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1. WO2020140043 - COMPOUNDS FOR USE AS THERAPEUTICALLY ACTIVE SUBSTANCES IN THE TREATMENT AND/OR PREVENTION OF NEURORETINAL DISEASES

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Claims


or a pharmaceutically acceptable salt thereof,

wherein :

A is a 5-oxazolyl residue or a pyridine-4-yl residue

Ri is selected from the group consisting of fluoro and chloro ;

R2, A3, It, As and R6 of the phenyl ring B are independently from each other selected from the group consisting of hydrogen, a linear or branched alkyl having 1 to 4 carbon atoms, trifluoromethyl, 2,2,2- trifluoroethyl, methylsulfanyl, ethylsulfanyl, methylsulfonyl, ethylsulfonyl, difluoromethoxy, trifluoromethoxy, fluoro, bromo, chloro, methoxy, ethoxy, propoxy, butoxy, hydroxy and amino; and

at least two of R2, R3, R4, R5 and R6 are hydrogens, with the proviso that if Ri is chloro, R5 is not methoxy.

2. The compound according to claim 1, wherein R2 is chloro. 3. The compound according to claim 1, wherein A is a 5- oxazolyl residue.

4. The compound according to claim 1, wherein the phenyl ring B is monosubstituted or disubstituted .

5. The compound according to claim 1, wherein the phenyl ring B is monosubstituted.

6. The compound according to claim 5, wherein R2 is selected from the group consisting of methyl, trifluoromethyl, methylsulfanyl, methylsulfonyl, difluoromethoxy, fluoro, bromo, chloro, methoxy and ethoxy, preferably difluoromethoxy or chloro.

7. The compound according to claim 5, wherein R3 or R4 is selected from the group consisting of trifluoromethyl, difluoromethoxy, methoxy, preferably trifluoromethyl and difluoromethoxy .

8. The compound according to claim 1, wherein the phenyl ring B is disubstituted.

9. The compound according to claim 8, wherein R2 is selected from the group consisting of fluoro, bromo, and chloro, and one of R3, R4 or R5 is selected from the group consisting of fluoro, bromo, and chloro.

10. The compound according to claim 10, wherein R2 is chloro and R5 is fluoro or wherein both R2 and R4 are fluoro.

11. Compound of formula (I) according to any of the preceding claims, wherein said compound is selected from the group consisting of


12. A pharmaceutical composition comprising a compound of the formula (la) for use in the treatment and /or prevention of a primary neuroretinal disease that leads to photoreceptor loss or degradation of the photoreceptor layer of the retina.


A is a 5-oxazolyl residue or a pyridine-4-yl residue

Ri' is selected from the group consisting of methoxy, hydrogen, fluoro and chloro;

R2, R3, R4, R5 and Rg of the phenyl ring B are independently from each other selected from the group consisting of hydrogen, a linear or branched alkyl having 1 to 4 carbon atoms, trifluoromethyl, 2,2,2- trifluoroethyl, methylsulfanyl, ethylsulfanyl, methylsulfonyl, ethylsulfonyl, difluoromethoxy, trifluoromethoxy, fluoro, bromo, chloro, methoxy, ethoxy, propoxy, butoxy, hydroxy and amino; and

at least two of R2, R3, R4, R5 and R6 are hydrogens,

with the proviso that if Ri' is hydrogen or methoxy, A is a pyridine-4-yl residue,

as a therapeutically active substance.

13. Composition for use according to claim 12, wherein the use is selected from the group consisting of inherited retinal dystrophies, acquired or drug-induced photoreceptor degeneration, infectious eye diseases and inflammatory eye diseases, wherein the pharmaceutical composition, upon administration, treats the retinal disease by inducing proliferation of retinal precursor cells, preferably for use in the treatment of a retinal disease from the group consisting of retinitis pigmentosa (RP) , including syndromic and non-syndromic forms, X-chromosome linked, recessive, dominant and sporadic forms, rod-cone dystrophies, Usher's syndrome, Stargardt's disease, cone-rod dystrophies, cone dystrophies, achromatopsia, blue cone monochromacy, enhanced S-cone syndrome, rod dystrophies, choroideremia, Leber's congenital amaurosis, juvenile X-chromosome linked retinoschisis (JXLR), fundus albipunctatus , retinitis punctata albescens, fleck retina of Kandori, bietti crystalline retinal dystrophy, fenestrated sheen macular dystrophy, adult-onset foveomacular vitelliform dystrophy, Batten's disease, congenital stationary night blindness, familial exudative vitreoretinopathy (FEVR), ocular albinism, oculocutaneous albinism, fovea hypoplasia, abetalipoproteinemia, Stickler syndrome, retinal dystrophy (Bothnia type) , crystalline maculopathy (drug-related, hyperoxaluria, cystinosis, Sjogren-Larsson syndrome) , west African crystalline maculopathy, solar retinopathy, talc retinopathy, diabetic retinopathy, sickle cell retinopathy, macular telangectasia, eales disease, retinal detachment, retinal dialysis, peripheral retinoschisis, central/branch retinal artery occlusion (CRAO/BRAO) , central/branch retinal vein occlusion (CRVO/BRVO) , haemorrhagic occlusive retinal vasculitis (HORV) , drug-induced maculopathies including chloroquine, hydroxychloroquine, phenothiazine, quinine sulfate, thioridazine, clofazimine, cholopromazine, deferoxamine, chloroquine-derivatives , cisplatin, carmustine, chlofazimine and vigabatrin; crystal- induced maculopathies including tamoxifen, talc, canthaxanthine, methoxyflurane and nitrofurantoin; cystoid macular edema (CME) including epinephrine, latanoprost, nicotinic acid, progressive outer retinal necrosis (PORN) , acute retinal necrosis (ARN) , CMV- retinitis, Sarcoidosis, acute syphilitic posterior placoid chorioretinitis, tuberculosis chorioretinitis, toxoplasmic retinochoroiditis , posterior Uveitis and retinal vasculitis, intermediate uveitis, pars planitis +/- CME, enophthalmitis (anterior and/or posterior) , posterior scleritis, masquerade syndromes, multifocal choroiditis and panuveitis (MCP) , punctate inner choroidopathy (PIC) , birdshot retinochoroidopathy, acute macular neuroretinopathy (AMN) and acute zonal occult outer retinopathy (AZOOR) ,

14. Composition for use according to claims 12 or 13 in the treatment and/or prevention of inherited retinal dystrophies, preferably for use in the treatment of retinitis pigmentosa (RP) .

15. Composition for the use according to any of claims 11 to 14 selected from the group consisting of


16. Composition for use according to claims 10 to 15, wherein said composition is suitable for intraocular inj ection .