PE20151977A1 - Nuevos derivados de purina - Google Patents

Nuevos derivados de purina

Info

Publication number
PE20151977A1
PE20151977A1 PE2015002327A PE2015002327A PE20151977A1 PE 20151977 A1 PE20151977 A1 PE 20151977A1 PE 2015002327 A PE2015002327 A PE 2015002327A PE 2015002327 A PE2015002327 A PE 2015002327A PE 20151977 A1 PE20151977 A1 PE 20151977A1
Authority
PE
Peru
Prior art keywords
purine derivatives
tert
butyl
new purine
pyrrolidin
Prior art date
Application number
PE2015002327A
Other languages
English (en)
Inventor
Stefanie Bendels
Uwe Grether
Atsushi Kimbara
Tanja Schulz-Gasch
Stephan Roever
Mark Rogers-Evans
Matthias Nettekoven
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 PE20151977A1 publication Critical patent/PE20151977A1/es

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D473/00Heterocyclic compounds containing purine ring systems
    • C07D473/26Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
    • C07D473/32Nitrogen atom
    • C07D473/34Nitrogen atom attached in position 6, e.g. adenine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52Purines, e.g. adenine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/12Drugs for disorders of the urinary system of the kidneys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/02Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/08Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00Drugs for disorders of the muscular or neuromuscular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/04Centrally acting analgesics, e.g. opioids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/14Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16Anti-Parkinson drugs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • A61P27/06Antiglaucoma agents or miotics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/06Immunosuppressants, e.g. drugs for graft rejection
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/04Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic 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
    • C07D403/04Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D473/00Heterocyclic compounds containing purine ring systems
    • C07D473/02Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
    • C07D473/16Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two nitrogen atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D473/00Heterocyclic compounds containing purine ring systems
    • C07D473/02Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
    • C07D473/18Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D519/00Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

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

Abstract

La invencion se refiere a un compuesto de la formula I, en la que A es CH2, CH2CH2, etc; R1 es tert-butilo, etc; R2 y R3 junto con el atomo de nitrogeno, al que estan unidos, forman un pirrolidinilo, etc; R4 es hidrogeno, fenilo, etc. Son compuestos preferidos: 2-tert-butil-9-[(4-clorofenil)metil]-6-(3,3-difluor-pirrolidin-1-il)purina, 2-tert-butil-9-[(2-clorofenil)metil]-6-(3,3-difluor-pirrolidin-1-il)purina, entre otros. Dichos compuestos son agonistas del receptor de canabinoides 2
PE2015002327A 2013-05-02 2014-04-28 Nuevos derivados de purina PE20151977A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP13166293 2013-05-02

Publications (1)

Publication Number Publication Date
PE20151977A1 true PE20151977A1 (es) 2016-01-07

Family

ID=48190399

Family Applications (1)

Application Number Title Priority Date Filing Date
PE2015002327A PE20151977A1 (es) 2013-05-02 2014-04-28 Nuevos derivados de purina

Country Status (32)

Country Link
US (1) US9505762B2 (es)
EP (1) EP2991987B1 (es)
JP (1) JP6513636B2 (es)
KR (2) KR102330794B1 (es)
CN (1) CN105209466B (es)
AR (1) AR096152A1 (es)
AU (1) AU2014261585B2 (es)
BR (1) BR112015027396B1 (es)
CA (1) CA2903588C (es)
CL (1) CL2015003195A1 (es)
CR (1) CR20150511A (es)
DK (1) DK2991987T3 (es)
EA (1) EA027497B1 (es)
ES (1) ES2680935T3 (es)
HK (1) HK1214245A1 (es)
HR (1) HRP20181141T1 (es)
HU (1) HUE039589T2 (es)
IL (1) IL242160B (es)
LT (1) LT2991987T (es)
MA (1) MA38460B1 (es)
MX (1) MX2015014757A (es)
PE (1) PE20151977A1 (es)
PH (1) PH12015502471B1 (es)
PL (1) PL2991987T3 (es)
PT (1) PT2991987T (es)
RS (1) RS57461B1 (es)
SG (1) SG11201509014UA (es)
SI (1) SI2991987T1 (es)
TR (1) TR201809417T4 (es)
TW (1) TWI649322B (es)
UA (1) UA116654C2 (es)
WO (1) WO2014177490A1 (es)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
LT2991988T (lt) 2013-05-02 2017-08-10 F. Hoffmann-La Roche Ag Pirol[2,3-d]pirimidino dariniai kaip cb2 receptorių agonistai
HUE041760T2 (hu) 2013-09-06 2019-05-28 Hoffmann La Roche Triazolo[4,5-d]pirimidin-származékok mint CBb2-receptor antagonisták
BR112017009629A2 (pt) * 2014-11-07 2017-12-19 Hoffmann La Roche triazolo [4,5-d] pirimidinas como agonistas do receptor canabinoide 2
FR3046792B1 (fr) * 2016-01-19 2018-02-02 Les Laboratoires Servier Nouveaux derives d'ammonium, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
EP3475280B1 (en) 2016-06-23 2020-04-08 H. Hoffnabb-La Roche Ag Novel [1,2,3]triazolo[4,5-d]pyrimidine derivatives
EP3475283B1 (en) 2016-06-23 2021-08-11 F. Hoffmann-La Roche AG Novel[1,2,3]triazolo[4,5-d]pyrimidine derivatives
CR20180615A (es) * 2016-06-23 2019-03-05 Hoffmann La Roche Nuevos derivados de [1,2,3]triazol[4,5-d]pirimidina
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
EP3388432A1 (en) * 2017-04-10 2018-10-17 Commissariat à l'Energie Atomique et aux Energies Alternatives Purine derivatives for use as medicament and for use in treating neurodegenerative or neuro-inflammatory disorders
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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NZ225447A (en) * 1987-07-20 1991-12-23 Merck & Co Inc Piperazinyl derivatives of purine and purine isosteres and pharmaceutical compositions
US5057517A (en) * 1987-07-20 1991-10-15 Merck & Co., Inc. Piperazinyl derivatives of purines and isosteres thereof as hypoglycemic agents
AU2001234958A1 (en) 2000-02-11 2001-08-20 Bristol-Myers Squibb Company Cannabinoid receptor modulators, their processes of preparation, and use of cannabinoid receptor modulators for treating respiratory and non-respiratory diseases
CA2479744A1 (en) 2002-03-28 2003-10-09 Paul E. Finke Substituted 2,3-diphenyl pyridines
US20030191973A1 (en) * 2002-04-04 2003-10-09 Johnson Carolynn Rae Temporary user suspension of automatic shutdown
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WO2004014911A1 (en) * 2002-08-08 2004-02-19 Memory Pharmaceuticals Corporation Phosphodiesterase 4 inhibitors
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AR051596A1 (es) 2004-10-26 2007-01-24 Irm Llc Compuestos heterociclicos condensados nitrogenados como inhibidores de la actividad del receptor canabinoide 1; composiciones farmaceuticas que los contienen y su empleo en la preparacion de medicamentos para el tratamiento de trastornos alimentarios
US20100227845A1 (en) 2007-10-18 2010-09-09 Zhicai Wu Substituted 1,2,4-oxadiazoles and analogs thereof as cb2 receptor modulators, useful in the treatment of pain, respiratory and non-respiratory diseases
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US9321727B2 (en) 2011-06-10 2016-04-26 Hoffmann-La Roche Inc. Pyridine derivatives as agonists of the CB2 receptor
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
EP2870139B1 (en) 2012-07-04 2016-06-15 F.Hoffmann-La Roche Ag Novel adamantyl derivatives as cannabinoid receptor 2 agonists
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MX2015007156A (es) 2012-12-07 2015-10-14 Hoffmann La Roche Piridina-2-amidas utiles como agonistas receptores de canabinoides 2 (cb2).
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PE20151089A1 (es) 2012-12-07 2015-08-06 Hoffmann La Roche Piridin-2-amidas utiles como agonistas de cb2
PL2964646T3 (pl) 2013-03-07 2017-09-29 F.Hoffmann-La Roche Ag Nowe pochodne pirazolu

Also Published As

Publication number Publication date
US9505762B2 (en) 2016-11-29
CN105209466A (zh) 2015-12-30
CL2015003195A1 (es) 2016-06-03
BR112015027396B1 (pt) 2023-04-11
IL242160B (en) 2019-06-30
DK2991987T3 (en) 2018-07-23
SG11201509014UA (en) 2015-11-27
PH12015502471A1 (en) 2016-02-22
WO2014177490A1 (en) 2014-11-06
HUE039589T2 (hu) 2019-01-28
PT2991987T (pt) 2018-07-13
PH12015502471B1 (en) 2016-02-22
HK1214245A1 (zh) 2016-07-22
PL2991987T3 (pl) 2018-10-31
CA2903588A1 (en) 2014-11-06
KR20160002871A (ko) 2016-01-08
MA38460A1 (fr) 2017-02-28
US20160046631A1 (en) 2016-02-18
AR096152A1 (es) 2015-12-09
SI2991987T1 (en) 2018-08-31
CN105209466B (zh) 2018-05-18
KR20210145303A (ko) 2021-12-01
EP2991987B1 (en) 2018-05-23
EA027497B1 (ru) 2017-07-31
AU2014261585B2 (en) 2018-03-08
JP2016517872A (ja) 2016-06-20
UA116654C2 (uk) 2018-04-25
TWI649322B (zh) 2019-02-01
EP2991987A1 (en) 2016-03-09
KR102330794B1 (ko) 2021-11-26
LT2991987T (lt) 2018-08-10
TW201533045A (zh) 2015-09-01
JP6513636B2 (ja) 2019-05-15
AU2014261585A1 (en) 2015-09-17
MX2015014757A (es) 2016-03-11
NZ712079A (en) 2021-03-26
BR112015027396A8 (pt) 2018-01-30
RS57461B1 (sr) 2018-09-28
CR20150511A (es) 2015-11-02
ES2680935T3 (es) 2018-09-11
HRP20181141T1 (hr) 2018-09-21
CA2903588C (en) 2021-10-26
BR112015027396A2 (pt) 2017-07-25
MA38460B1 (fr) 2017-10-31
EA201591976A1 (ru) 2016-03-31
TR201809417T4 (tr) 2018-07-23

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