NOVEL DUAL MODE OF ACTION SOLUBLE GUANYLATE CYCLASE ACTIVATORS AND PHOSPHODIESTERASE INHIBITORS AND USES THEREOF

• Main Authors: PETERKE Jeanette, LONE Esra, SPOERRI Michael, DI MAIO Selena, TENOR Hermann, KOCH Guido, MARTINI Elia, NAEF Reto
• Format: Patent
• Language: English; Spanish
• Published: 23.06.2021
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

The present invention relates to compounds of formula (I) or formula (II) or pharmaceutically acceptable salt, solvate or hydrate thereof, wherein said compound of formula (I) and said compound of formula II each comprises at least one ONO2 or ONO moiety; R1 is C1-C3alkyl; R2 is H, C1-C6alkyl, C3-C6cycloalkyl, C1-C2alkoxy, C2-C4alkenyl; R3 is C1-C4alkyl optionally substituted with C1-C2alkoxy, C3-C4cycloalkyl, C2-C4alkenyl; R4 and R5 are each independently H or C1-C6alkyl optionally substituted with F, OH, ONO, ONO2, COOH, C1-C3alkoxy, C3-C6cycloalkyl; or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from aziridine, azetidine, pyrollidine, piperidine, morpholine, piperazine, homo-piperazine, 2,5-diazabicyclo[2,2,1]heptane and 3,7-diazabicyclo[3,3,0]octane, wherein said heterocyclic ring is optionally substituted with independently one or more R6; R6 is C1-C6alkyl optionally substituted with independently one or more halogen, OH, ONO, ONO2, C1-C3alkoxy, C1-C3haloalkoxy, COOR7, NR8R9, C=NR10; R7 is H, or C1-C4alkyl optionally substituted with F, OH, ONO, ONO2, NR8R9; R8 and R9 are independently H, or C1-C4alkyl optionally substituted with ONO, ONO2; R10 is C1-C4alkyl optionally substituted with F, ONO, ONO2; C3-C6cycloalkyl; pharmaceutical compositions thereof, and their use in methods of treating or preventing a disease alleviated by inhibition of PDE5 in a human or in a non-human mammal. La presente invención se refiere a compuestos de la Fórmula I o la Fórmula II (ver Fórmulas) o una sal, solvato o hidrato aceptable desde el punto de vista farmacéutico de estos, en donde cada uno de dicho compuesto de la Fórmula I y dicho compuesto de la Fórmula II comprende al menos una porción ONO2 u ONO; R1 es C1-C3alquilo; R2 es H, C1-C6alquilo, C3-C6cicloalquilo, C1-C2alcoxi, C2-C4alquenilo; R3 es C1-C4alquilo opcionalmente sustituido con C1-C2alcoxi, C3-C4cicloalquilo, C2-C4alquenilo; cada uno de R4 y R5 es independientemente H o C1-C6alquilo opcionalmente sustituido con F, OH, ONO, ONO2, COOH, C1-C3alcoxi, C3-C6cicloalquilo; o, junto con el átomo de nitrógeno al que está unido, forma un anillo heterocíclico, en donde dicho anillo heterocíclico se selecciona preferentemente de aziridina, azetidina, pirrolidina, piperidina, morfolina, piperazina, homopiperazina, 2,5-diazabiciclo[2,2,1]heptano y 3,7-diazabiciclo[3,3,0]octano, en donde dicho anillo heterocíclico está opcionalmente sustituido independientemente con uno o más R6; R6 es C1-C6alquilo opcionalmente sustituido independientemente con uno o más de halógeno, OH, ONO, ONO2, C1-C3alcoxi, C1-C3haloalcoxi, COOR7, NR8R9, C=NR10; R7 es H o C1-C4alquilo opcionalmente sustituido con F, OH, ONO, ONO2, NR8R9; R8 y R9 son independientemente H o C1-C4alquilo opcionalmente sustituido con ONO, ONO2; R10 es C1-C4alquilo opcionalmente sustituido con F, ONO, ONO2; C3-C6cicloalquilo; composiciones farmacéuticas de estos, y su uso en métodos de tratamiento o prevención de una enfermedad que se alivia mediante la inhibición de PDE5 en un ser humano o en un mamífero no humano.