PT2078022E - Espiro benzazepinas utilizadas como antagonistas de vasopressina - Google Patents

Info

Publication number

PT2078022E

PT2078022E PT07842799T PT07842799T PT2078022E PT 2078022 E PT2078022 E PT 2078022E PT 07842799 T PT07842799 T PT 07842799T PT 07842799 T PT07842799 T PT 07842799T PT 2078022 E PT2078022 E PT 2078022E

Authority

PT

Portugal

Prior art keywords

phenyl

benzazepine

carbonyl

dihydro

spiro

Prior art date

2006-09-22

Links

• Espacenet
• Global Dossier
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• -1 Spiro benzazepines Chemical class 0.000 title claims description 87
• 229940116211 Vasopressin antagonist Drugs 0.000 title description 6
• 239000003038 vasopressin antagonist Substances 0.000 title description 6
• 150000001875 compounds Chemical class 0.000 claims abstract description 195
• 206010019280 Heart failures Diseases 0.000 claims abstract description 31
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 21
• 201000006370 kidney failure Diseases 0.000 claims abstract description 18
• 206010007559 Cardiac failure congestive Diseases 0.000 claims abstract description 17
• 206010020772 Hypertension Diseases 0.000 claims abstract description 17
• 208000001647 Renal Insufficiency Diseases 0.000 claims abstract description 17
• 206010021036 Hyponatraemia Diseases 0.000 claims abstract description 16
• 206010048962 Brain oedema Diseases 0.000 claims abstract description 9
• 208000007342 Diabetic Nephropathies Diseases 0.000 claims abstract description 9
• 208000006011 Stroke Diseases 0.000 claims abstract description 9
• 208000006752 brain edema Diseases 0.000 claims abstract description 9
• 206010008118 cerebral infarction Diseases 0.000 claims abstract description 9
• 208000033679 diabetic kidney disease Diseases 0.000 claims abstract description 9
• 206010003225 Arteriospasm coronary Diseases 0.000 claims abstract description 8
• 201000006474 Brain Ischemia Diseases 0.000 claims abstract description 8
• 206010008120 Cerebral ischaemia Diseases 0.000 claims abstract description 8
• 208000003890 Coronary Vasospasm Diseases 0.000 claims abstract description 8
• 208000019425 cirrhosis of liver Diseases 0.000 claims abstract description 8
• 201000011634 coronary artery vasospasm Diseases 0.000 claims abstract description 8
• 208000031225 myocardial ischemia Diseases 0.000 claims abstract description 8
• 206010016807 Fluid retention Diseases 0.000 claims abstract description 7
• 206010047163 Vasospasm Diseases 0.000 claims abstract description 6
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 104
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 82
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 66
• GTKIGDZXPDCIKR-UHFFFAOYSA-N 2-phenylbenzamide Chemical compound NC(=O)C1=CC=CC=C1C1=CC=CC=C1 GTKIGDZXPDCIKR-UHFFFAOYSA-N 0.000 claims description 65
• 125000000217 alkyl group Chemical group 0.000 claims description 40
• KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 claims description 38
• 239000000203 mixture Substances 0.000 claims description 34
• 108010004977 Vasopressins Proteins 0.000 claims description 31
• GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 claims description 30
• 102000002852 Vasopressins Human genes 0.000 claims description 30
• 229960003726 vasopressin Drugs 0.000 claims description 30
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
• 150000001408 amides Chemical class 0.000 claims description 18
• 125000003118 aryl group Chemical group 0.000 claims description 16
• 201000010099 disease Diseases 0.000 claims description 16
• 150000003839 salts Chemical class 0.000 claims description 15
• 239000003937 drug carrier Substances 0.000 claims description 13
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
• 210000003169 central nervous system Anatomy 0.000 claims description 11
• 150000002148 esters Chemical class 0.000 claims description 11
• 125000004494 ethyl ester group Chemical group 0.000 claims description 11
• 229910052736 halogen Inorganic materials 0.000 claims description 11
• 150000002367 halogens Chemical class 0.000 claims description 11
• 125000000623 heterocyclic group Chemical group 0.000 claims description 10
• 230000016571 aggressive behavior Effects 0.000 claims description 8
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
• 229910052799 carbon Inorganic materials 0.000 claims description 8
• 229910052801 chlorine Inorganic materials 0.000 claims description 8
• 229910052731 fluorine Inorganic materials 0.000 claims description 8
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• 206010013935 Dysmenorrhoea Diseases 0.000 claims description 7
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• 208000007536 Thrombosis Diseases 0.000 claims description 7
• 230000036506 anxiety Effects 0.000 claims description 7
• 125000001153 fluoro group Chemical group F* 0.000 claims description 7
• 229910052739 hydrogen Inorganic materials 0.000 claims description 7
• 208000001738 Nervous System Trauma Diseases 0.000 claims description 6
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
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• 208000028412 nervous system injury Diseases 0.000 claims description 6
• 229910052757 nitrogen Inorganic materials 0.000 claims description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 5
• 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 5
• 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 description 5
• 208000005171 Dysmenorrhea Diseases 0.000 claims description 5
• 208000027601 Inner ear disease Diseases 0.000 claims description 5
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
• 230000002401 inhibitory effect Effects 0.000 claims description 5
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 4
• 238000002156 mixing Methods 0.000 claims description 4
• 229940107700 pyruvic acid Drugs 0.000 claims description 4
• 125000003003 spiro group Chemical group 0.000 claims description 4
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
• 150000004677 hydrates Chemical class 0.000 claims description 3
• 238000004519 manufacturing process Methods 0.000 claims description 3
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• 239000012453 solvate Substances 0.000 claims description 2
• 239000003112 inhibitor Substances 0.000 claims 3
• QEFDWAHQMRHBBT-UHFFFAOYSA-N 1'-benzylspiro[2,3-dihydro-1-benzazepine-4,3'-pyrrolidine] Chemical compound C(C1=CC=CC=C1)N1CC2(CC1)CCN=C1C(=C2)C=CC=C1 QEFDWAHQMRHBBT-UHFFFAOYSA-N 0.000 claims 1
• RHYALBGLTAGZOO-UHFFFAOYSA-N 1'-methylspiro[2,3-dihydro-1-benzazepine-4,3'-pyrrolidine] Chemical compound CN1CC2(CC1)CCN=C1C(=C2)C=CC=C1 RHYALBGLTAGZOO-UHFFFAOYSA-N 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 31
• 102000004136 Vasopressin Receptors Human genes 0.000 abstract description 18
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• 230000000694 effects Effects 0.000 abstract description 16
• 239000002536 vasopressin receptor antagonist Substances 0.000 abstract description 16
• 230000002792 vascular Effects 0.000 abstract description 5
• 206010008132 Cerebral thrombosis Diseases 0.000 abstract 1
• 201000001429 Intracranial Thrombosis Diseases 0.000 abstract 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 84
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 65
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
• 239000011541 reaction mixture Substances 0.000 description 41
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 37
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 34
• 238000011282 treatment Methods 0.000 description 27
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• 239000000243 solution Substances 0.000 description 21
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• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
• 102000005962 receptors Human genes 0.000 description 18
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• 125000004432 carbon atom Chemical group C* 0.000 description 10
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