IL124915A - History of thiol, method of preparation and pharmaceutical preparations containing them - Google Patents

History of thiol, method of preparation and pharmaceutical preparations containing them

Info

Publication number: IL124915A
Authority: IL; Israel
Prior art keywords: group; groups; mercapto; methyl ester; alkyl
Prior art date: 1995-12-28

Application number

IL12491596A

Other languages

English (en)

Hebrew (he)

Other versions

IL124915A0 (en

Original Assignee

Zambon Spa

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.)

1995-12-28

Filing date

1996-12-17

Publication date

2001-10-31

1996-12-17 Application filed by Zambon Spa filed Critical Zambon Spa

1999-01-26 Publication of IL124915A0 publication Critical patent/IL124915A0/xx

2001-10-31 Publication of IL124915A publication Critical patent/IL124915A/en

Links

125000003396 thiol group Chemical class [H]S* 0.000 title claims abstract description 10
238000002360 preparation method Methods 0.000 title claims description 16
238000000034 method Methods 0.000 title claims description 8
239000008194 pharmaceutical composition Substances 0.000 title claims description 8
230000008569 process Effects 0.000 title claims description 4
150000001875 compounds Chemical class 0.000 claims abstract description 92
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 28
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 25
125000000217 alkyl group Chemical group 0.000 claims abstract description 24
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 15
125000003118 aryl group Chemical group 0.000 claims abstract description 14
-1 amino-sulphonyl groups Chemical group 0.000 claims abstract description 13
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 12
150000003839 salts Chemical class 0.000 claims abstract description 10
125000003545 alkoxy group Chemical group 0.000 claims abstract description 9
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 8
125000005843 halogen group Chemical group 0.000 claims abstract description 8
239000001301 oxygen Chemical group 0.000 claims abstract description 8
229910052760 oxygen Inorganic materials 0.000 claims abstract description 8
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 7
239000005864 Sulphur Substances 0.000 claims abstract description 7
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 7
125000005842 heteroatom Chemical group 0.000 claims abstract description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 6
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 5
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 4
125000001153 fluoro group Chemical group F* 0.000 claims abstract description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 4
125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 3
125000004414 alkyl thio group Chemical group 0.000 claims abstract description 3
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 3
125000001424 substituent group Chemical group 0.000 claims abstract 6
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 3
125000004442 acylamino group Chemical group 0.000 claims abstract 2
150000004702 methyl esters Chemical class 0.000 claims description 43
238000006243 chemical reaction Methods 0.000 claims description 9
208000024172 Cardiovascular disease Diseases 0.000 claims description 5
150000002993 phenylalanine derivatives Chemical class 0.000 claims description 5
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 4
125000004494 ethyl ester group Chemical group 0.000 claims description 4
229960005190 phenylalanine Drugs 0.000 claims description 4
229910052783 alkali metal Inorganic materials 0.000 claims description 3
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 2
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
150000001340 alkali metals Chemical class 0.000 claims description 2
229910052744 lithium Inorganic materials 0.000 claims description 2
VSDUZFOSJDMAFZ-VIFPVBQESA-N methyl L-phenylalaninate Chemical compound COC(=O)[C@@H](N)CC1=CC=CC=C1 VSDUZFOSJDMAFZ-VIFPVBQESA-N 0.000 claims description 2
229910052700 potassium Inorganic materials 0.000 claims description 2
239000011591 potassium Substances 0.000 claims description 2
229910052708 sodium Inorganic materials 0.000 claims description 2
239000011734 sodium Substances 0.000 claims description 2
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims 1
239000003814 drug Substances 0.000 claims 1
125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
125000003884 phenylalkyl group Chemical group 0.000 claims 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims 1
125000003710 aryl alkyl group Chemical group 0.000 abstract description 3
125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract description 2
125000004390 alkyl sulfonyl group Chemical group 0.000 abstract description 2
230000000694 effects Effects 0.000 description 33
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 25
238000005481 NMR spectroscopy Methods 0.000 description 23
230000002401 inhibitory effect Effects 0.000 description 22
108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 17
102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 17
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 description 16
101150041968 CDC13 gene Proteins 0.000 description 13
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 13
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 13
239000000203 mixture Substances 0.000 description 13
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
102000003729 Neprilysin Human genes 0.000 description 11
108090000028 Neprilysin Proteins 0.000 description 11
150000002148 esters Chemical class 0.000 description 11
239000000243 solution Substances 0.000 description 11
239000011541 reaction mixture Substances 0.000 description 10
238000003756 stirring Methods 0.000 description 10
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
238000011699 spontaneously hypertensive rat Methods 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
238000007796 conventional method Methods 0.000 description 8
108010036928 Thiorphan Proteins 0.000 description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
LJJKNPQAGWVLDQ-SNVBAGLBSA-N thiorphan Chemical compound OC(=O)CNC(=O)[C@@H](CS)CC1=CC=CC=C1 LJJKNPQAGWVLDQ-SNVBAGLBSA-N 0.000 description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
238000003818 flash chromatography Methods 0.000 description 6
210000004072 lung Anatomy 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
102000005741 Metalloproteases Human genes 0.000 description 5
108010006035 Metalloproteases Proteins 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
239000002253 acid Substances 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
239000000872 buffer Substances 0.000 description 5
230000009977 dual effect Effects 0.000 description 5
210000003734 kidney Anatomy 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
150000003573 thiols Chemical class 0.000 description 5
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 5
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
102000004190 Enzymes Human genes 0.000 description 4
108090000790 Enzymes Proteins 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 4
229960000830 captopril Drugs 0.000 description 4
239000012458 free base Substances 0.000 description 4
239000012528 membrane Substances 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
125000004076 pyridyl group Chemical group 0.000 description 4
239000000725 suspension Substances 0.000 description 4
ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 3
239000005541 ACE inhibitor Substances 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
229940024606 amino acid Drugs 0.000 description 3
235000001014 amino acid Nutrition 0.000 description 3
150000001413 amino acids Chemical class 0.000 description 3
229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
229940126142 compound 16 Drugs 0.000 description 3
239000003480 eluent Substances 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
238000000338 in vitro Methods 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
239000003208 petroleum Substances 0.000 description 3
125000006239 protecting group Chemical group 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
210000001519 tissue Anatomy 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
108010016626 Dipeptides Proteins 0.000 description 2
102000048186 Endothelin-converting enzyme 1 Human genes 0.000 description 2
108030001679 Endothelin-converting enzyme 1 Proteins 0.000 description 2
206010019280 Heart failures Diseases 0.000 description 2
206010020772 Hypertension Diseases 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
230000009471 action Effects 0.000 description 2
238000007792 addition Methods 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 2
230000000052 comparative effect Effects 0.000 description 2
239000002792 enkephalinase inhibitor Substances 0.000 description 2
230000002255 enzymatic effect Effects 0.000 description 2
238000011156 evaluation Methods 0.000 description 2
125000000524 functional group Chemical group 0.000 description 2
239000002223 garnet Substances 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
238000010253 intravenous injection Methods 0.000 description 2
DWKPPFQULDPWHX-VKHMYHEASA-N l-alanyl ester Chemical compound COC(=O)[C@H](C)N DWKPPFQULDPWHX-VKHMYHEASA-N 0.000 description 2
239000007788 liquid Substances 0.000 description 2
239000002207 metabolite Substances 0.000 description 2
MWVNSXPNTJYJDR-DHIUTWEWSA-N n-[(2r,4r)-1,4-dihydroxy-4-phenylbutan-2-yl]tetradecanamide Chemical compound CCCCCCCCCCCCCC(=O)N[C@@H](CO)C[C@@H](O)C1=CC=CC=C1 MWVNSXPNTJYJDR-DHIUTWEWSA-N 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
239000012071 phase Substances 0.000 description 2
NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
108090000765 processed proteins & peptides Proteins 0.000 description 2
229940002612 prodrug Drugs 0.000 description 2
239000000651 prodrug Substances 0.000 description 2
238000000926 separation method Methods 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000002904 solvent Substances 0.000 description 2
239000000758 substrate Substances 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
238000010189 synthetic method Methods 0.000 description 2
239000003826 tablet Substances 0.000 description 2
238000002560 therapeutic procedure Methods 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
AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 1
QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
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QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/26—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/55—Acids; Esters
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/12—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- 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
- C07D307/38—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
Heart & Thoracic Surgery (AREA)
Epidemiology (AREA)
Cardiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Thiazole And Isothizaole Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines Containing Plant Substances (AREA)
Treatment Of Fiber Materials (AREA)
Preliminary Treatment Of Fibers (AREA)
Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Furan Compounds (AREA)
Pyridine Compounds (AREA)

IL12491596A 1995-12-28 1996-12-17 History of thiol, method of preparation and pharmaceutical preparations containing them IL124915A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
IT95MI002773A IT1277737B1 (it)	1995-12-28	1995-12-28	Derivati tiolici ad attivita' inibitrice delle metallopeptidasi
PCT/EP1996/005663 WO1997024342A1 (en)	1995-12-28	1996-12-17	Thiol derivatives with metallopeptidase inhibitory activity

Publications (2)

Publication Number	Publication Date
IL124915A0 IL124915A0 (en)	1999-01-26
IL124915A true IL124915A (en)	2001-10-31

Family

ID=11372827

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL12491596A IL124915A (en)	1995-12-28	1996-12-17	History of thiol, method of preparation and pharmaceutical preparations containing them

Country Status (30)

Country	Link
EP (1)	EP0877740B1 (is)
JP (1)	JP2000502687A (is)
KR (1)	KR19990076809A (is)
CN (1)	CN1071325C (is)
AP (1)	AP1186A (is)
AR (1)	AR004413A1 (is)
AT (1)	ATE292123T1 (is)
AU (1)	AU713156B2 (is)
BG (1)	BG63942B1 (is)
BR (1)	BR9612373A (is)
CA (1)	CA2241414A1 (is)
CZ (1)	CZ204698A3 (is)
DE (1)	DE69634543D1 (is)
EA (1)	EA000991B1 (is)
EE (1)	EE03766B1 (is)
GE (1)	GEP19991871B (is)
IL (1)	IL124915A (is)
IS (1)	IS1885B (is)
IT (1)	IT1277737B1 (is)
NO (1)	NO310914B1 (is)
NZ (1)	NZ325785A (is)
OA (1)	OA10704A (is)
PL (1)	PL188151B1 (is)
RO (1)	RO119882B1 (is)
SK (1)	SK282977B6 (is)
TR (1)	TR199801229T2 (is)
UA (1)	UA62923C2 (is)
UY (1)	UY24425A1 (is)
WO (1)	WO1997024342A1 (is)
ZA (1)	ZA9610891B (is)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IT1289522B1 (it) *	1996-12-24	1998-10-15	Zambon Spa	Processo per la preparazione di eteroaril-fenilalanine
MY153569A (en)	1998-01-20	2015-02-27	Mitsubishi Tanabe Pharma Corp	Inhibitors of ?4 mediated cell adhesion
US8168616B1 (en)	2000-11-17	2012-05-01	Novartis Ag	Combination comprising a renin inhibitor and an angiotensin receptor inhibitor for hypertension
GB0203665D0 (en) *	2002-02-15	2002-04-03	Glaxo Group Ltd	Process
MY140707A (en)	2002-02-28	2010-01-15	Mitsubishi Tanabe Pharma Corp	Process for preparing a phenylalanine derivative and intermediates thereof
EP1481967B1 (en)	2002-03-05	2011-05-04	Sumitomo Chemical Company, Limited	Process for the preparation of biaryl compounds
GB0213122D0 (en) *	2002-06-07	2002-07-17	Glaxo Group Ltd	Compounds
AU2003232941A1 (en) *	2002-06-07	2003-12-22	Glaxo Group Limited	N-mercaptoacyl phenyalanine derivatives, process for their preparation, and pharmaceutical compositions containing them
US7045653B2 (en)	2002-12-23	2006-05-16	Pfizer, Inc.	Pharmaceuticals
GB0327839D0 (en)	2003-12-01	2003-12-31	Novartis Ag	Organic compounds
KR20070006774A (ko)	2004-03-17	2007-01-11	노파르티스 아게	치료에서 레닌 억제제의 용도
US9004163B2 (en)	2009-04-03	2015-04-14	Statoil Petroleum As	Equipment and method for reinforcing a borehole of a well while drilling
EP2531465A4 (en) *	2010-02-03	2015-12-30	Meh Associates Inc	MULTIPLE SUBSTITUTED FLUOROMETHANES AS SELECTIVE AND BIOACTIVE ISOSTERES
WO2011116115A1 (en)	2010-03-16	2011-09-22	Novartis Ag	Aliskiren composition comprising a medium chain fatty acid, their process of manufacturing

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4401677A (en) *	1981-10-09	1983-08-30	E. R. Squibb & Sons, Inc.	Enkephalinase inhibitors
FR2652087B1 (fr) *	1989-09-15	1993-10-15	Bioprojet Ste Civile	Derives d'amino-acides, leur procede de preparation et leurs applications therapeutiques.
FR2682952B1 (fr) *	1991-10-25	1993-12-03	Institut Nal Sante Recherc Medic	Nouveaux n-(mercaptoacyl) amino-acides, leur preparation et les compositions pharmaceutiques qui les contiennent.
IT1273455B (it) *	1995-01-27	1997-07-08	Zambon Spa	Derivati tiolici ad attivita' inibitrice delle metallopeptidasi

1995
- 1995-12-28 IT IT95MI002773A patent/IT1277737B1/it active IP Right Grant
1996
- 1996-12-17 NZ NZ325785A patent/NZ325785A/en unknown
- 1996-12-17 BR BR9612373A patent/BR9612373A/pt not_active Application Discontinuation
- 1996-12-17 CN CN96199354A patent/CN1071325C/zh not_active Expired - Fee Related
- 1996-12-17 TR TR1998/01229T patent/TR199801229T2/xx unknown
- 1996-12-17 AU AU13018/97A patent/AU713156B2/en not_active Ceased
- 1996-12-17 EA EA199800544A patent/EA000991B1/ru not_active IP Right Cessation
- 1996-12-17 EP EP96944583A patent/EP0877740B1/en not_active Expired - Lifetime
- 1996-12-17 EE EE9800192A patent/EE03766B1/xx not_active IP Right Cessation
- 1996-12-17 WO PCT/EP1996/005663 patent/WO1997024342A1/en not_active Ceased
- 1996-12-17 AT AT96944583T patent/ATE292123T1/de not_active IP Right Cessation
- 1996-12-17 JP JP09524001A patent/JP2000502687A/ja not_active Ceased
- 1996-12-17 RO RO98-01109A patent/RO119882B1/ro unknown
- 1996-12-17 CZ CZ982046A patent/CZ204698A3/cs unknown
- 1996-12-17 DE DE69634543T patent/DE69634543D1/de not_active Expired - Lifetime
- 1996-12-17 KR KR1019980704934A patent/KR19990076809A/ko not_active Ceased
- 1996-12-17 IL IL12491596A patent/IL124915A/en not_active IP Right Cessation
- 1996-12-17 PL PL96327580A patent/PL188151B1/pl not_active IP Right Cessation
- 1996-12-17 AP APAP/P/1998/001264A patent/AP1186A/en active
- 1996-12-17 UA UA98074090A patent/UA62923C2/uk unknown
- 1996-12-17 CA CA002241414A patent/CA2241414A1/en not_active Abandoned
- 1996-12-17 GE GEAP19964406A patent/GEP19991871B/en unknown
- 1996-12-17 SK SK889-98A patent/SK282977B6/sk unknown
- 1996-12-23 ZA ZA9610891A patent/ZA9610891B/xx unknown
- 1996-12-27 AR ARP960105957A patent/AR004413A1/es not_active Application Discontinuation
- 1996-12-27 UY UY24425A patent/UY24425A1/es not_active IP Right Cessation
1998
- 1998-06-18 BG BG102553A patent/BG63942B1/bg unknown
- 1998-06-22 IS IS4780A patent/IS1885B/is unknown
- 1998-06-26 NO NO19982977A patent/NO310914B1/no unknown
- 1998-06-26 OA OA9800094A patent/OA10704A/en unknown

Also Published As

Publication number	Publication date
ITMI952773A1 (it)	1997-06-28
AP1186A (en)	2003-07-07
BR9612373A (pt)	1999-07-13
BG102553A (en)	1999-04-30
EE03766B1 (et)	2002-06-17
NO982977L (no)	1998-08-27
OA10704A (en)	2002-11-28
IS1885B (is)	2003-08-15
SK282977B6 (sk)	2003-01-09
WO1997024342A1 (en)	1997-07-10
JP2000502687A (ja)	2000-03-07
SK88998A3 (en)	1998-12-02
TR199801229T2 (xx)	1998-09-21
ATE292123T1 (de)	2005-04-15
EP0877740B1 (en)	2005-03-30
RO119882B1 (ro)	2005-05-30
IT1277737B1 (it)	1997-11-12
BG63942B1 (bg)	2003-07-31
PL188151B1 (pl)	2004-12-31
DE69634543D1 (de)	2005-05-04
NO982977D0 (no)	1998-06-26
AP9801264A0 (en)	1998-06-30
KR19990076809A (ko)	1999-10-15
NO310914B1 (no)	2001-09-17
HK1018008A1 (en)	1999-12-10
EP0877740A1 (en)	1998-11-18
GEP19991871B (en)	1999-12-06
UA62923C2 (en)	2004-01-15
NZ325785A (en)	1999-09-29
PL327580A1 (en)	1998-12-21
EA199800544A1 (ru)	1999-02-25
CZ204698A3 (cs)	1998-11-11
IS4780A (is)	1998-06-22
AR004413A1 (es)	1998-11-04
ITMI952773A0 (is)	1995-12-28
AU713156B2 (en)	1999-11-25
IL124915A0 (en)	1999-01-26
CN1206411A (zh)	1999-01-27
AU1301897A (en)	1997-07-28
CN1071325C (zh)	2001-09-19
CA2241414A1 (en)	1997-07-10
ZA9610891B (en)	1997-06-27
EE9800192A (et)	1998-12-15
EA000991B1 (ru)	2000-08-28
UY24425A1 (es)	1997-01-09

Publication	Publication Date	Title
IL124915A (en)	2001-10-31	History of thiol, method of preparation and pharmaceutical preparations containing them
US5760241A (en)	1998-06-02	Thiol derivatives with metallopeptidase inhibitory activity
US6166051A (en)	2000-12-26	Thiol derivatives with metallopeptidase (ACE/NEP) inhibitory activity
DE69614508T2 (de)	2002-04-11	Thiol derivate mit metallopeptidase inhibierender aktivitat
AU707570B2 (en)	1999-07-15	Phosphonic acid derivatives with metallopeptidase inhibitory activity
AU713081B2 (en)	1999-11-25	Phosphinic acid derivatives with metallopeptidase inhibitory activity
HUP9903636A2 (hu)	2000-02-28	Metallopeptidáz-gátló hatású tiolszármazékok, eljárás azok előállítására, ilyen tiolszármazékokat tartalmazó gyógyszerkészítmények és eljárás azok alkalmazására

Legal Events

Date	Code	Title
2002-05-23	KB	Patent renewed
2003-02-12	KB	Patent renewed
2007-08-19	MM9K	Patent not in force due to non-payment of renewal fees