Patent ES-2687893-T3 (ES)
Title: Macrociclos de pirazolopirimidina como inhibidores de la replicación del virus de la inmunodeficiencia humana
Inventor: NAIDU B NARASIMHULU
IPC: C07D498/16
Filed: 2014-02-19
Granted: 2018-10-29
Abstract: Un compuesto seleccionado del grupo que consiste en Ácido (2S)-2-(terc-butoxi)-2-[(22S)-4,22,28-trimetil-17-(trifluorometil)-21,27-dioxa-1,5,7,8-tetraazahexaciclo- [26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S) 5 -17,18-difluoro-4,22,28-trimetil-21,27-dioxa-1,5,7,8-tetraazahexaciclo- [26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-16,18-difluoro-4,22,28-trimetil-21,27-dioxa-1,5,7,8-tetraazahexaciclo- [26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S,24E)-16-fluoro-4,18,22,28-tetrametil-21,27-dioxa-1,5,7,8-tetraazahexaciclo- [26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18,24-undecaen-3- il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-16-fluoro-4,18,22,28-tetrametil-21,27-dioxa-1,5,7,8-tetraazahexaciclo- [26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-17-etil-4,22,28-trimetil-21,27-dioxa-1,5,7,8-tetraazahexaciclo- [26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18,24-undecaen-3- il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-17-etil-4,22,28-trimetil-21,27-dioxa-1,5,7,8-tetraazahexaciclo- [26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-17-metoxi-4,22,28-trimetil-21,27-dioxa-1,5,7,8-tetraazahexaciclo- [26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(23E)-18-fluoro-4,22,27-trimetil-21,26-dioxa-1,5,7,8-tetraazahexaciclo- [25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18,23-undecaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-18-fluoro-4,22,27-trimetil-21,26-dioxa-1,5,7,8-tetraazahexaciclo- [25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18-decaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S,23E)-16-fluoro-4,17,22,27-tetrametil-21,26-dioxa-1,5,7,8-tetraazahexaciclo- [25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18,23-undecaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-16-fluoro-4,17,22,27-tetrametil-21,26-dioxa-1,5,7,8-tetraazahexaciclo- [25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18-decaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S,23E)-17-fluoro-4,22,27-trimetil-21,26-dioxa-1,5,7,8-tetraazahexaciclo- [25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18,23-undecaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-17-fluoro-4,22,27-trimetil-21,26-dioxa-1,5,7,8-tetraazahexaciclo- [25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18-decaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S,23E)-4,18,22,27-tetrametil-21,26-dioxa-1,5,7,8-tetraazahexaciclo- [25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18,23-undecaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-4,18,22,27-tetrametil-21,26-dioxa-1,5,7,8-tetraazahexaciclo- [25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18-decaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S,23E)-16-fluoro-4,18,22,27-tetrametil-21,26-dioxa-1,5,7,8-tetraazahexaciclo- [25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18,23-undecaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-16-fluoro-4,18,22,27-tetrametil-21,26-dioxa-1,5,7,8-tetraazahexaciclo- [25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18-decaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S,25Z)-4,17,22,28-tetrametil-21,27-dioxa-1,5,7,8-tetraazahexaciclo- [26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18,25-undecaen-3- il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-4,17,22,28-tetrametil-21-oxa-1,5,7,8-tetraazahexaciclo- [26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18,24-undecaen-3- il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-4,17,22,28-tetrametil-21-oxa-1,5,7,8-tetraazahexaciclo- [26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-17-ciano-4,22,28-trimetil-21-oxa-1,5,7,8-tetraazahexaciclo- [26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18,24-undecaen-3- il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-17-ciano-4,22,28-trimetil-21-oxa-1,5,7,8-tetraazahexaciclo- [26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-17-carbamoil-4,22,28-trimetil-21-oxa-1,5,7,8-tetraazahexaciclo- [26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-17-[(3,3-dimetilbutil)carbamoil]-4,22,28-trimetil-21,27-dioxa-1,5,7,8- tetraazahexaciclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18- decaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-11,18-difluoro-4,22,28-trimetil-21,27-dioxa-1,5,7,8-tetraazahexaciclo- [26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-12,18-difluoro-4,22,28-trimetil-21,27-dioxa-1,5,7,8-tetraazahexaciclo- [26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-13,18-difluoro-4,22,28-trimetil-21,27-dioxa-1,5,7,8-tetraazahexaciclo- [26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-4,16,17,22,27-pentametil-21,26-dioxa-1,5,7,8-tetraazahexaciclo- [25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18,23-undecaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-4,16,17,22,27-pentametil-21,26-dioxa-1,5,7,8-tetraazahexaciclo- [25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18-decaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-17-fluoro-4,16,22,27-tetrametil-21,26-dioxa-1,5,7,8-tetraazahexaciclo- [25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18,23-undecaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-17-fluoro-4,16,22,27-tetrametil-21,26-dioxa-1,5,7,8-tetraazahexaciclo- [25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18-decaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-16,18-difluoro-4,22,27-trimetil-21,26-dioxa-1,5,7,8-tetraazahexaciclo- [25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18,23-undecaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-16,18-difluoro-4,22,27-trimetil-21,26-dioxa-1,5,7,8-tetraazahexaciclo- [25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18-decaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-4,17,18,22,27-pentametil-21,26-dioxa-1,5,7,8-tetraazahexaciclo- [25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18,23-undecaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-4,17,18,22,27-pentametil-21,26-dioxa-1,5,7,8-tetraazahexaciclo- [25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18-decaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-17-fluoro-4,18,22,27-tetrametil-21,26-dioxa-1,5,7,8-tetraazahexaciclo- [25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18,23-undecaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-17-fluoro-4,18,22,27-tetrametil-21,26-dioxa-1,5,7,8-tetraazahexaciclo- [25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18-decaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-17,18-difluoro-4,22,27-trimetil-21,26-dioxa-1,5,7,8-tetraazahexaciclo- [25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18,23-undecaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-17,18-difluoro-4,22,27-trimetil-21,26-dioxa-1,5,7,8-tetraazahexaciclo- [25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18-decaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-18-fluoro-4,17,22,27-tetrametil-21,26-dioxa-1,5,7,8-tetraazahexaciclo- [25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18,23-undecaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-18-fluoro-4,17,22,27-tetrametil-21,26-dioxa-1,5,7,8-tetraazahexaciclo- [25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18-decaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-16-fluoro-4,22,27-trimetil-21,26-dioxa-1,5,7,8-tetraazahexaciclo- [25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18,23-undecaen-3-il]acético; Ácido (2S)-2-(terc-butoxi)-2-[(22S)-16-fluoro-4,22,27-trimetil-21,26-dioxa-1,5,7,8-tetraazahexaciclo- [25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18-decaen-3-il]acético;