US 12,391,680 B2
Compounds and compositions for the treatment of cystic fibrosis
Tiziano Bandiera, Genoa (IT); Fabio Bertozzi, Genoa (IT); Giorgia Zaetta, Genoa (IT); Frederico Sorana, Verona (IT); Emanuela Caci, Verona (IT); Loretta Ferrera, Verona (IT); Nicoletta Pedemonte, Genoa (IT); and Luis Juan Vicente Galietta, Genoa (IT)
Assigned to FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA, Genoa (IT); ISTITUTO GIANNINA GASLINI, Genoa (IT); and FONDAZIONE PER LA RICERCA SULLA FIBROSI CISTICA—ONLUS, Verona (IT)
Appl. No. 17/422,598
Filed by FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA, Genoa (IT); ISTITUTO GIANNINA GASLINI, Genoa (IT); and FONDAZIONE PER LA RICERCA SULLA FIBROSI CISTICA—ONLUS, Verona (IT)
PCT Filed Jan. 16, 2020, PCT No. PCT/IB2020/050350
§ 371(c)(1), (2) Date Jul. 13, 2021,
PCT Pub. No. WO2020/148703, PCT Pub. Date Jul. 23, 2020.
Claims priority of application No. 102019000000687 (IT), filed on Jan. 16, 2019.
Prior Publication US 2022/0089584 A1, Mar. 24, 2022
Int. Cl. C07D 413/14 (2006.01); C07D 413/04 (2006.01)
CPC C07D 413/14 (2013.01) [C07D 413/04 (2013.01)] 9 Claims
 
1. A compound of Formula (Ia):

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or pharmaceutically acceptable salts, hydrates, solvates, clathrates, polymorphs, stereoisomers thereof wherein:
R1 and R2 are independently selected from the group consisting of hydrogen, C1-4alkyl, hydroxyC1-4alkyl, and C1-4alkyl-O—C1-4alkyl;
R3 is selected from the group consisting of hydrogen, C1-6alkyl, haloC1-6alkyl, OH, O—C1-6alkyl, C1-6alkyl-O—C1-6alkyl, CN, NO2 and halogen;
R4 is independently selected from the group consisting of hydrogen, C1-6alkyl, haloC1-6 alkyl and halogen;
A is selected from the group consisting of S, SO, and SO2;
B is selected from the group consisting of CRivRv, O, and NRii;
C is selected from the group consisting of C1-6alkyl, haloC1-6alkyl, C3-6cycloalkyl optionally substituted with one or more R5, C3-6heterocycloalkyl optionally substituted with one or more R5, aryl optionally substituted with one or more R5, heteroaryl optionally substituted with one or more R5, C1-6alkyl-O—C1-6alkyl, C1-6alkyl-O-aryl, C1-6alkyl-O-heteroaryl, C1-6alkyl-O—C3-6heterocycloalkyl, aryl-O-aryl, and aryl-O-heteroaryl;
R5 is selected from the group consisting of C1-6alkyl, haloC1-6alkyl, O—C1-6alkyl, C3-6cycloalkyl, C3-6heterocycloalkyl, aryl, heteroaryl, O-aryl, O-aryl-O—C1-6alkyl, O-heteroaryl, O—C3-6heterocycloalkyl, O-haloC1-6alkyl, OH, CN, NO2, SF6, halogen and COORi;
n is an integer comprised from 0 to 2;
m is an integer comprised from 0 to 2;
Ri is independently selected from the group consisting of hydrogen and C1-6alkyl;
Rii is independently selected from the group consisting of hydrogen and C1-6alkyl;
Riv and Rv are independently selected from the group consisting of hydrogen, C1-6alkyl and hydroxyC1-6alkyl;
provided that:
a) when A is S, B is O, R1 and R2 are both CH3, R3 and R4 are both hydrogen, C is not one of

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b) when A is S, B is O, R1 and R2 are respectively CH3 and hydrogen, R3 and R4 are both hydrogen, C is not one of

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c) when A is S, B is O, R1 and R2 are respectively isopropyl and hydrogen, R3 and R4 are both hydrogen, C is not one of

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d) when A is S, B is O, R1 and R2 are both H, R3 and R4 are both hydrogen, C is not one of

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e) when A is S, B is O, R1 and R2 are respectively hydrogen and CH2CH2OH, R3 and R4 are both hydrogen, C is not phenyl.