WO2004112785A1 - Nouvelle utilisation iii - Google Patents

Nouvelle utilisation iii Download PDF

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Publication number
WO2004112785A1
WO2004112785A1 PCT/SE2004/000957 SE2004000957W WO2004112785A1 WO 2004112785 A1 WO2004112785 A1 WO 2004112785A1 SE 2004000957 W SE2004000957 W SE 2004000957W WO 2004112785 A1 WO2004112785 A1 WO 2004112785A1
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WO
WIPO (PCT)
Prior art keywords
tetrahydro
methyl
wound healing
benzothiazol
oxo
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PCT/SE2004/000957
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English (en)
Inventor
Cecilia Nilsson
Catrine Dreifeldt
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Biovitrum Ab
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Publication of WO2004112785A1 publication Critical patent/WO2004112785A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/429—Thiazoles condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/428—Thiazoles condensed with carbocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like

Definitions

  • the present invention relates to the use of chemical compounds for wound healing, said compounds acting on the human 11- ⁇ -hydroxysteroid dehydrogenase type 1 enzyme (ll ⁇ HSDl).
  • Cortisol performs a broad range of metabolic functions and other functions.
  • the multitude of glucocorticoid action is exemplified in patients with prolonged increase in plasma glucocorticoids, so called "Cushing's syndrome".
  • Patients with Cushing's syndrome have prolonged increase in plasma glucocorticoids and exhibit impaired glucose tolerance, type 2 diabetes, central obesity, and osteoporosis. These patients also have impaired wound healing and brittle skin (1).
  • Glucocorticoids have been shown to increase risk of infection and delay healing of open wounds (2). Patients treated with glucocorticoids have 2-5-fold increased risk of complications when undergoing surgery (3).
  • the European patent application No. EP 0902288 discloses a method for diagnosing the status of wound healing in a patient, comprising detecting cortisol levels in said wound.
  • the authors suggest that elevated levels of cortisol in wound fluid, relative to normal plasma levels in healthy individuals, correlates with large, non-healing wounds (4).
  • the 1 l ⁇ -HSD catalyzes the conversion of cortisol to cortisone, and vice versa.
  • the parallel function of 1 l ⁇ -HSD in rodents is the interconversion of corticosterone and 11-dehydrocorticosterone (5).
  • 1 l ⁇ -HSD Two isoenzymes of 1 l ⁇ -HSD, 1 l ⁇ - HSD 1 and 1 l ⁇ -HSD2, have been characterized, and differ from each other in function and tissue distribution (6).
  • 1 l ⁇ -HSD 1 is expressed in numerous tissues like liver, adipose tissue, adrenal cortex, gonads, lung, pituitary, brain, eye etc (7-9).
  • the function of 11 ⁇ -HSD 1 is to fine-tune local glucocorticoid action.
  • 11 ⁇ -HSD activity has been shown in the skin of humans and rodents, in human fibroblasts and in rat skin pouch tissue (10-13).
  • Wound healing consists of serial events including inflammation, fibroblast proliferation, secretion of ground substances, collagen production, angiogenesis, wound contraction and epithelialization. It can be divided in three phases; inflammatory, proliferative and remodeling phase (reviewed in (2)).
  • glucocorticoids In surgical patients, treatment with glucocorticoids increases risk of wound infection and delay healing of open wounds. It has been shown in animal models that restraint stress slows down cutaneous wound healing and increases susceptibility to bacterial infection during wound healing. These effects were reversed by treatment with the glucocorticoid receptor antagonist RU486 (14, 15). Glucocorticoids produce these effects by suppressing inflammation, decrease wound strength, inhibit wound contracture and delay epithelialization (2). Glucocorticoids influence wound healing by interfering with production or action of cytokines and growth factors like IGF, TGF- ⁇ , EGF, KGF and PDGF (16-19). It has also been shown that glucocorticoids decrease collagen synthesis in rat and mouse skin in vivo and in rat and human fibroblasts (20).
  • WO 01/90094 discloses compounds of the formula (I) as defined hereinafter, which compounds inhibit the human 1 l ⁇ -HSD 1, and may be useful for treating disorders such as diabetes, obesity, glaucoma, osteoporosis, cognitive disorders and immune disorders.
  • Other 1 l ⁇ -HSD 1 inhibitors are disclosed in e.g. WO 01/90090; WO 01/90091; WO 01/90092; WO 01/90093; WO 03/044000; WO 03/044009; WO 03/043999; and Swedish patent application No. SE 0301504-7, filed on May 21, 2003.
  • WO 02/072084 relates to glycyrrhetinic acid derivatives, progesterone and progesterone derivatives as 1 l ⁇ -HSDl inhibitors for wound healing.
  • the use of the 11 ⁇ -HSDl inhibitors according to the present invention for wound healing has not previously been disclosed.
  • this invention provides a method for promoting wound healing, said method comprising administering to a mammal, including man, in need of wound healing an effective amount of an inhibitor of 11 ⁇ -hydroxysteroid dehydrogenase type 1 , wherein the inhibitor of 11 ⁇ - hydroxysteroid dehydrogenase type 1 is a compound of the formula (I):
  • E is a bond, -CH 2 - or -CO-;
  • L is a bond, -CH 2 -, -CHR 4 - or -NR 3 -;
  • R 3 is H, C 1-6 -alkyl, C 1-6 -acyl or -COR 4 ;
  • R 4 is morpholino or C 1-6 -amido
  • R 6 and R 7 are independently hydrogen or C ⁇ .6-alkyl
  • R 8 and R 9 are independently hydrogen or C 1-6 -alkyl; pharmaceutically acceptable salts, solvates, hydrates, geometrical isomers, tautomers, optical isomers, N-oxides and prodrug forms thereof. It is preferred that:
  • T is (I) thienyl, which is optionally substituted with at least one halogen selected from chloro and bromo, or
  • R 3 is methyl, acetyl or -COR 4 ;
  • R 4 is morpholinyl or propionamido; R 6 and R 7 are both hydrogen;
  • R 8 and R 9 are independently hydrogen or methyl.
  • the said method is a method for the treatment or prophylaxis of a medical condition involving delayed or impaired wound healing.
  • medical conditions are diabetes, and conditions caused by treatment with steroids, in particular glucocorticoids.
  • the method according to the invention is also intended for the promotion of wound healing in chronic wounds, such as diabetic ulcers, venous ulcers or pressure ulcers.
  • the compounds referred to above may also be used in the manufacture of a medicament for promoting wound healing, e.g. for the treatment or prophylaxis of a medical condition involving delayed or impaired wound healing.
  • a medical condition involving delayed or impaired wound healing.
  • medical conditions are diabetes, and conditions caused by treatment with steroids, in particular glucocorticoids.
  • the compounds referred to above may also be used for the promotion of wound healing in chronic wounds, such as diabetic ulcers, venous ulcers or pressure ulcers.
  • aryl in the present description is intended to include aromatic rings (monocyclic or bicyclic) having from 6 to 10 ring carbon atoms, such as phenyl (Ph) and naphthyl, which optionally may be substituted by C 1-6 -alkyl. Examples of substituted aryl groups are benzyl, and 2-methylphenyl.
  • heteroaryl means in the present description a monocyclic, bi- or tricyclic aromatic ring system (only one ring need to be aromatic) having from 5 to 14, preferably 5 to 10 ring atoms such as 5, 6, 7, 8, 9 or 10 ring atoms (mono- or bicyclic), in which one or more of the ring atoms are other than carbon, such as nitrogen, sulfur, oxygen and selenium.
  • heteroaryl rings examples include pyrrole, imidazole, thiophene, furan, thiazole, isothiazole, thiadiazole, oxazole, isoxazole, oxadiazole, pyridine, pyrazine, pyrimidine, pyridazine, pyrazole, triazole, tetrazole, chroman, isochroman, quinoline, quinoxaline, isoquinoline, phthalazine, cinnoline, quinazoline, indole, isoindole, indoline, isoindoline, benzothiophene, benzofuran, isobenzofuran, benzoxazole, 2,1,3-benzoxadiazole, benzothiazole, 2,1,3-benzothiazole, 2,1,3- benzoselenadiazole, benzimidazole, indazole, benzodioxane, indan
  • Examples of monocyclic heteroaryl rings are pyrrole, imidazole, thiophene, furan, thiazole, isothiazole, thiadiazole, oxazole, isoxazole, oxadiazole, pyridine, pyrazine, pyrimidine, pyridazine, pyrazole, triazole, and tetrazole.
  • heterocyclic in the present description is intended to include unsaturated as well as partially and fully saturated mono-, bi- and tricyclic rings having from 4 to 14, preferably 4 to 10 ring atoms, such as, for example, the heteroaryl groups mentioned above as well as the corresponding partially saturated or fully saturated heterocyclic rings.
  • exemplary saturated heterocyclic rings are azetidine, pyrrolidine, piperidine, piperazine, morpholine, thiomorpholine and 1,4-oxazepane.
  • Ci. ⁇ -alkyl in the compound of formula (I) according to the present application is preferably C ⁇ _4-alkyl.
  • Exemplary alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl, and isohexyl.
  • C 1-6 -alkyl For parts of the range "C 1-6 -alkyl" all subgroups thereof are contemplated such as C 1-5 -alkyl, C 1-4 -alkyl, C 2-6 -alkyl, C 2-5 -alkyl, C -4 -alkyl, C 2-3 - alkyl, C -6-alkyl, C 4-5 -alkyl, etc.
  • C2-6 _ lkyl in the compound of formula (I) according to the present application is preferably C2_4-alkyl.
  • Exemplary alkyl groups include ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl, and isohexyl.
  • C 2- 6-alkyl For parts of the range "C 2- 6-alkyl" all subgroups thereof are contemplated such as C 2-5 -alkyl, C 2-4 -alkyl, C 2-5 -alkyl, C 2-4 -alkyl, C -3 -alkyl, C 3-6 -alkyl, C 4-5 -alkyl, etc.
  • Cj.g-acyl in the compound of formula (I) according to the present application may be saturated or unsaturated and is preferably Cj_4-acyl.
  • exemplary acyl groups include formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, butenoyl (e.g. 3- butenoyl), hexenoyl (e.g. 5-hexenoyl).
  • C ⁇ - 6 -acyl For parts of the range "C ⁇ - 6 -acyl" all subgroups thereof are contemplated such as C 1-5 -acyl, C 1-4 -acyl, C 2- 6-acyl, C -5 -acyl, C 2- -acyl, C 2- -acyl, C 3-6 -acyl, C 4-5 -acyl, etc.
  • C -6 -alkenyl in the compound of formula (I) according to the present application is preferably C 2-4 -alkenyl.
  • Exemplary alkenyl groups include vinyl, 1-propenyl, 2-propenyl, isopropenyl, 1-butenyl, 2-butenyl, 1- pentenyl, 2-pentenyl, 1-hexenyl, and 2-hexenyl.
  • C 2-6 -alkenyl all subgroups thereof are contemplated such as C 2-5 -alkenyl, C -4 -alkenyl, C 2-3 -alkenyl, C 3 . 6 -alkenyl, C 4-5 -alkenyl, etc.
  • C ⁇ _6"-amido in the compound of formula (I) according to the present application may be saturated or unsaturated and is preferably C ⁇ _4-amido.
  • exemplary amido groups include formamido, acetamido, propionamido, butyramido, isobutyramido, valeramido, isovaleramido, butenamido (e.g. 3-butenamido), hexenamido (e.g. 5-hexenamido).
  • C 1-6 -amido For parts of the range "C 1-6 -amido" all subgroups thereof are contemplated such as C 1-5 - amido, C 1-4 -amido, C -6 -amido, C 2-5 -amido, C 2- -amido, C 2-3 -amido, C 3-6 -amido, C 4-5 - amido, etc.
  • halogen in the present description is intended to include fluorine, chlorine, bromine and iodine.
  • mono- or di-substituted is meant in the present description that the functionalities in question may be substituted with independently H, C 1-6 -acyl, C 1-6 - alkenyl, C 1-6 -(cyclo)alkyl, aryl, pyridylmethyl, or heterocyclic rings e.g. azetidine, pyrrolidine, piperidine, piperazine, morpholine and thiomorpholine, which heterocyclic rings optionally may be substituted with C ⁇ -6 -alkyl.
  • optionally mono- or disubstituted is meant in the present description that the functionalities in question may also be substituted with independently hydrogen.
  • stable referes to compounds which possess stability sufficient to allow manufacture and which maintains the integrity of the compound for a sufficient period of time to be useful for the purposes detailed herein (e.g., therapeutic administration to a subject for the treatment of disease, 11 - ⁇ -HSD 1 inhibition, 11 - ⁇ -HSD 1 -mediated disease).
  • prodrug forms in the present description means a pharmacologically acceptable derivative, such as an ester or an amide, which derivative is biotransformed in the body to form the active drug (see Goodman and Gilman's, The Pharmacological basis of Therapeutics, 8 th ed., McGraw-Hill, Int. Ed. 1992, "Biotransformation of Drugs, p. 13-15).
  • “Pharmaceutically acceptable” means in the present description being useful in preparing a pharmaceutical composition that is generally safe, non-toxic and neither biologically nor otherwise undesirable and includes being useful for veterinary use as well as human pharmaceutical use.
  • “Pharmaceutically acceptable salts” mean in the present description salts which are pharmaceutically acceptable, as defined above, and which possess the desired pharmacological activity.
  • Such salts include acid addition salts formed with organic and inorganic acids, such as hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfuric acid, phosphoric acid, acetic acid, glycolic acid, maleic acid, malonic acid, oxalic acid, methanesulfonic acid, trifluoroacetic acid, fumaric acid, succinic acid, tartaric acid, citric acid, benzoic acid, ascorbic acid and the like.
  • Base addition salts may be formed with organic and inorganic bases, such as sodium, ammonia, potassium, calcium, ethanolamine, diethanolamine, N-methylglucamine, choline and the like.
  • the compounds of formula (I) can be prepared according to the methods described in WO 01/90094.
  • the compounds of formula (I) can preferably be topically administered.
  • the compounds could also be administered by other routes, for instance orally, intraperitoneally, intraarticularly, intracranially, intradermally, intramuscularly, intraocularly, intrathecally, intravenously, subcutaneously.
  • Diabetic KKA y mice underwent surgery during anesthesia whereby a catheter was inserted in the jugularis vein. Oral treatment twice daily (200 mg/kg/day) with the 1 l ⁇ - HSD1 inhibitor BVT.2733 (disclosed as Example 172A in WO 01/90090), or vehicle started 4-6 days later and continued for 3.5 days.
  • 11 ⁇ -HSD 1 inhibitors are confirmed in in vitro studies. Proliferation of human keratinocytes and fibroblasts, which are important cell types in the wound healing process, are studied after incubation with the 11 ⁇ -HSD 1 inhibitor.
  • Hutchinson TC Swaniker HP. Wound diagnosis by quantitating cortisol in wound fluids.
  • Frey FJ Escher G
  • Frey BM Pharmacology of 11 beta-hydroxysteroid dehydrogenase. Steroids 1994;59(2):74-9.

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  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention a trait à un procédé pour favoriser la cicatrisation, comprenant l'administration à un mammifère, y compris l'homme, nécessitant un tel traitement d'une quantité efficace d'un inhibiteur de 11-β-hydroxystéroïde déshydrogénase de type 1(11β-HSD1), ledit inhibiteur de 11β-HSD1 étant de formule (I) dans laquelle : T, E, L, R6, R7, R8 et R9 sont tels que définis dans la description. Ces composés peuvent également être utilisés dans la fabrication d'un médicament pour favoriser la cicatrisation.
PCT/SE2004/000957 2003-06-25 2004-06-16 Nouvelle utilisation iii WO2004112785A1 (fr)

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SE0301884-3 2003-06-25

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006040178A1 (fr) * 2004-10-14 2006-04-20 Abbott Gmbh & Co.Kg Composes aromatiques d'arylsulfonylmethyle ou d'arylsulfonamide substitues permettant de traiter des troubles repondant a une modulation du recepteur d3 de la dopamine
WO2007025892A1 (fr) 2005-08-31 2007-03-08 F. Hoffmann-La Roche Ag Inhibiteur de la 11-bêta-hydroxystéroïde déhydrogénase-1 des diabètes de type 2-1
US7253196B2 (en) 2004-05-24 2007-08-07 Amgen, Inc. Inhibitors of 11-β-hydroxy steroid dehydrogenase type 1
US8541592B2 (en) 2005-11-22 2013-09-24 Amgen Inc. Inhibitors of 11-beta-hydroxysteroid dehydrogenase type 1
US8686011B2 (en) 2004-05-24 2014-04-01 Amgen Inc. Inhibitors of 11-β-hydroxy steroid dehydrogenase type 1
EP3235813A1 (fr) 2016-04-19 2017-10-25 Cidqo 2012, S.L. Dérivés aza-tétra-cycliques
EP3821892A1 (fr) * 2019-11-12 2021-05-19 University of Leeds Acide acétique (s)-2-(1-(5-(cyclohexylcarbamoyl)-6-(propylthio)pyridine-2-yl)pipéridine-3-yl) pour son utilisation dans la guérison de plaies

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1240545A (en) * 1967-07-17 1971-07-28 Research Corp Silver-containing therapeutic agents
WO1996031492A1 (fr) * 1995-04-04 1996-10-10 Texas Biotechnology Corporation Thienyl-, furyl-, pyrrolyl- et biphenyl sulfonamides et leurs derives modulant l'activite de l'endotheline
WO1998016520A1 (fr) * 1996-10-16 1998-04-23 American Cyanamid Company Preparation d'acides ortho-sulfonamido heteraryl-hydroxamiques et leur utilisation en tant qu'inhibiteurs des metalloproteinases matricielles et de tace
WO2001090094A1 (fr) * 2000-05-22 2001-11-29 Biovitrum Ab Inhibiteurs de 11-beta-hydroxy-steroide-deshydrogenase de type 1

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1240545A (en) * 1967-07-17 1971-07-28 Research Corp Silver-containing therapeutic agents
WO1996031492A1 (fr) * 1995-04-04 1996-10-10 Texas Biotechnology Corporation Thienyl-, furyl-, pyrrolyl- et biphenyl sulfonamides et leurs derives modulant l'activite de l'endotheline
WO1998016520A1 (fr) * 1996-10-16 1998-04-23 American Cyanamid Company Preparation d'acides ortho-sulfonamido heteraryl-hydroxamiques et leur utilisation en tant qu'inhibiteurs des metalloproteinases matricielles et de tace
WO2001090094A1 (fr) * 2000-05-22 2001-11-29 Biovitrum Ab Inhibiteurs de 11-beta-hydroxy-steroide-deshydrogenase de type 1

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
STOZOWSKA W. ET AL.: "Urinary silver and sulfathiazole levels in thermally injured guinea pigs during treatment with silver sulfathiazole cream", S.T.P. PHARMA SCIENCES, vol. 5, no. 6, 1995, pages 452 - 455, XP002981457 *

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7807700B2 (en) 2004-05-24 2010-10-05 Amgen Inc. Inhibitors of 11-β-hydroxy steroid dehydrogenase type 1
US8686011B2 (en) 2004-05-24 2014-04-01 Amgen Inc. Inhibitors of 11-β-hydroxy steroid dehydrogenase type 1
US7253196B2 (en) 2004-05-24 2007-08-07 Amgen, Inc. Inhibitors of 11-β-hydroxy steroid dehydrogenase type 1
US8969552B2 (en) 2004-10-14 2015-03-03 AbbVie Deutschland GmbH & Co. KG Arylsulfonylmethyl or arylsulfonamide substituted aromatic compounds suitable for treating disorders that respond to modulation of the dopamine D3 receptor
EP2439203A1 (fr) * 2004-10-14 2012-04-11 Abbott GmbH & Co. KG Composés aromatiques d'arylsulfonylmethyl ou arylsulfonamide pour la traitement des maladies concernent la modulation des réceptors de dopamin D3
CN101068801B (zh) * 2004-10-14 2012-11-14 艾博特股份有限两合公司 适用于治疗对于多巴胺d3受体的调节有反应的疾病的芳基磺酰基甲基或芳基磺酰胺取代的芳族化合物
WO2006040178A1 (fr) * 2004-10-14 2006-04-20 Abbott Gmbh & Co.Kg Composes aromatiques d'arylsulfonylmethyle ou d'arylsulfonamide substitues permettant de traiter des troubles repondant a une modulation du recepteur d3 de la dopamine
US7622492B2 (en) 2005-08-31 2009-11-24 Hoffmann-La Roche Inc. Pyrazolones as inhibitors of 11β-hydroxysteroid dehydrogenase
WO2007025892A1 (fr) 2005-08-31 2007-03-08 F. Hoffmann-La Roche Ag Inhibiteur de la 11-bêta-hydroxystéroïde déhydrogénase-1 des diabètes de type 2-1
US8541592B2 (en) 2005-11-22 2013-09-24 Amgen Inc. Inhibitors of 11-beta-hydroxysteroid dehydrogenase type 1
EP3235813A1 (fr) 2016-04-19 2017-10-25 Cidqo 2012, S.L. Dérivés aza-tétra-cycliques
WO2017182464A1 (fr) 2016-04-19 2017-10-26 Cidqo 2012, S.L. Nouveaux dérivés d'aza-tétracyclo
EP3821892A1 (fr) * 2019-11-12 2021-05-19 University of Leeds Acide acétique (s)-2-(1-(5-(cyclohexylcarbamoyl)-6-(propylthio)pyridine-2-yl)pipéridine-3-yl) pour son utilisation dans la guérison de plaies
WO2021094390A1 (fr) 2019-11-12 2021-05-20 University Of Leeds Acide (s)-2-(1-(5-(cyclohexylcarbamoyl)-6-(propylthio)pyridine-2-yl)pipéridine-3-yl) acétique à utiliser pour le traitement des plaies
US11590119B2 (en) 2019-11-12 2023-02-28 University Of Leeds (S)-2-(1-(5-(cyclohexylcarbamoyl)-6-(propylthio)pyridin-2-yl)piperidin-3-yl)acetic acid for use in medicine

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