OA10704A - Thiol derivatives with metallopeptidase inhibitoryactivity. - Google Patents

Thiol derivatives with metallopeptidase inhibitoryactivity. Download PDF

Info

Publication number: OA10704A
Authority: OA; OAPI
Prior art keywords: phenylalanine; mercapto; phenylmethylpropionyl; group; thiazolyl
Prior art date: 1995-12-28

Application number

OA9800094A

Other languages

English (en)

French (fr)

Inventor

Franco Pellacini

Mario Fantucci

Gabriele Norcini

Stefano Romagnano

Francesco Santangelo

Claudio Semeraro

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

1998-06-26

Publication date

2002-11-28

1998-06-26 Application filed by Zambon Spa filed Critical Zambon Spa

2002-11-28 Publication of OA10704A publication Critical patent/OA10704A/en

Links

125000003396 thiol group Chemical class [H]S* 0.000 title claims description 7
230000002401 inhibitory effect Effects 0.000 title description 24
102000005741 Metalloproteases Human genes 0.000 title description 7
108010006035 Metalloproteases Proteins 0.000 title description 7
150000001875 compounds Chemical class 0.000 claims abstract description 87
238000000034 method Methods 0.000 claims abstract description 14
238000011282 treatment Methods 0.000 claims abstract description 8
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 5
229960005190 phenylalanine Drugs 0.000 claims description 47
-1 amino-sulphonyl groups Chemical group 0.000 claims description 45
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
125000000217 alkyl group Chemical group 0.000 claims description 19
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
229910052757 nitrogen Inorganic materials 0.000 claims description 10
125000003118 aryl group Chemical group 0.000 claims description 9
238000006243 chemical reaction Methods 0.000 claims description 9
125000003545 alkoxy group Chemical group 0.000 claims description 8
125000005843 halogen group Chemical group 0.000 claims description 7
150000003839 salts Chemical class 0.000 claims description 7
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
125000004432 carbon atom Chemical group C* 0.000 claims description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
229910052760 oxygen Inorganic materials 0.000 claims description 6
239000001301 oxygen Substances 0.000 claims description 6
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
125000005842 heteroatom Chemical group 0.000 claims description 4
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 4
125000001424 substituent group Chemical group 0.000 claims description 4
125000003710 aryl alkyl group Chemical group 0.000 claims description 3
125000000623 heterocyclic group Chemical group 0.000 claims description 3
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 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
239000003513 alkali Substances 0.000 claims description 2
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
125000004414 alkyl thio group Chemical group 0.000 claims description 2
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
229910052744 lithium Inorganic materials 0.000 claims description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
229910052700 potassium Inorganic materials 0.000 claims description 2
239000011591 potassium Substances 0.000 claims description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
229910052708 sodium Inorganic materials 0.000 claims description 2
239000011734 sodium Substances 0.000 claims description 2
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims 4
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims 4
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims 2
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 2
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims 2
125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 2
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 2
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims 2
125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims 2
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims 2
229910052717 sulfur Inorganic materials 0.000 claims 2
239000011593 sulfur Substances 0.000 claims 2
101100386054 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) CYS3 gene Proteins 0.000 claims 1
125000004442 acylamino group Chemical group 0.000 claims 1
229910052799 carbon Inorganic materials 0.000 claims 1
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
229910052751 metal Inorganic materials 0.000 claims 1
239000002184 metal Substances 0.000 claims 1
150000002993 phenylalanine derivatives Chemical class 0.000 claims 1
125000003884 phenylalkyl group Chemical group 0.000 claims 1
101150035983 str1 gene Proteins 0.000 claims 1
125000000547 substituted alkyl group Chemical group 0.000 claims 1
230000000694 effects Effects 0.000 abstract description 41
239000004480 active ingredient Substances 0.000 abstract 1
238000005481 NMR spectroscopy Methods 0.000 description 38
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 30
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 28
150000002148 esters Chemical class 0.000 description 18
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
102100030988 Angiotensin-converting enzyme Human genes 0.000 description 16
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 16
108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 16
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 14
102000003729 Neprilysin Human genes 0.000 description 14
108090000028 Neprilysin Proteins 0.000 description 14
239000000203 mixture Substances 0.000 description 13
239000000243 solution Substances 0.000 description 11
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
150000004702 methyl esters Chemical class 0.000 description 10
239000011541 reaction mixture Substances 0.000 description 10
238000011699 spontaneously hypertensive rat Methods 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
238000003756 stirring Methods 0.000 description 9
101150041968 CDC13 gene Proteins 0.000 description 8
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
238000005160 1H NMR spectroscopy Methods 0.000 description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
108010036928 Thiorphan Proteins 0.000 description 7
210000004072 lung Anatomy 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
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-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
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 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
FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 6
229960000830 captopril Drugs 0.000 description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
238000003818 flash chromatography Methods 0.000 description 6
210000003734 kidney Anatomy 0.000 description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
125000004076 pyridyl group Chemical group 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
230000009977 dual effect Effects 0.000 description 5
239000012528 membrane Substances 0.000 description 5
229940073584 methylene chloride Drugs 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
125000000335 thiazolyl group Chemical group 0.000 description 5
150000003573 thiols Chemical class 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
239000000872 buffer Substances 0.000 description 4
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 4
239000012458 free base Substances 0.000 description 4
125000002541 furyl group Chemical group 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
239000003208 petroleum Substances 0.000 description 4
239000000725 suspension Substances 0.000 description 4
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 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
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
239000005864 Sulphur Substances 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
229940024606 amino acid Drugs 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
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
229940126142 compound 16 Drugs 0.000 description 3
238000007796 conventional method Methods 0.000 description 3
230000000875 corresponding effect Effects 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
125000006239 protecting group Chemical group 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
JBIJLHTVPXGSAM-UHFFFAOYSA-N 2-naphthylamine Chemical compound C1=CC=CC2=CC(N)=CC=C21 JBIJLHTVPXGSAM-UHFFFAOYSA-N 0.000 description 2
JRJDICNLCDSNRF-UHFFFAOYSA-N 4-methyl-2-phenacylpentanethioic s-acid Chemical compound CC(C)CC(C(S)=O)CC(=O)C1=CC=CC=C1 JRJDICNLCDSNRF-UHFFFAOYSA-N 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
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
206010019280 Heart failures Diseases 0.000 description 2
206010020772 Hypertension Diseases 0.000 description 2
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 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
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
239000007983 Tris buffer Substances 0.000 description 2
239000002253 acid Substances 0.000 description 2
125000002252 acyl group Chemical group 0.000 description 2
238000007792 addition Methods 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-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
239000000460 chlorine Chemical group 0.000 description 2
230000000052 comparative effect Effects 0.000 description 2
239000002792 enkephalinase inhibitor Substances 0.000 description 2
125000001153 fluoro group Chemical group F* 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
238000001990 intravenous administration Methods 0.000 description 2
238000010253 intravenous injection Methods 0.000 description 2
KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
210000000231 kidney cortex Anatomy 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
239000012071 phase Substances 0.000 description 2
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 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
239000002904 solvent Substances 0.000 description 2
239000000758 substrate Substances 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
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239000003826 tablet Substances 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
DZJXLMSJAUYLCS-UHFFFAOYSA-N trimethyl(1,3-thiazol-2-yl)stannane Chemical compound C[Sn](C)(C)C1=NC=CS1 DZJXLMSJAUYLCS-UHFFFAOYSA-N 0.000 description 2
229960004441 tyrosine Drugs 0.000 description 2
UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
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
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150000002391 heterocyclic compounds Chemical class 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
239000011539 homogenization buffer Substances 0.000 description 1
229940088597 hormone Drugs 0.000 description 1
239000005556 hormone Substances 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
238000011534 incubation Methods 0.000 description 1
229910052740 iodine Chemical group 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
LZWXEKDJEQRWHE-YANBTOMASA-N methyl (2s)-2-[[2-(acetylsulfanylmethyl)-3-(3-methoxyphenyl)propanoyl]amino]-3-[4-(1,3-thiazol-2-yl)phenyl]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)C(CSC(C)=O)CC=1C=C(OC)C=CC=1)C(C=C1)=CC=C1C1=NC=CS1 LZWXEKDJEQRWHE-YANBTOMASA-N 0.000 description 1
VNYCOUNWNVROGS-GEVKEYJPSA-N methyl (2s)-2-[[2-(benzoylsulfanylmethyl)-3-phenylpropanoyl]amino]-3-(4-thiophen-2-ylphenyl)propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)C(CSC(=O)C=1C=CC=CC=1)CC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CS1 VNYCOUNWNVROGS-GEVKEYJPSA-N 0.000 description 1
DZJQJKVARYLEPT-GITCGBDTSA-N methyl (2s)-2-[[2-(benzoylsulfanylmethyl)-3-thiophen-2-ylpropanoyl]amino]-3-[4-(1,3-thiazol-2-yl)phenyl]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)C(CSC(=O)C=1C=CC=CC=1)CC=1SC=CC=1)C(C=C1)=CC=C1C1=NC=CS1 DZJQJKVARYLEPT-GITCGBDTSA-N 0.000 description 1
SJESFSGYKOQFCN-IDMXKUIJSA-N methyl (2s)-2-amino-3-[4-(1,3-thiazol-2-yl)phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=NC=CS1 SJESFSGYKOQFCN-IDMXKUIJSA-N 0.000 description 1
VQSRKMNBWMHJKY-YTEVENLXSA-N n-[3-[(4ar,7as)-2-amino-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-7a-yl]-4-fluorophenyl]-5-methoxypyrazine-2-carboxamide Chemical compound C1=NC(OC)=CN=C1C(=O)NC1=CC=C(F)C([C@@]23[C@@H](CN(C2)C=2N=CC(F)=CN=2)CSC(N)=N3)=C1 VQSRKMNBWMHJKY-YTEVENLXSA-N 0.000 description 1
239000002833 natriuretic agent Substances 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
230000007170 pathology Effects 0.000 description 1
125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
230000012495 positive regulation of renal sodium excretion Effects 0.000 description 1
239000011698 potassium fluoride Substances 0.000 description 1
235000003270 potassium fluoride Nutrition 0.000 description 1
239000002243 precursor Substances 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
HZFPPBMKGYINDF-UHFFFAOYSA-N pyrimidin-5-ylboronic acid Chemical compound OB(O)C1=CN=CN=C1 HZFPPBMKGYINDF-UHFFFAOYSA-N 0.000 description 1
238000010992 reflux Methods 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
239000007787 solid Substances 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
238000013222 sprague-dawley male rat Methods 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
239000000126 substance Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
MYMLGBAVNHFRJS-UHFFFAOYSA-N trifluoromethanamine Chemical class NC(F)(F)F MYMLGBAVNHFRJS-UHFFFAOYSA-N 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
108010017949 tyrosyl-glycyl-glycine Proteins 0.000 description 1
229950009811 ubenimex Drugs 0.000 description 1
239000005526 vasoconstrictor agent Substances 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000005303 weighing Methods 0.000 description 1

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

Landscapes

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)
Cardiology (AREA)
Epidemiology (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)
Pyridine Compounds (AREA)
Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Furan Compounds (AREA)
Treatment Of Fiber Materials (AREA)
Preliminary Treatment Of Fibers (AREA)

OA9800094A 1995-12-28 1998-06-26 Thiol derivatives with metallopeptidase inhibitoryactivity. OA10704A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
IT95MI002773A IT1277737B1 (it)	1995-12-28	1995-12-28	Derivati tiolici ad attivita' inibitrice delle metallopeptidasi

Publications (1)

Publication Number	Publication Date
OA10704A true OA10704A (en)	2002-11-28

Family

ID=11372827

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA9800094A OA10704A (en)	1995-12-28	1998-06-26	Thiol derivatives with metallopeptidase inhibitoryactivity.

Country Status (30)

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

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
WO2003074478A1 (en)	2002-03-05	2003-09-12	Sumitomo Chemical Company, Limited	Process for the preparation of biaryl 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
GB0213122D0 (en) *	2002-06-07	2002-07-17	Glaxo Group Ltd	Compounds
US7045653B2 (en)	2002-12-23	2006-05-16	Pfizer, Inc.	Pharmaceuticals
GB0327839D0 (en)	2003-12-01	2003-12-31	Novartis Ag	Organic compounds
RU2426532C2 (ru)	2004-03-17	2011-08-20	Новартис Аг	Применение органических соединений
WO2010112050A1 (en)	2009-04-03	2010-10-07	Statoil Asa	Equipment and method for reinforcing a borehole of a well while drilling
JP2013518897A (ja) *	2010-02-03	2013-05-23	エムイーエイチアソシエイツ，インコーポレイテッド	選択的および生体活性的等配電子体としての多重置換フルオロメタン
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 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 AT AT96944583T patent/ATE292123T1/de not_active IP Right Cessation
- 1996-12-17 KR KR1019980704934A patent/KR19990076809A/ko not_active Ceased
- 1996-12-17 JP JP09524001A patent/JP2000502687A/ja not_active Ceased
- 1996-12-17 CA CA002241414A patent/CA2241414A1/en not_active Abandoned
- 1996-12-17 NZ NZ325785A patent/NZ325785A/en unknown
- 1996-12-17 PL PL96327580A patent/PL188151B1/pl not_active IP Right Cessation
- 1996-12-17 CZ CZ982046A patent/CZ204698A3/cs unknown
- 1996-12-17 AU AU13018/97A patent/AU713156B2/en not_active Ceased
- 1996-12-17 TR TR1998/01229T patent/TR199801229T2/xx unknown
- 1996-12-17 RO RO98-01109A patent/RO119882B1/ro unknown
- 1996-12-17 DE DE69634543T patent/DE69634543D1/de not_active Expired - Lifetime
- 1996-12-17 UA UA98074090A patent/UA62923C2/uk unknown
- 1996-12-17 BR BR9612373A patent/BR9612373A/pt not_active Application Discontinuation
- 1996-12-17 IL IL12491596A patent/IL124915A/en not_active IP Right Cessation
- 1996-12-17 SK SK889-98A patent/SK282977B6/sk unknown
- 1996-12-17 WO PCT/EP1996/005663 patent/WO1997024342A1/en not_active Ceased
- 1996-12-17 AP APAP/P/1998/001264A patent/AP1186A/en active
- 1996-12-17 CN CN96199354A patent/CN1071325C/zh not_active Expired - Fee Related
- 1996-12-17 GE GEAP19964406A patent/GEP19991871B/en unknown
- 1996-12-17 EE EE9800192A patent/EE03766B1/xx not_active IP Right Cessation
- 1996-12-23 ZA ZA9610891A patent/ZA9610891B/xx unknown
- 1996-12-27 UY UY24425A patent/UY24425A1/es not_active IP Right Cessation
- 1996-12-27 AR ARP960105957A patent/AR004413A1/es not_active Application Discontinuation
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
CN1071325C (zh)	2001-09-19
KR19990076809A (ko)	1999-10-15
PL188151B1 (pl)	2004-12-31
NO310914B1 (no)	2001-09-17
UY24425A1 (es)	1997-01-09
PL327580A1 (en)	1998-12-21
SK88998A3 (en)	1998-12-02
IS1885B (is)	2003-08-15
BR9612373A (pt)	1999-07-13
IS4780A (is)	1998-06-22
ITMI952773A1 (it)	1997-06-28
NZ325785A (en)	1999-09-29
AU713156B2 (en)	1999-11-25
BG102553A (en)	1999-04-30
EE9800192A (et)	1998-12-15
CZ204698A3 (cs)	1998-11-11
EP0877740B1 (en)	2005-03-30
AR004413A1 (es)	1998-11-04
EA199800544A1 (ru)	1999-02-25
EP0877740A1 (en)	1998-11-18
ITMI952773A0 (cs)	1995-12-28
IT1277737B1 (it)	1997-11-12
NO982977D0 (no)	1998-06-26
RO119882B1 (ro)	2005-05-30
HK1018008A1 (en)	1999-12-10
AP9801264A0 (en)	1998-06-30
GEP19991871B (en)	1999-12-06
IL124915A (en)	2001-10-31
CA2241414A1 (en)	1997-07-10
EE03766B1 (et)	2002-06-17
NO982977L (no)	1998-08-27
JP2000502687A (ja)	2000-03-07
WO1997024342A1 (en)	1997-07-10
ZA9610891B (en)	1997-06-27
CN1206411A (zh)	1999-01-27
DE69634543D1 (de)	2005-05-04
EA000991B1 (ru)	2000-08-28
UA62923C2 (en)	2004-01-15
IL124915A0 (en)	1999-01-26
BG63942B1 (bg)	2003-07-31
AP1186A (en)	2003-07-07
SK282977B6 (sk)	2003-01-09
TR199801229T2 (xx)	1998-09-21
AU1301897A (en)	1997-07-28
ATE292123T1 (de)	2005-04-15

Publication	Publication Date	Title
EP0877740B1 (en)	2005-03-30	Thiol derivatives with metallopeptidase inhibitory activity
US5994539A (en)	1999-11-30	Mercapto acyl aminoacid derivatives endowed with dual ACE-NEP inhibitory activity, useful in the treatment of cardiovascular diseases
EP0636621B1 (en)	1997-03-12	Beta-mercapto-propanamide derivatives useful in the treatment of cardiovascular diseases
DE69614508T2 (de)	2002-04-11	Thiol derivate mit metallopeptidase inhibierender aktivitat
EP0883612B1 (en)	2005-02-23	Thiol derivatives with metallopeptidase (ace/nep) inhibitory activity
US6548480B1 (en)	2003-04-15	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
US5760285A (en)	1998-06-02	Phosphonyldipeptides useful in the treatment of cardiovascular diseases
AU2260500A (en)	2000-06-29	Protease inhibitors - III