Granted Patent B2

US 12,527,776 · App. 17/428,502 · Granted Jan 20, 2026

Inventors: Oxana Ibraghimov-Beskrovnaya (Boston, MA); Nikolay O. Bukanov (Boston, MA); Hervé Husson (Bridgewater, NJ); Sarah E. Moreno (Woodstock, GA)

Assignee: Genzyme Corporation

A61K31/439A61P43/00

Abstract

Claims (25)

1 . A method for

(a) treating a ciliopathy selected from Joubert syndrome, Meckel-Gruber syndrome, Senior-Loken syndrome, Bardet-Biedl syndrome (BBS), Alstrom syndrome in a subject in need thereof,

(b) treating a disease or disorder selected from obesity, retinal degeneration, olfactory dysfunction, hyperlipedemia, and metabolic syndrome, in a subject suffering from a ciliopathy selected from Joubert syndrome, Meckel-Gruber syndrome, Senior-Loken syndrome, Bardet-Biedl syndrome (BBS), Alstrom syndrome,

the method comprising administering to the subject an effective amount of a compound of formula (I),

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is selected from hydrogen, halogen, cyano, nitro, hydroxy, thio, amino, C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 1-6 -alkyloxy, C 2-6 -alkenyloxy, and C 2-6 -alkynyloxy, wherein said alkyl, alkenyl, alkynyl, alkyloxy, alkenyloxy, or alkynyloxy is optionally substituted with one or more groups selected from halogen, cyano, nitro, hydroxy, thio or amino;

R 2 and R 3 are independently selected from C 1-6 -alkyl, optionally substituted by one or more halogens, or R 2 and R 3 together form a cyclopropyl or cyclobutyl group, optionally substituted by one or more halogens;

R 4 , R 5 and R 6 are each independently selected from hydrogen, halogen, nitro, hydroxy, thio, amino, C 1-6 -alkyl, and C 1-6 -alkyloxy, wherein said alkyl or alkyloxy is optionally substituted by one or more groups selected from halogen, hydroxy, cyano, and C 1-6 -alkyloxy; and

wherein A is phenyl or thiazolyl, optionally substituted with 1, 2 or 3 groups independently selected from halogen, hydroxy, thio, amino, nitro, C 1-6 alkoxy and C 1-6 alkyl.

2 . The method of claim 1 , wherein R 1 is selected from hydrogen, fluorine, methyl and ethyl, wherein said methyl or ethyl is optionally substituted by 1 or 2 groups selected from halogen, hydroxy, thio or amino.

3 . The method of claim 1 , wherein R 2 and R 3 are each independently selected from methyl and ethyl groups, optionally substituted with one or more fluorines.

4 . The method of claim 1 , wherein R 4 is selected from a halogen, C 1-3 -alkyl, and C 1-3 -alkyloxy, wherein said alkyl or alkyoxy is optionally substituted by one or more groups selected from a halogen and C 1-3 -alkyloxy.

5 . The method of claim 1 , wherein R 5 and R 6 are each hydrogen.

6 . The method of claim 1 , wherein R 4 is fluorine or 2-methoxyethoxy, and R 5 and R 6 are hydrogen.

7 . The method of claim 1 , wherein R 4 is positioned at the 4-position of the phenyl ring to which it is attached (i.e., para to the A substituent).

8 . The method of claim 1 , wherein A is phenyl, optionally substituted with 1, 2 or 3 groups independently selected from halogen, hydroxy, thio, amino, nitro, C 1-6 alkoxy and C 1-6 alkyl.

9 . The method of claim 8 , wherein the two groups attached to the A substituent are positioned in a 1,3- or a 1,4-relationship to each other (i.e., meta or para).

10 . The method of claim 1 , wherein said compound is a compound of formula (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), or (XI),

or a pharmaceutically acceptable salt thereof.

11 . The method of claim 10 , wherein R 4 is fluorine.

12 . The method of claim 1 , wherein said compound is selected from: quinuclidin-3-yl (2-(4′-fluoro-[1,1′-biphenyl]-3-yl)propan-2-yl)carbamate; (S)-quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate; (S)-quinuclidin-3-yl (2-(4′-(2-methoxyethoxy)-[1,1′-biphenyl]-4-yl) propan-2-yl)carbamate; and the pharmaceutically acceptable salts thereof.

13 . The method of claim 1 , wherein the ciliopathy is Bardet-Biedl syndrome (BBS).

14 . The method of claim 1 , wherein said subject is a human.

15 . The method of claim 1 , wherein said compound, or pharmaceutically acceptable salt thereof, is administered by systemic administration.

16 . The method of claim 15 , wherein said compound, or pharmaceutically acceptable salt thereof, is administered orally.

Assignments (1)

Continuity (3)

References Cited (400)