JPWO2020088659A5

JPWO2020088659A5 -

Info

Publication number: JPWO2020088659A5
Application number: JP2021525022A
Authority: JP
Publication date: 2022-11-01

Claims

Structural formula (VII):

(VII)
[In the formula,
R ¹ is selected from hydrogen, C ₁ -C ₆ unsubstituted or substituted alkyl, OR', COOR' and CONR'R'';
each R ³ is independently selected from hydrogen, C ₁ -C ₆ unsubstituted or substituted alkyl, OR′, COOR′, and CONR′R″;
R ⁴ is a group selected from hydrogen, halogen, CN, C ₁ -C ₆ unsubstituted or substituted alkyl, OR', and NHR';
R5 is ^Rx or ^NRxRy , each of ^Rx and ^Ry ^being independently selected from H, alkyl, cycloalkyl, heterocycloalkyl, aryl, ^heteroaryl , and ^Rx and R ^y may together form a 3- to 7-membered ring, and each of R ^x and R ^y is halogen, CN, OR', NR'R'', alkyl, haloalkyl, cyano optionally substituted with one or more of alkyl, hydroxyalkyl, and alkoxyalkyl; with the proviso that when ^R5 is ^Rx , ^Rx is not H;
each R _L is independently (CH ₂ ) _m and m is independently 0, 1, 2, or 3, and each bridge is absent when m is 0 with the proviso that at least one m is not 0,
each R' and R'' is independently selected from hydrogen and C ₁ -C ₆ unsubstituted and substituted alkyl, and R' and R'' together form a 3-7 membered ring and n is 1 or 2]
or a pharmaceutically acceptable form or isotopic derivative thereof.

2. The compound of claim 1, wherein no more than one _RL is absent.

2. The compound of claim 1, wherein each m is independently 1, 2 or 3.

2. The compound of claim 1, wherein each m is 1.

2. The compound of claim 1, wherein each m is two.

A compound according to any one of claims 1 to 5, wherein R ⁴ is H.

A compound according to any one of claims 1 to 6, wherein R ¹ is H.

A compound according to any one of claims 1 to 6, wherein R ¹ is methyl.

R ⁴ is H, n is 1, and structural formula (VIII):

(VIII)
7. The compound of claim 6, represented by

10. The compound of claim ⁹ , wherein ^R1 is methyl and R3 is H.

Both R ¹ and R ³ are H and structural formula (IX):

(IX)
10. The compound of claim 9, represented by

each R _L is CH ₂ and structural formula (X):

(X)
12. The compound of claim 11, represented by

A compound according to any one of claims 1 to 12, wherein R ⁵ is R ^x .

14. The compound of claim 13, wherein R ^x is a straight chain or branched C ₁ -C ₆ alkyl.

14. The compound of claim 13, wherein R ^x is a straight or branched chain C2 _- _C4 alkyl.

14. The compound of claim 13, wherein R ^x is n-propyl or isopropyl.

A compound according to any one of claims 1 to 12, wherein R ⁵ is NR ^x R ^y .

18. The compound of claim 17, wherein one of ^Rx and ^Ry is H.

R ^x and R ^y together with N in NR ^x R ^y are one of halogen, CN, OR', NR'R'', alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, and alkoxyalkyl The compound according to claim 17, which forms a 3- to 5-membered heterocyclic group optionally substituted with or more.

20. The compound of claim 19, wherein said heterocyclic group is a 4-membered heterocyclic group.

12. The compound of claim 11, wherein each _RL is ( _CH2 ) ₂ .

The following formula:

A compound selected from the group consisting of compounds represented by

The following formula:

A compound selected from the group consisting of compounds represented by

24. A pharmaceutical composition comprising a compound according to any one of claims 1-23 and a pharmaceutically acceptable excipient, carrier or diluent.

Use of a compound according to any one of claims 1 to 23, or a pharmaceutical composition according to claim 24, in the manufacture of a medicament for treating a disease or disorder, wherein said disease or disorder is an inflammatory disease , immune-mediated disease, and cancer.

26. Use according to claim 25, wherein said disease or disorder is an autoimmune disease.

Use of a compound according to any one of claims 1 to 23, or a pharmaceutical composition according to claim 24, in the manufacture of a medicament for treating a disease or disorder, wherein said disease or disorder is asthma, allergy , arthritis, juvenile arthritis, inflammatory bowel disease, endocrine disease, neurodegenerative disease, autism spectrum disorder, depression, Alzheimer's disease, Guillain-Barre syndrome, obsessive-compulsive disorder, optic neuritis, retinal degeneration, dry eye syndrome ( DES), Sjögren's syndrome, amyotrophic lateral sclerosis (ALS), Parkinson's disease, Huntington's disease, Guillain-Barre syndrome, myasthenia gravis, chronic idiopathic demyelinating disease (CID), vascular disease, skin disease, Hashimoto's thyroiditis, pernicious anemia, Cushing's disease, Addison's disease, chronic active hepatitis, polycystic ovary syndrome (PCOS), celiac disease, pemphigus, allograft rejection, graft-versus-host disease (GVDH) ), or diseases or disorders related thereto.

said disease or disorder is one of rheumatoid arthritis, ankylosing spondylitis, psoriasis, atopic dermatitis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, DES, vitiligo, alopecia areata, alopecia totalis 28. Use according to claim 27, which is or more.

said disease or disorder is hidradenitis suppurativa, giant cell arteritis, Takayasu's arteritis, polymyalgia rheumatoid arthritis, dermatomyositis, psoriatic arthritis, type 1 diabetes, Graves' disease, multiple sclerosis (MS), 28. according to claim 27, selected from autoimmune deafness, systemic vasculitis, atherosclerosis, acne vulgaris, dermatomyositis, pemphigus, systemic lupus erythematosus (SLE), discoid lupus erythematosus, alopecia Use as indicated.

Use according to any one of claims 25 to 29, wherein said therapeutic agent is for oral administration.

Use according to any one of claims 27-30, wherein said therapeutic agent is for topical administration.