ZA200105550B - Method for preparing bicyclic compounds and use of said method for preparing an interleukin-1 beta conversion enzyme (ICE) inhibitor. - Google Patents
Method for preparing bicyclic compounds and use of said method for preparing an interleukin-1 beta conversion enzyme (ICE) inhibitor. Download PDFInfo
- Publication number
- ZA200105550B ZA200105550B ZA200105550A ZA200105550A ZA200105550B ZA 200105550 B ZA200105550 B ZA 200105550B ZA 200105550 A ZA200105550 A ZA 200105550A ZA 200105550 A ZA200105550 A ZA 200105550A ZA 200105550 B ZA200105550 B ZA 200105550B
- Authority
- ZA
- South Africa
- Prior art keywords
- formula
- compound
- iopt
- dioxo
- protected
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 37
- 238000006243 chemical reaction Methods 0.000 title description 3
- 125000002619 bicyclic group Chemical group 0.000 title description 2
- LOGFVTREOLYCPF-KXNHARMFSA-N (2s,3r)-2-[[(2r)-1-[(2s)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoic acid Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]1CCCN1C(=O)[C@@H](N)CCCCN LOGFVTREOLYCPF-KXNHARMFSA-N 0.000 title 1
- 102000004190 Enzymes Human genes 0.000 title 1
- 108090000790 Enzymes Proteins 0.000 title 1
- 102000003777 Interleukin-1 beta Human genes 0.000 title 1
- 108090000193 Interleukin-1 beta Proteins 0.000 title 1
- 239000003112 inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 61
- 150000001412 amines Chemical group 0.000 claims description 24
- 238000002360 preparation method Methods 0.000 claims description 22
- 239000000203 mixture Substances 0.000 claims description 19
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 18
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 claims description 15
- -1 aralkyl radical Chemical class 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical group CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 10
- 238000007363 ring formation reaction Methods 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 150000003009 phosphonic acids Chemical class 0.000 claims description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000005544 phthalimido group Chemical group 0.000 claims description 6
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- QRKPPWPLSQRGSU-UHFFFAOYSA-N diazepine-1-carboxylic acid Chemical compound OC(=O)N1C=CC=CC=N1 QRKPPWPLSQRGSU-UHFFFAOYSA-N 0.000 claims description 5
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 5
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 150000005840 aryl radicals Chemical class 0.000 claims description 4
- 238000010511 deprotection reaction Methods 0.000 claims description 4
- 238000006345 epimerization reaction Methods 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- ICDLEMPZXFCQEB-VIFPVBQESA-N 2-[(3s)-2,6-dioxooxan-3-yl]isoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1[C@H]1CCC(=O)OC1=O ICDLEMPZXFCQEB-VIFPVBQESA-N 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 150000008064 anhydrides Chemical class 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- IIVWHGMLFGNMOW-UHFFFAOYSA-N 2-methylpropane Chemical group C[C](C)C IIVWHGMLFGNMOW-UHFFFAOYSA-N 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 239000005864 Sulphur Substances 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000013638 trimer Substances 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 239000000243 solution Substances 0.000 description 14
- 238000013019 agitation Methods 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 238000000605 extraction Methods 0.000 description 8
- 238000005406 washing Methods 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 5
- 239000012429 reaction media Substances 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 108090000426 Caspase-1 Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- QIWKCQDJZPRXNS-VIFPVBQESA-N (2s)-2-[(2-carboxybenzoyl)amino]pentanedioic acid Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)C1=CC=CC=C1C(O)=O QIWKCQDJZPRXNS-VIFPVBQESA-N 0.000 description 2
- FEFFSKLJNYRHQN-UHFFFAOYSA-N 2-Phthalimidoglutaricacid Chemical compound C1=CC=C2C(=O)N(C(CCC(=O)O)C(O)=O)C(=O)C2=C1 FEFFSKLJNYRHQN-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 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 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 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
- GTABLZQCIHCVPN-BYPYZUCNSA-N (3s)-diazinane-1,2,3-tricarboxylic acid Chemical compound OC(=O)[C@@H]1CCCN(C(O)=O)N1C(O)=O GTABLZQCIHCVPN-BYPYZUCNSA-N 0.000 description 1
- LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 description 1
- JDAVNLLRFXIKKD-UHFFFAOYSA-N 2,5-dibromopentanoic acid Chemical compound OC(=O)C(Br)CCCBr JDAVNLLRFXIKKD-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 102100035904 Caspase-1 Human genes 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
- FEFFSKLJNYRHQN-VIFPVBQESA-N N-phthaloyl-L-glutamic acid Chemical compound C1=CC=C2C(=O)N([C@@H](CCC(=O)O)C(O)=O)C(=O)C2=C1 FEFFSKLJNYRHQN-VIFPVBQESA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- VRHAQNTWKSVEEC-UHFFFAOYSA-N ethyl 1,3-dioxoisoindole-2-carboxylate Chemical compound C1=CC=C2C(=O)N(C(=O)OCC)C(=O)C2=C1 VRHAQNTWKSVEEC-UHFFFAOYSA-N 0.000 description 1
- 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9900227A FR2788276B1 (fr) | 1999-01-12 | 1999-01-12 | NOUVEAU PROCEDE DE PREPARATION DE COMPOSES BICYCLIQUES ET L'APPLICATION DE CE PROCEDE COMME ETAPE INTERMEDIAIRE POUR LA PREPARATION D'UN COMPOSE INHIBITEUR DE L'ENZYME DE CONVERSION DE L'INTERLEUKINE 1-BETA (ice) |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200105550B true ZA200105550B (en) | 2002-07-25 |
Family
ID=9540778
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200105550A ZA200105550B (en) | 1999-01-12 | 2001-07-05 | Method for preparing bicyclic compounds and use of said method for preparing an interleukin-1 beta conversion enzyme (ICE) inhibitor. |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US6512111B1 (xx) |
| EP (1) | EP1144436B1 (xx) |
| JP (1) | JP4601826B2 (xx) |
| KR (1) | KR100797349B1 (xx) |
| CN (1) | CN1240710C (xx) |
| AT (1) | ATE263780T1 (xx) |
| AU (1) | AU774752B2 (xx) |
| BR (1) | BR0007810B1 (xx) |
| CA (1) | CA2359964C (xx) |
| DE (1) | DE60009658T2 (xx) |
| DK (1) | DK1144436T3 (xx) |
| ES (1) | ES2215020T3 (xx) |
| FR (1) | FR2788276B1 (xx) |
| HK (1) | HK1045316B (xx) |
| HU (1) | HU230062B1 (xx) |
| IL (2) | IL144227A0 (xx) |
| NO (1) | NO328110B1 (xx) |
| NZ (1) | NZ512908A (xx) |
| PL (1) | PL196993B1 (xx) |
| PT (1) | PT1144436E (xx) |
| SI (1) | SI1144436T1 (xx) |
| TW (1) | TWI222443B (xx) |
| WO (1) | WO2000042061A1 (xx) |
| ZA (1) | ZA200105550B (xx) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6703500B2 (en) | 1998-08-19 | 2004-03-09 | Vertex Pharmaceuticals, Incorporated | Method of preparing bicyclic intermediates from piperazic acid or an ester thereof useful in the manufacture of caspase inhibitors |
| US6559304B1 (en) | 1998-08-19 | 2003-05-06 | Vertex Pharmaceuticals Incorporated | Method for synthesizing caspase inhibitors |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2128984B (en) * | 1982-05-12 | 1985-05-22 | Hoffmann La Roche | Diaza-bicyclic compounds |
| NZ204130A (en) * | 1982-05-12 | 1986-03-14 | Hoffmann La Roche | Bicyclic heterocyclic compounds and pharmaceutical compositions |
-
1999
- 1999-01-12 FR FR9900227A patent/FR2788276B1/fr not_active Expired - Fee Related
- 1999-12-10 TW TW088121699A patent/TWI222443B/zh not_active IP Right Cessation
-
2000
- 2000-01-11 HU HU0202665A patent/HU230062B1/hu not_active IP Right Cessation
- 2000-01-11 BR BRPI0007810-7A patent/BR0007810B1/pt not_active IP Right Cessation
- 2000-01-11 PT PT00900552T patent/PT1144436E/pt unknown
- 2000-01-11 CN CNB008048320A patent/CN1240710C/zh not_active Expired - Fee Related
- 2000-01-11 US US09/869,950 patent/US6512111B1/en not_active Expired - Lifetime
- 2000-01-11 PL PL348919A patent/PL196993B1/pl unknown
- 2000-01-11 WO PCT/FR2000/000041 patent/WO2000042061A1/fr active IP Right Grant
- 2000-01-11 AU AU30524/00A patent/AU774752B2/en not_active Ceased
- 2000-01-11 EP EP00900552A patent/EP1144436B1/fr not_active Expired - Lifetime
- 2000-01-11 NZ NZ512908A patent/NZ512908A/en not_active IP Right Cessation
- 2000-01-11 JP JP2000593628A patent/JP4601826B2/ja not_active Expired - Fee Related
- 2000-01-11 DK DK00900552T patent/DK1144436T3/da active
- 2000-01-11 CA CA2359964A patent/CA2359964C/fr not_active Expired - Fee Related
- 2000-01-11 DE DE60009658T patent/DE60009658T2/de not_active Expired - Lifetime
- 2000-01-11 IL IL14422700A patent/IL144227A0/xx active IP Right Grant
- 2000-01-11 KR KR1020017008755A patent/KR100797349B1/ko not_active IP Right Cessation
- 2000-01-11 ES ES00900552T patent/ES2215020T3/es not_active Expired - Lifetime
- 2000-01-11 AT AT00900552T patent/ATE263780T1/de active
- 2000-01-11 SI SI200030348T patent/SI1144436T1/xx unknown
-
2001
- 2001-07-05 ZA ZA200105550A patent/ZA200105550B/en unknown
- 2001-07-10 IL IL144227A patent/IL144227A/en not_active IP Right Cessation
- 2001-07-11 NO NO20013435A patent/NO328110B1/no not_active IP Right Cessation
-
2002
- 2002-09-18 HK HK02106828.3A patent/HK1045316B/zh not_active IP Right Cessation
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