MA38403A1 - Nouveaux dérivés de pyrazole modulateurs specifiques de cb2 - Google Patents

Nouveaux dérivés de pyrazole modulateurs specifiques de cb2

Info

Publication number
MA38403A1
MA38403A1 MA38403A MA38403A MA38403A1 MA 38403 A1 MA38403 A1 MA 38403A1 MA 38403 A MA38403 A MA 38403A MA 38403 A MA38403 A MA 38403A MA 38403 A1 MA38403 A1 MA 38403A1
Authority
MA
Morocco
Prior art keywords
pyrazole derivatives
modulators specific
new pyrazole
derivatives modulators
new
Prior art date
Application number
MA38403A
Other languages
English (en)
Inventor
Uwe Grether
Atsushi Kimbara
Matthias Nettekoven
Stephan Roever
Mark Rogers-Evans
Tanja Schulz-Gasch
Fabienne Ricklin
Original Assignee
Hoffmann La Roche
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche
Publication of MA38403A1 publication Critical patent/MA38403A1/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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
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    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P25/28—Drugs for disorders of the nervous system 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
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    • A61P27/00—Drugs for disorders of the senses
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
    • C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Epidemiology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Cardiology (AREA)
  • Diabetes (AREA)
  • Ophthalmology & Optometry (AREA)
  • Immunology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Hospice & Palliative Care (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Endocrinology (AREA)
  • Vascular Medicine (AREA)
  • Hematology (AREA)
  • Psychiatry (AREA)
  • Psychology (AREA)
  • Transplantation (AREA)
  • Obesity (AREA)
  • Pulmonology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Dermatology (AREA)

Abstract

L'invention concerne un composé représenté par la formule (i) dans laquelle a1 à a3 et r1 à r3 sont tels que définis dans la description et dans les revendications. Le composé de formule (i) peut être utilisé comme médicament.
MA38403A 2013-03-07 2014-03-04 Nouveaux dérivés de pyrazole modulateurs specifiques de cb2 MA38403A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP13158233 2013-03-07
PCT/EP2014/054107 WO2014135507A1 (fr) 2013-03-07 2014-03-04 Nouveaux dérivés de pyrazole

Publications (1)

Publication Number Publication Date
MA38403A1 true MA38403A1 (fr) 2017-11-30

Family

ID=47827068

Family Applications (1)

Application Number Title Priority Date Filing Date
MA38403A MA38403A1 (fr) 2013-03-07 2014-03-04 Nouveaux dérivés de pyrazole modulateurs specifiques de cb2

Country Status (34)

Country Link
US (2) US9512132B2 (fr)
EP (1) EP2964646B1 (fr)
JP (2) JP6514119B2 (fr)
KR (2) KR102217297B1 (fr)
CN (1) CN105143220B (fr)
AR (1) AR094978A1 (fr)
AU (1) AU2014224784B2 (fr)
BR (1) BR112015020795B1 (fr)
CA (1) CA2897513C (fr)
CL (1) CL2015002387A1 (fr)
CR (1) CR20150447A (fr)
CY (1) CY1118950T1 (fr)
DK (1) DK2964646T3 (fr)
EA (1) EA027935B1 (fr)
ES (1) ES2629751T3 (fr)
HR (1) HRP20170919T1 (fr)
HU (1) HUE034831T2 (fr)
IL (1) IL240327B (fr)
LT (1) LT2964646T (fr)
MA (1) MA38403A1 (fr)
MX (1) MX363727B (fr)
MY (1) MY176797A (fr)
NZ (1) NZ710052A (fr)
PE (1) PE20151539A1 (fr)
PH (1) PH12015501843B1 (fr)
PL (1) PL2964646T3 (fr)
PT (1) PT2964646T (fr)
RS (1) RS56148B1 (fr)
SG (1) SG11201507168XA (fr)
SI (1) SI2964646T1 (fr)
TW (1) TWI609866B (fr)
UA (1) UA118666C2 (fr)
WO (1) WO2014135507A1 (fr)
ZA (1) ZA201505073B (fr)

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CN105143220B (zh) * 2013-03-07 2018-06-22 豪夫迈·罗氏有限公司 吡唑衍生物
PE20151559A1 (es) 2013-03-26 2015-11-05 Hoffmann La Roche Nuevos derivados de piridina
HRP20181141T1 (hr) 2013-05-02 2018-09-21 F. Hoffmann - La Roche Ag Derivati purina kao agonisti cb2 receptora
BR112015027394A8 (pt) 2013-05-02 2018-01-30 Hoffmann La Roche derivados de pirrolo[2,3-d]pirimidina como agonistas de receptor cb2
AU2014317229B2 (en) 2013-09-06 2018-11-08 F. Hoffmann-La Roche Ag Novel triazolo(4,5-d)pyrimidine derivatives
JP2018507900A (ja) * 2015-03-13 2018-03-22 アッヴィ・インコーポレイテッド （インダゾール−４−イル）ヘキサヒドロピロロピロロン及び使用方法
WO2016191935A1 (fr) * 2015-05-29 2016-12-08 Merck Sharp & Dohme Corp. Composés 6-alkyle dihydropyrazolopyrimidinone utilisés en tant qu'inhibiteurs de pde2
WO2016192083A1 (fr) * 2015-06-04 2016-12-08 Merck Sharp & Dohme Corp. Composés dihydropyrazolopyrimidinone utilisés en tant qu'en tant qu'inhibiteurs de pde2
JP7090036B2 (ja) 2016-06-23 2022-06-23 エフ．ホフマン－ラ ロシュ アーゲー 新規な［１，２，３］トリアゾロ［４，５－ｄ］ピリミジン誘導体
CR20220661A (es) 2016-06-23 2023-02-21 Hoffmann La Roche NUEVOS DERIVADOS DE [1,2,3]TRIAZOLO[4,5-D]PIRIMIDINA (Divisional 2018-0615)
CN109311886B (zh) 2016-06-23 2021-11-09 豪夫迈·罗氏有限公司 [1,2,3]三唑并[4,5-d]嘧啶衍生物
JP7090037B2 (ja) 2016-06-23 2022-06-23 エフ．ホフマン－ラ ロシュ アーゲー 新規な［１，２，３］トリアゾロ［４，５－ｄ］ピリミジン誘導体
US12504353B2 (en) 2019-03-25 2025-12-23 Nikon Corporation Cell manipulation device and cell manipulation method
AU2021341508A1 (en) 2020-09-10 2023-05-25 Precirix N.V. Antibody fragment against fap
WO2023203135A1 (fr) 2022-04-22 2023-10-26 Precirix N.V. Anticorps radiomarqué amélioré
AU2023264245A1 (en) 2022-05-02 2024-12-19 Precirix N.V. Pre-targeting
CN115246832B (zh) * 2022-06-15 2024-05-24 深圳湾实验室 一类去泛素化酶usp25和usp28靶向抑制剂及制备和应用

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WO2009051705A1 (fr) 2007-10-18 2009-04-23 Merck & Co., Inc. 1,2,4-oxadiazoles substitués et leurs analogues comme modulateurs des récepteurs cb2, utiles dans le traitement de la douleur et de maladies respiratoires et non respiratoires
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UA111640C2 (uk) 2011-11-08 2016-05-25 Ф. Хоффманн-Ля Рош Аг ПОХІДНІ [1,2,3]ТРИАЗОЛО[4,5-d]ПІРИМІДИНУ ЯК АГОНІСТИ КАНАБІНОЇДНОГО РЕЦЕПТОРА 2
JP2015521652A (ja) 2012-07-04 2015-07-30 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ カンナビノイド受容体２アゴニストとしての新規アダマンチル誘導体
ES2643058T3 (es) 2012-12-07 2017-11-21 F. Hoffmann-La Roche Ag Piridina-2-amidas útiles como agonistas de CB2
SG11201504475QA (en) 2012-12-07 2015-07-30 Hoffmann La Roche Pyridine-2-amides useful as cb2 agonists
LT2928881T (lt) 2012-12-07 2018-06-11 F. Hoffmann-La Roche Ag Nauji piridino dariniai
WO2014086807A1 (fr) 2012-12-07 2014-06-12 F. Hoffmann-La Roche Ag Nouveaux dérivés de pyrazine comme agonistes des récepteurs cb2
CN105143220B (zh) * 2013-03-07 2018-06-22 豪夫迈·罗氏有限公司 吡唑衍生物

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MY176797A (en) 2020-08-21
KR102369407B1 (ko) 2022-03-02
SI2964646T1 (sl) 2017-08-31
IL240327B (en) 2019-01-31
JP6514119B2 (ja) 2019-05-15
US20170035769A1 (en) 2017-02-09
PL2964646T3 (pl) 2017-09-29
EA027935B1 (ru) 2017-09-29
EP2964646B1 (fr) 2017-04-19
MX363727B (es) 2019-04-01
BR112015020795B1 (pt) 2022-08-16
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US9512132B2 (en) 2016-12-06
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AR094978A1 (es) 2015-09-09
PH12015501843A1 (en) 2015-12-07
CA2897513A1 (fr) 2014-09-12
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ZA201505073B (en) 2016-07-27
CA2897513C (fr) 2021-03-16
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JP2019055986A (ja) 2019-04-11
KR102217297B1 (ko) 2021-02-22
KR20210019578A (ko) 2021-02-22
UA118666C2 (uk) 2019-02-25
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BR112015020795A2 (pt) 2017-07-18
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PH12015501843B1 (en) 2015-12-07
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HUE034831T2 (en) 2018-03-28
IL240327A0 (en) 2015-09-24
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