Polymorphic compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-2022017475-A1
Application number	US-201917265757-A
Country	US
Kind code	A1
Filing date	Aug 6, 2019
Priority date	Aug 6, 2018
Publication date	Jan 20, 2022
Grant date	—

Abstract

The present invention provides freebase and salt forms, and compositions and methods thereof, useful for treating various conditions in which aldehyde toxicity is implicated in the pathogenesis by the administration of small molecule therapeutics acting as a scavenger for toxic aldehydes.

First claim

We claim:

1 - 25 . (canceled)

26 . Compound A:

wherein the compound is crystalline.

27 . The compound of claim 26 , wherein compound A is substantially free of amorphous compound A.

28 . The compound of claim 27 , wherein compound A is at least 95% crystalline solid by weight.

29 . The compound of claim 26 , wherein compound A is of Form A characterized in that it has one or more peaks in its X-ray powder diffraction pattern selected from those at 8.2±0.2 degrees 2-theta, 16.2±0.2 degrees 2-theta, and 22.2±0.2 degrees 2-theta.

30 . The compound of claim 26 , wherein compound A is of Form A characterized in that it has peaks in its X-ray powder diffraction pattern at 8.2±0.2 degrees 2-theta, 16.2±0.2 degrees 2-theta, and 22.2±0.2 degrees 2-theta.

31 . The compound of claim 26 , wherein compound A is of Form A characterized in that it has an X-ray powder diffraction (XRPD) pattern substantially similar to the XRPD pattern provided in FIG. 1 .

32 . The compound of claim 26 , wherein compound A is of Form B characterized in that it has one or more peaks in its X-ray powder diffraction pattern selected from those at 10.2±0.2 degrees 2-theta, 11.5±0.2 degrees 2-theta, and 23.3±0.2 degrees 2-theta.

33 . The compound of claim 26 , wherein compound A is of Form B characterized in that it has peaks in its X-ray powder diffraction pattern at 10.2±0.2 degrees 2-theta, 11.5±0.2 degrees 2-theta, and 23.3±0.2 degrees 2-theta.

34 . The compound of claim 26 , wherein compound A is of Form B characterized in that it has an X-ray powder diffraction (XRPD) pattern substantially similar to the XRPD pattern provided in FIG. 3 .

35 . The compound of claim 26 , wherein compound A is of Form C characterized in that it has one or more peaks in its X-ray powder diffraction pattern selected from those at 15.8±0.2 degrees 2-theta, 23.0±0.2 degrees 2-theta, and 23.1±0.2 degrees 2-theta.

36 . The compound of claim 26 , wherein compound A is of Form C characterized in that it has peaks in its X-ray powder diffraction pattern at 15.8±0.2 degrees 2-theta, 23.0±0.2 degrees 2-theta, and 23.1±0.2 degrees 2-theta.

37 . The compound of claim 26 , wherein compound A is of Form C characterized in that it has an X-ray powder diffraction (XRPD) pattern substantially similar to the XRPD pattern provided in FIG. 5 .

38 . A compound selected from one of the following:
compound 2:

of Forms A, B or C;
compound 3:

of Forms A, B or C;
compound 4:

compound 5:

of Forms A, B or C;
compound 6:

compound 7:

of Forms A, B or C;
compound 8:

of Forms A or B;
compound 9:

compound 10:

compound 11:

and
compound 12:

39 . The compound of claim 38 , wherein the compound is compound 2.

40 . The compound of claim 38 , wherein the compound is compound 3.

41 . The compound of claim 38 , wherein the compound is compound 4.

42 . The compound of claim 38 , wherein the compound is compound 5 or 7.

43 . The compound of claim 38 , wherein the compound is compound 6, 8, 9, 10, 11, or

12 .

44 . A method of treating a condition selected from dry eye, cataracts, keratoconus, Fuch's endothelial dystrophy in the cornea, uveitis, allergic conjunctivitis, ocular cicatricial pemphigoid, conditions associated with photorefractive keratectomy (PRK) healing or other corneal healing, conditions associated with tear lipid degradation or lacrimal gland dysfunction, ocular rosacea (with or without meibomian gland dysfunction), skin cancer, psoriasis, contact dermatitis, atopic dermatitis, acne vulgaris, Sjogren-Larsson Syndrome, ischemic-reperfusion injury, inflammation, diabetes, Parkinson's disease, scleroderma, amyotrophic lateral sclerosis, lupus, atherosclerosis, and conditions associated with the injurious effects of blister agents; comprising administering to a subject in need thereof an effective amount of a compound of claim 26 .

45 . A method of treating a condition selected from diabetic macular edema (DME), atopic keratoconjunctivitis (AKC), vernal keratoconjunctivitis (VKC), age-related macular degeneration (AMD), dry eye disease (DED), allergic conjunctivitis (AC), dry eye disease with allergic conjunctivitis, non-infectious anterior uveitis, posterior uveitis, pan-uveitis, post-surgical ocular pain and inflammation, corneal fibrosis after radial keratotomy, corneal fibrosis after trauma or exposure to vesicants, corneal fibrosis after infection, non-clinically significant macular edema (Non-CSME), clinically significant macular edema (CSME), uveitis, anterior uveitis, non-infectious uveitis, Behcet's syndrome, ankylosing spondylitis, Lyme disease, sarcoidosis, and psoriasis; comprising administering to a subject in need thereof an effective amount of a compound of claim 26 .

Assignees

• Aldeyra Therapeutics Inc

Inventors

• Machatha Stephen Gitu
• Loughrey Jonathan J
• Mclachlan Hannah Ruth
• Sneddon Gregor

Classifications

• C07C59/10

  Polyhydroxy carboxylic acids · CPC title

• C07C55/08

  Malonic acid · CPC title

• C07C55/06

  Oxalic acid · CPC title

• C07D263/57 Primary

  Aryl or substituted aryl radicals · CPC title

• C07C309/30

  of six-membered aromatic rings substituted by alkyl groups · CPC title