CS242857B2 - Method of enzyme inhibitors production - Google Patents
Method of enzyme inhibitors production Download PDFInfo
- Publication number
- CS242857B2 CS242857B2 CS796150A CS615079A CS242857B2 CS 242857 B2 CS242857 B2 CS 242857B2 CS 796150 A CS796150 A CS 796150A CS 615079 A CS615079 A CS 615079A CS 242857 B2 CS242857 B2 CS 242857B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- compound
- formula
- proline
- lysyl
- methyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 77
- 238000004519 manufacturing process Methods 0.000 title claims description 21
- 239000002532 enzyme inhibitor Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 102
- 229960002429 proline Drugs 0.000 claims abstract description 80
- -1 phenylacetyl Chemical group 0.000 claims abstract description 64
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 24
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 18
- 238000002360 preparation method Methods 0.000 claims abstract description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 14
- 239000001257 hydrogen Substances 0.000 claims abstract description 13
- OMGHIGVFLOPEHJ-BYPYZUCNSA-N (2s)-2,5-dihydro-1h-pyrrole-2-carboxylic acid Chemical group OC(=O)[C@H]1NCC=C1 OMGHIGVFLOPEHJ-BYPYZUCNSA-N 0.000 claims abstract description 12
- 229930182821 L-proline Natural products 0.000 claims abstract description 11
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 11
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims abstract description 10
- 239000005541 ACE inhibitor Substances 0.000 claims abstract description 9
- 125000001176 L-lysyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C([H])([H])C([H])([H])C(N([H])[H])([H])[H] 0.000 claims abstract description 9
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims abstract description 9
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 9
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims abstract description 9
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 claims abstract description 8
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims abstract description 8
- 125000003412 L-alanyl group Chemical group [H]N([H])[C@@](C([H])([H])[H])(C(=O)[*])[H] 0.000 claims abstract description 6
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims abstract description 6
- 125000002059 L-arginyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])C(=N[H])N([H])[H] 0.000 claims abstract description 5
- 125000003440 L-leucyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C(C([H])([H])[H])([H])C([H])([H])[H] 0.000 claims abstract description 5
- 125000002435 L-phenylalanyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract description 5
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 5
- 125000001841 imino group Chemical group [H]N=* 0.000 claims abstract description 4
- 125000006638 cyclopentyl carbonyl group Chemical group 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 16
- 239000004472 Lysine Substances 0.000 claims description 11
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 9
- 239000011734 sodium Substances 0.000 claims description 9
- 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 claims description 8
- 229910052708 sodium Inorganic materials 0.000 claims description 7
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 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
- 150000007530 organic bases Chemical class 0.000 claims description 6
- 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 claims description 6
- 150000007529 inorganic bases Chemical class 0.000 claims description 5
- 125000000405 phenylalanyl group Chemical group 0.000 claims description 5
- 125000003301 D-leucyl group Chemical group N[C@@H](C(=O)*)CC(C)C 0.000 claims description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims description 3
- 239000011575 calcium Substances 0.000 claims description 3
- 229910052791 calcium Inorganic materials 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
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- 159000000000 sodium salts Chemical class 0.000 claims description 3
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- 125000000249 D-isoleucyl group Chemical group N[C@@H](C(=O)*)[C@@H](CC)C 0.000 claims description 2
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- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 2
- 235000009697 arginine Nutrition 0.000 claims description 2
- 159000000003 magnesium salts Chemical class 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical group CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 2
- 125000002436 D-phenylalanyl group Chemical group N[C@@H](C(=O)*)CC1=CC=CC=C1 0.000 claims 3
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 claims 2
- 125000000988 D-alanyl group Chemical group N[C@@H](C(=O)*)C 0.000 claims 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 2
- 239000011591 potassium Substances 0.000 claims 2
- WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 claims 2
- 101710129690 Angiotensin-converting enzyme inhibitor Proteins 0.000 claims 1
- 101710086378 Bradykinin-potentiating and C-type natriuretic peptides Proteins 0.000 claims 1
- 108010071840 Cytosol nonspecific dipeptidase Proteins 0.000 claims 1
- 125000002437 D-histidyl group Chemical group N[C@@H](C(=O)*)CC=1N=CNC1 0.000 claims 1
- DZLNHFMRPBPULJ-GSVOUGTGSA-N D-thioproline Chemical compound OC(=O)[C@H]1CSCN1 DZLNHFMRPBPULJ-GSVOUGTGSA-N 0.000 claims 1
- 125000003625 D-valyl group Chemical group N[C@@H](C(=O)*)C(C)C 0.000 claims 1
- 125000001980 alanyl group Chemical group 0.000 claims 1
- 125000003277 amino group Chemical group 0.000 claims 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims 1
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 claims 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 claims 1
- 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 claims 1
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- 125000002707 L-tryptophyl group Chemical group [H]C1=C([H])C([H])=C2C(C([C@](N([H])[H])(C(=O)[*])[H])([H])[H])=C([H])N([H])C2=C1[H] 0.000 abstract description 5
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- 125000003580 L-valyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(C([H])([H])[H])(C([H])([H])[H])[H] 0.000 abstract description 2
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- 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
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
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- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
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- Proteomics, Peptides & Aminoacids (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Enzymes And Modification Thereof (AREA)
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US94128978A | 1978-09-11 | 1978-09-11 | |
| US95818078A | 1978-11-06 | 1978-11-06 | |
| US06/064,901 US4695577A (en) | 1979-08-14 | 1979-08-14 | Anti-hypertensive agents |
| US06/064,900 US4690939A (en) | 1979-08-14 | 1979-08-14 | Anti-hypertensive agents |
| US06/064,897 US4690937A (en) | 1979-08-14 | 1979-08-14 | Anti-hypertensive agents |
| US06/064,899 US4698356A (en) | 1979-08-14 | 1979-08-14 | Anti-hypertensive agents |
| US06/064,903 US4698355A (en) | 1979-08-14 | 1979-08-14 | Anti-hypertensive agents |
| US06/064,898 US4690938A (en) | 1979-08-14 | 1979-08-14 | Anti-hypertensive agents |
| US06/064,902 US4690940A (en) | 1979-08-14 | 1979-08-14 | Anti-hypertensive agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS615079A2 CS615079A2 (en) | 1985-08-15 |
| CS242857B2 true CS242857B2 (en) | 1986-05-15 |
Family
ID=27578299
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS796150A CS242857B2 (en) | 1978-09-11 | 1979-09-11 | Method of enzyme inhibitors production |
Country Status (15)
| Country | Link |
|---|---|
| EP (1) | EP0009898B1 (en]) |
| AT (1) | AT390795B (en]) |
| AU (1) | AU532424B2 (en]) |
| BG (1) | BG34463A3 (en]) |
| CS (1) | CS242857B2 (en]) |
| DE (1) | DE2965443D1 (en]) |
| DK (1) | DK376179A (en]) |
| FI (1) | FI71749C (en]) |
| GR (1) | GR73585B (en]) |
| HU (1) | HU187258B (en]) |
| IL (1) | IL58223A (en]) |
| IT (1) | IT1193214B (en]) |
| NZ (1) | NZ191524A (en]) |
| PH (1) | PH19104A (en]) |
| PT (1) | PT70158A (en]) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA794723B (en) * | 1978-09-11 | 1980-08-27 | Univ Miami | Anti-hypertensive agents |
| ZA802420B (en) * | 1979-05-18 | 1981-04-29 | Squibb & Sons Inc | Aminoacyl derivatives of mercaptoacyl amino acids |
| PT70158A1 (en) * | 1980-03-03 | 1982-03-01 | Univ Miami | Process for preparing anti-hypertensive agents |
| US4690936A (en) * | 1980-03-05 | 1987-09-01 | University Of Miami | Anti-hypertensive agents |
| US4734420A (en) * | 1980-03-05 | 1988-03-29 | University Of Miami | Anti-hypertensive agents |
| EP0036713B1 (en) * | 1980-03-05 | 1984-01-18 | University Of Miami | Angiotensin converting enzyme inhibitors |
| FR2480747A1 (fr) * | 1980-04-17 | 1981-10-23 | Roques Bernard | Derives d'acides amines et leur application therapeutique |
| US4512979A (en) * | 1981-03-23 | 1985-04-23 | Merck & Co., Inc. | Dipeptides containing thialysine and related amino acids as antihypertensives |
| AT386603B (de) * | 1981-06-19 | 1988-09-26 | Chugai Pharmaceutical Co Ltd | Verfahren zur herstellung von neuen prolinderivaten |
| JPS57209270A (en) * | 1981-06-19 | 1982-12-22 | Chugai Pharmaceut Co Ltd | Proline derivative |
| HUT46044A (en) * | 1986-11-21 | 1988-09-28 | Richter Gedeon Vegyeszet | Process for producing immunstimulant peptides inhibiting multiplication of leukaemic cells and pharmaceutics comprising same |
| CN1081650C (zh) * | 1995-12-27 | 2002-03-27 | 罗纳-普朗克·维斯科苏希公司 | 缩聚物,尤其是聚酰胺6,6后冷凝的方法 |
| US20110081367A1 (en) | 2008-06-14 | 2011-04-07 | Veredus Laboratories Pte Ltd | Influenza sequences |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU509899B2 (en) * | 1976-02-13 | 1980-05-29 | E.R. Squibb & Sons, Inc. | Proline derivatives and related compounds |
| US4053651A (en) * | 1976-05-10 | 1977-10-11 | E. R. Squibb & Sons, Inc. | Compounds and method for alleviating angiotensin related hypertension |
| US4091024A (en) * | 1976-12-03 | 1978-05-23 | E. R. Squibb & Sons, Inc. | Pyrrolidine and piperidine-2-carboxylic acid derivatives |
| US4116962A (en) * | 1976-12-03 | 1978-09-26 | E. R. Squibb & Sons, Inc. | Pyrrolidine and piperidine-2-carboxylic acid derivatives |
| AU518147B2 (en) * | 1976-12-03 | 1981-09-17 | E.R. Squibb & Sons, Inc. | Derivatives of thiazolidine, thiazine and morpholine carboxylic acids |
| US4113715A (en) * | 1977-01-17 | 1978-09-12 | E. R. Squibb & Sons, Inc. | Amino acid derivatives |
| US4108886A (en) * | 1977-03-11 | 1978-08-22 | E. R. Squibb & Sons, Inc. | Thiopropanoylamino acid derivatives |
-
1979
- 1979-09-04 GR GR59962A patent/GR73585B/el unknown
- 1979-09-10 FI FI792806A patent/FI71749C/fi not_active IP Right Cessation
- 1979-09-10 HU HU79MI656A patent/HU187258B/hu not_active IP Right Cessation
- 1979-09-10 PT PT197970158A patent/PT70158A/pt unknown
- 1979-09-10 AU AU50705/79A patent/AU532424B2/en not_active Ceased
- 1979-09-10 AT AT0596279A patent/AT390795B/de not_active IP Right Cessation
- 1979-09-10 NZ NZ191524A patent/NZ191524A/xx unknown
- 1979-09-10 EP EP79301854A patent/EP0009898B1/en not_active Expired
- 1979-09-10 DK DK376179A patent/DK376179A/da not_active Application Discontinuation
- 1979-09-10 DE DE7979301854T patent/DE2965443D1/de not_active Expired
- 1979-09-11 CS CS796150A patent/CS242857B2/cs unknown
- 1979-09-11 IT IT25612/79A patent/IT1193214B/it active
- 1979-09-11 BG BG044830A patent/BG34463A3/xx unknown
- 1979-09-11 IL IL58223A patent/IL58223A/xx unknown
-
1981
- 1981-03-23 PH PH25401A patent/PH19104A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AT390795B (de) | 1990-06-25 |
| BG34463A3 (bg) | 1983-09-15 |
| FI792806A7 (fi) | 1980-03-12 |
| AU5070579A (en) | 1980-03-20 |
| PH19104A (en) | 1986-01-02 |
| DK376179A (da) | 1980-03-12 |
| GR73585B (en]) | 1984-03-26 |
| CS615079A2 (en) | 1985-08-15 |
| FI71749B (fi) | 1986-10-31 |
| HU187258B (en) | 1985-12-28 |
| NZ191524A (en) | 1982-12-07 |
| PT70158A (en) | 1979-09-30 |
| ATA596279A (de) | 1989-12-15 |
| EP0009898B1 (en) | 1983-05-18 |
| IT1193214B (it) | 1988-06-15 |
| DE2965443D1 (en) | 1983-07-07 |
| FI71749C (fi) | 1987-02-09 |
| IT7925612A0 (it) | 1979-09-11 |
| AU532424B2 (en) | 1983-09-29 |
| IL58223A (en) | 1984-01-31 |
| EP0009898A1 (en) | 1980-04-16 |
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