CA2521898A1 - Derives de diazabicyclononene - Google Patents

Derives de diazabicyclononene Download PDF

Info

Publication number: CA2521898A1
Authority: CA; Canada
Prior art keywords: lower alkyl; mixtures; general formula; compounds; diastereomers
Prior art date: 2003-05-02
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.): Abandoned

Application number

CA002521898A

Other languages

English (en)

Inventor

Olivier Bezencon

Daniel Bur

Walter Fischli

Lubos Remen

Sylvia Richard-Bildstein

Thomas Weller

Thierry Sifferlen

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Actelion Pharmaceuticals Ltd

Original Assignee

Individual

Priority date (The priority date 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 date listed.)

2003-05-02

Filing date

2004-04-26

Publication date

2004-11-11

2004-04-26 Application filed by Individual filed Critical Individual

2004-11-11 Publication of CA2521898A1 publication Critical patent/CA2521898A1/fr

Status Abandoned legal-status Critical Current

Links

QDFXRVAOBHEBGJ-UHFFFAOYSA-N 3-(cyclononen-1-yl)-4,5,6,7,8,9-hexahydro-1h-diazonine Chemical class C1CCCCCCC=C1C1=NNCCCCCC1 QDFXRVAOBHEBGJ-UHFFFAOYSA-N 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 81
238000000034 method Methods 0.000 claims abstract description 11
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
239000000203 mixture Substances 0.000 claims description 58
125000000217 alkyl group Chemical group 0.000 claims description 54
125000003118 aryl group Chemical group 0.000 claims description 26
-1 racemates Chemical class 0.000 claims description 25
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
125000000753 cycloalkyl group Chemical group 0.000 claims description 23
125000004432 carbon atom Chemical group C* 0.000 claims description 22
239000002904 solvent Chemical class 0.000 claims 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 claims description 18
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
125000001072 heteroaryl group Chemical group 0.000 claims description 17
230000036454 renin-angiotensin system Effects 0.000 claims description 17
150000003839 salts Chemical class 0.000 claims description 17
238000011282 treatment Methods 0.000 claims description 17
208000001647 Renal Insufficiency Diseases 0.000 claims description 15
229910052736 halogen Inorganic materials 0.000 claims description 15
201000006370 kidney failure Diseases 0.000 claims description 15
201000010099 disease Diseases 0.000 claims description 14
150000002367 halogens Chemical class 0.000 claims description 14
206010019280 Heart failures Diseases 0.000 claims description 13
125000003342 alkenyl group Chemical group 0.000 claims description 12
125000003545 alkoxy group Chemical group 0.000 claims description 11
239000012876 carrier material Substances 0.000 claims description 11
229910052739 hydrogen Inorganic materials 0.000 claims description 11
239000001257 hydrogen Substances 0.000 claims description 11
206010020772 Hypertension Diseases 0.000 claims description 9
229910052799 carbon Inorganic materials 0.000 claims description 9
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
XOJVVFBFDXDTEG-UHFFFAOYSA-N pristane Chemical compound CC(C)CCCC(C)CCCC(C)CCCC(C)C XOJVVFBFDXDTEG-UHFFFAOYSA-N 0.000 claims description 9
125000002947 alkylene group Chemical group 0.000 claims description 8
125000000623 heterocyclic group Chemical group 0.000 claims description 8
230000000877 morphologic effect Effects 0.000 claims description 8
238000011321 prophylaxis Methods 0.000 claims description 8
208000037803 restenosis Diseases 0.000 claims description 8
239000005541 ACE inhibitor Substances 0.000 claims description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
206010063897 Renal ischaemia Diseases 0.000 claims description 7
125000004450 alkenylene group Chemical group 0.000 claims description 7
125000006193 alkinyl group Chemical group 0.000 claims description 7
229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims description 7
208000031225 myocardial ischemia Diseases 0.000 claims description 7
201000001320 Atherosclerosis Diseases 0.000 claims description 6
206010007559 Cardiac failure congestive Diseases 0.000 claims description 6
208000002249 Diabetes Complications Diseases 0.000 claims description 6
206010012655 Diabetic complications Diseases 0.000 claims description 6
208000010228 Erectile Dysfunction Diseases 0.000 claims description 6
208000010412 Glaucoma Diseases 0.000 claims description 6
206010018364 Glomerulonephritis Diseases 0.000 claims description 6
206010038419 Renal colic Diseases 0.000 claims description 6
238000007675 cardiac surgery Methods 0.000 claims description 6
201000001881 impotence Diseases 0.000 claims description 6
210000000056 organ Anatomy 0.000 claims description 6
238000002054 transplantation Methods 0.000 claims description 6
230000002792 vascular Effects 0.000 claims description 6
238000007631 vascular surgery Methods 0.000 claims description 6
125000004093 cyano group Chemical group *C#N 0.000 claims description 5
208000002815 pulmonary hypertension Diseases 0.000 claims description 5
125000004104 aryloxy group Chemical group 0.000 claims description 4
208000035475 disorder Diseases 0.000 claims description 4
125000005842 heteroatom Chemical group 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
125000001424 substituent group Chemical group 0.000 claims description 4
208000024172 Cardiovascular disease Diseases 0.000 claims description 3
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 3
125000005553 heteroaryloxy group Chemical group 0.000 claims description 3
229940127291 Calcium channel antagonist Drugs 0.000 claims description 2
241001465754 Metazoa Species 0.000 claims description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
239000012190 activator Substances 0.000 claims description 2
239000002671 adjuvant Substances 0.000 claims description 2
239000002160 alpha blocker Substances 0.000 claims description 2
239000002333 angiotensin II receptor antagonist Substances 0.000 claims description 2
239000002876 beta blocker Substances 0.000 claims description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
239000002934 diuretic Substances 0.000 claims description 2
229940030606 diuretics Drugs 0.000 claims description 2
230000008482 dysregulation Effects 0.000 claims description 2
230000002526 effect on cardiovascular system Effects 0.000 claims description 2
239000002792 enkephalinase inhibitor Substances 0.000 claims description 2
208000017169 kidney disease Diseases 0.000 claims description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 2
125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 2
239000011591 potassium Substances 0.000 claims description 2
229910052700 potassium Inorganic materials 0.000 claims description 2
229960003975 potassium Drugs 0.000 claims description 2
230000000948 sympatholitic effect Effects 0.000 claims description 2
229940124549 vasodilator Drugs 0.000 claims description 2
239000003071 vasodilator agent Substances 0.000 claims description 2
229940125721 immunosuppressive agent Drugs 0.000 claims 3
239000003018 immunosuppressive agent Substances 0.000 claims 3
CYLMWXHNKGDKEL-REZFCLSBSA-N (1r,5s)-n-cyclopropyl-n-[(2,3-dichlorophenyl)methyl]-7-[4-[(2s)-2-methyl-3-(2,3,6-trifluorophenoxy)propoxy]phenyl]-3,9-diazabicyclo[3.3.1]non-6-ene-6-carboxamide Chemical compound C=1([C@@]2([H])CNC[C@](N2)(CC=1C=1C=CC(OC[C@H](C)COC=2C(=C(F)C=CC=2F)F)=CC=1)[H])C(=O)N(C1CC1)CC1=CC=CC(Cl)=C1Cl CYLMWXHNKGDKEL-REZFCLSBSA-N 0.000 claims 2
CYLMWXHNKGDKEL-NRVKVJMMSA-N (1s,5r)-n-cyclopropyl-n-[(2,3-dichlorophenyl)methyl]-7-[4-[(2s)-2-methyl-3-(2,3,6-trifluorophenoxy)propoxy]phenyl]-3,9-diazabicyclo[3.3.1]non-6-ene-6-carboxamide Chemical compound C=1([C@]2([H])CNC[C@@](N2)(CC=1C=1C=CC(OC[C@H](C)COC=2C(=C(F)C=CC=2F)F)=CC=1)[H])C(=O)N(C1CC1)CC1=CC=CC(Cl)=C1Cl CYLMWXHNKGDKEL-NRVKVJMMSA-N 0.000 claims 2
229940118365 Endothelin receptor antagonist Drugs 0.000 claims 1
239000002308 endothelin receptor antagonist Substances 0.000 claims 1
125000005843 halogen group Chemical group 0.000 claims 1
108090000783 Renin Proteins 0.000 abstract description 7
102100028255 Renin Human genes 0.000 abstract description 6
238000002360 preparation method Methods 0.000 abstract description 5
239000003112 inhibitor Substances 0.000 abstract description 4
230000008569 process Effects 0.000 abstract description 3
239000004480 active ingredient Substances 0.000 abstract description 2
YJTZZSKGEPHUTF-UHFFFAOYSA-N 3,9-diazabicyclo[3.3.1]non-4-ene Chemical class C1NC=C2CCCC1N2 YJTZZSKGEPHUTF-UHFFFAOYSA-N 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 20
239000000243 solution Substances 0.000 description 19
235000019439 ethyl acetate Nutrition 0.000 description 14
230000002829 reductive effect Effects 0.000 description 13
150000002148 esters Chemical class 0.000 description 12
125000006239 protecting group Chemical group 0.000 description 12
238000000746 purification Methods 0.000 description 12
239000002461 renin inhibitor Substances 0.000 description 12
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 11
229940086526 renin-inhibitors Drugs 0.000 description 11
WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 11
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
239000000284 extract Substances 0.000 description 9
229910052943 magnesium sulfate Inorganic materials 0.000 description 9
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 9
DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 9
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
239000003814 drug Substances 0.000 description 8
229920006395 saturated elastomer Polymers 0.000 description 8
239000007788 liquid Substances 0.000 description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
229910052757 nitrogen Inorganic materials 0.000 description 7
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
230000008878 coupling Effects 0.000 description 6
238000010168 coupling process Methods 0.000 description 6
238000005859 coupling reaction Methods 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
KJYVKUQRRKDPAX-UHFFFAOYSA-N n-[(2,3-dichlorophenyl)methyl]cyclopropanamine Chemical compound ClC1=CC=CC(CNC2CC2)=C1Cl KJYVKUQRRKDPAX-UHFFFAOYSA-N 0.000 description 6
125000004433 nitrogen atom Chemical group N* 0.000 description 6
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
102000004190 Enzymes Human genes 0.000 description 5
108090000790 Enzymes Proteins 0.000 description 5
102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 5
108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 5
125000005530 alkylenedioxy group Chemical group 0.000 description 5
125000005529 alkyleneoxy group Chemical group 0.000 description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
229910052760 oxygen Inorganic materials 0.000 description 5
239000001301 oxygen Substances 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
239000008279 sol Substances 0.000 description 5
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 description 4
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
239000001828 Gelatine Substances 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
239000002775 capsule Substances 0.000 description 4
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230000005764 inhibitory process Effects 0.000 description 4
229910052717 sulfur Inorganic materials 0.000 description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
239000002253 acid Substances 0.000 description 3
125000004448 alkyl carbonyl group Chemical group 0.000 description 3
SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 3
239000012267 brine Substances 0.000 description 3
238000010511 deprotection reaction Methods 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
229910052731 fluorine Inorganic materials 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
230000001506 immunosuppresive effect Effects 0.000 description 3
239000003921 oil Substances 0.000 description 3
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125000004430 oxygen atom Chemical group O* 0.000 description 3
239000000825 pharmaceutical preparation Substances 0.000 description 3
229920005862 polyol Polymers 0.000 description 3
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HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
239000007787 solid Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
125000004434 sulfur atom Chemical group 0.000 description 3
238000012360 testing method Methods 0.000 description 3
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 3
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 3
239000001993 wax Substances 0.000 description 3
VLSDXINSOMDCBK-BQYQJAHWSA-N (E)-1,1'-azobis(N,N-dimethylformamide) Chemical compound CN(C)C(=O)\N=N\C(=O)N(C)C VLSDXINSOMDCBK-BQYQJAHWSA-N 0.000 description 2
JVVRCYWZTJLJSG-UHFFFAOYSA-N 4-dimethylaminophenol Chemical compound CN(C)C1=CC=C(O)C=C1 JVVRCYWZTJLJSG-UHFFFAOYSA-N 0.000 description 2
229960000549 4-dimethylaminophenol Drugs 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
102000004881 Angiotensinogen Human genes 0.000 description 2
108090001067 Angiotensinogen Proteins 0.000 description 2
108010064733 Angiotensins Proteins 0.000 description 2
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108010017640 Aspartic Acid Proteases Proteins 0.000 description 2
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101800004538 Bradykinin Proteins 0.000 description 2
102400000967 Bradykinin Human genes 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
239000004129 EU approved improving agent Substances 0.000 description 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
239000003513 alkali Substances 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
125000005603 azodicarboxylic group Chemical group 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
238000009833 condensation Methods 0.000 description 2
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125000004122 cyclic group Chemical group 0.000 description 2
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150000002314 glycerols Chemical class 0.000 description 2
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
238000003018 immunoassay Methods 0.000 description 2
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238000004519 manufacturing process Methods 0.000 description 2
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BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
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239000002243 precursor Substances 0.000 description 2
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239000011593 sulfur Substances 0.000 description 2
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239000000725 suspension Substances 0.000 description 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
235000015112 vegetable and seed oil Nutrition 0.000 description 2
239000008158 vegetable oil Substances 0.000 description 2
239000011592 zinc chloride Substances 0.000 description 2
235000005074 zinc chloride Nutrition 0.000 description 2
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
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239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems
- 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
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
- 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
- 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
- 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
- A61P9/10—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)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
General Health & Medical Sciences (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Diabetes (AREA)
Endocrinology (AREA)
Urology & Nephrology (AREA)
Ophthalmology & Optometry (AREA)
Vascular Medicine (AREA)
Emergency Medicine (AREA)
Hematology (AREA)
Obesity (AREA)
Hospice & Palliative Care (AREA)
Gynecology & Obstetrics (AREA)
Reproductive Health (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

CA002521898A 2003-05-02 2004-04-26 Derives de diazabicyclononene Abandoned CA2521898A1 (fr)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
EP0304622		2003-05-02
EPPCT/EP03/04622		2003-05-02
PCT/EP2004/004372 WO2004096116A2 (fr)	2003-05-02	2004-04-26	Derives de diazabicyclononene

Publications (1)

Publication Number	Publication Date
CA2521898A1 true CA2521898A1 (fr)	2004-11-11

Family

ID=33395698

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002521898A Abandoned CA2521898A1 (fr)	2003-05-02	2004-04-26	Derives de diazabicyclononene

Country Status (10)

Country	Link
EP (1)	EP1622564A2 (fr)
JP (1)	JP2006525259A (fr)
KR (1)	KR20060015573A (fr)
CN (1)	CN1780838A (fr)
AU (1)	AU2004233577A1 (fr)
BR (1)	BRPI0409882A (fr)
CA (1)	CA2521898A1 (fr)
MX (1)	MXPA05011711A (fr)
RU (1)	RU2005137571A (fr)
WO (1)	WO2004096116A2 (fr)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2005040165A1 (fr) *	2003-10-13	2005-05-06	Actelion Pharmaceuticals Ltd	Derives de diazabicyclononene et leur utilisation en tant qu'inhibiteurs de la renine
CA2540817A1 (fr) *	2003-10-23	2005-05-06	Olivier Bezencon	Derives de diazabicyclononene et de tetrahydropyridine utilises comme inhibiteurs de la renine
AU2004295092A1 (en) *	2003-12-05	2005-06-16	Actelion Pharmaceuticals Ltd.	Azabicyclooctene and other tetrahydropyridine derivatives with a new side-chain
ATE462703T1 (de)	2004-08-25	2010-04-15	Actelion Pharmaceuticals Ltd	Bicyclononen-derivate als renin-inhibitoren
WO2006021403A1 (fr) *	2004-08-25	2006-03-02	Actelion Pharmaceuticals Ltd	Dérivés du bicyclononène
WO2006058546A1 (fr) *	2004-12-01	2006-06-08	Actelion Pharmaceuticals Ltd	Nouveaux dérivés de lactame en tant qu’inhibiteurs de la rénine
WO2006063610A1 (fr) *	2004-12-17	2006-06-22	Actelion Pharmaceuticals Ltd	Dérivés de diazabicyclononène substitués par des groupements hétéroaryle
GB0428526D0 (en)	2004-12-30	2005-02-09	Novartis Ag	Organic compounds
KR100938364B1 (ko) *	2005-01-28	2010-01-22	액테리온 파마슈티칼 리미티드	고혈압 치료를 위한, 레닌의 억제제로서의 7-｛4-[2-(2,6-디클로로-4-메틸페녹시)에톡시]페닐｝-3,9-디아자비시클로[3.3.1]논-6-엔-6-카르복실산 시클로프로필-(2,3-디메틸벤질)아미드
WO2006131884A2 (fr) *	2005-06-07	2006-12-14	Actelion Pharmaceuticals Ltd	Nouveaux derives de thiazole
GB0514203D0 (en)	2005-07-11	2005-08-17	Novartis Ag	Organic compounds
BRPI0620736A2 (pt)	2005-12-30	2011-12-20	Novartis Ag	compostos orgánicos
CA2646235A1 (fr) *	2006-03-16	2007-09-20	Nicox S.A.	Derives nitro d'inhibiteurs de renine non peptidiques
AU2008253519A1 (en)	2007-05-24	2008-11-27	Merck Frosst Canada Ltd	Novel case of renin inhibitors
SG182223A1 (en)	2007-06-25	2012-07-30	Novartis Ag	N5-(2-ethoxyethyl)-n3-(2-pyridinyl)-3,5-piperidinedicarboxamide derivatives for use as renin inhibitors
AU2008288648A1 (en)	2007-08-20	2009-02-26	Merck Frosst Canada Ltd.	Renin inhibitors
KR101403311B1 (ko)	2008-05-05	2014-06-05	액테리온 파마슈티칼 리미티드	레닌 억제제로서의 3,4-치환된 피페리딘 유도체
WO2013038936A1 (fr) *	2011-09-13	2013-03-21	タカラバイオ株式会社	Procédé d'arrêt d'une réaction peroxydasique, et agent d'arrêt pour ladite réaction

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3509161A (en) *	1967-07-10	1970-04-28	Boehringer & Soehne Gmbh	3-phenyl-granatene-(2)-derivatives
TR199800409T1 (xx) *	1995-09-07	1998-05-21	F.Hoffmann-La Roche Ag	Kalp ve b�brek yetersizli�inin tedavii�in yeni 4-(oksialkoksifenil)-3-oksi-piperidinler
CA2483241C (fr) *	2002-04-29	2011-05-31	Actelion Pharmaceuticals Ltd	Nouveaux derives de diazabicyclononene
RU2005102002A (ru) *	2002-06-27	2005-09-20	Актелион Фармасьютиклз Лтд. (Ch)	Новые производные тетрагидропиридина

2004
- 2004-04-26 EP EP04729414A patent/EP1622564A2/fr not_active Withdrawn
- 2004-04-26 RU RU2005137571/04A patent/RU2005137571A/ru not_active Application Discontinuation
- 2004-04-26 MX MXPA05011711A patent/MXPA05011711A/es not_active Application Discontinuation
- 2004-04-26 WO PCT/EP2004/004372 patent/WO2004096116A2/fr not_active Ceased
- 2004-04-26 CN CNA2004800116500A patent/CN1780838A/zh active Pending
- 2004-04-26 JP JP2006505261A patent/JP2006525259A/ja active Pending
- 2004-04-26 KR KR1020057020788A patent/KR20060015573A/ko not_active Withdrawn
- 2004-04-26 CA CA002521898A patent/CA2521898A1/fr not_active Abandoned
- 2004-04-26 AU AU2004233577A patent/AU2004233577A1/en not_active Abandoned
- 2004-04-26 BR BRPI0409882-0A patent/BRPI0409882A/pt not_active Application Discontinuation

Also Published As

Publication number	Publication date
KR20060015573A (ko)	2006-02-17
RU2005137571A (ru)	2006-05-10
MXPA05011711A (es)	2006-01-23
EP1622564A2 (fr)	2006-02-08
WO2004096116A3 (fr)	2005-03-24
WO2004096116A2 (fr)	2004-11-11
CN1780838A (zh)	2006-05-31
AU2004233577A1 (en)	2004-11-11
JP2006525259A (ja)	2006-11-09
BRPI0409882A (pt)	2006-05-23

Legal Events

Date	Code	Title	Description
2009-04-27	FZDE	Discontinued

Publication	Publication Date	Title
CA2521898A1 (fr)	2004-11-11	Derives de diazabicyclononene
US20060009497A1 (en)	2006-01-12	Novel tetrahydropyridine derivatives as renin inhibitors
CA2521938A1 (fr)	2004-11-11	Derives de 9-azabicyclo[3.3.1]non-6-ee a heteroatome en position 3 servant d'inhibiteurs de la renine
US20060217371A1 (en)	2006-09-28	Diazabicyclononene and tetrahydropyriddine derivatives as renin inhibitors
US20060235044A1 (en)	2006-10-19	Azabicyclononene derivatives
US20070135406A1 (en)	2007-06-14	Diazabicyclononene and tetrahydropyridine derivatives with a new side-chain
US20060205768A1 (en)	2006-09-14	Tropane derivatives and their use as ace inhibitors
EP1620403B1 (fr)	2007-11-28	Nouveaux derives de la 1,2,3,6-tetrahydropyridine 3,4-disubstituee
US20070142363A1 (en)	2007-06-21	Novel diazabicyclonene derivatives and use thereof
US20070135405A1 (en)	2007-06-14	Novel diazabicyclononene and tetrahydropyridine derivatives with a new polar side-chain
US20070111989A1 (en)	2007-05-17	Novel diazabicyclononene derivatives and use
US20060223795A1 (en)	2006-10-05	Novel diazabicyclononene derivatives
WO2006058546A1 (fr)	2006-06-08	Nouveaux dérivés de lactame en tant qu’inhibiteurs de la rénine
US20060235056A1 (en)	2006-10-19	Novel 3,4-disubstituted 1,2,3,6-tetrahydropyridine derivatives
EP1622906A1 (fr)	2006-02-08	Derives de diazabicyclononene et de tetrahydropyridine utilises comme inhibiteurs de la renine