US 12,410,164 B2
Heterocyclic compounds and medical use thereof
Paola Barraja, Palermo (IT); Ilaria Musante, Rome (IT); Luis Juan Vicente Galietta, Rome (IT); and Virginia Spano', Palermo (IT)
Assigned to FONDAZIONE TELETHON, Rome (IT); and UNIVERSITA DEGLI STUDI DI PALERMO, Palermo (IT)
Appl. No. 17/295,728
Filed by FONDAZIONE TELETHON, Rome (IT); and UNIVERSITA DEGLI STUDI DI PALERMO, Palermo (IT)
PCT Filed Nov. 20, 2019, PCT No. PCT/EP2019/081988
§ 371(c)(1), (2) Date May 20, 2021,
PCT Pub. No. WO2020/104558, PCT Pub. Date May 28, 2020.
Claims priority of application No. 102018000010466 (IT), filed on Nov. 20, 2018.
Prior Publication US 2022/0002295 A1, Jan. 6, 2022
Int. Cl. C07D 471/04 (2006.01); C07D 471/14 (2006.01); C07D 487/04 (2006.01)
CPC C07D 471/04 (2013.01) [C07D 471/14 (2013.01); C07D 487/04 (2013.01)] 19 Claims
 
1. A method for the treatment of a pathology associated with a defect in an ABC (ATP-binding cassette) transporter, the method comprising administering to a patient in need thereof a compound of general formula (I):

OG Complex Work Unit Chemistry
wherein:
A is a pentatomic aromatic heterocyclic ring, comprising one, two or three nitrogen atoms;
R is selected from the group consisting of: hydrogen, linear or branched C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, arylsulfonyl, halogen and alkylamine, wherein said linear or branched C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, arylsulfonyl or alkylamine is optionally substituted with one or more substituents independently selected from: linear or branched C1-C6 alkyl, nitro, amino, halogen, haloalkyl and alkoxy;
R1 and R2 are independently selected from the group consisting of: hydrogen, carboxylic acid, carboxylic ester, carboxamide from primary, secondary or tertiary amine, halogen, nitro, amine, azide, alkylamine, arylalkyl and trifluoroalkyl, wherein said carboxylic acid, carboxylic ester, carboxamide from primary, secondary or tertiary amine, halogen, nitro, amine, azide, alkylamine or trifluorolalkyl is optionally substituted with one or more substituents independently selected from: linear or branched C1-C6 alkyl, cycloalkyl, nitro, amino, halogen, arylsulfonyl, optionally substituted heteroaryl and haloalkyl;
R3 is absent or present and is selected from the group consisting of: carbonitrile, carboxylic ester, carboxamide, alkylsulfonyl, arylsulfonyl, wherein said carboxylic ester, carboxamide, alkylsulfonyl or arylsulfonyl is optionally substituted with one or more substituents independently selected from: linear or branched C1-C6 alkyl, nitro, amino, halogen and haloalkyl;
B is a cycloalkyl, aryl, or heterocycloalkyl ring wherein said heterocycloalkyl ring comprises one nitrogen;
R4 is selected from the group consisting of: hydrogen, alkyl, aryl, arylalkyl and heteroaryl;
X is selected from the group consisting of: C═O, C—O-alkyl, and C—NRaRb,
Ra and Rb are independently selected from the group consisting of: hydrogen, alkyl, cycloalkane, aryl, arylalkyl, heteroaryl, heteroarylalkyl, acetyl, arylsulfonyl; wherein said alkyl, cycloalkane, aryl, arylalkyl, heteroaryl, heteroarylalkyl, acetyl or arylsulfonyl is optionally substituted with one or more substituents independently selected from: C1-C6 alkyl, nitro, amino, halogen and haloalkyl;
Y is absent or present and is selected from the group consisting of: hydrogen, alkyl, aryl and alkylamine; wherein when X is C—O-alkyl or C—NRaRb, Y is absent;
Q is a carbon or nitrogen atom, wherein when Q is a nitrogen atom, R3 is absent;
n is 1;
m is 1;
or a pharmaceutically acceptable salt, tautomer, stereoisomer, deuterated derivative, thereof;
wherein the pathology is selected from the group consisting of: cystic fibrosis, limb-girdle muscular dystrophy (LGMD), congenital bilateral absence of vas deferens (CBAVD), acute, chronic, recurrent and/or autoimmune pancreatitis, disseminated bronchiectasis, asthma, allergic pulmonary aspergillosis, smoking-related lung pathology, dry eye syndrome, Sjogren's syndrome, chronic sinusitis, cholestatic jaundice, emphysema, idiopathic chronic pancreatitis, isolated obstructive azoospermia, sclerosing cholangitis, panbronchiolite, neonatal hypertripsinemia, adrenoleukodystrophy, Stargardt disease, Tangier disease, progressive familial intrahepatic cholestasis, Dubin-Johnson syndrome, elastic pseudoxantoma, persistent hyperinsulinemic hypoglycemia of infancy due to focal adenomatous hyperplasia, senile macular degeneration, retinitis pigmentosa and “cone-rod” retinal dystrophy.