Ccr6 compounds

Patent metadata

Field	Value
Publication number	US-2019167659-A1
Application number	US-201816150796-A
Country	US
Kind code	A1
Filing date	Oct 3, 2018
Priority date	Dec 2, 2013
Publication date	Jun 6, 2019
Grant date	—

Abstract

Compounds of formula (I) are provided which are useful in the treatment of diseases or conditions modulated at least in part by CCR6:

First claim

1 . A compound having formula (I):

or a pharmaceutically acceptable salt, hydrate, solvate, N-oxide or rotamer thereof,

wherein
A is a carboxylic acid moiety or a carboxylic acid isostere;
ring vertices a, b, c and d are independently selected from N, CH and C(R 1 );
each R 1 is independently selected from the group consisting of halogen, CN, —SF 5 , C 1-8 alkyl, C 3-8 cycloalkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-8 haloalkyl, —OR a , —SR a , —COR a , —NR a R b , and 5- or 6-membered heteroaryl, wherein the alkyl portions of R 1 are optionally further substituted with 1-3 R a ; and optionally, adjacent R 1 members are connected to form an additional 5- or 6-membered ring which is saturated or unsaturated having ring vertices selected from C, O, S and N, wherein the additional 5- or 6-membered ring is optionally substituted with one or two members selected from the group consisting of halogen, hydroxyl, C 1-4 alkyl, C 1-4 alkoxy and C 1-4 haloalkyl;
the subscript m is an integer of from 0 to 2;
the subscript n is an integer of from 0 to 3;
each R 2 and R 3 is independently selected from the group consisting of halogen, CN, C 1-8 alkyl, C 3-8 cycloalkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-8 haloalkyl, aryl, —OR a , —NR a R b and —N(R a )—C 1 -C 4 alkylene-OR b , and wherein the alkyl or aryl portions of R 2 and R 3 are optionally further substituted with 1-3 R a ;
Ar is a 5- or 6-membered aromatic or heteroaromatic ring that is optionally substituted with from 1 to 5 R 4 substituents independently selected from the group consisting of halogen, CN, —SF 5 , C 1-8 alkyl, C 3-8 cycloalkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-8 haloalkyl, C 1-8 hydroxyalkyl, —OR a , —NR a R b , 5- or 6-membered heteroaryl, and 3-, 4-, 5- or 6-membered heterocycloalkane wherein the heteroatoms present as ring vertices of the heteroaryl and heterocycloalkane rings are selected from N, O and S, and wherein the alkyl, cycloalkyl, aryl, heteroaryl and hetereocycloalkane portions of R 4 are optionally further substituted with 1-3 R a ;
each R a and R b is independently selected from the group consisting of hydrogen, hydroxyl, halogen, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 3-6 cycloalkyl, amino, C 1-8 alkylamino, and di C 1-8 alkylamino, or when attached to a nitrogen atom are optionally combined to form a 4- to 7-membered saturated ring, which is optionally substituted with oxo.

2 - 18 . (canceled)

19 . A compound of claim 1 , wherein Ar is selected from the group consisting of:

wherein the wavy line labeled w indicates the point of attachment to the S(O) 2 moiety.

20 . A compound of claim 1 , selected from the group consisting of:

21 . A compound of claim 1 , selected from the group consisting of:

or a pharmaceutically acceptable salt, hydrate, solvate, N-oxide or rotamer thereof.

22 . A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt, hydrate, solvate, N-oxide or rotamer thereof, with a pharmaceutically acceptable excipient.

23 . A method of treating a disease or condition modulated at least in part by CCR6, comprising administering to a subject in need thereof, a compound of claim 1 , or a pharmaceutically acceptable salt, hydrate, solvate, N-oxide or rotamer thereof.

24 . A method in accordance with claim 23 , wherein said disease or condition is an inflammatory disease or condition.

25 . A method in accordance with claim 23 , wherein said disease or condition is atopic dermatitis.

26 . A method in accordance with claim 23 , wherein said disease or condition is psoriasis.

27 . A method of treating a disease or condition modulated at least in part by CCR6, comprising administering to a subject in need thereof, a compound of claim 19 , or a pharmaceutically acceptable salt, hydrate, solvate, N-oxide or rotamer thereof.

28 . A method in accordance with claim 27 , wherein the compound is selected from the group consisting of:

or a pharmaceutically acceptable salt, hydrate, solvate, N-oxide or rotamer thereof.

29 . A method in accordance with claim 27 , wherein the compound is selected from the group consisting of:

or a pharmaceutically acceptable salt, hydrate, solvate, N-oxide or rotamer thereof.

Assignees

• Chemocentryx Inc

Inventors

• Dairaghi Daniel
• Dragoli Dean R
• Kalisiak Jaroslaw
• Lange Christopher W
• Leleti Manmohan Reddy
• Li Yandong
• Lui Rebecca M
• Mali Venkat Reddy
• Malathong Viengkham
• Powers Jay P
• Tanaka Hiroko
• Tan Joanne
• Walters Matthew J
• Yang Ju
• Zhang Penglie

Classifications

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P5/16

  for decreasing, blocking or antagonising the activity of the thyroid hormones · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title