CA1267902A - Derives de 2-azabicyclo[3.1.0] hexane et procede de preparation - Google Patents

Derives de 2-azabicyclo[3.1.0] hexane et procede de preparation

Info

Publication number: CA1267902A
Authority: CA; Canada
Prior art keywords: formula; compounds; cis; hexane; iiib
Prior art date: 1983-07-06
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.): Expired - Fee Related

Application number

CA000583193A

Other languages

English (en)

Inventor

Hansjorg Nrbach

Rainer Henning

Reinhard Becker

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.)

Hoechst AG

Original Assignee

Hoechst AG

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.)

1983-07-06

Filing date

1988-11-04

Publication date

1990-04-17

1983-07-06 Priority claimed from DE19833324263 external-priority patent/DE3324263A1/de

1988-11-04 Application filed by Hoechst AG filed Critical Hoechst AG

1988-11-04 Priority to CA000583193A priority Critical patent/CA1267902A/fr

1990-04-17 Application granted granted Critical

1990-04-17 Publication of CA1267902A publication Critical patent/CA1267902A/fr

2007-04-17 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 19
238000002360 preparation method Methods 0.000 title claims abstract description 9
WSSDGZWSPMAECX-UHFFFAOYSA-N 2-azabicyclo[3.1.0]hexane Chemical class C1CNC2CC21 WSSDGZWSPMAECX-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 75
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 23
239000001257 hydrogen Substances 0.000 claims abstract description 23
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 12
239000000203 mixture Substances 0.000 claims description 19
229910052736 halogen Inorganic materials 0.000 claims description 4
150000002367 halogens Chemical class 0.000 claims description 4
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
150000003839 salts Chemical class 0.000 abstract description 12
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 6
230000001077 hypotensive effect Effects 0.000 abstract description 3
102000004190 Enzymes Human genes 0.000 abstract description 2
108090000790 Enzymes Proteins 0.000 abstract description 2
206010020772 Hypertension Diseases 0.000 abstract description 2
239000003112 inhibitor Substances 0.000 abstract description 2
230000005923 long-lasting effect Effects 0.000 abstract description 2
230000003389 potentiating effect Effects 0.000 abstract description 2
239000005541 ACE inhibitor Substances 0.000 abstract 1
229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 abstract 1
239000000543 intermediate Substances 0.000 abstract 1
235000013350 formula milk Nutrition 0.000 description 57
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
-1 heterocyclic radical Chemical class 0.000 description 18
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
239000002253 acid Substances 0.000 description 15
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 13
235000002639 sodium chloride Nutrition 0.000 description 13
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
239000002585 base Substances 0.000 description 10
239000000741 silica gel Substances 0.000 description 10
229910002027 silica gel Inorganic materials 0.000 description 10
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
239000000047 product Substances 0.000 description 9
238000006243 chemical reaction Methods 0.000 description 8
150000002148 esters Chemical class 0.000 description 8
150000002431 hydrogen Chemical class 0.000 description 8
239000000243 solution Substances 0.000 description 8
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 7
238000005481 NMR spectroscopy Methods 0.000 description 7
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
229910052760 oxygen Inorganic materials 0.000 description 7
239000001301 oxygen Substances 0.000 description 7
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
150000003254 radicals Chemical class 0.000 description 7
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
238000001816 cooling Methods 0.000 description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
125000004432 carbon atom Chemical group C* 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
229940073584 methylene chloride Drugs 0.000 description 5
239000002904 solvent Substances 0.000 description 5
229910052717 sulfur Inorganic materials 0.000 description 5
238000005160 1H NMR spectroscopy Methods 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
239000012043 crude product Substances 0.000 description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
125000006413 ring segment Chemical group 0.000 description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
229960000583 acetic acid Drugs 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
230000001476 alcoholic effect Effects 0.000 description 3
125000003118 aryl group Chemical group 0.000 description 3
235000019445 benzyl alcohol Nutrition 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
230000003197 catalytic effect Effects 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
239000000499 gel Substances 0.000 description 3
239000003921 oil Substances 0.000 description 3
235000019198 oils Nutrition 0.000 description 3
150000002923 oximes Chemical class 0.000 description 3
108090000765 processed proteins & peptides Proteins 0.000 description 3
239000003981 vehicle Substances 0.000 description 3
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
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 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
239000004472 Lysine Substances 0.000 description 2
238000006683 Mannich reaction Methods 0.000 description 2
229910019213 POCl3 Inorganic materials 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
239000007868 Raney catalyst Substances 0.000 description 2
229910000564 Raney nickel Inorganic materials 0.000 description 2
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-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
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
125000002252 acyl group Chemical group 0.000 description 2
150000001340 alkali metals Chemical class 0.000 description 2
125000000217 alkyl group Chemical group 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
125000004429 atom Chemical group 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
239000003638 chemical reducing agent Substances 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
WBLIXGSTEMXDSM-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH2] WBLIXGSTEMXDSM-UHFFFAOYSA-N 0.000 description 2
MCWXGJITAZMZEV-UHFFFAOYSA-N dimethoate Chemical compound CNC(=O)CSP(=S)(OC)OC MCWXGJITAZMZEV-UHFFFAOYSA-N 0.000 description 2
229940079593 drug Drugs 0.000 description 2
238000001035 drying Methods 0.000 description 2
125000004494 ethyl ester group Chemical group 0.000 description 2
235000019253 formic acid Nutrition 0.000 description 2
239000012362 glacial acetic acid Substances 0.000 description 2
239000008103 glucose Substances 0.000 description 2
230000002140 halogenating effect Effects 0.000 description 2
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
229910000041 hydrogen chloride Inorganic materials 0.000 description 2
238000005984 hydrogenation reaction Methods 0.000 description 2
238000007327 hydrogenolysis reaction Methods 0.000 description 2
150000002576 ketones Chemical class 0.000 description 2
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
125000002950 monocyclic group Chemical group 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
210000000056 organ Anatomy 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
125000004430 oxygen atom Chemical group O* 0.000 description 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
239000011591 potassium Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
238000010992 reflux Methods 0.000 description 2
239000001632 sodium acetate Substances 0.000 description 2
235000017281 sodium acetate Nutrition 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
239000000126 substance Substances 0.000 description 2
239000011593 sulfur Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
125000001544 thienyl group Chemical group 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
FMCAFXHLMUOIGG-JTJHWIPRSA-N (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-JTJHWIPRSA-N 0.000 description 1
125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
NSMXQKNUPPXBRG-SECBINFHSA-N (R)-lisofylline Chemical group O=C1N(CCCC[C@H](O)C)C(=O)N(C)C2=C1N(C)C=N2 NSMXQKNUPPXBRG-SECBINFHSA-N 0.000 description 1
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
244000215068 Acacia senegal Species 0.000 description 1
RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
241000251468 Actinopterygii Species 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
NOTFZGFABLVTIG-UHFFFAOYSA-N Cyclohexylethyl acetate Chemical compound CC(=O)OCCC1CCCCC1 NOTFZGFABLVTIG-UHFFFAOYSA-N 0.000 description 1
208000006558 Dental Calculus Diseases 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
241000790917 Dioxys <bee> Species 0.000 description 1
238000006720 Favorskii reaction Methods 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
229920000084 Gum arabic Polymers 0.000 description 1
QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 1
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
208000001953 Hypotension Diseases 0.000 description 1
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 description 1
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241001465754 Metazoa Species 0.000 description 1
230000006181 N-acylation Effects 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
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DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 1
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150000008041 alkali metal carbonates Chemical class 0.000 description 1
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DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
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238000013375 chromatographic separation Methods 0.000 description 1
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229910052731 fluorine Inorganic materials 0.000 description 1
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ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
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125000001041 indolyl group Chemical group 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
239000008101 lactose Substances 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
239000001095 magnesium carbonate Substances 0.000 description 1
ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
235000014380 magnesium carbonate Nutrition 0.000 description 1
229960001708 magnesium carbonate Drugs 0.000 description 1
229910000021 magnesium carbonate Inorganic materials 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
VPCDQGACGWYTMC-UHFFFAOYSA-N nitrosyl chloride Chemical compound ClN=O VPCDQGACGWYTMC-UHFFFAOYSA-N 0.000 description 1
235000019392 nitrosyl chloride Nutrition 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
239000012071 phase Substances 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
229910000160 potassium phosphate Inorganic materials 0.000 description 1
235000011009 potassium phosphates Nutrition 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
230000008707 rearrangement Effects 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
239000012265 solid product Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
239000002600 sunflower oil Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
231100000563 toxic property Toxicity 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
235000013311 vegetables Nutrition 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
229910052727 yttrium Inorganic materials 0.000 description 1

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Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)

CA000583193A 1983-07-06 1988-11-04 Derives de 2-azabicyclo[3.1.0] hexane et procede de preparation Expired - Fee Related CA1267902A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000583193A CA1267902A (fr)	1983-07-06	1988-11-04	Derives de 2-azabicyclo[3.1.0] hexane et procede de preparation

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
DEN3324263.1		1983-07-06
DE19833324263 DE3324263A1 (de)	1983-07-06	1983-07-06	Derivate der 2-azabicyclo(3.1.0)hexan-3-carbonsaeure, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung sowie 2-azabicyclo(3.1.0)hexan-derivate als zwischenprodukte und verfahren zu deren herstellung
CA000458205A CA1263000A1 (fr)	1983-07-06	1984-07-05	Derives de l'acide 2-azabicyclo[3.1.0]hexane-3- carboxylique, procede de preparation, agents les contenant et leur utilisation et derives de 2- azabicyclo[3.1.0]hexane utilisescomme intermediaires et procede de preparation
CA000583193A CA1267902A (fr)	1983-07-06	1988-11-04	Derives de 2-azabicyclo[3.1.0] hexane et procede de preparation

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000458205A Division CA1263000A1 (fr)	1983-07-06	1984-07-05	Derives de l'acide 2-azabicyclo[3.1.0]hexane-3- carboxylique, procede de preparation, agents les contenant et leur utilisation et derives de 2- azabicyclo[3.1.0]hexane utilisescomme intermediaires et procede de preparation

Publications (1)

Publication Number	Publication Date
CA1267902A true CA1267902A (fr)	1990-04-17

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ID=25670434

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000583193A Expired - Fee Related CA1267902A (fr)	1983-07-06	1988-11-04	Derives de 2-azabicyclo[3.1.0] hexane et procede de preparation

Country Status (1)

Country	Link
CA (1)	CA1267902A (fr)

1988
- 1988-11-04 CA CA000583193A patent/CA1267902A/fr not_active Expired - Fee Related

Legal Events

Date	Code	Title	Description
1993-10-18	MKLA	Lapsed

Publication	Publication Date	Title
US4591598A (en)	1986-05-27	Derivatives of 2-azabicyclo[3.1.0]hexane-3-carboxylic acid, and hypotensive use thereof
US4879403A (en)	1989-11-07	Process for the preparation of cis, endo-2-azabicyclo-[3.3.0]-octane-3-carboxylic acids
US4714708A (en)	1987-12-22	Derivatives of cis, endo-2-azabicyclo[5.3.0]decane-3-carboxylic acid, and their use for treating hypertension
DK171256B1 (da)	1996-08-12	Analogifremgangsmåde til fremstilling af derivater af bicycliske aminosyrer eller fysiologisk acceptable salte deraf
JPH064586B2 (ja)	1994-01-19	新規な二環式化合物
US4614805A (en)	1986-09-30	Bicyclic amino acids as intermediates in the preparation of tricyclic amino acids and processes for their preparation
CA1172258A (fr)	1984-08-07	Acides 1-carboxy-aza-alcanoylindoline-2-carboxyliques
HU179734B (en)	1982-12-28	Process for producing pharmaceutically effective new n-2 above-bracket-1,2,3,4-tetrahydro-8-quinolyl-bracket closed-sulfonyl-l-arginine-amides
EP0049658A1 (fr)	1982-04-14	Iminodiacides substitués, leur préparation et compositions pharmaceutiques les contenant
US4620012A (en)	1986-10-28	Spirocyclic aminoacid derivatives, processes for their preparation, agents containing them and their use and new spirocyclic aminoacids as intermediates and processes for their preparation
EP0031741A1 (fr)	1981-07-08	Nouveaux iminoacides substitués, leurs procédés de préparation et leur emploi comme inhibiteurs d'enzymes
HU193876B (en)	1987-12-28	Process for preparing cycloalkane /c/ pyrrol-1-carboxypeptides and pharmaceutics comprising the same
EP0068173B1 (fr)	1984-09-26	Dérivés de perhydro-1,4-thiazépine-5-one et de perhydro-1,4-thiazocine-5-one, leur procédé de préparation et compositions pharmaceutiques les contenant
EP0105919B1 (fr)	1987-07-08	Acides 1-carboxyalkanoylperhydroindol-2-carboxyliques et leurs derives
EP0065301A1 (fr)	1982-11-24	Dérivés des acides isoquinoléine-carboxyliques, leur procédé de préparation et compositions pharmaceutiques qui les contiennent
CA1267902A (fr)	1990-04-17	Derives de 2-azabicyclo[3.1.0] hexane et procede de preparation
EP0057998B1 (fr)	1984-08-08	Composés alicycliques, leur préparation et utilisation
US4285935A (en)	1981-08-25	Dehydropeptide compounds, their production and their medical use
CA1310794C (fr)	1992-11-24	Derives d'acides amines bicycliques, procede pour leur preparation, agents en contenant et leur utilisation
US4390700A (en)	1983-06-28	1-Carboxyazaalkanoyl-tetrahydroquinoline-2-carboxylic acids
KR880001007B1 (ko)	1988-06-13	비사이클릭 화합물의 제조 방법
CA1310972C (fr)	1992-12-01	Derives d'acide amines bicycliques, procede pour leur preparation, agents en contenant et leur utilisation
CA1227212A (fr)	1987-09-22	Derives d'acide cis, endo-2-azabicyclo[5.3.0] decane-3-carboxylique; preparation; agents renfermant ces derives et applications
NZ214877A (en)	1988-01-08	Cepyrrol-2-ylcarboxylic acid derivatives
NO157103B (no)	1987-10-12	Analogifremgangsmaate for fremstilling av terapeutisk virksomme dicykliske forbindelser.