US 10,300,060 B2 · Trk-inhibiting compound

Abstract

The present invention provides a drug containing a compound having Trk-inhibiting activity as an active ingredient in prophylaxis and/or therapy for Trk-related diseases such as pain, pruritus, lower urinary tract dysfunction, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease. A compound represented by the general formula (I), wherein all symbols represent the same meanings as described in the specification, a salt thereof, an N-oxide thereof, a solvate thereof or a prodrug thereof is useful as a drug component having Trk-inhibiting activity in prophylaxis and/or therapy of diseases such as pain, pruritus, lower urinary tract dysfunction, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease.

A compound represented by the general formula (I) or a salt, an N-oxide, a solvate, or a prodrug thereof:

wherein:
Cy1 represents a ring selected from a C3-10 monocyclic or bicyclic carbocycle and a 4- to 10-membered monocyclic or bicyclic heterocycle;
Cy2 represents a 6- 4- to 10-membered monocyclic or bicyclic heterocycle;
R1 represents:
(1) a halogen;
(2) a C1-6 alkyl group, C2-6 alkenyl group or C2-6 alkynyl group optionally substituted with a substituent selected from the group consisting of (i) a halogen and (ii) a hydroxy group;
(3) a C5-6 monocyclic carbocycle optionally substituted with one or two R5 groups;
(4) a 5- to 6-membered monocyclic heterocycle optionally substituted with one or two R5 groups;
(5) —S(O)m1—R6;
(6) —SO2NR7R8;
(7) —C(O)OR9;
(8) —NR10C(O)R11;
(9) —C(O)NR12R13;
(10) —OR14;
(11) —NR15R16;
(12) a cyano group;
or
(13) a nitro group;
R5 represents:
(1) a halogen;
(2) —S(O)m2-R17;
(3) —SO2NR18R19;
(4) —C(O)OR20;
(5) —NR21C(O)R22;
(6) —C(O)NR23R24;
(7) —OR25;
(8) —NR26R27;
(9) a cyano group;
(10) a nitro group;
or
(11) a C1-3 alkyl group optionally substituted with a substituent selected from the group consisting of (i) a halogen, (ii) a hydroxy group and (iii) an oxo group;
wherein, if two R5 groups are present, the R5 groups may be independently the same or different;
and
wherein, if the two R5 groups are respectively and independently a C1-3 alkyl group or a hydroxy group, and are attached to carbon atoms adjacent to each other on the C5-6 monocyclic carbocycle or the 5- to 6-membered monocyclic heterocycle, the two R5 groups may, optionally, form a ring together;
R6 to R27 respectively and independently represent (1) a hydrogen atom or (2) a C1-6 alkyl group optionally substituted with (i) a halogen or (ii) a hydroxy group;
when R18 and R19 are respectively and independently a C1-6 alkyl group, R18 and R19 groups may together form a ring;
R2 represents:
(1) a halogen;
(2) a C1-6 alkyl group optionally substituted with (i) a halogen or (ii) a hydroxy group;
(3) a C3-6 cycloalkyl group optionally substituted with (i) a halogen or (ii) a hydroxy group;
(4) a C1-6 alkoxy group optionally substituted with a halogen;
(5) —NR28R29;
(6) a 3- to 7-membered monocyclic heterocycle;
or
(7) —O-(3- to 7-membered monocyclic heterocycle);
R28 and R29 respectively and independently represent (1) a hydrogen atom or (2) a C1-6 alkyl group optionally substituted with (i) a halogen or (ii) a hydroxy group;
A1 and A2 respectively and independently represent ═CR3- or ═N—;
A3, A4, A5 and A6 respectively and independently represent ═CR4— or ═N—;
R3 and R4 respectively and independently represent a hydrogen atom or a halogen;
m1 is an integer from 0 to 2;
m2 is an integer from 0 to 2;
p is an integer from 0 to 7;
q is an integer of 0 from 7;
r is an integer of 0 from 2;
wherein, when p is 2 or more, each R1 may respectively and independently represent the same or different group;
when q is 2 or more, each R2 may respectively and independently represent the same or different group;
and
when r is 2 or more, each R3 may respectively and independently represent the same or different group.

55 more elements

Facts

Application

15/975,130Filed 9 May 2018 · continuation

Priority

JP 2013-02956319 Feb 2013

Published

US 2018/0256573 A113 Sep 2018

Granted

28 May 2019

Term ends

Not estimatedThe source records don’t support an estimate.

Classification21 codes

A61K 31/506
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: not condensed and containing further heterocyclic rings
A61K 31/136
Having aromatic rings , e.g. ketamine, nortriptyline: having the amino group directly attached to the aromatic ring, e.g. benzeneamine
A61K 31/444
Containing further heterocyclic ring systems: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
A61K 31/519
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: ortho- or peri-condensed with heterocyclic rings

Family

PCT/JP2014/053683Parent of this continuation · filed 18 Feb 2014

Application15/173,161Parent of this continuation · filed 3 Jun 2016

US 9,463,192 B2Parent of this continuation · filed 11 Oct 2016

Application15/291,700Parent of this continuation · filed 12 Oct 2016

US 9,498,453 B2Parent of this continuation · filed 22 Nov 2016

Application15/679,568Parent of this continuation · filed 17 Aug 2017

US 9,763,943 B2Parent of this continuation · filed 19 Sep 2017

US 2018/0256573 A1Pre-grant publication · published 13 Sep 2018

US 9,993,479 B2Parent of this continuation

Application14/768,727Parent of this continuation

US 2016/0000783 A1Published application

US 2016/0280684 A1Published application

US 2017/0027939 A1Published application

US 2017/0340634 A1Published application

US 10,300,060 B2This patent

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

Trk-inhibiting compound

Life of this patent

Trk-inhibiting compound

Life of this patent

Abstract

Claims11