ES2724555T3 - Inhibidores de la aldosterona sintasa - Google Patents
Inhibidores de la aldosterona sintasa Download PDFInfo
- Publication number
- ES2724555T3 ES2724555T3 ES15785014T ES15785014T ES2724555T3 ES 2724555 T3 ES2724555 T3 ES 2724555T3 ES 15785014 T ES15785014 T ES 15785014T ES 15785014 T ES15785014 T ES 15785014T ES 2724555 T3 ES2724555 T3 ES 2724555T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- optionally substituted
- mmol
- heterocyclyl
- compound according
- 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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- 229940123338 Aldosterone synthase inhibitor Drugs 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 144
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 59
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 42
- 150000003839 salts Chemical class 0.000 claims abstract description 39
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 33
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims abstract description 17
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 13
- 150000002367 halogens Chemical class 0.000 claims abstract description 13
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims abstract description 12
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 9
- 125000002393 azetidinyl group Chemical group 0.000 claims abstract description 8
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 8
- 125000002757 morpholinyl group Chemical group 0.000 claims abstract description 8
- 125000003386 piperidinyl group Chemical group 0.000 claims abstract description 8
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims abstract description 8
- MESFXNGUDNODTJ-UHFFFAOYSA-N 2h-thiazine 1,1-dioxide Chemical compound O=S1(=O)NC=CC=C1 MESFXNGUDNODTJ-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims abstract description 7
- 125000000160 oxazolidinyl group Chemical group 0.000 claims abstract description 7
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 7
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 6
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims description 44
- -1 -OH Chemical group 0.000 claims description 36
- 108010009911 Cytochrome P-450 CYP11B2 Proteins 0.000 claims description 21
- 102100024329 Cytochrome P450 11B2, mitochondrial Human genes 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 16
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 206010020571 Hyperaldosteronism Diseases 0.000 claims description 12
- 201000009395 primary hyperaldosteronism Diseases 0.000 claims description 12
- 230000005764 inhibitory process Effects 0.000 claims description 11
- 201000010099 disease Diseases 0.000 claims description 10
- 201000005206 focal segmental glomerulosclerosis Diseases 0.000 claims description 10
- 206010020772 Hypertension Diseases 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 230000002861 ventricular Effects 0.000 claims description 8
- 208000035475 disorder Diseases 0.000 claims description 7
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 6
- 206010016654 Fibrosis Diseases 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 5
- 206010065673 Nephritic syndrome Diseases 0.000 claims description 5
- 230000004761 fibrosis Effects 0.000 claims description 5
- 206010061989 glomerulosclerosis Diseases 0.000 claims description 5
- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
- 208000008448 Congenital adrenal hyperplasia Diseases 0.000 claims description 4
- 208000016998 Conn syndrome Diseases 0.000 claims description 4
- 208000003037 Diastolic Heart Failure Diseases 0.000 claims description 4
- 208000010159 IgA glomerulonephritis Diseases 0.000 claims description 4
- 206010021263 IgA nephropathy Diseases 0.000 claims description 4
- 206010049694 Left Ventricular Dysfunction Diseases 0.000 claims description 4
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 claims description 4
- 208000008253 Systolic Heart Failure Diseases 0.000 claims description 4
- 230000005856 abnormality Effects 0.000 claims description 4
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 4
- 238000011049 filling Methods 0.000 claims description 4
- 208000013846 primary aldosteronism Diseases 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- 208000017169 kidney disease Diseases 0.000 claims description 3
- 206010052904 Musculoskeletal stiffness Diseases 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 229910006074 SO2NH2 Inorganic materials 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 131
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 117
- 239000000203 mixture Substances 0.000 description 95
- 239000000243 solution Substances 0.000 description 68
- 235000019439 ethyl acetate Nutrition 0.000 description 65
- 238000006243 chemical reaction Methods 0.000 description 56
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 51
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
- 238000003818 flash chromatography Methods 0.000 description 43
- 239000000543 intermediate Substances 0.000 description 43
- 239000000741 silica gel Substances 0.000 description 43
- 229910002027 silica gel Inorganic materials 0.000 description 43
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 34
- 239000010410 layer Substances 0.000 description 32
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
- 239000011541 reaction mixture Substances 0.000 description 28
- 239000002253 acid Substances 0.000 description 26
- 239000012044 organic layer Substances 0.000 description 24
- PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 description 22
- PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 0.000 description 22
- 229960002478 aldosterone Drugs 0.000 description 22
- 239000000047 product Substances 0.000 description 22
- 238000004808 supercritical fluid chromatography Methods 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 19
- 239000012267 brine Substances 0.000 description 19
- 239000012043 crude product Substances 0.000 description 19
- 230000000694 effects Effects 0.000 description 19
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 150000004702 methyl esters Chemical class 0.000 description 18
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 17
- 102000003979 Mineralocorticoid Receptors Human genes 0.000 description 15
- 108090000375 Mineralocorticoid Receptors Proteins 0.000 description 15
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- 125000003118 aryl group Chemical group 0.000 description 14
- 229920006395 saturated elastomer Polymers 0.000 description 13
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 12
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical group C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- 125000004093 cyano group Chemical group *C#N 0.000 description 10
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 10
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 125000004432 carbon atom Chemical group C* 0.000 description 9
- 239000002552 dosage form Substances 0.000 description 9
- 239000005909 Kieselgur Substances 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- PSJHLNFXHMZSSM-UHFFFAOYSA-N methyl 2-bromo-1,4-benzodioxine-5-carboxylate Chemical compound COC(=O)C1=CC=CC=2OC(=COC=21)Br PSJHLNFXHMZSSM-UHFFFAOYSA-N 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 229910052717 sulfur Inorganic materials 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 8
- 238000007792 addition Methods 0.000 description 7
- 150000001408 amides Chemical class 0.000 description 7
- 239000001257 hydrogen Substances 0.000 description 7
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 7
- 150000003254 radicals Chemical class 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
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- 229910052786 argon Inorganic materials 0.000 description 6
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- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 125000001072 heteroaryl group Chemical group 0.000 description 6
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- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
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- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4433—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
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- 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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- A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
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- A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/54—Improvements relating to the production of bulk chemicals using solvents, e.g. supercritical solvents or ionic liquids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
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- Cardiology (AREA)
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- Urology & Nephrology (AREA)
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- Vascular Medicine (AREA)
- Emergency Medicine (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pulmonology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462064234P | 2014-10-15 | 2014-10-15 | |
| PCT/US2015/055421 WO2016061161A1 (en) | 2014-10-15 | 2015-10-14 | Aldosterone synthase inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2724555T3 true ES2724555T3 (es) | 2019-09-12 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES15785014T Active ES2724555T3 (es) | 2014-10-15 | 2015-10-14 | Inhibidores de la aldosterona sintasa |
Country Status (33)
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2016089800A1 (en) * | 2014-12-02 | 2016-06-09 | Boehringer Ingelheim International Gmbh | Aldosterone synthase inhibitors |
| CA3055292A1 (en) * | 2016-12-29 | 2018-07-05 | Selenity Therapeutics (Bermuda), Ltd. | Metalloenzyme inhibitor compounds |
| CN113767095A (zh) | 2019-05-01 | 2021-12-07 | 勃林格殷格翰国际有限公司 | (r)-4-溴苯磺酸(2-甲基环氧乙烷-2-基)甲酯 |
| AU2021341508A1 (en) | 2020-09-10 | 2023-05-25 | Precirix N.V. | Antibody fragment against fap |
| AU2022415313A1 (en) | 2021-12-14 | 2024-05-02 | Boehringer Ingelheim International Gmbh | Aldosterone synthase inhibitors for treating chronic kidney disease |
| WO2023203135A1 (en) | 2022-04-22 | 2023-10-26 | Precirix N.V. | Improved radiolabelled antibody |
| AU2023264245A1 (en) | 2022-05-02 | 2024-12-19 | Precirix N.V. | Pre-targeting |
| CN121181527A (zh) * | 2024-06-21 | 2025-12-23 | 江苏豪森药业集团有限公司 | 双稠环类化合物、及其制备方法和应用 |
| WO2026093586A1 (en) | 2024-11-04 | 2026-05-07 | AstraZeneca Ireland Limited | Combination of a aldosterone synthase inhibitor (asi) and a sodium-glucose co-transporter 2 inhibitor (sglt2i) for use in methods of reducing the risk of cardiovascular and heart failure events in a subject |
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| AR073629A1 (es) * | 2008-10-07 | 2010-11-17 | Schering Corp | Analogos de benzodioxano moduladores de receptores adrenergicos alfa 2c, composiciones farmaceuticas que los contienen y uso de los mismos para tratar enfermedades respiratorias, alergicas, cardiacas, parkinson y/o alzheimer, entre otras |
| ES2459468T3 (es) * | 2009-05-15 | 2014-05-09 | Novartis Ag | Arilpiridinas como inhibidores de aldosterona sintasa |
| MX350717B (es) * | 2011-11-30 | 2017-09-14 | Hoffmann La Roche | Nuevos derivados biciclicos de dihidroisoquinolin-1-ona. |
| US9550750B2 (en) | 2012-10-05 | 2017-01-24 | Merck Sharp & Dohme Corp. | Indoline compounds as aldosterone synthase inhibitors |
| JP2016516004A (ja) * | 2013-02-22 | 2016-06-02 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | 抗糖尿病二環式化合物 |
| WO2014179186A1 (en) * | 2013-04-30 | 2014-11-06 | Boehringer Ingelheim International Gmbh | Aldosterone synthase inhibitors |
| ES2684050T3 (es) * | 2014-07-24 | 2018-10-01 | Boehringer Ingelheim International Gmbh | Inhibidores de aldosterona sintasa |
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