ES2688733T3 - Combinaciones de antagonistas de trpv4 - Google Patents
Combinaciones de antagonistas de trpv4 Download PDFInfo
- Publication number
- ES2688733T3 ES2688733T3 ES16162808T ES16162808T ES2688733T3 ES 2688733 T3 ES2688733 T3 ES 2688733T3 ES 16162808 T ES16162808 T ES 16162808T ES 16162808 T ES16162808 T ES 16162808T ES 2688733 T3 ES2688733 T3 ES 2688733T3
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- Prior art keywords
- alkyl
- het
- halo
- hydrogen
- antagonists
- 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.)
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- 239000005557 antagonist Substances 0.000 title abstract 2
- 101150098315 TRPV4 gene Proteins 0.000 title 1
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract 9
- 125000001475 halogen functional group Chemical group 0.000 abstract 6
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 abstract 5
- 239000001257 hydrogen Substances 0.000 abstract 5
- 229910052739 hydrogen Inorganic materials 0.000 abstract 5
- 150000002431 hydrogen Chemical group 0.000 abstract 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 4
- 125000000217 alkyl group Chemical group 0.000 abstract 3
- 125000004432 carbon atom Chemical group C* 0.000 abstract 3
- 125000001424 substituent group Chemical group 0.000 abstract 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 2
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 abstract 2
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 abstract 2
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 abstract 2
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 abstract 2
- 239000003112 inhibitor Substances 0.000 abstract 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 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
- AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 abstract 2
- 125000003226 pyrazolyl group Chemical group 0.000 abstract 2
- -1 tetrahydrofurfuryl Chemical group 0.000 abstract 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 abstract 2
- 108060003345 Adrenergic Receptor Proteins 0.000 abstract 1
- 102000017910 Adrenergic receptor Human genes 0.000 abstract 1
- 108090000312 Calcium Channels Proteins 0.000 abstract 1
- 102000003922 Calcium Channels Human genes 0.000 abstract 1
- LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 abstract 1
- 229940118365 Endothelin receptor antagonist Drugs 0.000 abstract 1
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 abstract 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 abstract 1
- 108010081348 HRT1 protein Hairy Proteins 0.000 abstract 1
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 abstract 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract 1
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 abstract 1
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical class O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 abstract 1
- 102000004136 Vasopressin Receptors Human genes 0.000 abstract 1
- 108090000643 Vasopressin Receptors Proteins 0.000 abstract 1
- 239000002170 aldosterone antagonist Substances 0.000 abstract 1
- 229940083712 aldosterone antagonist Drugs 0.000 abstract 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 abstract 1
- 229940124599 anti-inflammatory drug Drugs 0.000 abstract 1
- 239000000739 antihistaminic agent Substances 0.000 abstract 1
- 229940125715 antihistaminic agent Drugs 0.000 abstract 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 1
- 239000002876 beta blocker Substances 0.000 abstract 1
- 229940097320 beta blocking agent Drugs 0.000 abstract 1
- 229940124630 bronchodilator Drugs 0.000 abstract 1
- 239000000168 bronchodilator agent Substances 0.000 abstract 1
- 229910052799 carbon Inorganic materials 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 229960005156 digoxin Drugs 0.000 abstract 1
- LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 abstract 1
- LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 abstract 1
- 239000002934 diuretic Substances 0.000 abstract 1
- 229940030606 diuretics Drugs 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 239000002308 endothelin receptor antagonist Substances 0.000 abstract 1
- VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 abstract 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical group O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 abstract 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 abstract 1
- 239000003199 leukotriene receptor blocking agent Substances 0.000 abstract 1
- 125000002757 morpholinyl group Chemical group 0.000 abstract 1
- 239000003149 muscarinic antagonist Substances 0.000 abstract 1
- 239000002840 nitric oxide donor Substances 0.000 abstract 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 abstract 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 abstract 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 abstract 1
- 239000001301 oxygen Substances 0.000 abstract 1
- 229910052760 oxygen Inorganic materials 0.000 abstract 1
- 239000002590 phosphodiesterase V inhibitor Substances 0.000 abstract 1
- 125000003386 piperidinyl group Chemical group 0.000 abstract 1
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 abstract 1
- 125000003373 pyrazinyl group Chemical group 0.000 abstract 1
- 125000004076 pyridyl group Chemical group 0.000 abstract 1
- 125000000714 pyrimidinyl group Chemical group 0.000 abstract 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 abstract 1
- 239000002461 renin inhibitor Substances 0.000 abstract 1
- 229940086526 renin-inhibitors Drugs 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 230000003637 steroidlike Effects 0.000 abstract 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 abstract 1
- 229940124597 therapeutic agent Drugs 0.000 abstract 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero 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
- A61P1/04—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
- A61P1/10—Laxatives
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- 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
- A61P11/06—Antiasthmatics
-
- 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
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- 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
- A61P19/00—Drugs for skeletal disorders
-
- 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
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- 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
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D419/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms
- C07D419/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Cardiology (AREA)
- Pulmonology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Diabetes (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Hematology (AREA)
- Physical Education & Sports Medicine (AREA)
- Communicable Diseases (AREA)
- Hospice & Palliative Care (AREA)
- Otolaryngology (AREA)
- Oncology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Obesity (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Una combinación que comprende un compuesto de Fórmula (I):**Fórmula** en donde: R1 es hidrógeno, alquilo C1-3, CH2OH, CH2-O-CH3, CH2OCH2Ph, CH2CN, CN, halo o C(O)OCH3; R2 es independientemente hidrógeno, CN, CF3, halo, SO2alquilo C1-3, alquilo C1-3 o C≡CH; R3 es hidrógeno, alquilo C1-2, CF3 u OH; R4 es hidrógeno, halo o alquilo C1-3; X es CR4 o N; A es (CH2)n -Het; o A es (CH2)n-(CRaRb)-(CH2)m-Het; Ra es hidrógeno o alquilo C1-3, en donde el alquilo C1-3 puede estar sustituido adicionalmente con uno o más halos; Rb es alquilo C1-3; o Ra y Rb, junto con el átomo de carbono al que están unidos, forma un grupo cicloalquilo C3-6; uno o más de los átomos de carbono en el grupo cicloalquilo C3-6 formado por Ra y Rb pueden estar reemplazados con oxígeno para formar un oxetano, tetrahidrofurilo o tetrahidropiranilo; uno de los átomos de carbono en el grupo cicloalquilo C3-6 formado por Ra y Rb, puede estar reemplazado con nitrógeno para formar un grupo pirrolidinilo o piperidinilo; Het es:**^Fórmula** en donde Het puede estar sustituido con uno, dos o tres sustituyentes seleccionados entre: halo, alquilo C1-5, CN, CH2F, CHF2, CF3, cicloalquilo C3-6, (CH2)n-O-alquilo C1-3, (CH2)n-fenilo, (CH2)n-piridilo, pirimidinilo, pirazinilo, CH(CH3)-O-alquilo C1-3, CH(OH)-alquilo C1-5, C(CH3)2 - R5, C(O)N(CH3)p, N(alquilo C1-3)p, NH2, C(O)NH2, oxetano, oxetano-CH3, tetrahidrofurfurilo, tetrahidropiranilo, morfolinilo o pirazolilo; en donde el sustituyente fenilo, pirazolilo, y piridilo en el Het puede estar adicionalmente sustituido con uno o dos sustituyentes seleccionados entre: halo, CN, OCH3, alquilo C1-3 o CF3; y el sustituyentes alquilo C1-5 y cicloalquilo C3-6 en el Het puede estar adicionalmente sustituido con CN u OH; R5 es CN, O-alquilo C1-4, (CH2)m - OH, (CH2)p - O - C(O) - O -alquilo C1-5 o O-(CH2)p-O -R6; R6 es alquilo C1-4 o P(O)2(CH3)2; n es independientemente 0, 1 ó 2; m es independientemente 0, 1 ó 2; p es independientemente 1 ó 2; y y es 1, 2 ó 3; o una sal farmacéuticamente aceptable del mismo; y uno o más de otros agentes terapéuticos, seleccionados del grupo que consiste en antagonistas del receptor de endotelina, inhibidores de la enzima convertidora de angiotensina (ECA), antagonistas del receptor de angiotensina II, inhibidores de vasopeptidasa, moduladores del receptor de vasopresina, diuréticos, digoxina, beta-bloqueantes, antagonistas de aldosterona, iontroposs, AINES, donantes de óxido nítrico, moduladores de los canales de calcio, antagonistas muscarínicos, fármacos antiinflamatorios esteroideos, broncodilatadores, antihistamínicos, antagonistas de los leucotrienos, inhibidores de la HMG-CoA reductasa, antagonistas adrenorreceptores ß-adrenérgicos y α1- adrenoceptores no selectivos, inhibidores de la fosfodiesterasa tipo 5 e inhibidores de la renina.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201161498110P | 2011-06-17 | 2011-06-17 |
Publications (1)
Publication Number | Publication Date |
---|---|
ES2688733T3 true ES2688733T3 (es) | 2018-11-06 |
Family
ID=47558389
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ES16162808T Active ES2688733T3 (es) | 2011-06-17 | 2012-06-15 | Combinaciones de antagonistas de trpv4 |
ES12814591T Active ES2569193T3 (es) | 2011-06-17 | 2012-06-15 | Antagonistas de TRPV4 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ES12814591T Active ES2569193T3 (es) | 2011-06-17 | 2012-06-15 | Antagonistas de TRPV4 |
Country Status (38)
Country | Link |
---|---|
US (1) | US9187464B2 (es) |
EP (2) | EP2721016B1 (es) |
JP (1) | JP5969017B2 (es) |
KR (1) | KR101870003B1 (es) |
CN (1) | CN103732583B (es) |
AR (1) | AR086958A1 (es) |
AU (1) | AU2012284540B2 (es) |
BR (1) | BR112013032391B1 (es) |
CA (1) | CA2839743C (es) |
CL (1) | CL2013003602A1 (es) |
CO (1) | CO6821953A2 (es) |
CR (1) | CR20130671A (es) |
CY (1) | CY1117792T1 (es) |
DK (1) | DK2721016T3 (es) |
DO (1) | DOP2013000307A (es) |
EA (1) | EA023616B1 (es) |
ES (2) | ES2688733T3 (es) |
HK (1) | HK1195068A1 (es) |
HR (1) | HRP20160539T1 (es) |
HU (1) | HUE029594T2 (es) |
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UY (1) | UY34138A (es) |
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Families Citing this family (14)
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ES2571409T3 (es) | 2011-06-17 | 2016-05-25 | Glaxosmithkline Intellectual Property (No 2) Ltd | Antagonistas espiro-cíclicos de TRPV4 |
EP2720697B1 (en) * | 2011-06-17 | 2016-07-20 | Glaxosmithkline Intellectual Property (No. 2) Limited | Trpv4 antagonists |
US9499533B2 (en) | 2012-03-27 | 2016-11-22 | Shionogi & Co., Ltd. | Aromatic 5-membered heterocyclic derivative having TRPV4-Inhibiting activity |
JPWO2015046193A1 (ja) | 2013-09-25 | 2017-03-09 | 塩野義製薬株式会社 | Trpv4阻害活性を有する芳香族複素環式アミン誘導体 |
JP6970691B2 (ja) * | 2016-05-19 | 2021-11-24 | グラクソスミスクライン、インテレクチュアル、プロパティー、(ナンバー2)、リミテッドGlaxosmithkline Intellectual Property (No.2) Limited | Trpv4拮抗薬 |
US10968209B2 (en) | 2016-05-19 | 2021-04-06 | Glaxosmithkline Intellectual Property (No.2) Limited | TRPV4 antagonist |
TN2019000087A1 (en) | 2016-10-03 | 2020-07-15 | Janssen Pharmaceutica Nv | Novel monocyclic and bicyclic ring system substituted carbanucleoside analogues for use as prmt5 inhibitors |
WO2018185701A1 (en) | 2017-04-06 | 2018-10-11 | Glaxosmithkline Intellectual Property (No.2) Limited | Trpv4 antagonists as antitussive agents |
SG11202003825TA (en) * | 2017-11-01 | 2020-05-28 | Bristol Myers Squibb Co | Spirocyclic compounds as farnesoid x receptor modulators |
WO2021170811A1 (en) | 2020-02-27 | 2021-09-02 | Glaxosmithkline Intellectual Property (No.2) Limited | Method of treating eye disease using trpv4 antagonists |
EP4142874A4 (en) | 2020-04-30 | 2024-05-22 | RaQualia Pharma Inc. | PYRIMIDIN-4(3H)-ONE DERIVATIVES AS TRPV4 ANTAGONISTS |
CN111704613B (zh) * | 2020-06-23 | 2021-07-06 | 中国人民解放军军事科学院军事医学研究院 | 咪唑类衍生物及其作为trpv4抑制剂的用途 |
CN115776890A (zh) | 2020-07-16 | 2023-03-10 | 拉夸里亚创药株式会社 | 作为眼病治疗剂的trpv4抑制剂 |
TW202409024A (zh) | 2022-07-08 | 2024-03-01 | 美商愛克堤歐生物科學公司 | 治療性化合物及方法 |
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AU3851199A (en) * | 1998-05-26 | 1999-12-13 | Chugai Seiyaku Kabushiki Kaisha | Heterocyclic indole derivatives and mono- or diazaindole derivatives |
CA2531619A1 (en) * | 2003-07-16 | 2005-01-27 | Neurogen Corporation | Biaryl piperazinyl-pyridine analogues |
CA2630617C (en) * | 2005-11-23 | 2014-03-25 | Painceptor Pharma Corporation | Compositions and methods for modulating gated ion channels |
WO2007067756A2 (en) | 2005-12-08 | 2007-06-14 | Amphora Discovery Corporation | Certain chemical entities, compositions, and methods for modulating trpv1 |
TWI649092B (zh) * | 2005-12-22 | 2019-02-01 | 海卓勒生物科學公司 | 用於調節trpa1功能之化合物 |
TW200819457A (en) * | 2006-08-30 | 2008-05-01 | Actelion Pharmaceuticals Ltd | Spiro antibiotic derivatives |
JP2010517967A (ja) * | 2007-02-01 | 2010-05-27 | グラクソ グループ リミテッド | 摂食障害の治療のための1−オキサ−3−アザスピロ[4,5]デカン−2−オン誘導体 |
GB0707934D0 (en) * | 2007-04-24 | 2007-05-30 | Glaxo Group Ltd | Chemical compounds |
US7998982B2 (en) * | 2007-08-09 | 2011-08-16 | Abbott Laboratories | Amide derivatives as TRPV1 antagonists |
TW200944520A (en) * | 2008-01-29 | 2009-11-01 | Glaxo Group Ltd | Spiro compounds as NPY Y5 receptor antagonists |
JP5607046B2 (ja) * | 2008-07-25 | 2014-10-15 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー | Trpv4拮抗薬 |
JP2012006837A (ja) * | 2008-09-30 | 2012-01-12 | Mochida Pharmaceut Co Ltd | 2−インドールアクリルアミド類縁体 |
EP2605658B1 (en) * | 2010-08-18 | 2016-03-23 | Merck Sharp & Dohme Corp. | Spiroxazolidinone compounds |
EP2720697B1 (en) * | 2011-06-17 | 2016-07-20 | Glaxosmithkline Intellectual Property (No. 2) Limited | Trpv4 antagonists |
ES2571409T3 (es) * | 2011-06-17 | 2016-05-25 | Glaxosmithkline Intellectual Property (No 2) Ltd | Antagonistas espiro-cíclicos de TRPV4 |
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