Azabicyclo and diazepine derivatives

Patent metadata

Field	Value
Publication number	US-11306090-B2
Application number	US-201816760192-A
Country	US
Kind code	B2
Filing date	Nov 2, 2018
Priority date	Nov 3, 2017
Publication date	Apr 19, 2022
Grant date	Apr 19, 2022

Abstract

The present invention provides in one aspect azabicyclo and diazepine derivatives useful as modulators of muscarinic receptors. In another aspect, the present invention provides pharmaceutical compositions for treating ocular diseases, the compositions comprising at least one muscarinic receptor modulator.

First claim

What is claimed is:

1. A compound or a pharmaceutically acceptable salt thereof, wherein the compound is presented by formula (I):

wherein
Me=CH 3 ;
A=NR 5 ;
X=—OH, —O—Y—Z, —S—Y—Z, or —NR 5 —Y—Z;
R 1 and R 2 are independently H, D, hydroxyl, alkoxy, nitrile, halogen atoms, C 1 -C 20 straight, branched or cyclo alkyl groups optionally substituted with halogen atoms; or
R 1 and R 2 are independently phenyl or benzyl groups being optionally substituted with one or more substituents selected from C 1 -C 20 straight, branched or cyclo alkyl groups, halo alkyl groups, hydroxyl, alkoxy, nitrile, nitro, amino, amide, ester, sulfone, sulfoxide, sulfonamide, and halogen atoms; or
R 1 and R 2 are independently a heterocyclic saturated, unsaturated or aromatic 5- or 6-member ring containing one or more heteroatoms selected from nitrogen, oxygen and sulfur and being optionally substituted with one or more substituents selected from C 1 -C 20 straight, branched or cyclo alkyl, halo alkyl groups, hydroxyl, alkoxy, nitrile, nitro, amino, amide, ester, sulfone, sulfoxide or halogen atoms;
R 3 and R 4 are independently hydrogen, C 1 -C 10 straight or branched or cyclo alkyl or halo alkyl groups or
R 3 and R 4 can combine to form 3- to 6-membered rings;
R 5 ═H, a C 1 -C 20 straight or branched alkyl groups, or a C 1 -C 10 straight or branched haloalkyl groups;
Y is a bivalent radical having the following meaning:
a) Straight or branched C 1 -C 20 alkyl, being optionally substituted with one or more of the substituents selected from the group consisting of: halogen atoms and hydroxyl;
b) —C(O)(C 1 -C 10 alkyl)- or —C(O)(CH 2 ) n C(O)O—(C 1 -C 10 alkyl)- or —(C 1 -C 10 alkyl)-;
c)

d)

e)

or
f)

wherein n is an integer from 0 to 20;

R 6 and R 7 are independently H or C 1 -C 10 , straight or branched alkyl groups, C 1 -C 10 straight or branched haloalkyl groups; or
R 6 and R 7 can combine to form 3- to 6-membered rings; and
Z is H, —OH, C 1-6 alkoxy, —COOH, —NR 8 R 9 ;
R 8 and R 9 are independently C 1 -C 20 alkyl, being optionally substituted with one or more substituents selected from hydroxyl, amino, ester, carboxylic acid, and halogen atoms; or
R 8 and R 9 can combine to form 3- to 6-membered rings containing one or more heteroatoms which are selected from the group consisting of:

2. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is

3. A pharmaceutical composition comprising: (1) a compound of claim 1 and/or a pharmaceutically acceptable salt thereof; and (2) one or more pharmaceutically acceptable carriers.

4. The composition according to claim 3 , wherein said composition is a topical composition.

5. The composition according to claim 3 , wherein said composition is an ophthalmically compatible composition.

6. The composition according to claim 5 , wherein said composition is a topical composition.

7. The composition according to claim 5 , wherein said composition comprises a therapeutically effective amount of said compound, and/or said pharmaceutically acceptable salt.

8. The composition according to claim 7 , wherein said composition is a topical composition.

9. The composition according to claim 5 , wherein said composition comprises from about 0.01 to about 10.0 weight percent of said compound and/or said pharmaceutically acceptable salt.

10. The composition according to claim 9 , wherein said composition is a topical composition.

11. The composition according to claim 5 , wherein said composition comprises: from about 0.01 percent weight/volume to about 5 weight/volume percent of said compound and/or said pharmaceutically acceptable salt; or from about 0.1 to 5.0 weight percent of said compound and/or said pharmaceutically acceptable salt.

12. The composition according to claim 11 , wherein said composition is a topical composition.

13. A combination comprising: (1) a therapeutically effective amount of a compound according to claim 1 and/or a pharmaceutically acceptable salt thereof; and (2) one or more therapeutically active agents.

14. A method of treating a mammalian subject having or at risk of having an ocular disorder, said method comprising administering to the subject an effective amount of: (a) a compound according to claim 1 and/or (b) a pharmaceutically acceptable salt thereof.

Assignees

• Alcon Inc

Inventors

• Ellis David
• Ketelson Howard Allen

Classifications

• C07D471/08 Primary

  Bridged systems · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61P27/10 Primary

  for accommodation disorders, e.g. myopia · CPC title

• C07D243/38

  [b, e]- or [b, f]-condensed with six-membered rings · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title