IP Library › Patent Application 18984391
Patent Application
App. No. 18/984,391

DEUTERATED CFTR POTENTIATORS

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Quick Facts
Patent No.
US None
App. No.
18/984,391
Abstract

This invention relates to compounds of Formula I: and pharmaceutically acceptable salts thereof. This invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering a CFTR potentiator.

Claims (394)

1 .- 19 . (canceled)

20 . A pharmaceutical composition suitable for oral administration comprising a compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:

each of X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , and X 7 is independently hydrogen or deuterium;

each of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , and Y 6 is independently CH 3 or CD 3 ;

provided that if each of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , and Y 6 is CH 3 , then at least one of X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , and X 7 is deuterium, and

wherein the pharmaceutical composition further comprises one or more additional therapeutic agents.

21 . The pharmaceutical composition of claim 20 , wherein X 1 , X 2 , X 3 , and X 4 of the compound of Formula I are the same.

22 . The pharmaceutical composition of claim 20 , wherein Y 1 , Y 2 , and Y 3 of the compound of Formula I are the same.

23 . The pharmaceutical composition of claims 20 , wherein Y 4 , Y 5 , and Y 6 of the compound of Formula I are the same.

24 . The pharmaceutical composition of claim 20 , wherein X 6 and X 7 of the compound of Formula I are the same.

25 . The pharmaceutical composition of claim 20 , wherein X 5 of the compound of Formula I is deuterium.

26 . The pharmaceutical composition of claim 20 , wherein Y 1 , Y 2 , and Y 3 of the compound of Formula I are CD 3 .

27 . The pharmaceutical composition of claim 20 , wherein Y 4 , Y 5 , and Y 6 of the compound of Formula I are CD 3 .

28 . The pharmaceutical composition of claim 20 , wherein any atom not designated as deuterium is present at its natural isotopic abundance.

29 . The pharmaceutical composition of claim 20 , wherein the compound of Formula I is any one of the compounds in the table below:

TABLE 1

Cmpd

#

X 1

X 2

X 3

X 4

X 5

X 6

X 7

Y 1

Y 2

Y 3

Y 4

Y 5

Y 6

100

D

D

D

D

D

D

D

CD 3

CD 3

CD 3

CD 3

CD 3

CD 3

101

H

H

H

H

D

H

H

CD 3

CD 3

CD 3

CD 3

CD 3

CD 3

102

H

H

H

H

D

H

H

CD 3

CD 3

CD 3

CH 3

CH 3

CH 3

103

H

H

H

H

D

H

H

CH 3

CH 3

CH 3

CD 3

CD 3

CD 3

104

H

H

H

H

D

H

H

CH 3

CH 3

CH 3

CH 3

CH 3

CH 3

105

H

H

H

H

H

H

H

CD 3

CD 3

CD 3

CD 3

CD 3

CD 3

106

H

H

H

H

H

H

H

CD 3

CD 3

CD 3

CH 3

CH 3

CH 3

107

H

H

H

H

H

H

H

CH 3

CH 3

CH 3

CD 3

CD 3

CD 3

or a pharmaceutically acceptable salt thereof, wherein any atom not designated as deuterium is present at its natural isotopic abundance.

30 . The pharmaceutical composition of claim 20 , wherein the compound of Formula I is any one of the compounds in the table below:

Cmpd #

X 1

X 2

X 3

X 4

X 5

X 6

X 7

Y 1

Y 2

Y 3

Y 4

Y 5

Y 6

110

H

H

H

H

H

D

D

CD 3

CD 3

CD 3

CD 3

CD 3

CD 3

111

H

H

H

H

D

D

D

CD 3

CD 3

CD 3

CD 3

CD 3

CD 3

112

H

H

H

H

D

D

D

CD 3

CD 3

CD 3

CH 3

CH 3

CH 3

113

H

H

H

H

D

D

D

CH 3

CH 3

CH 3

CD 3

CD 3

CD 3

114

H

H

H

H

D

D

D

CH 3

CH 3

CH 3

CH 3

CH 3

CH 3

115

H

H

H

H

H

D

D

CD 3

CD 3

CD 3

CH 3

CH 3

CH 3

116

H

H

H

H

H

D

D

CH 3

CH 3

CH 3

CD 3

CD 3

CD 3

117

D

D

D

D

D

D

D

CD 3

CD 3

CD 3

CH 3

CH 3

CH 3

118

D

D

D

D

D

D

D

CH 3

CH 3

CH 3

CD 3

CD 3

CD 3

119

D

D

D

D

D

H

H

CD 3

CD 3

CD 3

CH 3

CH 3

CH 3

120

D

D

D

D

D

H

H

CH 3

CH 3

CH 3

CD 3

CD 3

CD 3

121

H

H

H

H

H

H

D

CD 3

CD 3

CD 3

CD 3

CD 3

CD 3

122

H

H

H

H

H

H

D

CD 3

CD 3

CD 3

CH 3

CH 3

CH 3

123

H

H

H

H

H

H

D

CH 3

CH 3

CH 3

CD 3

CD 3

CD 3

or a pharmaceutically acceptable salt thereof, wherein any atom not designated as deuterium is present at its natural isotopic abundance.

31 . The pharmaceutical composition of claim 20 , wherein the compound of Formula I is the compound in the table below:

Cmpd #

X 1

X 2

X 3

X 4

X 5

X 6

X 7

Y 1

Y 2

Y 3

Y 4

Y 5

Y 6

106

H

H

H

H

H

H

H

CD 3

CD 3

CD 3

CH 3

CH 3

CH 3

or a pharmaceutically acceptable salt thereof.

32 . The pharmaceutical composition of claim 20 , wherein the pharmaceutical composition is in unit dosage form.

33 . The pharmaceutical composition of claim 32 , wherein the unit dosage form is a tablet.

34 . The pharmaceutical composition of claim 20 , wherein the one or more additional therapeutic agents are useful in the treatment of cystic fibrosis.

35 . The pharmaceutical composition of claim 34 , wherein the one or more additional therapeutic agents comprises a CFTR corrector.

36 . The pharmaceutical composition of claim 34 , wherein the one or more additional therapeutic agents comprises lumacaftor or tezacaftor.

37 . The pharmaceutical composition of claim 36 , wherein the one or more additional therapeutic agents comprises tezacaftor.

38 . A method of treating cystic fibrosis comprising administering to a patient in need thereof the pharmaceutical composition of claim 20 .