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US 2014/0179682 A1Published application

Metabotrophic glutamate receptor 5 modulators and methods of use thereof

AssigneeSunovion Pharmaceuticals Inc.

InventorsMichele L. R. Heffernan, Larry Wendell Hardy, Frank Xinhe Wu, Lakshmi D. Saraswat, Kerry L. Spear

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Abstract Drawings Claims Description

Abstract

Compounds that modulate GluR5 activity and methods of using the same are disclosed.

Claims20

Dependent claims

Claim 1A compound of formula (I) or a pharmaceutically acceptable salt thereof · 263 words11 dependent Claim 2A compound of formula (II) or a pharmaceutically acceptable salt thereof · 167 wordsNo dependents Claim 3A compound of formula (III) or a pharmaceutically acceptable salt thereof · 332 wordsNo dependents Claim 4A compound of formula (IV) or a pharmaceutically acceptable salt thereof · 240 wordsNo dependents Claim 5A compound of formula (V) or a pharmaceutically acceptable salt thereof · 118 wordsNo dependents Claim 6A compound of formula (VI) or a pharmaceutically acceptable salt thereof wherein m and n are independently 0 or 1 · 316 wordsNo dependents Claim 7A compound of formula (VII) or a pharmaceutically acceptable salt thereof · 14 wordsNo dependents Claim 8A compound selected from · 10 wordsNo dependents Claim 9(canceled) · 1 wordNo dependents

A compound of formula (I) or a pharmaceutically acceptable salt thereof:

wherein
Q is CR9 or N;
m and n are each independently 0 or 1;
X is F, Cl, Br, or I;
R1, R2, R3, R4, R3, R6, R7, and R8 are each independently hydrogen, X, alkyl, heteroalkyl, or alkenyl;
or any two of R1, R2, R3, R4, R5 and R6 together with the atoms to which they are attached, form a cycloalkyl ring;
and
R9 is hydrogen or alkyl;
provided that
at least one of R1, R2, R3, R4, R5, R6, R7, and R8 is either X, or alkyl or heteroalkyl substituted with at least one X;
or a cycloalkyl ring formed by any two of R1, R2, R3, R4, R5 and R6 together with the atoms to which they are attached is substituted with at least one X;
at least one of R3 and R4 is not hydrogen;
when m and n are both 1, Q is CH, and R1, R2, R4, R5, and R6 are all H, then R3 is not CF3 or F;
when m and n are both 1, Q is CH, and R1, R2, R5, and R6 are all H, then R3 and R4 are not both F;
when m and n are both 1, Q is CH, R1, R2, R5, and R6 are all H, and R3 is unsubstituted alkyl, then R4 is not F;
and
when m is 1, n is 0, Q is CH, R1, R2, R5, and R6 are all H, and R3 is H or F, then R4 is not F.

14 more elements

A compound of formula (II) or a pharmaceutically acceptable salt thereof:

wherein
Q is CR7 or N;
G is CH2 or O;
R1 and R2 are independently hydrogen, alkyl, cyano, or heteroalkyl;
or R1 and R2 together with the atom to which they are attached form a cycloalkyl or heterocycloalkyl ring;
and
R7 is selected from hydrogen and alkyl
provided that
when Q is N and G is CH2, then at least one of R1 and R2 is not hydrogen;
when Q is N, G is CH2, and one of R1 and R2 is methyl, then the other of R1 and R2 is not hydrogen or methyl;
when Q is N, G is CH2, and one of R1 and R2 is hydroxymethyl or methoxymethyl, then the other of R1 and R2 is not hydrogen;
and
when Q is N, G is CH2, and R1 and R2 together with the atom to which they are attached form a heterocycloalkyl ring, then R1 and R2 together are not —(CH2)2—O—(CH2)2—.

10 more elements

A compound of formula (III) or a pharmaceutically acceptable salt thereof:

wherein
R1, R2, R3, and R4 are each independently hydrogen, alkyl, hydroxyl, alkenyl, heteroalkyl, or cyano;
or
R1 and R2 or R3 and R4 together with the atom to which they are attached form a cycloalkyl or heterocycloalkyl ring;
or
R2 and R3 together with the atoms to which they are attached form a cycloalkyl ring;
R3 is hydrogen or alkyl;
R6, R7, and R8 are each independently hydrogen, CN, heteroalkyl, alkyl, or X;
and
X is F, Cl, Br, or I;
provided that
R3 and R4 cannot together form ═CH2;
when R1, R2, R3, and R4 are all hydrogen, then at least one of R5, R6, R7, and R8 is not hydrogen
when both R1 and R2 are methyl, then at least one of R3, R4, R5, R6, R7, and R is other than hydrogen;
when both R3 and R4 are methyl, then at least one of R1, R2, R3, R6, R7, and R8 is not hydrogen;
when one of R1, R2, R3, and R4 is methyl, and the other three of R1, R2, R3, and R4 are all hydrogen, then at least one of R5, R6, R7, and R8 is not hydrogen;
when one of R1 and R2 is hydroxymethyl or methoxymethyl and the other of R1 and R2 is hydrogen, then at least one of R3, R4, R5, R6, R7, and R8 is not hydrogen;
when one of R3 and R4 is hydroxymethyl, hydroxy, methoxy, methoxymethyl, or fluoro, and the other of R3 and R4 is hydrogen, then at least one of R1, R2, R5, R6, R7, and R8 is not hydrogen;
when one of R3 and R4 is methyl and the other of R3 and R4 is hydroxyl or methoxy, then at least one of R1, R2, R5, R6, R7, and R8 is not hydrogen;
when R3 and R4 are both F, then at least one of R1, R2, R5, R6, R7, and R8 is not hydrogen.

17 more elements

A compound of formula (IV) or a pharmaceutically acceptable salt thereof:

wherein
m and n are each independently 0 or 1;
R1, R2, R3, R4, R5, and R6 are each independently hydrogen, alkyl, or heteroalkyl;
or
R1 and R2, R3 and R4, or R5 and R6 together with the atom to which they are bonded form a cycloalkyl or heterocycloalkyl ring;
provided that
at least one of R1, R2, R3, R4, R5, and R6 is not hydrogen;
when m and n are both 1 or both in and n are 0, one of R3 and R4 is methyl, and the other of R3 and R4 is hydrogen, then at least one of R1, R2, R5, and R6 is not hydrogen;
when in is 0, n is 1, and both R5 and R6 are methyl, then at least one of R1, R2, R3, and R4 is not hydrogen;
when m is 1, n is 0, and both R3 and R4 are methyl, then at least one of R1, R2, R5, and R6 is not hydrogen;
when m and n are both 0 and both R3 and R4 are methyl, then at least one of R1, R2, R5 and R6 is not hydrogen;
and
when m and n are both 0, one of R5 and R6 is hydroxymethyl or methoxymethyl, and the other of R5 and R6 is hydrogen, then at least one of R1, R2, R3, and R4 is not hydrogen.

10 more elements

A compound of formula (V) or a pharmaceutically acceptable salt thereof:

wherein
m and n are independently 0 or 1;
Z is
R1, R2, R3, R4, R5, and R6 are each independently hydrogen or alkyl;
Q is O or S;
R7 and R8 are hydrogen or alkyl;
or R7 and R8 together with the atoms to which they are attached form a cyclolalkyl, heterocycloalkyl, aryl, or heteroaryl ring;
provided that
when in is 1, n is 1, Z is
Q is S, R7 is methyl and R8 is hydrogen, one of R3 and R4 is methyl, and the other of R3 and R4 is hydrogen, then at least one of R1, R2, R5 and R6 is not hydrogen.

7 more elements

A compound of formula (VI) or a pharmaceutically acceptable salt thereof

wherein
m and n are independently 0 or 1;
L is —R8C═CR8—, —OC(R9)2—, C(O)NR10—, or —NR10C(O)—;
X is F, Cl, Br, or I;
R1, R2, R3, R4, R5, and R6 are each independently hydrogen, alkyl, or X;
R7 is hydrogen or cyano;
each R8 is hydrogen or X;
R9 and R10 are each independently hydrogen or alkyl;
provided that
when in is 0, n is 0, L is —HC═CH—, one of R3 and R4 is methyl, the other of R3 and R4 is hydrogen, R1, R2, R5, and R6 are all hydrogen, and R7 is hydrogen, then Pyr is not 2-pyridyl;
when m is 0, n is 1, L is —HC═CH—, R1, R2, R3, and R4 are all hydrogen, R5 and R6 are both methyl, and R7 is hydrogen or cyano, then Pyr is not
when m is 1, n is 0, L is —HC═CH—, R1, R2, R5, and R6 are all hydrogen, R3 and R4 are both methyl, and R7 is hydrogen or cyano, then Pyr is not
when m is 0, n is 1, L is —HC═CH—, R1, R2, R5, and R6 are all hydrogen, R3 and R4 are both methyl, and R7 is hydrogen or cyano, then Pyr is not
when in is 1, n is 0, L is —HC═CH—, R3, R4, R5, and R6 are all hydrogen, R1 and R2 are both methyl, and R7 is hydrogen or cyano, then Pyr is not
when m is 1, n is 1, L is —HC═CH—, one of R3 and R4 is methyl, the other of R3 and R4 is hydrogen, R1, R5, and R6 are all hydrogen, and R7 is hydrogen or cyano, then Pyr is
and
when m is 1, n is 1, L is —HC═CH—, R1, R2, R3, R4, R5, R6, and R7 are all hydrogen, then Pyr is not 2-pyridyl.

14 more elements

A compound of formula (VII) or a pharmaceutically acceptable salt thereof:

wherein Z is

A compound selected from:

or a pharmaceutically acceptable salt thereof.

(canceled)

Dependencies are inferred from the claim text.

Facts

Application: 14/124,455Filed 8 Jun 2012
Priority: 8 Jun 2011
Published: 26 Jun 2014
Term ends: Not estimatedThe source records don’t support an estimate.

Classification12 codes

C07D 487/04
In which the condensed system contains two hetero rings: ortho-condensed systems
C07D 471/04
In which the condensed system contains two hetero rings: ortho-condensed systems
C07D 471/14
In which the condensed system contains three hetero rings: ortho-condensed systems
C07D 471/20
In which the condensed system contains three hetero rings: spiro-condensed systems

Family

Application61/494,731Us provisional application · filed 8 Jun 2011
US 9,260,452 B2Related patent
US 2014/0179682 A1This patent

From the US filing history. Foreign family members aren’t listed.

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