HRP20110253T1 - Derivati 1,3-dihidroimidazol-2-tiona kao inhibitori dopamin-beta-hidroksilaze - Google Patents
Derivati 1,3-dihidroimidazol-2-tiona kao inhibitori dopamin-beta-hidroksilaze Download PDFInfo
- Publication number
- HRP20110253T1 HRP20110253T1 HR20110253T HRP20110253T HRP20110253T1 HR P20110253 T1 HRP20110253 T1 HR P20110253T1 HR 20110253 T HR20110253 T HR 20110253T HR P20110253 T HRP20110253 T HR P20110253T HR P20110253 T1 HRP20110253 T1 HR P20110253T1
- Authority
- HR
- Croatia
- Prior art keywords
- inhibitors
- antagonists
- agonists
- compound according
- compound
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title claims 4
- 108010015720 Dopamine beta-Hydroxylase Proteins 0.000 title claims 2
- 102100033156 Dopamine beta-hydroxylase Human genes 0.000 title claims 2
- OXFSTTJBVAAALW-UHFFFAOYSA-N 1,3-dihydroimidazole-2-thione Chemical class SC1=NC=CN1 OXFSTTJBVAAALW-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract 31
- 229910052736 halogen Inorganic materials 0.000 claims abstract 10
- 150000002367 halogens Chemical class 0.000 claims abstract 10
- 125000000217 alkyl group Chemical group 0.000 claims abstract 7
- 125000003118 aryl group Chemical group 0.000 claims abstract 7
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract 7
- 239000000203 mixture Substances 0.000 claims abstract 6
- 125000003545 alkoxy group Chemical group 0.000 claims abstract 5
- -1 nitro, amino Chemical group 0.000 claims abstract 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract 4
- 229910052731 fluorine Inorganic materials 0.000 claims abstract 4
- 239000011737 fluorine Substances 0.000 claims abstract 4
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract 4
- 239000001257 hydrogen Substances 0.000 claims abstract 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract 4
- 150000003839 salts Chemical class 0.000 claims abstract 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical class [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract 3
- 229910052794 bromium Inorganic materials 0.000 claims abstract 3
- 239000000460 chlorine Substances 0.000 claims abstract 3
- 229910052801 chlorine Inorganic materials 0.000 claims abstract 3
- 150000002148 esters Chemical class 0.000 claims abstract 3
- 239000011630 iodine Substances 0.000 claims abstract 3
- 229910052740 iodine Inorganic materials 0.000 claims abstract 3
- 125000001624 naphthyl group Chemical group 0.000 claims abstract 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract 2
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract 2
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims abstract 2
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims abstract 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract 2
- 229910052717 sulfur Inorganic materials 0.000 claims abstract 2
- 125000004434 sulfur atom Chemical group 0.000 claims abstract 2
- 239000000556 agonist Substances 0.000 claims 9
- 239000002792 enkephalinase inhibitor Substances 0.000 claims 9
- 108010005094 Advanced Glycation End Products Proteins 0.000 claims 6
- 101800001288 Atrial natriuretic factor Proteins 0.000 claims 6
- 102400001282 Atrial natriuretic peptide Human genes 0.000 claims 6
- 101800001890 Atrial natriuretic peptide Proteins 0.000 claims 6
- 102000003729 Neprilysin Human genes 0.000 claims 6
- 108090000028 Neprilysin Proteins 0.000 claims 6
- 102000008052 Nitric Oxide Synthase Type III Human genes 0.000 claims 6
- 108010075520 Nitric Oxide Synthase Type III Proteins 0.000 claims 6
- 239000002876 beta blocker Substances 0.000 claims 6
- NSQLIUXCMFBZME-MPVJKSABSA-N carperitide Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 NSQLIUXCMFBZME-MPVJKSABSA-N 0.000 claims 6
- 239000003795 chemical substances by application Substances 0.000 claims 6
- 238000000034 method Methods 0.000 claims 6
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 claims 3
- 239000005541 ACE inhibitor Substances 0.000 claims 3
- 229940124258 Adenosine A1 receptor antagonist Drugs 0.000 claims 3
- 108010064733 Angiotensins Proteins 0.000 claims 3
- 102000015427 Angiotensins Human genes 0.000 claims 3
- 229940127291 Calcium channel antagonist Drugs 0.000 claims 3
- 229940122434 Calcium sensitizer Drugs 0.000 claims 3
- 108010056643 Corticotropin-Releasing Hormone Receptors Proteins 0.000 claims 3
- 102100038018 Corticotropin-releasing factor receptor 1 Human genes 0.000 claims 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 3
- 108050009340 Endothelin Proteins 0.000 claims 3
- 102000002045 Endothelin Human genes 0.000 claims 3
- 102400000322 Glucagon-like peptide 1 Human genes 0.000 claims 3
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 claims 3
- 101800000224 Glucagon-like peptide 1 Proteins 0.000 claims 3
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 3
- 102000003505 Myosin Human genes 0.000 claims 3
- 108060008487 Myosin Proteins 0.000 claims 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 3
- 229940116211 Vasopressin antagonist Drugs 0.000 claims 3
- 239000012190 activator Substances 0.000 claims 3
- 239000002598 adenosine A1 receptor antagonist Substances 0.000 claims 3
- 239000000362 adenosine triphosphatase inhibitor Substances 0.000 claims 3
- 239000000048 adrenergic agonist Substances 0.000 claims 3
- 239000000674 adrenergic antagonist Substances 0.000 claims 3
- 239000002160 alpha blocker Substances 0.000 claims 3
- 239000002333 angiotensin II receptor antagonist Substances 0.000 claims 3
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims 3
- 239000005557 antagonist Substances 0.000 claims 3
- 230000003288 anthiarrhythmic effect Effects 0.000 claims 3
- 239000003416 antiarrhythmic agent Substances 0.000 claims 3
- 229940082988 antihypertensives serotonin antagonists Drugs 0.000 claims 3
- 239000003420 antiserotonin agent Substances 0.000 claims 3
- 229940049706 benzodiazepine Drugs 0.000 claims 3
- 239000000480 calcium channel blocker Substances 0.000 claims 3
- 239000000801 calcium channel stimulating agent Substances 0.000 claims 3
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 claims 3
- 239000002738 chelating agent Substances 0.000 claims 3
- 239000003601 chymase inhibitor Substances 0.000 claims 3
- 239000002934 diuretic Substances 0.000 claims 3
- 229940030606 diuretics Drugs 0.000 claims 3
- 230000009977 dual effect Effects 0.000 claims 3
- 239000002857 endothelin converting enzyme inhibitor Substances 0.000 claims 3
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 claims 3
- 239000003623 enhancer Substances 0.000 claims 3
- 229930182470 glycoside Natural products 0.000 claims 3
- 150000002338 glycosides Chemical class 0.000 claims 3
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims 3
- 150000002632 lipids Chemical class 0.000 claims 3
- 150000002823 nitrates Chemical class 0.000 claims 3
- 239000002762 nociceptin receptor agonist Substances 0.000 claims 3
- 239000002571 phosphodiesterase inhibitor Substances 0.000 claims 3
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 claims 3
- 239000011591 potassium Substances 0.000 claims 3
- 229910052700 potassium Inorganic materials 0.000 claims 3
- 238000005932 reductive alkylation reaction Methods 0.000 claims 3
- 239000002461 renin inhibitor Substances 0.000 claims 3
- 229940086526 renin-inhibitors Drugs 0.000 claims 3
- 239000011734 sodium Substances 0.000 claims 3
- 229910052708 sodium Inorganic materials 0.000 claims 3
- 230000002103 transcriptional effect Effects 0.000 claims 3
- 229960005486 vaccine Drugs 0.000 claims 3
- 229940124549 vasodilator Drugs 0.000 claims 3
- 239000003071 vasodilator agent Substances 0.000 claims 3
- 239000003038 vasopressin antagonist Substances 0.000 claims 3
- 239000003064 xanthine oxidase inhibitor Substances 0.000 claims 3
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 208000035475 disorder Diseases 0.000 claims 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 claims 1
- CWWWTTYMUOYSQA-LLVKDONJSA-N 4-(2-aminoethyl)-3-[(3r)-6,8-difluoro-3,4-dihydro-2h-chromen-3-yl]-1h-imidazole-2-thione Chemical compound NCCC1=CNC(=S)N1[C@@H]1CC2=CC(F)=CC(F)=C2OC1 CWWWTTYMUOYSQA-LLVKDONJSA-N 0.000 claims 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims 1
- 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 claims 1
- 206010002383 Angina Pectoris Diseases 0.000 claims 1
- 208000019901 Anxiety disease Diseases 0.000 claims 1
- 206010007558 Cardiac failure chronic Diseases 0.000 claims 1
- 206010007559 Cardiac failure congestive Diseases 0.000 claims 1
- 208000024172 Cardiovascular disease Diseases 0.000 claims 1
- 206010019280 Heart failures Diseases 0.000 claims 1
- 208000019695 Migraine disease Diseases 0.000 claims 1
- 208000012322 Raynaud phenomenon Diseases 0.000 claims 1
- 206010003119 arrhythmia Diseases 0.000 claims 1
- 230000006793 arrhythmia Effects 0.000 claims 1
- 230000036772 blood pressure Effects 0.000 claims 1
- 239000003054 catalyst Substances 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 claims 1
- 230000001684 chronic effect Effects 0.000 claims 1
- 229960003638 dopamine Drugs 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 238000005984 hydrogenation reaction Methods 0.000 claims 1
- 230000033444 hydroxylation Effects 0.000 claims 1
- 238000005805 hydroxylation reaction Methods 0.000 claims 1
- 206010027599 migraine Diseases 0.000 claims 1
- 229960002748 norepinephrine Drugs 0.000 claims 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 claims 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims 1
- 238000000746 purification Methods 0.000 claims 1
- 238000006722 reduction reaction Methods 0.000 claims 1
- 229910000033 sodium borohydride Inorganic materials 0.000 claims 1
- 239000012279 sodium borohydride Substances 0.000 claims 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 claims 1
- 229930195733 hydrocarbon Natural products 0.000 abstract 1
- 150000002430 hydrocarbons Chemical class 0.000 abstract 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 abstract 1
Classifications
-
- 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
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
-
- 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
- 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
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- A61P9/06—Antiarrhythmics
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- 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
-
- 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
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Spoj, naznačen time, da je prikazan formulom I: pri čemu R1, R2 i R3 su isti ili različiti i označavaju vodik, halogen, alkil, nitro, amino, alkilkarbonilamino, alkilamino ili dialkilamino skupinu; R4 označava -alkil-aril ili -alkil-heteroaril; X označava CH2, atom kisika ili atom sumpora; n je 2 ili 3; pojedini (R)- i (S)-enantiomeri ili njegove enantiomerne smjese; ili njegove farmaceutski prihvatljive soli ili esteri, pri čemu termin alkil označava lance ugljikovodika, ravne ili razgranate, koji sadrže od jedan do šest atoma ugljika, a proizvoljno su supstituirani sa arilnom, alkoksi, halogen, alkoksikarbonilnom ili hidroksikarbonilnom skupinom; te termin aril označava fenilnu ili naftilnu skupinu, koja je proizvoljno supstituirana sa alkilnom, alkiloksi, halogen ili nitro skupinom; a termin halogen označava fluor, klor, brom ili jod; i termin heteroaril označava heteroaromatsku skupinu. Patent sadrži još 21 patentni zahtjev.
Claims (22)
1. Spoj, naznačen time, da je prikazan formulom I:
[image]
pri čemu R1, R2 i R3 su isti ili različiti i označavaju vodik, halogen, alkil, nitro, amino, alkilkarbonilamino, alkilamino ili dialkilamino skupinu; R4 označava -alkil-aril ili -alkil-heteroaril; X označava CH2, atom kisika ili atom sumpora; n je 2 ili 3; pojedini (R)- i (S)-enantiomeri ili njegove enantiomerne smjese; ili njegove farmaceutski prihvatljive soli ili esteri, pri čemu termin alkil označava lance ugljikovodika, ravne ili razgranate, koji sadrže od jedan do šest atoma ugljika, a proizvoljno su supstituirani sa arilnom, alkoksi, halogen, alkoksikarbonilnom ili hidroksikarbonilnom skupinom; te termin aril označava fenilnu ili naftilnu skupinu, koja je proizvoljno supstituirana sa alkilnom, alkiloksi, halogen ili nitro skupinom; a termin halogen označava fluor, klor, brom ili jod; i termin heteroaril označava heteroaromatsku skupinu.
2. Spoj prema zahtjevu 1, naznačen time, da n je 2.
3. Spoj prema zahtjevima 1 ili 2, naznačen time, da X je O.
4. Spoj prema bilo kojem od prethodnih zahtjeva, naznačen time, da R4 označava -CH2-aril ili -CH2-heteroaril.
5. Spoj prema bilo kojem od prethodnih zahtjeva, naznačen time, da arilna skupina iz R4 je fenil.
6. Spoj prema bilo kojem od prethodnih zahtjeva, naznačen time, da jedan od R1, R2 i R3 je vodik, a ostali su fluor.
7. Postupak za dobivanje individualnih (R)- i (S)-enantiomera ili njihovih enantiomernih smjesa i farmaceutski prihvatljivih soli ili estera spoja sa formulom I kako je definirano u zahtjevu 1, naznačen time, da sadrži reakciju samostalnog (R)- ili (S)-enantiomera ili enantiomernih smjesa spoja sa Formulom III
[image]
pri čemu X, R1, R2, R3 i n imaju isto značenje kao u zahtjevu 1, sa spojem formule IV
[image]
pri čemu R5 označava aril ili heteroaril, a pri čemu termin aril označava fenilnu ili naftilnu skupinu, koja je proizvoljno supstituirana sa alkilnom, alkiloksi, halogenom ili nitro skupinom; te termin halogen označava fluor, klor, brom ili jod; a termin heteroaril označava heteroaromatsku skupinu; pri uvjetima redukcijske alkilacije.
8. Spoj prema zahtjevu 1, naznačen time, da je prikazan formulom X:
[image]
njegov (R) ili (S) enantiomer ili njegova smjesa (R) i (S) enantiomera ili njegove farmaceutski prihvatljive soli.
9. Spoj prema zahtjevu 8, naznačen time, da navedeni spoj je (R) enantiomer spoja Formule X.
10. Spoj prema zahtjevu 8 ili 9, naznačeno time, da sadrži klorovodičnu sol spoja Formule X.
11. Postupak prema zahtjevu 7, naznačen time, da se koristi za dobivanje spoja formule X prema bilo kojem od zahtjeva od 8 do koji sadrži tretiranje (R)-5-(2-aminoetil)-1-(6,8-difluoro-hroman-3-il)-1,3-dihidroimidazol-2-tiona i benzaldehida u redukcijskim alkilacijskim reakcijskim uvjetima.
12. Postupak prema zahtjevu 11, naznačen time, da se redukcijska alkilacija provodi uz prisutnost redukcijskog reagensa, kao što je natrij cijanoborohidrid, natrij triacetoksiborohidrid, natrij borohidrid ili vodik u prisutnosti katalizatora za hidrogenizaciju.
13. Postupak prema zahtjevima 11 ili 12, naznačen time, da navedena obrada nastupa u smjesi metanola i diklorometana.
14. Postupak prema bilo kojem od zahtjeva od 11 do 13, naznačen time, da navedeni postupak dodatno uključuje korak pročišćavanja.
15. Farmaceutski pripravak, naznačen time, da sadrži terapeutski učinkovitu količinu spoja prema bilo kojem od zahtjeva od 1 do 6 ili od 8 do 10 kombiniranu sa farmaceutski učinkovitim nosačem.
16. Farmaceutski pripravak prema zahtjevu 15, naznačen time, da dodatno sadrži spoj koji je odabran iz jednog ili više spojeva iz slijedećih razreda spojeva:
diuretici; beta-adrenergični antagonisti; alfa2-adrenergični agonisti; alfa1-adrenergični antagonisti; dvojni beta- i alfa-adrenergični antagonisti; blokatori kanala kalcija; aktivatori kanala kalcija; anti-aritmici; inhibitori ACE; antagonisti AT1 receptora; inhibitori renina; sredstva za smanjivanje količine lipida, inhibitori vazopeptidaze; nitrati; antagonisti endotelina; inhibitori neutralne endopeptidaze; cjepiva protiv angiotenzina; vazodilatatori; inhibitori fosfodiesteraze; kardio glikozidi; antagonisti serotonina; sredstva koja djeluju na CNS; senzibilizatori kalcija; inhibitori HMG CoA reduktaze; antagonisti vazopresina; antagonisti receptora za adenozin A1; agonisti atrijalnog natriuretičnog peptida (ANP); kelirajuća sredstva; receptor faktora za oslobađanje kortikotropina; agonisti glukagonu sličnog peptida-1; inhibitori natrij i kalij ATPaze; napredni glikozilacijski konačni produkti (AGE) koji narušavaju unakrsne veze; miješani inhibitori enzima koji konvertira neprilizin/endotelin (NEP/ECE); agonisti receptora za nociceptin (ORL-1); inhibitori ksantin oksidaze; agonisti benzodiazepina; kardio miozin aktivatori; inhibitori kimaze; transkripcijski pojačivači endotelialne dušikov oksid sintaze (ENOS) i inhibitori neutralne endopeptidaze.
17. Spoj prema bilo kojem od zahtjeva od 1 do 6 ili od 8 do 10, naznačen time, da se upotrebljava kao lijek.
18. Spoj prema bilo kojem od zahtjeva od 1 do 6 ili od 8 do 10, naznačen time, da je namijenjen za liječenje poremećaja gdje je redukcija hidroksilacije dopamina u noradrenalin terapeutski korisna.
19. Spoj prema bilo kojem od zahtjeva od 1 do 6 ili od 8 do 10, naznačen time, da je namijenjen za liječenje subjekta koji pati od poremećaja anksioznosti, migrene, kardiovaskularnih poremećaja, povišenog krvnog tlaka ili kroničnog ili kongestivnog zastoja srca; ili za liječenje jedne ili više slijedećih indikacija: angine, aritmije i cirkulatornih poremećaja poput Raynaud-ovog fenomena.
20. Spoj prema bilo kojem od zahtjeva od 1 do 6 ili od 8 do 10, naznačen time, da se upotrebljava za inhibiciju dopamin-β-hidroksilaze.
21. Spoj prema bilo kojem od zahtjeva od 17 do 20, naznačen time, da se kombinira sa spojem koji je odabran iz jednog ili više od slijedećih razreda spojeva:
diuretici; beta-adrenergični antagonisti; alfa2-adrenergični agonisti; alfa1-adrenergični antagonisti; dvojni beta- i alfa-adrenergični antagonisti; blokatori kanala kalcija; aktivatori kanala kalcija; anti-aritmici; inhibitori ACE; antagonisti AT1 receptora; inhibitori renina; sredstva za smanjivanje količine lipida, inhibitori vazopeptidaze; nitrati; antagonisti endotelina; inhibitori neutralne endopeptidaze; cjepiva protiv angiotenzina; vazodilatatori; inhibitori fosfodiesteraze; kardio glikozidi; antagonisti serotonina; sredstva koja djeluju na CNS; senzibilizatori kalcija; inhibitori HMG CoA reduktaze; antagonisti vazopresina; antagonisti receptora za adenozin A1; agonisti atrijalnog natriuretičnog peptida (ANP); kelirajuća sredstva; receptor faktora za oslobađanje kortikotropina; agonisti glukagonu sličnog peptida-1; inhibitori natrij i kalij ATPaze; napredni glikozilacijski konačni produkti (AGE) koji narušavaju unakrsne veze; miješani inhibitori enzima koji konvertira neprilizin/endotelin (NEP/ECE); agonisti receptora za nociceptin (ORL-1); inhibitori ksantin oksidaze; agonisti benzodiazepina; kardio miozin aktivatori; inhibitori kimaze; transkripcijski pojačivači endotelialne dušikov oksid sintaze (ENOS) i inhibitori neutralne endopeptidaze.
22. Spoj prema bilo kojem od zahtjeva od 17 do 20, naznačen time, da se upotrebljava za simultano ili sekvencijalno davanje zajedno sa spojem koji je odabran iz jednog ili više od slijedećih razreda spojeva:
diuretici; beta-adrenergični antagonisti; alfa2-adrenergični agonisti; alfa1-adrenergični antagonisti; dvojni beta- i alfa-adrenergični antagonisti; blokatori kanala kalcija; aktivatori kanala kalcija; anti-aritmici; inhibitori ACE; antagonisti AT1 receptora; inhibitori renina; sredstva za smanjivanje količine lipida, inhibitori vazopeptidaze; nitrati; antagonisti endotelina; inhibitori neutralne endopeptidaze; cjepiva protiv angiotenzina; vazodilatatori; inhibitori fosfodiesteraze; kardio glikozidi; antagonisti serotonina; sredstva koja djeluju na CNS; senzibilizatori kalcija; inhibitori HMG CoA reduktaze; antagonisti vazopresina; antagonisti receptora za adenozin A1; agonisti atrijalnog natriuretičnog peptida (ANP); kelirajuća sredstva; receptor faktora za oslobađanje kortikotropina; agonisti glukagonu sličnog peptida-1; inhibitori natrij i kalij ATPaze; napredni glikozilacijski konačni produkti (AGE) koji narušavaju unakrsne veze; miješani inhibitori enzima koji konvertira neprilizin/endotelin (NEP/ECE); agonisti receptora za nociceptin (ORL-1); inhibitori ksantin oksidaze; agonisti benzodiazepina; kardio miozin aktivatori; inhibitori kimaze; transkripcijski pojačivači endotelialne dušikov oksid sintaze (ENOS) i inhibitori neutralne endopeptidaze.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0708818.0A GB0708818D0 (en) | 2007-05-08 | 2007-05-08 | Compounds |
| PCT/PT2008/000019 WO2008136695A1 (en) | 2007-05-08 | 2008-05-06 | 1, 3-dihydroimidazole- 2 -thione derivatives as inhibitors of dopamine-beta-hydroxylase |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20110253T1 true HRP20110253T1 (hr) | 2011-05-31 |
Family
ID=38198874
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20110253T HRP20110253T1 (hr) | 2007-05-08 | 2011-04-07 | Derivati 1,3-dihidroimidazol-2-tiona kao inhibitori dopamin-beta-hidroksilaze |
Country Status (30)
| Country | Link |
|---|---|
| US (5) | US8481582B2 (hr) |
| EP (1) | EP2155731B1 (hr) |
| JP (1) | JP5559677B2 (hr) |
| KR (1) | KR101598482B1 (hr) |
| CN (1) | CN101687858B (hr) |
| AR (2) | AR066457A1 (hr) |
| AT (1) | ATE499367T1 (hr) |
| AU (1) | AU2008246443B2 (hr) |
| BR (1) | BRPI0811275B8 (hr) |
| CA (1) | CA2686387C (hr) |
| CL (1) | CL2008001321A1 (hr) |
| CY (1) | CY1111517T1 (hr) |
| DE (1) | DE602008005141D1 (hr) |
| DK (1) | DK2155731T3 (hr) |
| ES (1) | ES2360841T3 (hr) |
| GB (1) | GB0708818D0 (hr) |
| HK (1) | HK1142898A1 (hr) |
| HR (1) | HRP20110253T1 (hr) |
| IL (1) | IL201921A (hr) |
| MX (1) | MX2009012041A (hr) |
| NO (1) | NO20093275L (hr) |
| NZ (1) | NZ580962A (hr) |
| PL (1) | PL2155731T3 (hr) |
| RS (1) | RS51692B (hr) |
| RU (1) | RU2501796C2 (hr) |
| SI (1) | SI2155731T1 (hr) |
| TW (1) | TWI458722B (hr) |
| UA (1) | UA104844C2 (hr) |
| WO (1) | WO2008136695A1 (hr) |
| ZA (1) | ZA200908612B (hr) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0708818D0 (en) | 2007-05-08 | 2007-06-13 | Portela & Ca Sa | Compounds |
| JP6075621B2 (ja) * | 2010-08-10 | 2017-02-08 | 塩野義製薬株式会社 | 新規複素環誘導体およびそれらを含有する医薬組成物 |
| ES2632351T3 (es) * | 2010-12-22 | 2017-09-12 | Bial-Portela & Ca, S.A. | Formas cristalinas y procedimientos para su preparación |
| ES2667099T3 (es) * | 2011-06-29 | 2018-05-09 | Bial-Portela & Ca, S.A. | Procedimiento |
| SI2919780T1 (sl) | 2012-11-14 | 2018-12-31 | Bial - Portela & Ca., S.A. | Derivati 1,3-dihidroimidazol-2-tiona za uporabo v zdravljenju pljučne arterijske hipertenzije in poškodbe pljuč |
| CN103356671B (zh) * | 2013-06-24 | 2015-11-25 | 顾祥茂 | Houttuynoid C在制备治疗或预防慢性心衰的药物中的应用 |
| GB201316410D0 (en) * | 2013-09-13 | 2013-10-30 | Bial Portela & Ca Sa | Processes for preparing peripherally-selective inhibitors of dopamine-?-hydroxylase and intermediates for use therein |
| JOP20190050A1 (ar) | 2016-09-23 | 2019-03-20 | Bial Portela & C? S A | مثبطات دوبامين-b-هيدروكسيلاز تخترق حاجز المخ الدموي |
| AU2018332887B2 (en) | 2017-09-13 | 2022-12-08 | Amgen Inc. | Bisamide sarcomere activating compounds and uses thereof |
| JP7167155B2 (ja) | 2017-12-04 | 2022-11-08 | ビアル－ポルテラ エ コンパニア，ソシエダッド アノニマ | ドーパミン－β－ヒドロキシラーゼ阻害剤 |
| GB201810395D0 (en) | 2018-06-25 | 2018-08-08 | Bial Portela & Ca Sa | Formulations comprising dopamine-beta-hydroxylase inhibitors and methods for their preparation |
| GB201908044D0 (en) | 2019-06-05 | 2019-07-17 | Bial Portela & Ca Sa | Dopamine-B-Hydroxylase inhibitors |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4217347A (en) * | 1977-12-27 | 1980-08-12 | E. R. Squibb & Sons, Inc. | Method of treating hypertension and medicaments therefor |
| US4962128A (en) * | 1989-11-02 | 1990-10-09 | Pfizer Inc. | Method of treating anxiety-related disorders using sertraline |
| US5298497A (en) * | 1990-05-15 | 1994-03-29 | E. R. Squibb & Sons, Inc. | Method for preventing onset of hypertension employing a cholesterol lowering drug |
| BR9507517A (pt) * | 1994-04-26 | 1997-09-16 | Syntex Inc | Derivados de benzocicloalquilazotetiona |
| AR032711A1 (es) * | 2001-02-21 | 2003-11-19 | Solvay Pharm Bv | Derivados de fenilpiperazina, un metodo para la preparacion de los mismos y una composicion farmaceutica que los contiene |
| US7125904B2 (en) * | 2002-10-11 | 2006-10-24 | Portela & C.A., S.A. | Peripherally-selective inhibitors of dopamine-β-hydroxylase and method of their preparation |
| GB2393958A (en) * | 2002-10-11 | 2004-04-14 | Portela & Ca Sa | Peripherally-selective imidazole inhibitors of dopamine-beta-hydroxylase |
| GB0708818D0 (en) | 2007-05-08 | 2007-06-13 | Portela & Ca Sa | Compounds |
-
2007
- 2007-05-08 GB GBGB0708818.0A patent/GB0708818D0/en not_active Ceased
-
2008
- 2008-05-06 RS RS20110165A patent/RS51692B/en unknown
- 2008-05-06 RU RU2009145270/04A patent/RU2501796C2/ru active
- 2008-05-06 DE DE602008005141T patent/DE602008005141D1/de active Active
- 2008-05-06 AU AU2008246443A patent/AU2008246443B2/en not_active Ceased
- 2008-05-06 MX MX2009012041A patent/MX2009012041A/es active IP Right Grant
- 2008-05-06 KR KR1020097025071A patent/KR101598482B1/ko active IP Right Grant
- 2008-05-06 NZ NZ580962A patent/NZ580962A/en not_active IP Right Cessation
- 2008-05-06 UA UAA200912720A patent/UA104844C2/uk unknown
- 2008-05-06 PL PL08741778T patent/PL2155731T3/pl unknown
- 2008-05-06 JP JP2010507348A patent/JP5559677B2/ja not_active Expired - Fee Related
- 2008-05-06 EP EP08741778A patent/EP2155731B1/en active Active
- 2008-05-06 WO PCT/PT2008/000019 patent/WO2008136695A1/en active Application Filing
- 2008-05-06 ES ES08741778T patent/ES2360841T3/es active Active
- 2008-05-06 CN CN2008800151606A patent/CN101687858B/zh not_active Expired - Fee Related
- 2008-05-06 CA CA2686387A patent/CA2686387C/en active Active
- 2008-05-06 BR BRPI0811275A patent/BRPI0811275B8/pt not_active IP Right Cessation
- 2008-05-06 AR ARP080101912A patent/AR066457A1/es not_active Application Discontinuation
- 2008-05-06 AT AT08741778T patent/ATE499367T1/de active
- 2008-05-06 US US12/599,014 patent/US8481582B2/en active Active
- 2008-05-06 DK DK08741778.8T patent/DK2155731T3/da active
- 2008-05-06 SI SI200830191T patent/SI2155731T1/sl unknown
- 2008-05-07 TW TW097116854A patent/TWI458722B/zh not_active IP Right Cessation
- 2008-05-07 CL CL2008001321A patent/CL2008001321A1/es unknown
-
2009
- 2009-11-03 NO NO20093275A patent/NO20093275L/no not_active Application Discontinuation
- 2009-11-04 IL IL201921A patent/IL201921A/en active IP Right Grant
- 2009-12-04 ZA ZA2009/08612A patent/ZA200908612B/en unknown
-
2010
- 2010-09-29 HK HK10109325.5A patent/HK1142898A1/xx not_active IP Right Cessation
-
2011
- 2011-04-07 HR HR20110253T patent/HRP20110253T1/hr unknown
- 2011-04-26 CY CY20111100414T patent/CY1111517T1/el unknown
-
2013
- 2013-06-13 US US13/917,385 patent/US9630951B2/en active Active
-
2017
- 2017-03-09 US US15/454,201 patent/US20170369478A1/en not_active Abandoned
-
2018
- 2018-09-05 AR ARP180102520A patent/AR112789A2/es unknown
-
2019
- 2019-05-03 US US16/402,454 patent/US20190322648A1/en not_active Abandoned
-
2021
- 2021-05-10 US US17/315,791 patent/US20210261533A1/en not_active Abandoned
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HRP20110253T1 (hr) | Derivati 1,3-dihidroimidazol-2-tiona kao inhibitori dopamin-beta-hidroksilaze | |
| JP2010526136A5 (hr) | ||
| JP7252972B2 (ja) | ３－ヒドロキシ－Ｎ－（３－（７Ｈ－ピロロ［２，３－ｄ］ピリミジン－４－イル）フェニル）ピロリジン－１－カルボキサミド誘導体 | |
| KR102400920B1 (ko) | 리신 특이적 데메틸라제-1의 억제제 | |
| EP3856719B1 (en) | Compounds as neuronal histamine receptor-3 antagonists and uses thereof | |
| AU2020390962B2 (en) | Pyrimidoimidazole compounds used as DNA-PK inhibitors | |
| MX2009002274A (es) | Compuestos de enlace fxr heterociclicos. | |
| SI2091948T1 (sl) | Novi inhibitorji glutaminil ciklaze | |
| WO2017213910A1 (en) | Mutant idh1 inhibitors | |
| PE20050462A1 (es) | COMPUESTOS DE 5,7-DIAMINOPIRAZOLO[4,3-d]PIRIMIDINAS COMO INHIBIDORES DE LA FOSFODIESTERASA TIPO 5 (PDE-5) | |
| RU2009132881A (ru) | Производные пуринила и их применение в качестве модуляторов калиевых каналов | |
| EP3774732A2 (en) | Substituted pyridine and pyrimidines and their use as glun2b receptor modulators | |
| Yin et al. | Tailor-made amino acid-derived pharmaceuticals approved by the FDA in 2019 | |
| AU2018225312A1 (en) | Use of biomarkers in identifying cancer patients that will be responsive to treatment with a PRMT5 inhibitor | |
| UY32034A (es) | Nuevo procedimiento de resolución de enantiómeros de (3,4-dimetoxi-biciclo[4.2.0]octa-1,3,5-trien-7-il)nitrilo y aplicación en la sistesis de ivabradina | |
| JP6244353B2 (ja) | ピリジニルピラゾロキノリン化合物 | |
| EP2970201B1 (en) | 6-[4-(1h-imidazol-2-yl)piperidin-1-yl]pyrimidin-4-amine derivatives as modulators of kinase activity | |
| MA30703B1 (fr) | Dérivés de 5,6-bisaryl-2-pyridine-carboxamide, leur préparation et leur application en thérapeutique comme antagonistes des recepteurs a l'urotensine ii. | |
| PT2046396E (pt) | Agentes de fluoração anidro 18f radioactivamente marcados e métodos para a sua produção e utilização | |
| TNSN06260A1 (en) | Process for the preparation of tryptase inhibitors | |
| TW201718475A (zh) | 尿素衍生物及其用途 | |
| MA37751B1 (fr) | Procédé de préparation de composés d'acides aminés | |
| Wang et al. | A new facile synthetic route to [11C] GSK189254, a selective PET radioligand for imaging of CNS histamine H3 receptor | |
| CA2986954C (en) | Separation of enantiomers of 3-ethylbicyclo[3.2.0]hept-3-en-6-one | |
| Romagnoli et al. | Synthesis and biological evaluation of a new series of 2-amino-3-aroyl thiophene derivatives as agonist allosteric modulators of the A1 adenosine receptor. A position-dependent effect study |