ES2650372T3 - Compuestos tricíclicos como inhibidores de CFTR - Google Patents
Compuestos tricíclicos como inhibidores de CFTR Download PDFInfo
- Publication number
- ES2650372T3 ES2650372T3 ES13826624T ES13826624T ES2650372T3 ES 2650372 T3 ES2650372 T3 ES 2650372T3 ES 13826624 T ES13826624 T ES 13826624T ES 13826624 T ES13826624 T ES 13826624T ES 2650372 T3 ES2650372 T3 ES 2650372T3
- Authority
- ES
- Spain
- Prior art keywords
- carbon atoms
- alkyl
- amino
- atoms
- alkoxy
- Prior art date
- Legal status (The legal status 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 status listed.)
- Active
Links
- 150000001875 compounds Chemical class 0.000 title abstract 2
- 239000003112 inhibitor Substances 0.000 title 1
- 125000004432 carbon atom Chemical group C* 0.000 abstract 59
- 125000000217 alkyl group Chemical group 0.000 abstract 22
- 125000003545 alkoxy group Chemical group 0.000 abstract 6
- 125000004429 atom Chemical group 0.000 abstract 4
- 125000001188 haloalkyl group Chemical group 0.000 abstract 4
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 3
- 229910052799 carbon Inorganic materials 0.000 abstract 3
- 229910052739 hydrogen Inorganic materials 0.000 abstract 3
- 239000001257 hydrogen Substances 0.000 abstract 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 abstract 3
- 229910052760 oxygen Inorganic materials 0.000 abstract 3
- 125000001424 substituent group Chemical group 0.000 abstract 3
- 125000004103 aminoalkyl group Chemical group 0.000 abstract 2
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 2
- 125000000392 cycloalkenyl group Chemical group 0.000 abstract 2
- 229910052736 halogen Inorganic materials 0.000 abstract 2
- 150000002367 halogens Chemical class 0.000 abstract 2
- 125000005842 heteroatom Chemical group 0.000 abstract 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract 2
- 229910052757 nitrogen Inorganic materials 0.000 abstract 2
- 229910052717 sulfur Inorganic materials 0.000 abstract 2
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 abstract 1
- 125000003341 7 membered heterocyclic group Chemical group 0.000 abstract 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 abstract 1
- 125000003710 aryl alkyl group Chemical group 0.000 abstract 1
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract 1
- 125000002541 furyl group Chemical group 0.000 abstract 1
- 125000004438 haloalkoxy group Chemical group 0.000 abstract 1
- 239000001301 oxygen Substances 0.000 abstract 1
- 125000004430 oxygen atom Chemical group O* 0.000 abstract 1
- 125000003226 pyrazolyl group Chemical group 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 125000004434 sulfur atom Chemical group 0.000 abstract 1
- 125000000335 thiazolyl group Chemical group 0.000 abstract 1
- 125000001544 thienyl group Chemical group 0.000 abstract 1
Classifications
-
- 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
- C07D487/12—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 three hetero rings
- C07D487/14—Ortho-condensed 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
- A61K31/495—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
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P1/12—Antidiarrhoeals
-
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/14—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Un compuesto de la fórmula (I), o una sal farmacéuticamente aceptable del mismo:**Fórmula** en donde R1 representa fenilo, cicloalquenilo (de 4 a 7 átomos de carbono) o Het1, cuyo grupo R1 puede estar insustituido o sustituido sobre uno o dos átomos de carbono por sustituyentes Ra, y puede estar además sustituido sobre un átomo de nitrógeno con un sustituyente Ra1; cada Ra independientemente representa alquilo (de 1 a 4 átomos de carbono), halógeno, halo-alquilo (de 1 a 4 átomos de carbono), ciano, hidroxi-alquilo (de 1 a 4 átomos de carbono), alcoxilo (de 1 a 4 átomos de carbono), halo-alcoxilo (de 1 a 4 átomos de carbono), alcoxilo (de 1 a 4 átomos de carbono)-alquilo (de 1 a 4 átomos de carbono)-, R6OC(O)-, o R6OC(O)alquilo (de 1 a 4 átomos de carbono)-; Ra1 representa alquilo (de 1 a 4 átomos de carbono), hidroxi-alquilo (de 1 a 4 átomos de carbono), alcoxilo (de 1 a 4 átomos de carbono)-alquilo (de 1 a 4 átomos de carbono)-, alquilo (de 1 a 4 átomos de carbono)-aminoalquilo (de 1 a 4 átomos de carbono)-, di-[alquilo (de 1 a 4 átomos de carbono)]-amino-alquilo (de 1 a 4 átomos de carbono)-, aril-alquilo (de 1 a 4 átomos de carbono)- o R6OC(O)alquilo (de 1 a 4 átomos de carbono)-; R2 representa alquilo (de 1 a 6 átomos de carbono), cicloalquilo (de 3 a 7 átomos de carbono), cicloalquenilo (de 4 a 7 átomos de carbono), fenilo, furanilo, tiazolilo, tienilo o pirazolilo, cuyo R2 puede estar insustituido o sustituido sobre uno a tres átomos de carbono con sustituyentes Rb, y puede estar además sustituido sobre un átomo de nitrógeno con alquilo (de 1 a 4 átomos de carbono); cada Rb independientemente representa alquilo (de 1 a 4 átomos de carbono), halógeno, halo-alquilo (de 1 a 4 átomos de carbono), ciano, alquilo (de 1 a 4 átomos de carbono)-amino-alquilo (de 1 a 4 átomos de carbono)-, di-[alquilo (de 1 a 4 átomos de carbono)]- amino-alquilo (de 1 a 4 átomos de carbono)-, (R6)2NC(O)alquilo (de 1 a 4 átomos de carbono)- o R6OC(O)alquilo (de 1 a 4 átomos de carbono)-; X representa O, NH o NMe; o X representa -CH2-O-, en donde el átomo de oxígeno (O) se une al átomo de -C(R4)(R4') del anillo; cada R3 independientemente representa metilo o etilo; R4 representa hidrógeno, alquilo (de 1 a 4 átomos de carbono), halo-alquilo (de 1 a 4 átomos de carbono), hidroxi-alquilo (de 1 a 4 átomos de carbono), alcoxilo (de 1 a 4 átomos de carbono)-alquilo (de 1 a 4 átomos de carbono)-, amino-alquilo (de 1 a 4 átomos de carbono)-, alquilo (de 1 a 4 átomos de carbono)-amino-alquilo (de 1 a 4 átomos de carbono)-, di-[alquilo (de 1 a 4 átomos de carbono)]-amino-alquilo (de 1 a 4 átomos de carbono)- , fenilo, Het1alquilo (de 1 a 4 átomos de carbono)-, Het2alquilo (de 1 a 4 átomos de carbono)-, alquilo (de 1 a 4 átomos de carbono)S(O)2NH-alquilo (de 1 a 4 átomos de carbono)-, o R7C(O)NH-alquilo (de 1 a 4 átomos de carbono)-; R4' representa H o metilo; R4a representa hidrógeno, alquilo (de 1 a 4 átomos de carbono), halo-alquilo (de 1 a 4 átomos de carbono), amino-alquilo (de 1 a 4 átomos de carbono)-, alquilo (de 1 a 4 átomos de carbono)-amino-alquilo (de 1 a 4 átomos de carbono)-, di-[alquilo (de 1 a 4 átomos de carbono)]-amino-alquilo (de 1 a 4 átomos de carbono)-, Het1alquilo (de 1 a 4 átomos de carbono)-, Het2alquilo (de 1 a 4 átomos de carbono)-, o R6OC(O)-; R6 representa hidrógeno, alquilo (de 1 a 4 átomos de carbono); R7 representa alquilo (de 1 a 2 átomos de carbono), alcoxilo (de 1 a 2 átomos de carbono), alcoxilo (de 1 a 2 átomos de carbono)-alquilo (de 1 a 2 átomos de carbono) o fenilo; Het1 representa un anillo de heteroarilo de 5 o 6 miembros que comprende: a) un átomo de oxígeno o de azufre, y opcionalmente uno o dos átomos de nitrógeno; o b) de uno a cuatro átomos de nitrógeno; y Het2 representa un anillo heterocíclico de 4 a 7 miembros que comprende: a) 1 o 2 heteroátomos seleccionados a partir de N, O y S; o b) -C(O)- y 1 o 2 heteroátomos seleccionados a partir de N y O.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261739337P | 2012-12-19 | 2012-12-19 | |
| US201361906154P | 2013-11-19 | 2013-11-19 | |
| PCT/IB2013/061041 WO2014097147A1 (en) | 2012-12-19 | 2013-12-17 | Tricyclic compounds as cftr inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2650372T3 true ES2650372T3 (es) | 2018-01-18 |
Family
ID=50030371
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES13826624T Active ES2650372T3 (es) | 2012-12-19 | 2013-12-17 | Compuestos tricíclicos como inhibidores de CFTR |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US9303035B2 (es) |
| EP (1) | EP2935277B1 (es) |
| JP (1) | JP6284545B2 (es) |
| KR (1) | KR20150095925A (es) |
| CN (1) | CN105008370B (es) |
| AR (1) | AR094123A1 (es) |
| AU (1) | AU2013365827A1 (es) |
| BR (1) | BR112015014433A2 (es) |
| CA (1) | CA2895656A1 (es) |
| EA (1) | EA201591175A1 (es) |
| ES (1) | ES2650372T3 (es) |
| MX (1) | MX2015007940A (es) |
| TW (1) | TW201429976A (es) |
| UY (1) | UY35209A (es) |
| WO (1) | WO2014097147A1 (es) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2882807T3 (es) | 2011-09-16 | 2021-12-02 | Novartis Ag | Heterociclil carboxamidas N-sustituidas |
| WO2014097147A1 (en) | 2012-12-19 | 2014-06-26 | Novartis Ag | Tricyclic compounds as cftr inhibitors |
| EP2935278B1 (en) | 2012-12-19 | 2017-03-15 | Novartis AG | Tricyclic compounds for inhibiting the cftr channel |
| ES3066112T3 (en) | 2015-12-24 | 2026-05-11 | The Regents Of The Univ Of California | Cftr regulators and methods of use thereof |
| RU2730855C2 (ru) | 2015-12-24 | 2020-08-26 | Дзе Риджентс Оф Дзе Юниверсити Оф Калифорниа | Кфтр регуляторы и способы их применения |
| EP3672598A4 (en) | 2017-08-24 | 2021-04-28 | The Regents of The University of California | OCULAR PHARMACEUTICAL COMPOSITIONS |
| CN112724157B (zh) * | 2021-01-23 | 2022-04-19 | 中国科学院新疆理化技术研究所 | 二氢噁唑并[5,4-d]吡咯并[1,2-a]嘧啶-9(5H)-酮类衍生物及用途 |
| IL307863A (en) | 2021-04-29 | 2023-12-01 | Novartis Ag | Diubiquitinase-directed chimeras and related methods |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW224974B (es) * | 1991-07-02 | 1994-06-11 | Hoffmann La Roche | |
| AU6729600A (en) | 1999-08-25 | 2001-03-19 | Banyu Pharmaceutical Co., Ltd. | Novel isoindole derivatives |
| JP2002255967A (ja) | 2001-02-27 | 2002-09-11 | Banyu Pharmaceut Co Ltd | イソインドール誘導体を有効成分とする糖尿病の治療剤、糖尿病の慢性合併症の予防剤又は肥満の治療剤。 |
| CA2514733A1 (en) | 2003-02-28 | 2004-09-16 | Transform Pharmaceuticals, Inc. | Pharmaceutical co-crystal compositions of drugs such as carbamazepine, celecoxib, olanzapine, itraconazole, topiramate, modafinil, 5-fluorouracil, hydrochlorothiazide, acetaminophen, aspirin, flurbiprofen, phenytoin and ibuprofen |
| JP2010512389A (ja) | 2006-12-12 | 2010-04-22 | シェーリング コーポレイション | アスパルチルプロテアーゼ阻害剤 |
| US20110015137A1 (en) * | 2007-07-05 | 2011-01-20 | Trustees Of Boston University | Reca inhibitors and their uses as microbial inhibitors or potentiators of antibiotic activity |
| US8642660B2 (en) | 2007-12-21 | 2014-02-04 | The University Of Rochester | Method for altering the lifespan of eukaryotic organisms |
| EP2464354B1 (en) * | 2009-08-10 | 2015-04-01 | The Regents of The University of California | Pyrimido-pyrrolo-quinoxalinedione inhibitors of cystic fibrosis transmembrane conductance regulator protein and uses therefor |
| USRE48842E1 (en) * | 2011-05-27 | 2021-12-07 | The Regents Of The University Of California | Pyrimido-pyrrolo-oxazine-dione compound inhibitors of the cystic fibrosis transmembrane conductance regulator protein and uses therefor |
| WO2014097147A1 (en) | 2012-12-19 | 2014-06-26 | Novartis Ag | Tricyclic compounds as cftr inhibitors |
| EP2935278B1 (en) * | 2012-12-19 | 2017-03-15 | Novartis AG | Tricyclic compounds for inhibiting the cftr channel |
-
2013
- 2013-12-17 WO PCT/IB2013/061041 patent/WO2014097147A1/en not_active Ceased
- 2013-12-17 EA EA201591175A patent/EA201591175A1/ru unknown
- 2013-12-17 ES ES13826624T patent/ES2650372T3/es active Active
- 2013-12-17 EP EP13826624.2A patent/EP2935277B1/en not_active Not-in-force
- 2013-12-17 KR KR1020157019356A patent/KR20150095925A/ko not_active Withdrawn
- 2013-12-17 MX MX2015007940A patent/MX2015007940A/es unknown
- 2013-12-17 JP JP2015548836A patent/JP6284545B2/ja not_active Expired - Fee Related
- 2013-12-17 CA CA2895656A patent/CA2895656A1/en not_active Abandoned
- 2013-12-17 US US14/109,927 patent/US9303035B2/en active Active
- 2013-12-17 AU AU2013365827A patent/AU2013365827A1/en not_active Abandoned
- 2013-12-17 CN CN201380073219.8A patent/CN105008370B/zh not_active Expired - Fee Related
- 2013-12-17 BR BR112015014433A patent/BR112015014433A2/pt not_active IP Right Cessation
- 2013-12-18 TW TW102147022A patent/TW201429976A/zh unknown
- 2013-12-19 UY UY0001035209A patent/UY35209A/es not_active Application Discontinuation
- 2013-12-19 AR ARP130104862A patent/AR094123A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| TW201429976A (zh) | 2014-08-01 |
| CA2895656A1 (en) | 2014-06-26 |
| CN105008370A (zh) | 2015-10-28 |
| EP2935277A1 (en) | 2015-10-28 |
| WO2014097147A1 (en) | 2014-06-26 |
| AR094123A1 (es) | 2015-07-08 |
| US20140171412A1 (en) | 2014-06-19 |
| EA201591175A1 (ru) | 2015-11-30 |
| CN105008370B (zh) | 2017-06-09 |
| EP2935277B1 (en) | 2017-08-30 |
| UY35209A (es) | 2014-07-31 |
| MX2015007940A (es) | 2016-03-11 |
| AU2013365827A1 (en) | 2015-07-09 |
| KR20150095925A (ko) | 2015-08-21 |
| BR112015014433A2 (pt) | 2017-07-11 |
| US9303035B2 (en) | 2016-04-05 |
| JP6284545B2 (ja) | 2018-02-28 |
| JP2016507498A (ja) | 2016-03-10 |
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