ZA200206221B - Amino acid derivatives and use thereof as NEP, ACE and ECE inhibitors. - Google Patents

Amino acid derivatives and use thereof as NEP, ACE and ECE inhibitors. Download PDF

Info

Publication number: ZA200206221B
Authority: ZA; South Africa
Prior art keywords: formula; compound; compounds; pharmaceutically acceptable; acceptable acid
Prior art date: 2000-02-17

Application number

ZA200206221A

Other languages

English (en)

Inventor

Bernard P Roques

Marie-Claude Fournie-Zaluski

Nicolas Inguimbert

Herve Poras

Elizabeth Scalbert

Caroline Bennejean

Pierre Renard

Original Assignee

Inst Nat Rech Medicale

Servier Lab

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.)

2000-02-17

Filing date

2002-08-05

Publication date

2003-08-20

2002-08-05 Application filed by Inst Nat Rech Medicale, Servier Lab filed Critical Inst Nat Rech Medicale

2003-08-20 Publication of ZA200206221B publication Critical patent/ZA200206221B/en

Links

239000003112 inhibitor Substances 0.000 title description 9
150000003862 amino acid derivatives Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 96
150000003839 salts Chemical class 0.000 claims description 30
239000002253 acid Substances 0.000 claims description 29
125000000217 alkyl group Chemical group 0.000 claims description 26
-1 cyano, nitro, amino Chemical group 0.000 claims description 19
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 18
125000002252 acyl group Chemical group 0.000 claims description 16
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
125000003342 alkenyl group Chemical group 0.000 claims description 14
125000005843 halogen group Chemical group 0.000 claims description 13
125000003545 alkoxy group Chemical group 0.000 claims description 12
125000003118 aryl group Chemical group 0.000 claims description 12
125000004432 carbon atom Chemical group C* 0.000 claims description 12
125000000304 alkynyl group Chemical group 0.000 claims description 10
125000000753 cycloalkyl group Chemical group 0.000 claims description 10
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
125000006684 polyhaloalkyl group Polymers 0.000 claims description 10
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
125000001072 heteroaryl group Chemical group 0.000 claims description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
125000004414 alkyl thio group Chemical group 0.000 claims description 7
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 6
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
125000003282 alkyl amino group Chemical group 0.000 claims description 6
125000003368 amide group Chemical group 0.000 claims description 6
125000003435 aroyl group Chemical group 0.000 claims description 6
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 6
125000004663 dialkyl amino group Chemical group 0.000 claims description 6
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 6
238000000926 separation method Methods 0.000 claims description 6
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 6
125000003710 aryl alkyl group Chemical group 0.000 claims description 5
238000000034 method Methods 0.000 claims description 5
238000002360 preparation method Methods 0.000 claims description 5
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FCDJBUMHEIZGOC-ACBHZAAOSA-N (2s)-2-[[2-(5-bromo-2,3-dihydro-1h-inden-1-yl)-3-sulfanylpropanoyl]amino]-3-(1h-pyrrolo[2,3-b]pyridin-3-yl)propanoic acid Chemical compound C1CC2=CC(Br)=CC=C2C1C(CS)C(=O)N[C@H](C(=O)O)CC1=CNC2=NC=CC=C12 FCDJBUMHEIZGOC-ACBHZAAOSA-N 0.000 claims description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 4
238000004587 chromatography analysis Methods 0.000 claims description 4
239000007822 coupling agent Substances 0.000 claims description 4
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239000007858 starting material Substances 0.000 claims description 4
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125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
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229910052757 nitrogen Inorganic materials 0.000 claims description 3
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STCPANYJWPVHTG-GRERDSQWSA-N (2s)-2-[[2-(5-bromo-2,3-dihydro-1h-inden-1-yl)-3-sulfanylpropanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound C1CC2=CC(Br)=CC=C2C1C(CS)C(=O)N[C@H](C(=O)O)CC1=CNC2=CC=CC=C12 STCPANYJWPVHTG-GRERDSQWSA-N 0.000 claims description 2
RHLTYGGPIVOIQX-XTXLOEGASA-N (2s)-2-[[2-(5-bromo-2,3-dihydro-1h-inden-1-yl)-3-sulfanylpropanoyl]amino]-3-(5-fluoro-1h-indol-3-yl)propanoic acid Chemical compound C1CC2=CC(Br)=CC=C2C1C(CS)C(=O)N[C@H](C(=O)O)CC1=CNC2=CC=C(F)C=C12 RHLTYGGPIVOIQX-XTXLOEGASA-N 0.000 claims description 2
YJSMEONIEBYZRH-AOMIVXANSA-N (2s)-3-(1h-indol-3-yl)-2-[[2-(5-methoxy-2,3-dihydro-1h-inden-1-yl)-3-sulfanylpropanoyl]amino]propanoic acid Chemical compound C1=CC=C2C(C[C@H](NC(=O)C(CS)C3C4=CC=C(C=C4CC3)OC)C(O)=O)=CNC2=C1 YJSMEONIEBYZRH-AOMIVXANSA-N 0.000 claims description 2
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QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 2
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NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
239000005864 Sulphur Substances 0.000 claims description 2
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 2
230000009471 action Effects 0.000 claims description 2
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235000004279 alanine Nutrition 0.000 claims description 2
150000001412 amines Chemical class 0.000 claims description 2
238000002399 angioplasty Methods 0.000 claims description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
208000026106 cerebrovascular disease Diseases 0.000 claims description 2
239000003638 chemical reducing agent Substances 0.000 claims description 2
239000003795 chemical substances by application Substances 0.000 claims description 2
208000020832 chronic kidney disease Diseases 0.000 claims description 2
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206010012601 diabetes mellitus Diseases 0.000 claims description 2
150000002366 halogen compounds Chemical class 0.000 claims description 2
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125000005842 heteroatom Chemical group 0.000 claims description 2
125000002950 monocyclic group Chemical group 0.000 claims description 2
208000031225 myocardial ischemia Diseases 0.000 claims description 2
125000001624 naphthyl group Chemical group 0.000 claims description 2
229910052760 oxygen Inorganic materials 0.000 claims description 2
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GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 claims description 2
XGJQUUGDYWNJSW-ZNIKRAEXSA-N (2s)-2-[[2-(5-bromo-2,3-dihydro-1h-inden-1-yl)-3-sulfanylpropanoyl]amino]-3-(5-methoxy-1h-indol-3-yl)propanoic acid Chemical compound C1CC2=CC(Br)=CC=C2C1C(CS)C(=O)N[C@H](C(O)=O)CC1=CNC2=CC=C(OC)C=C21 XGJQUUGDYWNJSW-ZNIKRAEXSA-N 0.000 claims 1
VDSMHDIVRBRETF-AOMIVXANSA-N (2s)-3-(1h-indol-3-yl)-2-[[2-(5-methylsulfanyl-2,3-dihydro-1h-inden-1-yl)-3-sulfanylpropanoyl]amino]propanoic acid Chemical compound C1=CC=C2C(C[C@H](NC(=O)C(CS)C3C4=CC=C(C=C4CC3)SC)C(O)=O)=CNC2=C1 VDSMHDIVRBRETF-AOMIVXANSA-N 0.000 claims 1
QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims 1
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125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims 1
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ITAFCRHBHGSAFR-AOMIVXANSA-N (2s)-2-[[2-(5-bromo-2,3-dihydro-1h-inden-1-yl)-3-sulfanylpropanoyl]amino]-3-quinolin-2-ylpropanoic acid Chemical compound C1CC2=CC(Br)=CC=C2C1C(CS)C(=O)N[C@H](C(=O)O)CC1=CC=C(C=CC=C2)C2=N1 ITAFCRHBHGSAFR-AOMIVXANSA-N 0.000 description 1
YSSFDJTWUJEZTK-GRERDSQWSA-N (2s)-2-[[2-(5-chloro-2,3-dihydro-1h-inden-1-yl)-3-sulfanylpropanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound C1CC2=CC(Cl)=CC=C2C1C(CS)C(=O)N[C@H](C(=O)O)CC1=CNC2=CC=CC=C12 YSSFDJTWUJEZTK-GRERDSQWSA-N 0.000 description 1
BPQNVNSPWLYVKD-AOMIVXANSA-N (2s)-2-[[2-(5-cyano-2,3-dihydro-1h-inden-1-yl)-3-sulfanylpropanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound C1CC2=CC(C#N)=CC=C2C1C(CS)C(=O)N[C@H](C(=O)O)CC1=CNC2=CC=CC=C12 BPQNVNSPWLYVKD-AOMIVXANSA-N 0.000 description 1
CSKOMJRLLWCZKY-BBHUYCHWSA-N (2s)-2-[[2-(5-ethoxy-2,3-dihydro-1h-inden-1-yl)-3-sulfanylpropanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound C1=CC=C2C(C[C@H](NC(=O)C(CS)C3C4=CC=C(C=C4CC3)OCC)C(O)=O)=CNC2=C1 CSKOMJRLLWCZKY-BBHUYCHWSA-N 0.000 description 1
XGAXYDYJXGHUKF-MHJFOBGBSA-N (2s)-3-(1-benzothiophen-3-yl)-2-[[2-(5-bromo-2,3-dihydro-1h-inden-1-yl)-3-sulfanylpropanoyl]amino]propanoic acid Chemical compound C1CC2=CC(Br)=CC=C2C1C(CS)C(=O)N[C@H](C(=O)O)CC1=CSC2=CC=CC=C12 XGAXYDYJXGHUKF-MHJFOBGBSA-N 0.000 description 1
NEVHGNNWXYABCA-AOMIVXANSA-N (2s)-3-(1h-indol-3-yl)-2-[[3-sulfanyl-2-(1,2,3,4-tetrahydronaphthalen-1-yl)propanoyl]amino]propanoic acid Chemical compound C1CCC2=CC=CC=C2C1C(CS)C(=O)N[C@H](C(=O)O)CC1=CNC2=CC=CC=C12 NEVHGNNWXYABCA-AOMIVXANSA-N 0.000 description 1
RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
208000024172 Cardiovascular disease Diseases 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
229910003691 SiBr Inorganic materials 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
238000009825 accumulation Methods 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000004913 activation Effects 0.000 description 1
230000002411 adverse Effects 0.000 description 1
JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 description 1
238000006243 chemical reaction Methods 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
230000013632 homeostatic process Effects 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
230000007774 longterm Effects 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
229940107700 pyruvic acid Drugs 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000001117 sulphuric acid Substances 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
230000006442 vascular tone Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- 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
- A61P9/08—Vasodilators for multiple indications
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- 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
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—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
- C07D209/20—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 substituted additionally by nitrogen atoms, e.g. tryptophane
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/36—Oxygen atoms in position 3, e.g. adrenochrome
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D215/14—Radicals substituted by oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
- C07D219/02—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems with only hydrogen, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the ring system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- 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
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D333/60—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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
General Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Urology & Nephrology (AREA)
Hospice & Palliative Care (AREA)
Diabetes (AREA)
Hematology (AREA)
Vascular Medicine (AREA)
Toxicology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Quinoline Compounds (AREA)
Other In-Based Heterocyclic Compounds (AREA)
Pyridine Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Indole Compounds (AREA)

ZA200206221A 2000-02-17 2002-08-05 Amino acid derivatives and use thereof as NEP, ACE and ECE inhibitors. ZA200206221B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
FR0001937A FR2805259B1 (fr)	2000-02-17	2000-02-17	Nouveaux derives d'aminoacides n-mercaptoacyles, leur procede de preparation et les compositions pharmaceutiques qui les contiennent

Publications (1)

Publication Number	Publication Date
ZA200206221B true ZA200206221B (en)	2003-08-20

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ID=8847077

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200206221A ZA200206221B (en)	2000-02-17	2002-08-05	Amino acid derivatives and use thereof as NEP, ACE and ECE inhibitors.

Country Status (24)

Country	Link
US (1)	US6716852B2 (de)
EP (1)	EP1255757B1 (de)
JP (1)	JP2003523343A (de)
KR (1)	KR100491605B1 (de)
CN (1)	CN1186344C (de)
AR (1)	AR029468A1 (de)
AT (1)	ATE243210T1 (de)
AU (2)	AU2001235698B2 (de)
BR (1)	BR0108409A (de)
CA (1)	CA2400537A1 (de)
CZ (1)	CZ20022811A3 (de)
DE (1)	DE60100388T2 (de)
DK (1)	DK1255757T3 (de)
EA (1)	EA005004B1 (de)
ES (1)	ES2202279T3 (de)
FR (1)	FR2805259B1 (de)
HU (1)	HUP0300248A3 (de)
MX (1)	MXPA02007973A (de)
NO (1)	NO323871B1 (de)
PL (1)	PL357243A1 (de)
PT (1)	PT1255757E (de)
SK (1)	SK11822002A3 (de)
WO (1)	WO2001060822A1 (de)
ZA (1)	ZA200206221B (de)

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KR20030019349A (ko)	2000-04-14	2003-03-06	커런트 테크놀로지스, 엘엘씨	중간 전압 전력 분배선을 사용한 디지털 통신
FR2823212B1 (fr) *	2001-04-10	2005-12-02	Inst Nat Sante Rech Med	Inhibiteurs de la toxine botulique de type b
PL1696920T3 (pl)	2003-12-19	2015-03-31	Plexxikon Inc	Związki i sposoby opracowywania modulatorów Ret
WO2008063888A2 (en)	2006-11-22	2008-05-29	Plexxikon, Inc.	Compounds modulating c-fms and/or c-kit activity and uses therefor
US20100190777A1 (en)	2007-07-17	2010-07-29	Plexxikon Inc.	Compounds and methods for kinase modulation, and indications therefor
FR2931151A1 (fr) *	2008-05-13	2009-11-20	Pharmaleads Soc Par Actions Si	Nouveaux derives d'amino-acides, leur procede de preparation et leur utilisation therapeutique
HUE027598T2 (en)	2009-04-03	2016-10-28	Hoffmann La Roche	Propane-1-sulfonic acid {3- [5- (4-chlorophenyl) -1H-pyrrolo [2,3-B] pyridine-3-carbonyl] -2,4-difluorophenyl} amide compositions and their uses
ES2633317T3 (es)	2009-11-06	2017-09-20	Plexxikon, Inc.	Compuestos y métodos para la modulación de quinasas, e indicaciones para ello
MA34948B1 (fr)	2011-02-07	2014-03-01	Plexxikon Inc	Composes et procedes de modulation de kinase, et leurs indications
TWI558702B (zh)	2011-02-21	2016-11-21	普雷辛肯公司	醫藥活性物質的固態形式
US9150570B2 (en)	2012-05-31	2015-10-06	Plexxikon Inc.	Synthesis of heterocyclic compounds

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CA2038379C (en) *	1990-03-22	2002-11-05	Norma G. Delaney	Trifluoromethyl mercaptan and mercaptoacyl derivatives and method of using same
IT1277736B1 (it) *	1995-12-28	1997-11-12	Zambon Spa	Derivati tiolici ad attivita' inibitrice delle metallopeptidasi
FR2745571B1 (fr) *	1996-03-04	1998-06-19	Inst Nat Sante Rech Med	Nouveaux derives soufres comportant une liaison amide, leur procede de preparation, leur application a titre de medicaments, et les compositions pharmaceutiques les renfermant

2000
- 2000-02-17 FR FR0001937A patent/FR2805259B1/fr not_active Expired - Fee Related
2001
- 2001-02-15 AR ARP010100675A patent/AR029468A1/es unknown
- 2001-02-16 CA CA002400537A patent/CA2400537A1/fr not_active Abandoned
- 2001-02-16 AU AU2001235698A patent/AU2001235698B2/en not_active Ceased
- 2001-02-16 KR KR10-2002-7010552A patent/KR100491605B1/ko not_active Expired - Fee Related
- 2001-02-16 EP EP01907822A patent/EP1255757B1/de not_active Expired - Lifetime
- 2001-02-16 EA EA200200807A patent/EA005004B1/ru not_active IP Right Cessation
- 2001-02-16 DK DK01907822T patent/DK1255757T3/da active
- 2001-02-16 WO PCT/FR2001/000463 patent/WO2001060822A1/fr not_active Ceased
- 2001-02-16 AU AU3569801A patent/AU3569801A/xx active Pending
- 2001-02-16 CN CNB018050921A patent/CN1186344C/zh not_active Expired - Fee Related
- 2001-02-16 MX MXPA02007973A patent/MXPA02007973A/es active IP Right Grant
- 2001-02-16 JP JP2001560206A patent/JP2003523343A/ja active Pending
- 2001-02-16 ES ES01907822T patent/ES2202279T3/es not_active Expired - Lifetime
- 2001-02-16 CZ CZ20022811A patent/CZ20022811A3/cs unknown
- 2001-02-16 US US10/203,704 patent/US6716852B2/en not_active Expired - Fee Related
- 2001-02-16 AT AT01907822T patent/ATE243210T1/de not_active IP Right Cessation
- 2001-02-16 SK SK1182-2002A patent/SK11822002A3/sk unknown
- 2001-02-16 PT PT01907822T patent/PT1255757E/pt unknown
- 2001-02-16 HU HU0300248A patent/HUP0300248A3/hu unknown
- 2001-02-16 DE DE60100388T patent/DE60100388T2/de not_active Expired - Fee Related
- 2001-02-16 PL PL01357243A patent/PL357243A1/xx not_active Application Discontinuation
- 2001-02-16 BR BR0108409-7A patent/BR0108409A/pt not_active IP Right Cessation
2002
- 2002-08-05 ZA ZA200206221A patent/ZA200206221B/en unknown
- 2002-08-16 NO NO20023893A patent/NO323871B1/no unknown

Also Published As

Publication number	Publication date
CN1186344C (zh)	2005-01-26
AR029468A1 (es)	2003-07-02
ES2202279T3 (es)	2004-04-01
US20030055086A1 (en)	2003-03-20
CN1400974A (zh)	2003-03-05
AU3569801A (en)	2001-08-27
PL357243A1 (en)	2004-07-26
SK11822002A3 (sk)	2003-03-04
EP1255757B1 (de)	2003-06-18
PT1255757E (pt)	2003-10-31
KR20020072581A (ko)	2002-09-16
JP2003523343A (ja)	2003-08-05
US6716852B2 (en)	2004-04-06
WO2001060822A1 (fr)	2001-08-23
CZ20022811A3 (cs)	2003-01-15
FR2805259B1 (fr)	2002-03-29
AU2001235698B2 (en)	2005-02-17
FR2805259A1 (fr)	2001-08-24
DE60100388T2 (de)	2004-05-19
CA2400537A1 (fr)	2001-08-23
MXPA02007973A (es)	2005-10-05
HK1050896A1 (en)	2003-07-11
EA200200807A1 (ru)	2002-12-26
DK1255757T3 (da)	2003-10-13
EP1255757A1 (de)	2002-11-13
EA005004B1 (ru)	2004-10-28
KR100491605B1 (ko)	2005-05-27
DE60100388D1 (de)	2003-07-24
NO20023893L (no)	2002-08-16
NO20023893D0 (no)	2002-08-16
BR0108409A (pt)	2003-03-11
WO2001060822A8 (fr)	2001-09-27
HUP0300248A3 (en)	2005-07-28
HUP0300248A2 (hu)	2003-06-28
ATE243210T1 (de)	2003-07-15
NO323871B1 (no)	2007-07-16

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