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Lta4h inhibitors for the treatment of hidradenitis suppurativa

A technology of hidradenitis suppurativa and inhibitors, applied in the direction of medical preparations containing active ingredients, pill delivery, organic active ingredients, etc., which can solve problems such as debility

Pending Publication Date: 2021-08-13
NOVARTIS AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Since there is no medical cure for HS and the disease is both physically and psychologically debilitating, there is clearly an unmet need to provide HS patients with safe and effective long-term treatments, particularly oral treatments

Method used

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  • Lta4h inhibitors for the treatment of hidradenitis suppurativa
  • Lta4h inhibitors for the treatment of hidradenitis suppurativa
  • Lta4h inhibitors for the treatment of hidradenitis suppurativa

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 2

[0099]Embodiment 2A relates to the method of embodiment 2 comprising administering to the subject a therapeutically effective amount of a compound of formula (II) or a pharmaceutically acceptable salt thereof,

[0100]

[0101] wherein the variables R1, R2 and Y have the meanings as defined in Example 1.

[0102] Embodiment 2B relates to the method of embodiment 2 comprising administering to the subject a therapeutically effective amount of a compound of formula (III) or a pharmaceutically acceptable salt thereof,

[0103]

[0104] wherein the variables R1, R2 and Y have the meanings as defined in Example 1.

[0105] Embodiment 2C is directed to the method of embodiment 2, comprising administering to the subject a therapeutically effective amount of a compound of formula (IV) or a pharmaceutically acceptable salt thereof,

[0106]

[0107] wherein the variables R1, R2 and Y have the meanings as defined in Example 1.

[0108] Embodiment 2D is directed to the method o...

example 1

[0368] Example 1: (S)-3-amino-4-(5-(4-((5-chloro-3-fluoropyridin-2-yl)oxy)phenyl)-2H-tetrazol-2-yl) Butyric Acid (Form B)

[0369]

[0370] Example 29 (28 g, 35 mmol) as described in WO 2015 / 092740 and a solvent mixture containing 360 g water and 40 g THF were mixed together and stirred for 20 minutes. The mixture was filtered and washed with aqueous NaHCO 3 The filtrate was adjusted to pH=5. Stirring was continued for 18 h before the mixture was filtered to give 25.6 g of the free acid (Int-1 ) in a wet cake which was used without further purification to prepare polymorph Form B. 505 mg of free acid (Int-1) was weighed into a 20 ml glass vial and 6 mL of methanol was added. The slurry was heated to 50 °C and stirred using a magnetic stirrer for 4 days. The suspension was cooled to room temperature and filtered. The recovered solid was dried under vacuum at 40 °C for 2.5 h. The white solid was analyzed by XRPD, DSC and TGA (respectively Figure 1-3 ).

[0371] An al...

example 2

[0386] Compound of Example 1 as a formulation of capsules

[0387]

[0388] 1 of vegetable origin

[0389] 2 removed during processing

[0390] 3 The composition of the capsule shell is given in the table below

[0391] Components of a capsule shell

[0392]

[0393] E: Refers to the official number used by the European Union for colorants

[0394] Regulation (EU) 231 / 2012: Commission Regulation (EU) laying down the specifications for food additives. Capsules were purchased from Lonza (now Capsugel)

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PUM

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Abstract

The present disclosure relates to methods for treating Hidradenitis Suppurativa using a LTA4H inhibitor. Also disclosed herein are the LTA4H inhibitors, for treating Hidradenitis Suppurativa patients, as well as medicaments, dosing regimens, pharmaceutical formulations, combinations, dosage forms, and kits for use in the disclosed uses and methods.

Description

technical field [0001] The present disclosure relates to methods of treating hidradenitis suppurativa using leukotriene A4 hydrolase (LTA4H) inhibitors. Background technique [0002] Hidradenitis suppurativa (HS) (also known as acne inversa or Verneuil's disease) is a chronic, relapsing, inflammatory disease characterized by deep nodules, Sinus tracts and abscesses leading to fibrosis of the axilla, groin, breast folds, and anogenital area. (Revuz and Jemec (2016) Dermatol Clin [Dermatol Clinic] 34: 1-5; Jemec GB. (2012) N Engl J Med [New England Journal of Medicine] 366: 158-64). It is associated with severe pain and comorbidities, including metabolic, psychiatric, and autoimmune disorders, and an increased risk of skin cancer. (Revuz (2016); Shlyankevich et al (2014) J Am Acad Dermatol 71:1144-50; Kohorst et al (2015) J Am Acad Dermatol 73:S27- 35; Wolkenstein et al (2007) J Am Acad Dermatol 56:621-3). [0003] The reported prevalence of HS varies from <1% to 4% of ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/454A61K31/4995A61K45/06A61K9/00A61P17/02A61P17/10A61P17/00
CPCA61K31/454A61K31/4995A61K45/06A61P17/02A61P17/00A61P17/10A61K9/20A61K9/48A61K31/4439
Inventor C·洛斯切C·彭诺T·罗恩G·维佐利克
Owner NOVARTIS AG
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