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US 2026/0199369 A1Published application
Compounds for the treatment of neuromuscular disorders
AssigneeNmd Pharma A/S
InventorsLars J.S. KNUTSEN, Nicholas Michael KELLY, Neerja SARASWAT, Richard J. HAMLYN
Life of this patent
Estimating the term…
Abstract
The present disclosure relates to compounds suitable for treating, ameliorating and/or preventing neuromuscular disorders, including the reversal of drug-induced neuromuscular blockade. The compounds as defined herein can inhibit the CIC-1 ion channel.
Claims15
A compound of Formula (I):
- wherein:
- M is CR5R6, NR7, O or S;
- Q is CR5R6, NR8, O or S;
- T is CR5R6, NR8, O or S;
- X is absent, CR5R6, NR8, O or S;
- Z is CR5R6, NR9, O or S;
- two or more of M, Q, T, X and Z are NR7, NR8, NR9, O or S;
- R1 is selected from the group consisting of F;
- Cl;
- Br;
- C1-3 alkyl optionally substituted with one or more, identical or different, substituents R10;
- C2-3 alkenyl optionally substituted with one or more, identical or different, substituents R10;
- —OC1-3 alkyl optionally substituted with one or more, identical or different, substituents R10;
- —OC3-5 cycloalkyl optionally substituted with one or more, identical or different, substituents R10;
- —SC1-3 alkyl optionally substituted with one or more, identical or different, substituents R10 and —SC3-5 cycloalkyl optionally substituted with one or more, identical or different, substituents R10;
- R2 is selected from the group consisting of H;
- F;
- Cl;
- Br;
- and C1-3 alkyl optionally substituted with one or more, identical or different, substituents R10;
- R3 is selected from the group consisting of H, F and Cl;
- R4 is selected from the group consisting of H;
- C1-5 alkyl optionally substituted with one or more, identical or different, substituents R10;
- C2-5 alkenyl optionally substituted with one or more, identical or different, substituents R10;
- C2-5 alkynyl optionally substituted with one or more, identical or different, substituents R10;
- C3-6 cycloalkyl optionally substituted with one or more, identical or different, substituents R10;
- phenyl optionally substituted with one or more, identical or different, substituents R11;
- and benzyl optionally substituted with one or more, identical or different, substituents R11;
- R5 is independently selected from the group consisting of H, deuterium, F and C1-5 alkyl optionally substituted with one or more, identical or different, substituents R10;
- R6 is independently selected from the group consisting of H, deuterium, F and C1-5 alkyl optionally substituted with one or more, identical or different, substituents R10;
- R7 is independently selected from the group consisting of H, C1-5 alkyl optionally substituted with one or more, identical or different, substituents R10;
- C1-3 alkyl substituted with C3-5 cycloalkyl optionally substituted with one or more, identical or different, substituents R10;
- C1-3 alkyl substituted with phenyl optionally substituted with one or more, identical or different, substituents R11;
- C1-3 alkyl substituted with C5 heteroaryl optionally substituted with one or more, identical or different, substituents R11;
- and C3-5 cycloalkyl optionally substituted with one or more, identical or different, substituents R10;
- R8 is independently selected from benzyl optionally substituted with one or more, identical or different, substituents R11;
- R9 is independently selected from the group consisting of H, C1-5 alkyl optionally substituted with one or more, identical or different, substituents R10;
- C1-3 alkyl substituted with C3-5 cycloalkyl optionally substituted with one or more, identical or different, substituents R10;
- C1-3 alkyl substituted with phenyl optionally substituted with one or more, identical or different, substituents R11;
- C1-3 alkyl substituted with naphthyl optionally substituted with one or more, identical or different, substituents R11;
- C1-3 alkyl substituted with a 5- to 10-membered heteroaryl optionally substituted with one or more, identical or different, substituents R11;
- and C3-5 cycloalkyl optionally substituted with one or more, identical or different, substituents R10;
- R10 is independently selected from the group consisting of H, deuterium, F, Cl and —OC1-3 alkyl;
- and
- —R11 is independently selected from the group consisting of deuterium, methoxy, —OCF3, Me, CF3, CF2Cl, CF2H, CFH2, CD3, cyclopropyl, NH2, —NHAc, —C(═O)—NH2, nitro, cyano, Cl, Br, I, and F;
- when R5 and R6 are individually C1-5 alkyl optionally substituted with one or more, identical or different, substituents R10, then R5 and R6 are optionally joined together to form a ring;
- or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof provided that:
- only one of M, Q, T, X and Z is O;
- and
- when M is O, Q and T are CH2, X is absent, Z is NH, R1 is Cl, R2 is H and R3 is H then R4 is not H.
47 more elements
(canceled)
A method for treating, ameliorating and/or preventing a neuromuscular disorder and/or reversing and/or ameliorating a neuromuscular blockade comprising:
- administering to a subject in need thereof a compound of Formula (I):
- wherein
- M is CR5R6, NR7, O or S;
- Q is CR5R6, NR8, O or S;
- T is CR5R6, NR8, O or S;
- X is absent, CR5R6, NR8, O or S;
- Z is CR5R6, NR9, O or S;
- two or more of M, Q, T, X and Z are NR7, NR8, NR9, O or S;
- R1 is selected from the group consisting of H;
- F;
- Cl;
- Br;
- C1-3 alkyl optionally substituted with one or more, identical or different, substituents R10;
- C2-3 alkenyl optionally substituted with one or more, identical or different, substituents R10;
- —OC1-3 alkyl optionally substituted with one or more, identical or different, substituents R10;
- —OC3-5 cycloalkyl optionally substituted with one or more, identical or different, substituents R10;
- —SC1-3 alkyl optionally substituted with one or more, identical or different, substituents R10 and —SC3-5 cycloalkyl optionally substituted with one or more, identical or different, substituents R10;
- R2 is selected from the group consisting of H;
- F;
- Cl;
- Br;
- C1-3 alkyl optionally substituted with one or more, identical or different, substituents R10 and OC1-3 alkyl optionally substituted with one or more, identical or different, substituents R10;
- R3 is selected from the group consisting of H, F and Cl;
- R4 is selected from the group consisting of H;
- C1-5 alkyl optionally substituted with one or more, identical or different, substituents R10;
- C2-5 alkenyl optionally substituted with one or more, identical or different, substituents R10;
- C2-5 alkynyl optionally substituted with one or more, identical or different, substituents R10;
- C3-6 cycloalkyl optionally substituted with one or more, identical or different, substituents R10;
- phenyl optionally substituted with one or more, identical or different, substituents R11;
- and benzyl optionally substituted with one or more, identical or different, substituents R11;
- R5 is independently selected from the group consisting of H, deuterium, F and C1-5 alkyl optionally substituted with one or more, identical or different, substituents R10;
- R6 is independently selected from the group consisting of H, deuterium, F and C1-5 alkyl optionally substituted with one or more, identical or different, substituents R10;
- R7 is independently selected from the group consisting of H, C1-5 alkyl optionally substituted with one or more, identical or different, substituents R10;
- C1-3 alkyl substituted with C3-5 cycloalkyl optionally substituted with one or more, identical or different, substituents R10;
- C1-3 alkyl substituted with phenyl optionally substituted with one or more, identical or different, substituents R11;
- C1-3 alkyl substituted with C5 heteroaryl optionally substituted with one or more, identical or different, substituents R11;
- and C3-5 cycloalkyl optionally substituted with one or more, identical or different, substituents R10;
- R8 is independently selected from benzyl optionally substituted with one or more, identical or different, substituents R11;
- R9 is independently selected from the group consisting of H, C1-5 alkyl optionally substituted with one or more, identical or different, substituents R10;
- C1-3 alkyl substituted with C3-5 cycloalkyl optionally substituted with one or more, identical or different, substituents R10;
- C1-3 alkyl substituted with phenyl optionally substituted with one or more, identical or different, substituents R11;
- C1-3 alkyl substituted with naphthyl optionally substituted with one or more, identical or different, substituents R11;
- C1-3 alkyl substituted with a 5- to 10-membered heteroaryl optionally substituted with one or more, identical or different, substituents R11;
- and C3-5 cycloalkyl optionally substituted with one or more, identical or different, substituents R10;
- R10 is independently selected from the group consisting of H, deuterium, F, Cl and —OC1-3 alkyl;
- and
- R11 is independently selected from the group consisting of deuterium, methoxy, —OCF3, Me, CF3, CF2Cl, CF2H, CFH2, CD3, cyclopropyl, NH2, —NHAc, —C(═O)—NH2, nitro, cyano, Cl, Br, I, and F;
- when R5 and R6 are individually C1-5 alkyl optionally substituted with one or more, identical or different, substituents R10, then R5 and R6 are optionally joined together to form a ring;
- or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof.
46 more elements
Dependencies are inferred from the claim text.