Hematopoietic growth factor mimetic small molecule compounds and their uses

Patent metadata

Field	Value
Publication number	US-9622991-B2
Application number	US-201514713930-A
Country	US
Kind code	B2
Filing date	May 15, 2015
Priority date	Oct 13, 2009
Publication date	Apr 18, 2017
Grant date	Apr 18, 2017

Abstract

The present embodiments relate to compounds with physiological effects, such as the activation of hematopoietic growth factor receptors. The present embodiments also relate to use of the compounds to treat a variety of conditions, diseases and ailments such as hematopoietic conditions and disorders.

First claim

What is claimed is:

1. A compound of formula VIIIb:

and pharmaceutically acceptable salts thereof,
wherein:
A-J is

 and Q-G is

or A-J is

 and Q-G is

or A-J is

 and Q-G is

or A-J is

 and Q-G is

each E is separately selected from the group consisting of —CR 10a — and N (nitrogen);
each R 10a is separately selected from the group consisting of H (hydrogen), halogen, cyano, C 1 -C 6 alkyl optionally substituted with up to five fluoro, C 1 -C 6 alkoxy optionally substituted with up to five fluoro, C 2 -C 6 alkenyl optionally substituted with up to five fluoro, C 2 -C 6 alkynyl optionally substituted with up to five fluoro, C 3 -C 7 cycloalkyl optionally substituted with up to five fluoro, and C 3 -C 7 cycloalkenyl optionally substituted with up to five fluoro;
A 4 is selected from the group consisting of C 3 -C 7 cycloalkenyl, C 3 -C 7 cycloalkyl, C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, C 2 -C 6 alkenyl, C 1 -C 6 alkoxy, —(CH 2 ) m NR P R L , heterocycle, polycyclic heterocyclyl, aryl, and heteroaryl, said C 3 -C 7 cycloalkenyl, C 3 -C 7 cycloalkyl, C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, C 2 -C 6 alkenyl, heterocycle, polycyclic heterocyclyl, aryl, and heteroaryl, each optionally substituted with one or more substituents selected from the group consisting of R 1 , R 2 , and R 3 ;
G 4 is selected from the group consisting of polycyclic heterocyclyl, aryl, and heteroaryl, each optionally substituted with one or more substituents selected from the group consisting of R 4 , R 5 , and R 6 ;
A 5 is selected from the group consisting of polycyclic heterocyclyl, aryl and heteroaryl, each optionally substituted with one or more substituents selected from the group consisting of R 1 , R 2 , and R 3 ;
each R B is separately selected from the group consisting of hydrogen, an optionally substituted C 1 -C 6 alkyl, an optionally substituted C 2 -C 6 alkenyl, and an optionally substituted C 3 -C 7 cycloalkyl;
each —NR E R F is separately selected, wherein each R E is independently selected from the group consisting of hydrogen and an optionally C 1 -C 6 alkyl, and each R F is independently selected from the group consisting of aryl and heteroaryl, said aryl and heteroaryl in the definition of R F are each optionally substituted with halogen, cyano, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkenyl, —C(═O)NR N R O , —OC(═O)NR N R O , —NHC(═O)NR N R O , —O(CH 2 ) q NR N R O , —NH(CH 2 ) q NR N R O —(CH 2 ) p NR N R O , an optionally substituted aryl and an optionally substituted heteroaryl, and said aryl and heteroaryl in the definition of R F are each further optionally fused with an optionally substituted nonaromatic heterocycle or an optionally substituted nonaromatic carbocycle;
R G is selected from the group consisting of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 8 cycloalkenyl, C 1 -C 6 heteroalkyl, C 2 -C 6 heteroalkenyl, C 2 -C 6 heteroalkynyl, heterocycle, aryl, and heteroaryl, each optionally substituted with one or more substituents selected from the group consisting of R 4 , R 5 , and R 6 , said aryl and heteroaryl in the definition of R G are each further optionally fused with an optionally substituted nonaromatic heterocycle or an optionally substituted nonaromatic carbocycle, or R G is —OR L or —NR P R L ;
R H is selected from the group consisting of hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 3 -C 7 cycloalkyl, and C 1 -C 3 haloalkyl, or —NR G R H is an optionally substituted non-aromatic heterocycle linked through a ring nitrogen atom;
each R 1 is separately selected from the group consisting of halogen, cyano, an optionally substituted C 1 -C 6 alkyl, an optionally substituted C 1 -C 6 alkoxy, an optionally substituted C 2 -C 6 alkenyl, an optionally substituted C 2 -C 6 alkynyl, an optionally substituted C 3 -C 7 cycloalkyl, optionally substituted C 3 -C 7 cycloalkenyl, an optionally substituted C 1 -C 6 haloalkyl, an optionally substituted C 1 -C 6 heteroalkyl, an optionally substituted aryl, and an optionally substituted heteroaryl;
each R 2 is separately selected from the group consisting of halogen, —O(CH 2 ) m OR I , —(CH 2 ) m OR I , —NR J R K , —(CH 2 ) m SR I , —C(═O)R L , —(CH 2 ) m R L , an optionally substituted C 1 -C 6 alkyl, an optionally substituted C 1 -C 6 alkoxy, an optionally substituted C 2 -C 6 alkenyl, an optionally substituted C 1 -C 6 haloalkyl, an optionally substituted C 1 -C 6 heteroalkyl, and an optionally substituted C 3 -C 7 cycloalkyl where said C 3 -C 7 cycloalkyl is further optionally fused with aryl or heteroaryl;
each R 3 is separately selected from the group consisting of halogen, —(CH 2 ) m OR G , —NR L C(═O)R M , —NR L C(═O)OR M , —NR L C(═O)NR N R O , —NR N R O , —(CH 2 ) m S(O) 0-2 R M , —(CH 2 ) m NHS(O) 0-2 R M , —(CH 2 ) m NO 2 , —(CH 2 ) m CN, —(CH 2 ) m R P , C 1 -C 6 alkyl C 1 -C 6 alkoxy, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 6 haloalkyl, heterocycle, aryl, polycyclic heterocyclyl, and heteroaryl, said heterocycle, aryl polycyclic heterocyclyl, and heteroaryl in the definition of R 3 are each optionally substituted with halogen, hydroxy, cyano, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, —C(═O)OR M , or —NR J R K ;
each R 4 is separately selected from the group consisting of halogen, cyano, an optionally substituted C 1 -C 6 alkyl, an optionally substituted C 1 -C 6 alkoxy, an optionally substituted C 2 -C 6 alkenyl, an optionally substituted C 2 -C 6 alkynyl, an optionally substituted C 3 -C 7 cycloalkyl, an optionally substituted C 1 -C 6 haloalkyl, an optionally substituted C 1 -C 6 heteroalkyl, an optionally substituted aryl, and an optionally substituted heteroaryl;
each R 5 is separately selected from the group consisting of halogen, —O(CH 2 ) m OR I , —(CH 2 ) m OR I , —NR J R K , —(CH 2 ) m SR I , —(CH 2 ) m C(═O)R L , —(CH 2 ) m R L , an optionally substituted C 1 -C 6 alkyl, an optionally substituted C 1 -C 6 alkoxy, an optionally substituted C 2 -C 6 alkenyl, an optionally substituted C 3 -C 7 cycloalkyl, an optionally substituted C 1 -C 6 haloalkyl, and an optionally substituted C 1 -C 6 heteroalkyl;
each R 6 is separately selected from the group consisting of halogen, —(CH 2 ) m OR G , —NR L C(═O)R M , —NR L C(═O)OR M , —NR L C(═O)NR N R O , —NR N R O , —(CH 2 ) m S(O) 0-2 R M , —(CH 2 ) m NHS(O) 0-2 R M , —(CH 2 ) m NO 2 , —(CH 2 ) m CN, —(CH 2 ) m R P , C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 6 haloalkyl, C 1 -C 6 heteroalkyl, heterocycle, aryl, polycyclic heterocyclyl, and heteroaryl, said heterocycle, aryl, polycyclic heterocyclyl, and heteroaryl in the definition of R 6 are each optionally substituted

Assignees

• Ligand Pharm Inc

Inventors

• Zhi Lin
• Hudson Andrew R
• Van Oeveren Cornelis A
• Roach Steven L
• Pedram Bijan
• Shen Yixing
• Valdez Lino J
• Basinger Jillian
• Grant Virginia Heather Sharron
• Pickens Jason C

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P7/06

  Antianaemics · CPC title