-isoindol-4- il]amino}etoxi)etoxi]fenil}etil]acetamida; 2-[(9S)-7-(4-clorofenil)-4,5,13-trimetil-3-tia-1,8,11,12-tetraazatriciclo[8.3.0.02,6]-trideca-2(6),4,7,10,12-pentaen-9- il]-N-[2-(2-{[2-(2,6-dioxopiperidin-3-il)-1-oxo-2,3-dihidro-1H-isoindol-4-il]amino}etoxi)etil]acetamida; 2-[(9S)-7-(4-clorofenil)-4,5,13-trimetil-3-tia-1,8,11,12-tetraazatriciclo[8.3.0.02,6]tri-deca-2(6),4,7,10,12-pentaen-9- il]-N-[(1S)-1-{4-[5-(3-{[2-(2,6-dioxopiperidin-3-il)-1,3-dioxo-2,3-dihidro-1H-isoindol-4-il]amino}propoxi)pirimidin-2- il]fenil}etil]acetamida; 2-[(9S)-7-(4-clorofenil)-4,5,13-trimetil-3-tia-1,8,11,12-tetraazatriciclo[8.3.0.02,6]tri-deca-2(6),4,7,10,12-pentaen-9- il]-N-[(1S)-1-{4-[3-(2-{[2-(2,6-dioxopiperidin-3-il)-1,3-dioxo-2,3-dihidro-1H-isoindol-4- il]amino}etoxi)propoxi]fenil}etil]acetamida; 2-[(9S)-7-(4-clorofenil)-4,5,13-trimetil-3-tia-1,8,11,12-tetraazatriciclo[8.3.0.02,6]tri-deca-2(6),4,7,10,12-pentaen-9- il]-N-[(1S)-1-{4-[2-(2-{[2-(2,6-dioxopiperidin-3-il)-1-oxo-2,3-dihidro-1H-isoindol-4- il]amino}etoxi)etoxi]fenil}etil]acetamida; 2-[(9S)-7-(4-clorofenil)-4,5,13-trimetil-3-tia-1,8,11,12-tetraazatriciclo[8.3.0.02,6]tri-deca-2(6),4,7,10,12-pentaen-9- il]-N-(4-{[2-(2,6-dioxopiperidin-3-il)-1,3-dioxo-2,3-dihidro-1H-isoindol-4-il]amino}butil)acetamida; 2-[(9S)-7-(4-clorofenil)-4,5,13-trimetil-3-tia-1,8,11,12-tetraazatriciclo[8.3.0.02,6]tri-deca-2(6),4,7,10,12-pentaen-9- il]-N-(2-{[2-(2,6-dioxopiperidin-3-il)-1,3-dioxo-2,3-dihidro-1H-isoindol-4-il]amino}etil)acetamida; 2-[(9S)-7-(4-clorofenil)-4,5,13-trimetil-3-tia-1,8,11,12-tetraazatriciclo[8.3.0.02,6]tri-deca-2(6),4,7,10,12-pentaen-9- il]-N-(5-{[2-(2,6-dioxopiperidin-3-il)-1,3-dioxo-2,3-dihidro-1H-isoindol-4-il]amino}pentil)acetamida; 2-[(9S)-7-(4-clorofenil)-4,5,13-trimetil-3-tia-1,8,11,12-tetraazatriciclo[8.3.0.02,6]tri-deca-2(6),4,7,10,12-pentaen-9- il]-N-(3-{[2-(2,6-dioxopiperidin-3-il)-1-oxo-2,3-dihidro-1H-isoindol-4-il]amino}propil)acetamida; 2-[(9S)-7-(4-clorofenil)-4,5,13-trimetil-3-tia-1,8,11,12-tetraazatriciclo[8.3.0.02,6]tri-deca-2(6),4,7,10,12-pentaen-9- il]-N-(4-{[2-(2,6-dioxopiperidin-3-il)-1-oxo-2,3-dihidro-1H-isoindol-4-il]amino}butil)acetamida; 2-[(9S)-7-(4-clorofenil)-4,5,13-trimetil-3-tia-1,8,11,12-tetraazatriciclo[8.3.0.02,6]tri-deca-2(6),4,7,10,12-pentaen-9- il]-N-[(1S)-1-{4-[2-(2-{[2-(2,6-dioxopiperidin-3-il)-1,3-dioxo-2,3-dihidro-1H-isoindol-4-il]amino}etoxi)etoxi]-3- fluorofenil}etil]-acetamida; 2-[(9S)-7-(4-clorofenil)-4,5,13-trimetil-3-tia-1,8,11,12-tetraazatriciclo[8.3.0.02,6]tri-deca-2(6),4,7,10,12-pentaen-9- il]-N-[4-({1-[2-(3-metil-2,6-dioxopiperidin-3-il)-1,3-dioxo-2,3-dihidro-1H-isoindol-4-il]-4,7,10-trioxa-1-azadodecan- 12-il}oxi)fenil]-acetamida; 2-[(9S)-7-(4-clorofenil)-4,5,13-trimetil-3-tia-1,8,11,12-tetraazatriciclo[8.3.0.02,6]tri-deca-2(6),4,7,10,12-pentaen-9- il]-N-[4-({1-[2-(1-metil-2,6-dioxopiperidin-3-il)-1,3-dioxo-2,3-dihidro-1H-isoindol-4-il]-4,7,10-trioxa-1-azadodecan- 12-il}oxi)fenil]-acetamida; 2-[(9S)-7-(4-clorofenil)-4,5,13-trimetil-3-tia-1,8,11,12-tetraazatriciclo[8.3.0.02,6]tri-deca-2(6),4,7,10,12-pentaen-9- il]-N-[(1R)-1-[3-(3-{[2-(2,6-dioxopiperidin-3-il)-1-oxo-2,3-dihidro-1H-isoindol-4-il]amino}propoxi)fenil]etil]acetamida; 2-[(9S)-7-(4-clorofenil)-4,5,13-trimetil-3-tia-1,8,11,12-tetraazatriciclo[8.3.0.02,6]tri-deca-2(6),4,7,10,12-pentaen-9- il]-N-[(3S)-1-{4-[(2-{[2-(2,6-dioxopiperidin-3-il)-1,3-dioxo-2,3-dihidro-1H-isoindol-4- il]amino}etil)amino]benzoil}pirrolidin-3-il]acetamida; 2-[(9S)-7-(4-clorofenil)-4,5,13-trimetil-3-tia-1,8,11,12-tetraazatriciclo[8.3.0.02,6]tri-deca-2(6),4,7,10,12-pentaen-9- il]-N-[2-(2-{[3-(2,6-dioxopiperidin-3-il)-2-metil-4-oxo-3,4-dihidroquinazolin-5-il]amino}etoxi)etil]acetamida; 2-[(9S)-7-(4-clorofenil)-4,5,13-trimetil-3-tia-1,8,11,12-tetraazatriciclo[8.3.0.02,6]tri-deca-2(6),4,7,10,12-pentaen-9- il]-N-[3-(3-{[2-(2,6-dioxopiperidin-3-il)-1-oxo-2,3-dihidro-1H-isoindol-4-il]amino}propoxi)propil]acetamida; 2-[(9S)-7-(4-clorofenil)-4,5,13-trimetil-3-tia-1,8,11,12-tetraazatriciclo[8.3.0.02,6]tri-deca-2(6),4,7,10,12-pentaen-9- il]-N-[(3S)-1-[4-(2-{[2-(2,6-dioxopiperidin-3-il)-1,3-dioxo-2,3-dihidro-1H-isoindol-4-il]amino}etoxi)benzoil]pirrolidin-3- il]acetamida; 2-[(9S)-7-(4-clorofenil)-4,5,13-trimetil-3-tia-1,8,11,12-tetraazatriciclo[8.3.0.02,6]tri-deca-2(6),4,7,10,12-pentaen-9- il]-N-(4-{2-[2-(2-{[3-(2,6-dioxopiperidin-3-il)-2-metil-4-oxo-3,4-dihidroquinazolin-5- il]amino}etoxi)etoxi]etoxi}fenil)acetamida; 2-[(9S)-7-(4-clorofenil)-4,5,13-trimetil-3-tia-1,8,11,12-tetraazatriciclo[8.3.0.02,6]tri-deca-2(6),4,7,10,12-pentaen-9- il]-N-(5-{[2-(2,6-dioxopiperidin-3-il)-1-oxo-2,3-dihidro-1H-isoindol-4-il]amino}pentil)acetamida; 2-[(9S)-7-(4-clorofenil)-4,5,13-trimetil-3-tia-1,8,11,12-tetraazatriciclo[8.3.0.02,6]tri-deca-2(6),4,7,10,12-pentaen-9- il]-N-[3-(3-{[3-(2,6-dioxopiperidin-3-il)-2-metil-4-oxo-3,4-dihidroquinazolin-5-il]amino}propoxi)propil]acetamida; 2-[(9S)-7-(4-clorofenil)-4,5,13-trimetil-3-tia-1,8,11,12-tetraazatriciclo[8.3.0.02,6]tri-deca-2(6),4,7,10,12-pentaen-9- il]-N-[(3S)-1-[4-(2-{[2-(2,6-dioxopiperidin-3-il)-1-oxo-2,3-dihidro-1H-isoindol-4-il]amino}etoxi)benzoil]pirrolidin-3- il]acetamida; 2-[(9S)-7-(4-clorofenil)-4,5,13-trimetil-3-tia-1,8,11,12-tetraazatriciclo[8.3.0.02,6]tri-deca-2(6),4,7,10,12-pentaen-9- il]-N-[(1R)-1-[3-(2-{[2-(2,6-dioxopiperidin-3-il)-1-oxo-2,3-dihidro-1H-isoindol-4-il]amino}etoxi)fenil]etil]acetamida; 4-(4-{[(5Z)-3-{1-[2-(2,6-dioxopiperidin-3-il)-1,3-dioxo-2,3-dihidro-1H-isoindol-4-il]-4,7,10,13-tetraoxa-1- azapentadecan-15-il}-2,4-dioxo-1,3-tiazolidin-5-iliden]metil}-2-metoxifenoxi)-3-(trifluorometil)benzonitrilo; 4-(4-{[(5Z)-3-{1-[2-(2,6-dioxopiperidin-3-il)-1,3-dioxo-2,3-dihidro-1H-isoindol-4-il]-4,7,10-trioxa-1-azadodecan-12- il}-2,4-dioxo-1,3-tiazolidin-5-iliden]metil}-2-metoxifenoxi)-3-(trifluorometil)benzonitrilo; 4-(4-{[(5Z)-3-{1-[2-(2,6-dioxopiperidin-3-il)-1,3-dioxo-2,3-dihidro-1H-isoindol-4-il]-4,7,10,13,16-pentaoxa-1- azaoctadecan-18-il}-2,4-dioxo-1,3-tiazolidin-5-iliden]metil}-2-metoxifenoxi)-3-(trifluorometil)benzonitrilo; y 4-(4-{[(5Z)-3-{1-[2-(2,6-dioxopiperidin-3-il)-1,3-dioxo-2,3-dihidro-1H-isoindol-4-il]-4,7,10,13,16,19-hexaoxa-1- azahenicosan-21-il}-2,4-dioxo-1,3-tiazolidin-5-iliden]metil}-2-metoxifenoxi)-3-(trifluorometil)benzonitrilo, incluyendo formas de sal farmacéuticamente aceptables del mismo.