Deuterated Meclizine

Patent metadata

Field	Value
Publication number	US-2018208566-A1
Application number	US-201615745929-A
Country	US
Kind code	A1
Filing date	Jul 21, 2016
Priority date	Jul 21, 2015
Publication date	Jul 26, 2018
Grant date	—

Abstract

This invention relates to deuterated forms of meclizine, and pharmaceutically acceptable salts or hydrates 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 meclizine and other Constitutive Androstane Receptor agonists or FGFR3 antagonists.

First claim

1 . A compound of Formula I:

or a pharmaceutically acceptable salt or hydrate thereof, wherein:
each instance of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , Y 7 , Y 8 , Y 9 , Y 10 , Y 11 , Y 12 and Y 13 is independently selected from hydrogen and deuterium;
R 1 is —CH 3 , —CH 2 D, —CHD 2 , or —CD 3 ;
when each Y 7 is hydrogen, then R 1 is —CH 2 D, —CHD 2 , or —CD 3 ; and
when each Y 7 and each Y 8 is deuterium and R 1 is —CH 3 , at least one of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , Y 9 , Y 10 , Y 11 , Y 12 or Y 13 is deuterium.

2 - 3 . (canceled)

4 . The compound of claim 1 , wherein each Y 7 is the same and each Y 8 is the same.

5 - 6 . (canceled)

7 . The compound of claim 1 , wherein R 1 is —CH 3 or —CD 3 .

8 . The compound of claim 1 , wherein:
each Y 1 and Y 2 are all the same; each Y 3 , each Y 4 and Y 5 are all the same; each Y 9 is the same; Y 10 , Y 11 , Y 12 and Y 13 are the same; and R 1 is selected from —CH 3 and —CD 3 .

9 . The compound of claim 8 , wherein each Y 7 is the same; and each Y 8 is the same.

10 . The compound of claim 9 , wherein each Y 7 and each Y 8 are all the same.

11 . The compound of claim 1 , wherein any atom not designated as deuterium is present at its natural isotopic abundance.

12 . The compound of claim 1 , wherein each Y 1 and each Y 2 are all the same; each Y 3 , each Y 4 and Y 5 are all the same; each Y 7 and each Y 8 are all the same; Y 10 ,Y 11 , Y 12 and Y 13 are the same; and the compound is selected from any one of the compounds set forth in the table below:

Compound

Y 10 /Y 11 /

#
Y 1 /Y 2
Y 3 /Y 4 /Y 5
Y 6
Y 7 /Y 8
Y 9
Y 12 /Y 13
R 1

100
D
H
H
H
H
H
CH 3

101
H
D
H
H
H
H
CH 3

102
H
H
D
H
H
H
CH 3

103
H
H
H
H
D
H
CH 3

104
H
H
H
H
H
D
CH 3

105
D
D
H
H
H
H
CH 3

106
D
H
D
H
H
H
CH 3

107
D
H
H
D
H
H
CH 3

108
D
H
H
H
D
H
CH 3

109
D
H
H
H
H
D
CH 3

110
H
D
D
H
H
H
CH 3

111
H
D
H
D
H
H
CH 3

112
H
D
H
H
D
H
CH 3

113
H
D
H
H
H
D
CH 3

114
H
H
D
D
H
H
CH 3

115
H
H
D
H
D
H
CH 3

116
H
H
D
H
H
D
CH 3

117
H
H
H
D
D
H
CH 3

118
H
H
H
D
H
D
CH 3

119
H
H
H
H
D
D
CH 3

120
D
D
D
H
H
H
CH 3

121
D
D
H
D
H
H
CH 3

122
D
D
H
H
D
H
CH 3

123
D
D
H
H
H
D
CH 3

124
D
H
D
D
H
H
CH 3

125
D
H
D
H
D
H
CH 3

126
D
H
D
H

Assignees

• Concert Pharmaceuticals Inc

Inventors

• Graham Philip B
• Liu Julie F

Classifications

• C07D295/073 Primary

  with the ring nitrogen atoms and the substituents separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings · CPC title

• A61K31/495

  having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53}) · CPC title

• A61K45/06

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