CA1154782A - Processes for preparing proline derivatives and analogous compounds - Google Patents
Processes for preparing proline derivatives and analogous compoundsInfo
- Publication number
- CA1154782A CA1154782A CA000370546A CA370546A CA1154782A CA 1154782 A CA1154782 A CA 1154782A CA 000370546 A CA000370546 A CA 000370546A CA 370546 A CA370546 A CA 370546A CA 1154782 A CA1154782 A CA 1154782A
- Authority
- CA
- Canada
- Prior art keywords
- formula
- compound
- chemical equivalent
- whenever prepared
- obvious chemical
- Prior art date
- 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
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 39
- 238000000034 method Methods 0.000 title claims description 21
- 150000003147 proline derivatives Chemical class 0.000 title description 3
- 239000000126 substance Substances 0.000 claims abstract description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- 239000000203 mixture Substances 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical group C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 6
- 239000007822 coupling agent Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 150000001718 carbodiimides Chemical class 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 125000005907 alkyl ester group Chemical group 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 abstract description 4
- 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 abstract 2
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 abstract 2
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 abstract 2
- 239000003112 inhibitor Substances 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 10
- 239000000543 intermediate Substances 0.000 description 9
- 238000010511 deprotection reaction Methods 0.000 description 8
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 7
- 229960000830 captopril Drugs 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- 229910001868 water Inorganic materials 0.000 description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- BUPXDXGYFXDDAA-UHFFFAOYSA-N 3-bromo-2-methylpropanoic acid Chemical compound BrCC(C)C(O)=O BUPXDXGYFXDDAA-UHFFFAOYSA-N 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 229960002429 proline Drugs 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- XJJBXZIKXFOMLP-ZETCQYMHSA-N tert-butyl (2s)-pyrrolidine-2-carboxylate Chemical compound CC(C)(C)OC(=O)[C@@H]1CCCN1 XJJBXZIKXFOMLP-ZETCQYMHSA-N 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 108010064733 Angiotensins Proteins 0.000 description 2
- 102000015427 Angiotensins Human genes 0.000 description 2
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 125000000174 L-prolyl group Chemical class [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 2
- -1 alkyl acrylic acid Chemical compound 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 235000017550 sodium carbonate Nutrition 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 102400000344 Angiotensin-1 Human genes 0.000 description 1
- 101800000734 Angiotensin-1 Proteins 0.000 description 1
- 102400000345 Angiotensin-2 Human genes 0.000 description 1
- 101800000733 Angiotensin-2 Proteins 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- HEMHJVSKTPXQMS-DYCDLGHISA-M Sodium hydroxide-d Chemical compound [Na+].[2H][O-] HEMHJVSKTPXQMS-DYCDLGHISA-M 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 1
- 229950006323 angiotensin ii Drugs 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- JJCFRYNCJDLXIK-UHFFFAOYSA-N cyproheptadine Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2C=CC2=CC=CC=C21 JJCFRYNCJDLXIK-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical class C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- VOVZXURTCKPRDQ-CQSZACIVSA-N n-[4-[chloro(difluoro)methoxy]phenyl]-6-[(3r)-3-hydroxypyrrolidin-1-yl]-5-(1h-pyrazol-5-yl)pyridine-3-carboxamide Chemical compound C1[C@H](O)CCN1C1=NC=C(C(=O)NC=2C=CC(OC(F)(F)Cl)=CC=2)C=C1C1=CC=NN1 VOVZXURTCKPRDQ-CQSZACIVSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyrrole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000424590A CA1155443A (en) | 1980-02-26 | 1983-03-25 | Processes for preparing proline derivatives and analogous compounds |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8006414 | 1980-02-26 | ||
| GB8006414 | 1980-02-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1154782A true CA1154782A (en) | 1983-10-04 |
Family
ID=10511671
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000370546A Expired CA1154782A (en) | 1980-02-26 | 1981-02-10 | Processes for preparing proline derivatives and analogous compounds |
Country Status (11)
| Country | Link |
|---|---|
| US (4) | US4349480A (en, 2012) |
| EP (1) | EP0035336B1 (en, 2012) |
| JP (2) | JPS56128755A (en, 2012) |
| AR (2) | AR227663A1 (en, 2012) |
| AU (2) | AU544337B2 (en, 2012) |
| CA (1) | CA1154782A (en, 2012) |
| DE (1) | DE3174292D1 (en, 2012) |
| GB (1) | GB2070005B (en, 2012) |
| IE (1) | IE50839B1 (en, 2012) |
| PH (3) | PH16751A (en, 2012) |
| ZA (1) | ZA81743B (en, 2012) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE50839B1 (en) * | 1980-02-26 | 1986-07-23 | Wyeth John & Brother Ltd | Novel processes for preparing proline derivatives and analogous compounds |
| NL180746C (nl) * | 1983-11-18 | 1987-04-16 | Matthijs Cornelis Evers | Werkwijze ter bereiding van captopril. |
| JPH0662671B2 (ja) * | 1986-01-17 | 1994-08-17 | 株式会社大塚製薬工場 | プロリン誘導体 |
| HU196368B (en) * | 1986-07-04 | 1988-11-28 | Egyt Gyogyszervegyeszeti Gyar | Process for production of 1-/3-brom-/25/-methil-prophionil/-pirrolidin-/25/-carbonic acid |
| US4847384A (en) * | 1987-03-12 | 1989-07-11 | Sandoz Pharm. Corp. | Process for the preparation of certain nitrogen-containing mono- and bicyclic ace inhibitors, and novel intermediates useful therefor |
| US5237073A (en) * | 1988-08-26 | 1993-08-17 | Sepracor, Inc. | Derivatives and precursors of captopril and its analogues |
| IL91581A (en) * | 1988-09-13 | 1993-07-08 | Sepracor Inc | Methods for preparing optically active captopril and its analogues |
| US5166361A (en) * | 1988-09-13 | 1992-11-24 | Sepracor, Inc. | Methods for preparing captopril and its analogues |
| US5430145A (en) * | 1990-10-18 | 1995-07-04 | Merrell Dow Pharmaceuticals Inc. | Mercaptoacetylamide derivatives useful as inhibitors of enkephalinase and ace |
| US5308841A (en) * | 1990-12-21 | 1994-05-03 | Merrell Dow Pharmaceuticals Inc. | Amino and nitro containing tricyclic compounds useful as inhibitors of ACE |
| US5457196A (en) * | 1991-09-27 | 1995-10-10 | Merrell Dow Pharmaceuticals Inc. | 2-substituted indane-2-carboxyalkyl derivatives useful as inhibitors of enkephalinase and ACE |
| US5455242A (en) * | 1991-09-27 | 1995-10-03 | Merrell Dow Pharmaceuticals Inc. | Carboxyalkyl tricyclic derivatives useful as inhibitors of enkephalinase and ace |
| DK0534363T3 (da) * | 1991-09-27 | 1997-09-22 | Merrell Pharma Inc | 2-substituerede indan-2-mercaptoacetylamid-forbindelse med inhiberende virkning på enkephalinase og ACE. |
| CA2078759C (en) * | 1991-09-27 | 2003-09-16 | Alan M. Warshawsky | Novel carboxyalkyl derivatives useful as inhibitors of enkephalinase and ace |
| HU220596B1 (hu) * | 1992-02-14 | 2002-03-28 | Merrell Dow Pharmaceuticals Inc. | 7-Szubsztituált pirido-benzazepin-karbonsav-származékok, ezeket tartalmazó gyógyszerkészítmények és eljárás előállításukra |
| EP0640086B1 (en) * | 1992-05-15 | 1999-08-04 | Merrell Pharmaceuticals Inc. | MERCAPTOACETYLAMIDO PYRIDAZO[ 1,2-a][1,2]DIAZEPINE DERIVATIVES USEFUL AS INHIBITORS OF ENKEPHALINASE AND ACE |
| US5420271A (en) * | 1992-08-24 | 1995-05-30 | Merrell Dow Pharmaceuticals, Inc. | 2-substituted indane-2-mercaptoacetylamide tricyclic derivatives useful as inhibitors of enkephalinase |
| WO1994010193A1 (en) * | 1992-10-30 | 1994-05-11 | Merrell Dow Pharmaceuticals Inc. | Novel mercaptoacetylamide bicyclic lactam derivatives useful as inhibitors of enkephalinase and ace |
| ES2145267T3 (es) * | 1994-02-14 | 2000-07-01 | Merrell Pharma Inc | Nuevos derivados bisulfuro de mercaptoacetilamido de 1,3,4,5-tetrahidro-benzo(c)azepin-3-ona utiles como inhibidores de la encefalinasa y del enzima de conversion de la angiotensina. |
| AU689192B2 (en) * | 1994-02-14 | 1998-03-26 | Merrell Pharmaceuticals Inc. | Novel 2-substituted indane-2-mercaptoacetylamide disulfide derivatives useful as inhibitors of enkephalinase and ace |
| US5530013A (en) * | 1994-02-14 | 1996-06-25 | American Home Products Corporation | Venlafaxine in the inducement of cognition enhancement |
| FI963166L (fi) * | 1994-02-14 | 1996-08-13 | Merrell Pharma Inc | Uusia merkaptoasetyyliamididisulfidijohdannaisia, jotka ovat käyttökelpoisia enkefalinaasin ja ACE:n inhibiittoreina |
| PT745081E (pt) * | 1994-02-14 | 2002-04-29 | Merrell Pharma Inc | Derivados de dissulfureto de inda-2-mercaptoacetilamida uteis como inibidores da encefalinase |
| US5484783A (en) * | 1994-03-24 | 1996-01-16 | Merrell Dow Pharmaceuticals Inc. | Hypocholesterolemic, antiatherosclerotic and hypotriglyceridemic mercaptoacetylamide and benzazapine derivatives |
| AU698320B2 (en) * | 1994-03-24 | 1998-10-29 | Merrell Pharmaceuticals Inc. | Hypocholesterolemic, antiatherosclerotic and hypotriglyceridemic aminoacetylmercapto derivatives |
| DK0751774T3 (da) * | 1994-03-24 | 2003-12-08 | Merrell Pharma Inc | Hypocholesterolæmiske mercaptoacetylamiddisulfid-derivater |
| GB0119305D0 (en) | 2001-04-12 | 2001-10-03 | Aventis Pharma Gmbh | Mercaptoacetylamide derivatives,a process for their preparation and their use |
| US7531217B2 (en) * | 2004-12-15 | 2009-05-12 | Iowa State University Research Foundation, Inc. | Methods for making high-temperature coatings having Pt metal modified γ-Ni +γ′-Ni3Al alloy compositions and a reactive element |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT986630B (it) * | 1972-04-20 | 1975-01-30 | Pierres Holding Sa | Procedimento per la lavorazione di precisione di pezzi mediante radiazioni laser e dispositivo per l esecuzione del procedi mento |
| US4105776A (en) * | 1976-06-21 | 1978-08-08 | E. R. Squibb & Sons, Inc. | Proline derivatives and related compounds |
| US4129566A (en) * | 1978-02-15 | 1978-12-12 | E. R. Squibb & Sons, Inc. | Derivatives of dehydrocyclicimino acids |
| US4127535A (en) * | 1977-06-16 | 1978-11-28 | Coy David Howard | Novel dipeptides, intermediates therefor, and compositions and methods employing said dipeptides |
| US4154935A (en) * | 1978-02-21 | 1979-05-15 | E. R. Squibb & Sons, Inc. | Halogen substituted mercaptoacylamino acids |
| CA1109475A (en) * | 1978-07-27 | 1981-09-22 | Miguel A. Ondetti | Thiopropanoylamino acid derivatives |
| US4192945A (en) * | 1978-12-07 | 1980-03-11 | E. R. Squibb & Sons, Inc. | Process for preparing proline and homoproline derivatives |
| EP0017390A3 (en) * | 1979-03-23 | 1981-06-24 | American Home Products Corporation | Bicyclic oxo-thiolactones, pharmaceutical compositions containing them, processes for their preparation and compounds useful as intermediates for their preparation |
| US4303583A (en) * | 1979-08-13 | 1981-12-01 | American Home Products Corporation | 1H,5H-[1,4]Thiazepino[4,3-a]indole-1,5-diones |
| US4291040A (en) * | 1979-10-22 | 1981-09-22 | E. R. Squibb & Sons, Inc. | Mercaptoacyl derivatives of 4-disubstituted prolines and 4-substituted dehydroprolines |
| GB2065643B (en) * | 1979-12-13 | 1983-08-24 | Kanegafuchi Chemical Ind | Optically active n-mercaptoalkanoylamino acids |
| HU184082B (en) * | 1979-12-29 | 1984-06-28 | Egyt Gyogyszervegyeszeti Gyar | Process for preparing 1-3-/3mercapto-/2s/-methyl-propinyl/-pyrrolidine-/2s/-carboxylic acid |
| IE50839B1 (en) * | 1980-02-26 | 1986-07-23 | Wyeth John & Brother Ltd | Novel processes for preparing proline derivatives and analogous compounds |
| US4454291A (en) * | 1981-07-20 | 1984-06-12 | American Home Products Corporation | N-(2-Substituted-1-oxoalkyl)-2,3-dihydro-1H-indole-2-carboxylic acid derivatives |
-
1981
- 1981-02-03 IE IE210/81A patent/IE50839B1/en not_active IP Right Cessation
- 1981-02-04 ZA ZA00810743A patent/ZA81743B/xx unknown
- 1981-02-05 AU AU66941/81A patent/AU544337B2/en not_active Expired
- 1981-02-10 CA CA000370546A patent/CA1154782A/en not_active Expired
- 1981-02-11 AR AR284267A patent/AR227663A1/es active
- 1981-02-12 JP JP1957481A patent/JPS56128755A/ja active Pending
- 1981-02-12 PH PH25215A patent/PH16751A/en unknown
- 1981-02-12 DE DE8181300568T patent/DE3174292D1/de not_active Expired
- 1981-02-12 EP EP81300568A patent/EP0035336B1/en not_active Expired
- 1981-02-12 GB GB8104412A patent/GB2070005B/en not_active Expired
- 1981-02-20 US US06/236,350 patent/US4349480A/en not_active Expired - Lifetime
-
1982
- 1982-02-19 PH PH26893A patent/PH17373A/en unknown
- 1982-02-19 PH PH26894A patent/PH17181A/en unknown
- 1982-03-26 AR AR288889A patent/AR231987A1/es active
- 1982-05-10 US US06/376,355 patent/US4506082A/en not_active Expired - Lifetime
- 1982-05-10 US US06/376,354 patent/US4578480A/en not_active Expired - Lifetime
- 1982-05-10 US US06/376,356 patent/US4391752A/en not_active Expired - Lifetime
-
1985
- 1985-02-25 AU AU39126/85A patent/AU566441B2/en not_active Expired - Fee Related
-
1987
- 1987-06-05 JP JP1987086778U patent/JPS62199283U/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| AU566441B2 (en) | 1987-10-22 |
| IE50839B1 (en) | 1986-07-23 |
| GB2070005B (en) | 1984-12-19 |
| AU3912685A (en) | 1985-07-11 |
| US4349480A (en) | 1982-09-14 |
| DE3174292D1 (en) | 1986-05-15 |
| AU544337B2 (en) | 1985-05-23 |
| PH16751A (en) | 1984-02-10 |
| JPS62199283U (en, 2012) | 1987-12-18 |
| GB2070005A (en) | 1981-09-03 |
| EP0035336A3 (en) | 1981-11-25 |
| AR227663A1 (es) | 1982-11-30 |
| JPS56128755A (en) | 1981-10-08 |
| AU6694181A (en) | 1981-09-03 |
| US4506082A (en) | 1985-03-19 |
| AR231987A1 (es) | 1985-04-30 |
| US4578480A (en) | 1986-03-25 |
| EP0035336B1 (en) | 1986-04-09 |
| EP0035336A2 (en) | 1981-09-09 |
| PH17373A (en) | 1984-08-06 |
| ZA81743B (en) | 1982-09-29 |
| IE810210L (en) | 1981-08-26 |
| PH17181A (en) | 1984-06-13 |
| US4391752A (en) | 1983-07-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA1154782A (en) | Processes for preparing proline derivatives and analogous compounds | |
| Lowe et al. | Amino acids bearing nucleobases for the synthesis of novel peptidenucleic acids | |
| Webb et al. | Conformationally restricted arginine analogs | |
| Moyer et al. | Intramolecular nitrogen-hydrogen, oxygen-hydrogen and sulfur-hydrogen insertion reactions. Synthesis of heterocycles from. alpha.-diazo. beta.-keto esters | |
| SU747422A3 (ru) | Способ получени производных пролина | |
| DK173456B1 (da) | Fremgangsmåde til fremstilling af cis-enantiomere af 1-carba-3-cephem-4-carboxylsyrer og derivater deraf samt forskellige 3 | |
| JPS6059226B2 (ja) | プロリン誘導体および関連化合物 | |
| CA2179935C (en) | Novel dipeptide compound or pharmaceutically acceptable salt thereof and medical use thereof | |
| Kataoka et al. | Studies of unusual amino acids and their peptides. VI. The synthese and the optical resolutions of. BETA.-methylphenylalanine and its dipeptide present in bottromycin. | |
| CZ299634B6 (cs) | Derivát amidinu a jeho použití | |
| CA1317960C (en) | Derivatives of bicyclic aminocarboxylic acids, a process and intermediates for their preparation, and their use | |
| Obrecht et al. | A novel synthesis of (R)-and (S)-α-alkylated aspartic and glutamic acids: α-alkylated aspartic succinimides as new type of β-turn type II and II′ mimetics | |
| US4296033A (en) | 4-Azido-1-mercaptoacyl proline | |
| Waldmann et al. | Asymmetric Control of 1, 3‐Dipolar Cycloaddition Reactions with Azomethine Ylides by Means of Proline Esters as Chiral Auxiliary Groups | |
| CA1126728A (en) | Pyrrolo or pyrido [2,1-c][1,4] thiazines or thiazepines | |
| Tamura et al. | Synthesis of lactivicin analogues | |
| SU882409A3 (ru) | Способ получени галоидзамещенных меркаптоациламинокислот | |
| SU1272981A3 (ru) | Способ получени @ -лактамов (его варианты) | |
| Caturla et al. | (E)-5-tosyl-4-pentenamide: A vinyl sulfone for the one-pot general synthesis of indolizidine derivatives | |
| EP0536512B1 (en) | A method and intermediates for the preparation of 6-fluorobenzisothiazoles | |
| JPS61145170A (ja) | アミノチアゾール酢酸誘導体の製造方法 | |
| ZA200500290B (en) | Process for the preparation of amino-pyrrolidine derivatives. | |
| US5079359A (en) | Chiral amino-methyl ferrocene derivatives | |
| Dumitrascu et al. | New pyrazoles by 1, 3-dipolar cycloaddition reactions between sydnones and activated alkynes | |
| US5212311A (en) | Chiral amino-methyl ferrocene derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |