ME01708B - Postupak za dobijanje aminskih derivata alkiloksifuranona, dobijena jedinjenja i upotreba ovih jedinjenja - Google Patents
Postupak za dobijanje aminskih derivata alkiloksifuranona, dobijena jedinjenja i upotreba ovih jedinjenjaInfo
- Publication number
- ME01708B ME01708B MEP-2000-15A MEP200015A ME01708B ME 01708 B ME01708 B ME 01708B ME P200015 A MEP200015 A ME P200015A ME 01708 B ME01708 B ME 01708B
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- Montenegro
- Prior art keywords
- formula
- compound
- iii
- action
- acid
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims 42
- 238000000034 method Methods 0.000 title claims 19
- -1 alkyloxy furanone derivatives Chemical class 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims 21
- 239000002253 acid Substances 0.000 claims 10
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 claims 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 6
- 238000006243 chemical reaction Methods 0.000 claims 6
- 238000002425 crystallisation Methods 0.000 claims 6
- 230000008025 crystallization Effects 0.000 claims 6
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 claims 6
- 150000001412 amines Chemical class 0.000 claims 5
- 125000004432 carbon atom Chemical group C* 0.000 claims 5
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical class OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 claims 5
- 238000006345 epimerization reaction Methods 0.000 claims 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 4
- 238000000926 separation method Methods 0.000 claims 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims 3
- 150000007513 acids Chemical class 0.000 claims 3
- 125000000217 alkyl group Chemical group 0.000 claims 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 3
- 238000007327 hydrogenolysis reaction Methods 0.000 claims 3
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 claims 2
- 102000004190 Enzymes Human genes 0.000 claims 2
- 108090000790 Enzymes Proteins 0.000 claims 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 claims 2
- 229960005215 dichloroacetic acid Drugs 0.000 claims 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- 230000002401 inhibitory effect Effects 0.000 claims 2
- 229940098779 methanesulfonic acid Drugs 0.000 claims 2
- 125000003884 phenylalkyl group Chemical group 0.000 claims 2
- CAEWJEXPFKNBQL-UHFFFAOYSA-N prop-2-enyl carbonochloridate Chemical compound ClC(=O)OCC=C CAEWJEXPFKNBQL-UHFFFAOYSA-N 0.000 claims 2
- 150000003254 radicals Chemical class 0.000 claims 2
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims 1
- KPZGRMZPZLOPBS-UHFFFAOYSA-N 1,3-dichloro-2,2-bis(chloromethyl)propane Chemical compound ClCC(CCl)(CCl)CCl KPZGRMZPZLOPBS-UHFFFAOYSA-N 0.000 claims 1
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims 1
- 102000015696 Interleukins Human genes 0.000 claims 1
- 108010063738 Interleukins Proteins 0.000 claims 1
- 238000007112 amidation reaction Methods 0.000 claims 1
- 150000004982 aromatic amines Chemical class 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 claims 1
- QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical group C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 239000010413 mother solution Substances 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 238000001953 recrystallisation Methods 0.000 claims 1
- 125000003107 substituted aryl group Chemical group 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 claims 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/32—Oxygen atoms
- C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B57/00—Separation of optically-active compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/32—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/60—Two oxygen atoms, e.g. succinic anhydride
-
- 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
- C07K5/10—Tetrapeptides
- C07K5/1024—Tetrapeptides with the first amino acid being heterocyclic
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Furan Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Plural Heterocyclic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Claims (19)
1. Jedinjenja formula (IVa), (IVb), (IVc) ili (IVd) koje slede: gde je R1, alkil grupa koja sadrži od 1 do 4 atoma ugljenika ili fenilalkil grupa koja sadrži od 7 do 11 atoma ugljenika, kao i njihove adicione soli sa kiselinama.
2. Jedinjenje, naznačeno time, što ima formulu (IVd) kao što je defmisano u zahtevu 1, kao njegove adicione soli sa kiselinama.
3. Jedinjenje formule (IVd) prema zahtevu 2, naznačeno time, štoje R1, etil grupa, kao i njegove adicione soli sa kiselinama.
4. Postupak za dobijanjejedinjenja formule (IVa), (IVb), (IVc) ili (IVd) kao što je definisano u zahtevu 1, naznačen time, što obuhvata bar jedan od sledećih stupnjeva: a) delovanje arilamina formule R3R4CHNH2 gde je R3, atom vodonika ili alkil grupa koja sadrži od 1 do 4 atoma ugljenika i R4 je aril koji je eventualno supstituisan, na racemski alkiloksifuranon formule (II): gde R1 je grupa alkil koja sadrži od 1 do 4 atoma ugljenika, ili fenilalkil grupa koja sadrži od 7 do 11 atoma ugljenika, i dobijanje izomernih jedinjenja trans (4R, 5R) i (4S, 5S), pojedinačno, formula (IIIa) i (IIIb): koja se zatim - razdvajaju kristalizacijom, izvodeći, po potrebi, jednu ili više reakcija pretvaranja u so, - ili, kada je R3, atom vodonika, razdvajaju se dejstvom optički aktivne kiseline, b) po potrebi, reakciju epimerizacije jedinjenja formule (IIIa) ili (IIIb) u obliku soli ili ne, u prisustvu kiseline radi dobijanja izomernih jedinjenja cis (4R, 5S) ili (4S, 5R) formule (IIIc) ili (IIId) koja se po potrebi pretvore u so, c) reakciju hidrogenolize, - bilo na trans izomeru (4R, 5R) ili (4S, 5S) formule (IIIa) ili (IIIb) u obliku soli ili ne radi dobijanja jedinjenja formule (IVa) ili (IVb) u obliku trans izomera (4R, 5R) ili (4S, 5S) koji je po potrebi pretvoren u so i/ili zaštićen, - ili na cis izomeru (4R, 5S) ili (4S, 5R) formule (IIIc) ili (IIId), u obliku soli ili ne, radi dobijanja jedinjenja formule (IVc) ili (IVd) u obliku cis izomera (4R, 5S) ili (4S, 5R), koji je po potrebi pretvoren u so i/ili zaštićen.
5. Postupak prema zahtevu 4, naznačen time, što se reakcija zaštite amina formule (IVa), (IVb), (IVc) ili (IVd), u obliku soli ili ne, izvodi dejstvom hlorformijata formule CI-CO-O-CH2-R2, gde R2 predstavlja radikal terc-butil, (C2-C4)-alkenil, (C2-C4)-alkinil ili fenil, supstituisan ili nesupstituisan radi dobijanja jedinjenja formule (Ia), (Ib), (Ic) ili (Id), po istom redosledu, u obliku trans (dijasteroizomera 4R, 5R), (4S, 5S) ili cis (4R, 5S), (4S, 5R), koji su po potrebi pretvoreni u so,
6. Postupak prema zahtevu 4, naznačen time, što se razdvajanje jedinjenja formula (IIIa) i (Illb) kao što je definisano u zahtevu 4, kristalizacijom izvodi: a) defovanjem trihlorsirćetne kiseline radi dobijanja odgovarajuće soli (IIIa) ili (IIIb), b) i zatim delovanjem monohlorsirćetne kiseline, na matični rastvor radi dobijanja odgovarajuće soli drugih stereoizomera formule (IIIa) ili (IIIb).
7. Postupak za dobijanje prema zahtevu 4, jedinjenja formule (IVd) kako je definisano u zahtevu 2 ili jedinjenja formule (Id) kako je definisano u zahtevu 5, naznačen time, što obuhvata bar jedan od sledećih stupnjeva: a) delovanje R feniletilamina na jedinjenje formule (II) radi dobijanja jedinjenja sledećih formula (III'a) i (III'b): b) razdvajanje trans stereoizomera formula (III'a) i (III'b) dejstvom trihlorsirćetne kiseline radi dobijanja stereoizomera (III’b) (4S, 5S) u obliku soli trihlorsirćetne kiseline, a zatim dejstvom monohlorsirćetne kiseline radi dobijanja stereoizomera (III’a) (4R, 5R) u obliku soli monohlorsirćetne kiseline, c) po potrebi, vraćanje u slobodan amin delovanjem baze, d) reakcije epimerizacije stereoizomera (4S, 5S) formule (III'b) u prisustvu jedne od kiselina, radi dobijanja cis stereoizomera (4S, 5R) formule (III'd): e) po potrebi, kristalizacija posle pretvaranja u so delovanjem monohlorsirćetne kiseline ili dihlorsirćetne kiseline, f) po potrebi, vraćanje u slobodan amin delovanjem baze, g) po potrebi, kristalizacija posle pretvaranja u so uglavnom u oblik hidrohlorida, h) hidrogenoliza cis stereoizomera (4S, 5R) formule (III'd) radi dobijanja jedinjenja formule (IVd) u obliku cis dijastereoizomera (4S, 5R), i) po potrebi, delovanje alil hlorformijata na jedinjenje formule (IVd) radi dobijanja jedinjenja formule (Id) u obliku dijastereoizomera cis (4S, 5R) sa R2 koji predstavlja-CH=CH2.
8. Postupak dobijanja prema zahetevu 4 jedinjenja formule (IVd) kako je definisano u zahtevu 2 ili jedinjenja formule (Id) kao što je definisano u zahtevu 5, naznačen time, što obuhvata bar jedan od sledećih stupnjeva: a) delovanje S feniletilamina na jedinjenje formule (II) radi dobijanja jedinjenja sledećih formula (III"a) i (III''b): b) razdvajanje trans strereoizomera formula (III"a) i (III"b) delovanjem trihlorsirćetne kiseline radi dobijanja (4R, 5R) stereoizomera (III"a) u obliku soli trihlorsirćetne kiseline, a zatim delovanjem monohlorsirćetne kiseline radi dobijanja (4S, 5S)stereoizomera (III"b) u obliku soli monohlorsirćetne kiseline, c) po potrebi, desalifikacija delovanjem baze, d) reakcija epimerizacije stereoizomera (4S, 5S) formule (III"b) u prisustvu kiseline radi dobijanja jednog cis dijastereoizomera (4S, 5R) formule (III"d): e) po potrebi, kristalizacija posle salifikacije delovanjem kiseline kao što je monohlorsirćetna kiselina ili dihlorsirćetna kiselina, f) po potrebi, vraćanje u slobodan amin delovanjem baze, g) po potrebi, rekristalizacija posle pretvaranja u so, naročito u oblik hidrohlorida, h) hidrogenoliza cis stereoizomera (4S, 5R) formule (III"d), radi dobijanja jedinjenja formule (IVd) u obliku cis dijastereoizomera (4S, 5R), i) po potrebi, delovanje alil hlorformijata na jedinjenje formule (IVd), radi dobijanja jedinjenja formule (Id) u obliku cis dijastereoizomera (4S, 5R), gde R2 predstavlja -CH = CH2 radikal.
9. Postupak prema bilo kojem od zahteva 4 do 8, naznačen time, što se dodavanje amina na jedinjenje formule (II) kao što je definisano u zahtevu 4, izvodi u dimetilformamidu ili u vodenom izopropanolu.
10. Postupak prema bilo kojem od zahteva 4 do 8, naznačen time, što se reakcija epimerizacije izvodi sa kalaj tetrahloridom ili metan sulfonskom kiselinom.
11. Postupak prema bilo kojem od zahteva 4 do 8, naznačen time, Stoje R1, etil radikal.
12. Postupak prema bilo kojem od zahteva 8 do 11, naznačen time, što se razdvajanje trans stereoizomera delovanjem trihlorsirćetne kiseline (stupanj b) izvodi u vodenom izopropanolu.
13. Postupak prema bilo kojem od zahteva 8 do 11, naznačen time, što se reakcija epimerizacije (4S, 5S) stereoizomera formule (III"b, stupanj d) izvodi u prisustvu metansulfonske kiseline u toluenu.
14. Postupak prema bilo kojem od zahteva 8 do 11, naznačen time, što se kristalizacija (stupanj e) izvodi delovanjem dihlorsirćetne kiseline u toluenu.
15. Primena: - bilo jedinjenja formule (IVa), (IVb), (IVc) ili (IVd) kao što je definisano u zahtevu 1 ili dobijenih u postupku kao što je defmisano u zahtevu 4, - ili jedinjenja formule (Ia), (lb), (Ic) ili (ld) nastalih u postupku kako je definisano u zahtevu 5 u reakciji amidacije polazeći od kiseline formule A-COOH radi dobijanja jedinjenja sledeće formule (V): gde A predstavlja bilo koji organski radikal.
16. Primena: - bilo jedinjenja formule (IVb) ili (IVd) kao što je definisano u zahtevu 1 ili nastalih u postupku kao što je opisano u zahtevu 4, - ili jedinjenja formule (Ib) ili (Id) nastalih u postupku kako je definisano u zahtevu 5 u sintezi jedinjenja formule (V) koje ima inhibitorsku aktivnost na interleukin konvertujući enzim.
17. Primena: - bilo jedinjenja formule (IVd) sa R1 = etil kao što je definisano u zahtevu 3 ili nastalog u postupku kao što je definisano u zahtevu 7 ili zahtevu 8, - ili jedinjenja formule (Id) sa R1= etil nastalog u postupku kako je definisano u zahtevu 5 u dobijanju jedinjenja formule (V) koje ima inhibitorsku aktivnost nainterleukin konvertujući enzim.
18. Primena prema zahtevu 17 jedinjenja formule (IVd) ili (Id) kako je definisano u zahtevu 17 za dobijanju jedinjenja formule (V) koje ima sledeću strukturu:
19. Jedinjenja formula (IIIa), (IIIb), (IIIc), (IIId) kao novih intermedijernih jedinjenja, isto kao i njihove adicione soli sa kiselinama sa izuzetkom jedinjenja formula (III"a) i (III"b) kao što je definisano u zahtevu 8 sa R1 = metil.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9708932A FR2766188B1 (fr) | 1997-07-15 | 1997-07-15 | Nouveau procede de preparation de derives amines d'alkyloxy furanone, composes issus de ce procede et utilisation de ces composes |
| PCT/FR1998/001480 WO1999003852A1 (fr) | 1997-07-15 | 1998-07-09 | Procede de preparation de derives amines d'alkyloxyfuranone, composes issus de ce procede et utilisation de ces composes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ME01708B true ME01708B (me) | 2008-08-07 |
Family
ID=9509210
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MEP-2000-15A ME01708B (me) | 1997-07-15 | 1998-07-09 | Postupak za dobijanje aminskih derivata alkiloksifuranona, dobijena jedinjenja i upotreba ovih jedinjenja |
Country Status (34)
| Country | Link |
|---|---|
| US (1) | US6235899B1 (me) |
| EP (1) | EP0998470B1 (me) |
| JP (1) | JP4450987B2 (me) |
| KR (1) | KR100519691B1 (me) |
| CN (1) | CN100363355C (me) |
| AP (1) | AP1071A (me) |
| AR (1) | AR015924A1 (me) |
| AT (1) | ATE239713T1 (me) |
| AU (1) | AU744272B2 (me) |
| BG (1) | BG64050B1 (me) |
| BR (1) | BR9810896A (me) |
| CA (1) | CA2296742C (me) |
| CZ (1) | CZ295312B6 (me) |
| DE (1) | DE69814395T2 (me) |
| DK (1) | DK0998470T3 (me) |
| EA (1) | EA002883B1 (me) |
| EE (1) | EE03873B1 (me) |
| ES (1) | ES2197489T3 (me) |
| FR (1) | FR2766188B1 (me) |
| HR (1) | HRP20000027B1 (me) |
| HU (1) | HU230148B1 (me) |
| ID (1) | ID23784A (me) |
| IL (1) | IL134031A (me) |
| ME (1) | ME01708B (me) |
| NO (1) | NO324508B1 (me) |
| NZ (1) | NZ502338A (me) |
| PL (1) | PL200820B1 (me) |
| PT (1) | PT998470E (me) |
| RS (1) | RS49832B (me) |
| SK (1) | SK284168B6 (me) |
| TR (1) | TR200000117T2 (me) |
| UA (1) | UA66364C2 (me) |
| WO (1) | WO1999003852A1 (me) |
| ZA (1) | ZA986203B (me) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7053056B2 (en) | 1998-07-02 | 2006-05-30 | Idun Pharmaceuticals, Inc. | C-terminal modified oxamyl dipeptides as inhibitors of the ICE/ced-3 family of cysteine proteases |
| IL152393A (en) * | 2000-04-24 | 2008-03-20 | Vertex Pharma | Process for making aspartic acid acetal derivatives |
| PE20011350A1 (es) | 2000-05-19 | 2002-01-15 | Vertex Pharma | PROFARMACO DE UN INHIBIDOR DE ENZIMA CONVERTIDORA DE INTERLEUCINA-1ß (ICE) |
| JP2003327568A (ja) * | 2000-09-20 | 2003-11-19 | Kanegafuchi Chem Ind Co Ltd | 光学活性β−アミノ酸誘導体の製造方法 |
| JPWO2002055478A1 (ja) * | 2001-01-16 | 2004-05-13 | 鐘淵化学工業株式会社 | 光学活性アミノラクトン誘導体の製造法およびその中間体 |
| EP1718639A2 (en) | 2004-02-27 | 2006-11-08 | Vertex Pharmaceuticals Incorporated | Caspase inhibitors and uses thereof |
| KR101135765B1 (ko) | 2004-03-12 | 2012-04-23 | 버텍스 파마슈티칼스 인코포레이티드 | 아스파르트산 아세탈 카스파아제 억제제의 제조를 위한방법 및 중간체 |
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| US6204261B1 (en) * | 1995-12-20 | 2001-03-20 | Vertex Pharmaceuticals Incorporated | Inhibitors of interleukin-1β Converting enzyme inhibitors |
| US5716929A (en) * | 1994-06-17 | 1998-02-10 | Vertex Pharmaceuticals, Inc. | Inhibitors of interleukin-1β converting enzyme |
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1997
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