Pharmaceutical Compositions and Administrations Thereof

Patent metadata

Field	Value
Publication number	US-2016022664-A2
Application number	US-201514629097-A
Country	US
Kind code	A2
Filing date	Feb 23, 2015
Priority date	Apr 22, 2010
Publication date	Jan 28, 2016
Grant date	—

Abstract

The present invention relates to pharmaceutical compositions comprising a compound of Formula I in combination with one or both of a Compound of Formula II and/or a Compound of Formula III. The invention also relates to solid forms and to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis.

First claim

What is claimed is:

1 . A pharmaceutical composition comprising:
A Compound of Formula I

or pharmaceutically acceptable salts thereof, wherein:
ring A is selected from:

R 1 is —CF 3 , —CN, or —C≡CCH 2 N(CH 3 ) 2 ;
R 2 is hydrogen, —CH 3 , —CF 3 , —OH, or —CH 2 OH;
R 3 is hydrogen, —CH 3 , —OCH 3 , or —CN;

provided that both R 2 and R 3 are not simultaneously hydrogen; and

one or both of the following:
B. A Compound of Formula II

or pharmaceutically acceptable salts thereof, wherein:
T is —CH 2 —, —CH 2 CH 2 —, —CF 2 —, —C(CH 3 ) 2 —, or —C(O)—;
R 1 ′ is H, C 1-6 aliphatic, halo, CF 3 , CHF 2 , O(C 1-6 aliphatic); and
R D1 or R D2 is Z D R 9
wherein:
Z D is a bond, CONH, SO 2 NH, SO 2 N(C 1-6 alkyl), CH 2 NHSO 2 , CH 2 N(CH 3 )SO 2 , CH 2 NHCO, COO, SO 2 , or CO; and
R 9 is H, C 1-6 aliphatic, or aryl; and/or

C. A Compound of Formula III

or pharmaceutically acceptable salts thereof, wherein:
R is H, OH, OCH 3 or two R taken together form —OCH 2 O— or —OCF 2 O—;
R 4 is H or alkyl;
R 5 is H or F;
R 6 is H or CN;
R 7 is H, —CH 2 CH(OH)CH 2 OH, —CH 2 CH 2 N + (CH 3 ) 3 , or —CH 2 CH 2 OH;
R 8 is H, OH, —CH 2 CH(OH)CH 2 OH, —CH 2 OH, or R 7 and R 8 taken together form a five membered ring.

2 . The pharmaceutical composition of claim 1 , comprising a Compound of Formula I and a Compound of Formula II.

3 . The pharmaceutical composition of claim 1 , comprising a Compound of Formula I and a Compound of Formula III.

4 . The pharmaceutical composition of claim 1 , comprising a Compound of Formula I, a Compound of Formula II and a Compound of Formula III.

5 . The pharmaceutical composition of any one of claims 1 - 4 , wherein the Compound of Formula I is Compound 1

6 . The pharmaceutical composition of any one of claims 1 - 5 , wherein the Compound of Formula II is Compound 2

7 . The pharmaceutical composition of any one of claims 1 - 6 , wherein the Compound of Formula III is Compound 3

8 . A pharmaceutical composition comprising a component selected from any embodiment described in Column A of Table I in combination with one or both of the following:
a) a component selected from any embodiment described in Column B of Table I; and/or b) a component selected from any embodiment described in Column C of Table I.

TABLE I

Column A
Column B
Column C

Embodiments
Embodiments
Embodiments

Section
Heading
Section
Heading
Section
Heading

II.A.1. 
Compounds of
II.B.1. 
Compounds of
II.C.1.  
Compounds of

Formula I

Formula II

Formula III

II.A.2. 
Compound 1
II.B.2. 
Compound 2
II.C.2. 
Compound 3

III.A.1.a.
Compound 1
III.B.1.a.
Compound 2
III.C.1.a.
Compound 3

Form A

Form I

Form A

III.A.2.a.
Compound 1
III.B.2.a.
Compound 2
III.C.2.a.
Compound 3

Form A-HCl

Solvate Form A

Amorphous Form

III.A.3.a.
Compound 1
III.B.3.a.
Compound 2

Form B-HCl

HCl Salt Form A

III.A.4.a.
Compound 1
IV.A.1.a.
Compound 2
IV.B.1.a.
Compound 3

Form B

Form I Aqueous

Tablet

Formulation

Formulation

IV.A.2.a.
Compound 2

Form I Capsule

Formulation

IV.A.3.a.
Compound 2

Form I Tablet

Formulation

9 . A method of treating a CFTR mediated disease in a human comprisi

Assignees

• Vertex Pharma

Inventors

• Van Goor Fredrick F
• Alargova Rossitza Gueorguieva
• Alcacio Tim Edward
• Binch Hayley Marie
• Botfield Martyn Curtis
• Fanning Lev Tyler Dewey
• Grootenhuis Peter Diederik Jan
• Hurley Dennis James
• Kadiyala Irina Nikolaevna
• Kaushik Ritu Rohit
• Keshavarz-Shokri Ali
• Krawiec Mariusz
• Lee Elaine Chungmin
• Luisi Brian
• Medek Ales
• Numa Mehdi
• Sheth Urvi Jagdishbhai
• Silina Alina
• Verwijs Marinus Jacobus
• Yang Xiaoqing
• Young Christopher Ryan
• Zaman Noreen Tasneem
• Zhang Beili
• Zhang Yuegang
• Zlokarnik Gregor

Classifications

• A61K31/4709 Primary

  Non-condensed quinolines and containing further heterocyclic rings · CPC title

• G01N2500/04

  Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A) · CPC title

• A61K31/443

  containing a five-membered ring with oxygen as a ring hetero atom · CPC title

• A61K31/404

  Indoles, e.g. pindolol · CPC title

• C12Q1/34

  involving hydrolase · CPC title