Novel 5-hydroxytryptamine receptor 7 activity modulators and their method of use

Patent metadata

Field	Value
Publication number	US-2018016261-A1
Application number	US-201715716752-A
Country	US
Kind code	A1
Filing date	Sep 27, 2017
Priority date	Mar 11, 2013
Publication date	Jan 18, 2018
Grant date	—

Abstract

Pharmaceutical compositions of the invention comprise functionalized lactone derivatives having a disease-modifying action in the treatment of diseases associated with dysregulation of 5-hydroxytryptamine receptor 7 activity.

First claim

What is claimed is:

1 . A compound having formula (I):

Including hydrates, solvates, pharmaceutically acceptable salts, and complexes thereof, wherein:
A is selected from a group consisting of

R 1a and R 1b are independently selected from a group consisting of hydrogen, C 1-6 linear alkyl, C 1-6 branched alkyl, and optionally substituted aryl that is substituted with 0 to 3 units selected from halogen, —CN, —NO 2 , —OH, —NH 2 , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-8 alkenyl, C 2-8 alkynyl, and C 3-14 cycloalkyl;
R 1a and R 1b are taken together with the atom to which they are bound to form a ring having from 3 to 7 ring atoms;
R 2a and R 2b are hydrogen;
R 3 is selected from a group consisting of C 1-6 linear alkyl, C 1-6 branched alkyl, C 3-7 cycloalkyl,

 optionally substituted aryl, and optionally substituted heteroaryl,
wherein the optionally substituted aryl is substituted with 0 to 3 units selected from halogen, —CN, —NO 2 , —OH, —NH 2 , C 1-6 alkyl, C 3-7 branched alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-8 alkenyl, and C 2-8 alkynyl;
and wherein the optionally substituted aryl is substituted with 0 to 1 units selected from C 3-14 cycloalkyl, aryl, heterocycle, and heteroaryl;
and wherein the optionally substituted heteroaryl is substituted with 0 to 3 units selected from halogen, —CN, —NO 2 , —OH, —NH 2 , C 1-6 alkyl, C 3-7 branched alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-8 alkenyl, and C 2-8 alkynyl;
and wherein the optionally substituted heteroaryl is substituted with 0 to 1 units selected from C 3-14 cycloalkyl, aryl, heterocycle, and heteroaryl;

R 4 is optionally substituted aryl,
wherein the optionally substituted aryl is substituted with 0 to 3 units selected from halogen, —CN, —NO 2 , —OH, —NH 2 , C 1-6 alkyl, C 3-7 branched alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-8 alkenyl, and C 2-8 alkynyl;
and wherein the optionally substituted aryl is substituted with 0 to 1 units selected from C 3-14 cycloalkyl, aryl, heterocycle, and heteroaryl;

R 5a and R 5b are each independently optionally substituted aryl,
wherein the optionally substituted aryl that is substituted with 0 to 3 units selected from halogen, —CN, —NO 2 , —OH, —NH 2 , C 1-6 alkyl, C 3-7 branched alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-8 alkenyl, and C 2-8 alkynyl;
and wherein the optionally substituted aryl is substituted with 0 to 1 units selected from C 3-14 cycloalkyl, aryl, heterocycle, and heteroaryl;

R 6a , R 6b , R 6c , and R 6d are each independently selected from a group consisting of hydrogen, halogen, OH, C 1-6 linear alkyl, C 1-6 branched alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, C 1-6 haloalkoxy, cyano, NH(C 1-6 alkyl), N(C 1-6 alkyl) 2 , NHC(O)R 7 , C(O)NHR 7 , C(O)N(R 7 ) 2 , SH, SC 1-6 alkyl, SO 2 NH 2 , SO 2 NHR 7 , SO 2 R 7 , and NHSO 2 R 7 ;
R 7 is independently selected at each occurrence from a group consisting of C 1-6 linear alkyl, C 1-6 branched alkyl, and C 3-7 cycloalkyl;
HetAr is optionally substituted heteroaryl,
wherein the optionally substituted heteroaryl is substituted with 0 to 3 units selected from halogen, —CN, —NO 2 , —OH, —NH 2 , C 1-6 alkyl, C 3-7 branched alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-8 alkenyl, and C 2-8 alkynyl;
and wherein the optionally substituted heteroaryl is substituted with 0 to 1 units selected from C 3-14 cycloalkyl, aryl, heterocycle, and heteroaryl;

n is 2 or 3;
and m is 1 or 2.

2 . The compound of claim 1 , having the formula (XXXXII):

Including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, and complexes thereof.

3 . The compound of claim 1 , having the formula (XXXXIV):

Including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, and complexes thereof.

4 . The compound of claim 1 , having the formula (XXXXVI):

Including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, and complexes thereof.

5 . The compound of claim 1 , having the formula (XXXXVIII):

Including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, and complexes thereof.

6 . The compound of claim 1 , having the formula (XXXXX):

Including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, and complexes thereof.

7 . The compound of claim 1 , having the formula (XXXXXI):

Including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, and complexes thereof.

8 . The compound of claim 1 , having the formula (XXXXXII):

Including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, and complexes thereof.

9 . The compound of claim 1 , having the formula (XXXXXIII):

Including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, and complexes thereof.

10 . The compound of claim 1 , having the formula (XXXXXIV):

Including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, and complexes thereof.

11 . The compound of claim 1 , having the formula (XXXXXV):

Including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, and complexes thereof.

12 . The compound of claim 1 , having the formula (XXXXXVI):

Including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, and complexes thereof.

13 . The compound of claim 1 , having the formula (XXXXXVII):

Including hydrates, solvates, enantiomers, diasteromers, pharmaceutically acceptable salts, and complexes thereof.

14 . The compound of claim 1 , having the formula (XXXXXVIII):

In

Assignees

• Univ Temple

Inventors

• Canney Daniel J
• Blass Benjamin E
• Gao Rong
• Abou-Gharbia Magid

Classifications

• A61P9/12

  Antihypertensives · CPC title

• A61P25/18

  Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P3/00

  Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) · CPC title

• A61P25/24

  Antidepressants · CPC title