SK176299A3 - New 'beta'-amino and 'beta'-azidocarboxylic acid derivatives, the production thereof and the use thereof as endothelin receptor antagonists - Google Patents

New 'beta'-amino and 'beta'-azidocarboxylic acid derivatives, the production thereof and the use thereof as endothelin receptor antagonists Download PDF

Info

Publication number: SK176299A3
Authority: SK; Slovakia
Prior art keywords: alkyl; substituted; phenyl; unsubstituted; amino
Prior art date: 1997-06-19

Application number

SK1762-99A

Other languages

English (en)

Slovak (sk)

Inventor

Wilhelm Amberg

Andreas Kling

Dagmar Klinge

Hartmut Riechers

Stefan Hergenroder

Manfred Raschack

Liliane Unger

Original Assignee

Basf Ag

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.)

1997-06-19

Filing date

1998-06-05

Publication date

2000-06-12

1998-06-05 Application filed by Basf Ag filed Critical Basf Ag

2000-06-12 Publication of SK176299A3 publication Critical patent/SK176299A3/sk

Links

229940118365 Endothelin receptor antagonist Drugs 0.000 title claims abstract description 7
239000002308 endothelin receptor antagonist Substances 0.000 title claims abstract description 7
238000004519 manufacturing process Methods 0.000 title claims abstract description 5
239000002253 acid Substances 0.000 title claims description 9
150000001732 carboxylic acid derivatives Chemical class 0.000 claims abstract description 8
-1 alkali metal cation Chemical class 0.000 claims description 98
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 70
150000001875 compounds Chemical class 0.000 claims description 49
229910052736 halogen Inorganic materials 0.000 claims description 33
150000002367 halogens Chemical class 0.000 claims description 33
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 32
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
229910052757 nitrogen Inorganic materials 0.000 claims description 28
229910052739 hydrogen Inorganic materials 0.000 claims description 22
239000001257 hydrogen Substances 0.000 claims description 20
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 20
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 20
150000002431 hydrogen Chemical class 0.000 claims description 16
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 13
102000002045 Endothelin Human genes 0.000 claims description 13
108050009340 Endothelin Proteins 0.000 claims description 13
ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 claims description 13
229910052717 sulfur Inorganic materials 0.000 claims description 11
125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 10
125000001624 naphthyl group Chemical group 0.000 claims description 10
125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 9
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 9
125000000217 alkyl group Chemical group 0.000 claims description 8
125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 8
229910052760 oxygen Inorganic materials 0.000 claims description 8
239000001301 oxygen Substances 0.000 claims description 8
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 7
239000011593 sulfur Substances 0.000 claims description 7
229910052783 alkali metal Inorganic materials 0.000 claims description 6
239000003112 inhibitor Substances 0.000 claims description 6
238000011282 treatment Methods 0.000 claims description 6
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 claims description 5
102000004270 Peptidyl-Dipeptidase A Human genes 0.000 claims description 5
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229910052784 alkaline earth metal Inorganic materials 0.000 claims description 5
239000003814 drug Substances 0.000 claims description 5
125000005843 halogen group Chemical group 0.000 claims description 5
125000001072 heteroaryl group Chemical group 0.000 claims description 5
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 4
206010020772 Hypertension Diseases 0.000 claims description 4
125000004450 alkenylene group Chemical group 0.000 claims description 4
125000002947 alkylene group Chemical group 0.000 claims description 4
IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 claims description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
201000010099 disease Diseases 0.000 claims description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 4
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 4
125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
125000004434 sulfur atom Chemical group 0.000 claims description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 3
102000010180 Endothelin receptor Human genes 0.000 claims description 3
108050001739 Endothelin receptor Proteins 0.000 claims description 3
206010060862 Prostate cancer Diseases 0.000 claims description 3
208000000236 Prostatic Neoplasms Diseases 0.000 claims description 3
230000008878 coupling Effects 0.000 claims description 3
238000010168 coupling process Methods 0.000 claims description 3
238000005859 coupling reaction Methods 0.000 claims description 3
208000002815 pulmonary hypertension Diseases 0.000 claims description 3
230000036454 renin-angiotensin system Effects 0.000 claims description 3
150000003839 salts Chemical class 0.000 claims description 3
125000003831 tetrazolyl group Chemical group 0.000 claims description 3
208000009304 Acute Kidney Injury Diseases 0.000 claims description 2
229940123413 Angiotensin II antagonist Drugs 0.000 claims description 2
206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 2
201000006474 Brain Ischemia Diseases 0.000 claims description 2
206010007558 Cardiac failure chronic Diseases 0.000 claims description 2
206010008120 Cerebral ischaemia Diseases 0.000 claims description 2
208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 2
208000033626 Renal failure acute Diseases 0.000 claims description 2
CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 2
230000001154 acute effect Effects 0.000 claims description 2
201000011040 acute kidney failure Diseases 0.000 claims description 2
208000012998 acute renal failure Diseases 0.000 claims description 2
125000005133 alkynyloxy group Chemical group 0.000 claims description 2
239000002333 angiotensin II receptor antagonist Substances 0.000 claims description 2
206010008118 cerebral infarction Diseases 0.000 claims description 2
208000020832 chronic kidney disease Diseases 0.000 claims description 2
208000022831 chronic renal failure syndrome Diseases 0.000 claims description 2
238000007911 parenteral administration Methods 0.000 claims description 2
239000002461 renin inhibitor Substances 0.000 claims description 2
229940086526 renin-inhibitors Drugs 0.000 claims description 2
208000037803 restenosis Diseases 0.000 claims description 2
SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 2
102000003729 Neprilysin Human genes 0.000 claims 2
108090000028 Neprilysin Proteins 0.000 claims 2
125000000304 alkynyl group Chemical group 0.000 claims 2
125000004448 alkyl carbonyl group Chemical group 0.000 claims 1
125000004414 alkyl thio group Chemical group 0.000 claims 1
MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims 1
239000002876 beta blocker Substances 0.000 claims 1
229940097320 beta blocking agent Drugs 0.000 claims 1
230000015572 biosynthetic process Effects 0.000 claims 1
CTMZLDSMFCVUNX-VMIOUTBZSA-N cytidylyl-(3'->5')-guanosine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=C(C(N=C(N)N3)=O)N=C2)O)[C@@H](CO)O1 CTMZLDSMFCVUNX-VMIOUTBZSA-N 0.000 claims 1
239000012634 fragment Substances 0.000 claims 1
238000007912 intraperitoneal administration Methods 0.000 claims 1
239000007858 starting material Substances 0.000 claims 1
238000003786 synthesis reaction Methods 0.000 claims 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
239000000470 constituent Substances 0.000 abstract 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 122
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 32
150000003254 radicals Chemical class 0.000 description 32
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
125000004093 cyano group Chemical group *C#N 0.000 description 18
239000000203 mixture Substances 0.000 description 18
239000002904 solvent Substances 0.000 description 18
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
238000006243 chemical reaction Methods 0.000 description 12
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 12
102000005962 receptors Human genes 0.000 description 11
108020003175 receptors Proteins 0.000 description 11
239000002585 base Substances 0.000 description 10
238000002844 melting Methods 0.000 description 10
230000008018 melting Effects 0.000 description 10
238000012360 testing method Methods 0.000 description 10
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 9
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 8
229910052943 magnesium sulfate Inorganic materials 0.000 description 8
235000019341 magnesium sulphate Nutrition 0.000 description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 8
239000012074 organic phase Substances 0.000 description 8
125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 description 7
241001465754 Metazoa Species 0.000 description 7
230000027455 binding Effects 0.000 description 7
238000000605 extraction Methods 0.000 description 7
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
210000004027 cell Anatomy 0.000 description 6
238000001816 cooling Methods 0.000 description 6
239000013078 crystal Substances 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
238000002360 preparation method Methods 0.000 description 6
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
239000000126 substance Substances 0.000 description 5
125000001424 substituent group Chemical group 0.000 description 5
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DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 4
102100033902 Endothelin-1 Human genes 0.000 description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
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230000020477 pH reduction Effects 0.000 description 4
238000005160 1H NMR spectroscopy Methods 0.000 description 3
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 3
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 description 3
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MUKKVUDEZUPZFU-UHFFFAOYSA-N methyl 3-azido-2-hydroxy-3,3-diphenylpropanoate Chemical compound C=1C=CC=CC=1C(N=[N+]=[N-])(C(O)C(=O)OC)C1=CC=CC=C1 MUKKVUDEZUPZFU-UHFFFAOYSA-N 0.000 description 3
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239000003826 tablet Substances 0.000 description 3
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125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
YNTJKQDWYXUTLZ-UHFFFAOYSA-N 2-(3-chlorophenoxy)propanoic acid Chemical compound OC(=O)C(C)OC1=CC=CC(Cl)=C1 YNTJKQDWYXUTLZ-UHFFFAOYSA-N 0.000 description 2
CIOYFILREMJKAN-UHFFFAOYSA-N 2-(4,6-dimethoxypyrimidin-2-yl)oxy-3-[(2-methoxyacetyl)amino]-3,3-diphenylpropanoic acid Chemical compound COC1=NC(=NC(=C1)OC)OC(C(=O)O)C(C1=CC=CC=C1)(C1=CC=CC=C1)NC(COC)=O CIOYFILREMJKAN-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
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NAQKEMDYTJCALL-UHFFFAOYSA-N 3-amino-2-[(4-methoxy-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)oxy]-3,3-diphenylpropanoic acid Chemical compound COC1=NC(=NC2=C1CCC2)OC(C(=O)O)C(C2=CC=CC=C2)(C2=CC=CC=C2)N NAQKEMDYTJCALL-UHFFFAOYSA-N 0.000 description 2
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125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000002674 ointment Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
150000002902 organometallic compounds Chemical class 0.000 description 1
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
229940049954 penicillin Drugs 0.000 description 1
125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
238000005222 photoaffinity labeling Methods 0.000 description 1
230000001766 physiological effect Effects 0.000 description 1
239000004014 plasticizer Substances 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
210000002307 prostate Anatomy 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
238000000159 protein binding assay Methods 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
238000000746 purification Methods 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
239000002287 radioligand Substances 0.000 description 1
229910052761 rare earth metal Inorganic materials 0.000 description 1
229940044551 receptor antagonist Drugs 0.000 description 1
239000002464 receptor antagonist Substances 0.000 description 1
238000001525 receptor binding assay Methods 0.000 description 1
108091006082 receptor inhibitors Proteins 0.000 description 1
206010038464 renal hypertension Diseases 0.000 description 1
230000000717 retained effect Effects 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
229910052708 sodium Inorganic materials 0.000 description 1
CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
238000012453 sprague-dawley rat model Methods 0.000 description 1
230000006641 stabilisation Effects 0.000 description 1
238000011105 stabilization Methods 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
229960005322 streptomycin Drugs 0.000 description 1
HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
150000003457 sulfones Chemical class 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
239000000725 suspension Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
239000012588 trypsin Substances 0.000 description 1
238000002604 ultrasonography Methods 0.000 description 1
230000002792 vascular Effects 0.000 description 1
230000006442 vascular tone Effects 0.000 description 1
239000005526 vasoconstrictor agent Substances 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- 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
- A61P13/08—Drugs for disorders of the urinary system of the prostate
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
- 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
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- 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
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
- 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
- A61P9/10—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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C247/00—Compounds containing azido groups
- C07C247/02—Compounds containing azido groups with azido groups bound to acyclic carbon atoms of a carbon skeleton
- C07C247/12—Compounds containing azido groups with azido groups bound to acyclic carbon atoms of a carbon skeleton being further substituted by carboxyl groups
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three 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
- C07D237/14—Oxygen atoms
- C07D237/16—Two oxygen atoms
- 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
- C07D239/28—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/34—One oxygen atom
- 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
- C07D239/28—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
- C07D251/22—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to two ring carbon atoms

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Urology & Nephrology (AREA)
Pulmonology (AREA)
Neurosurgery (AREA)
Diabetes (AREA)
Vascular Medicine (AREA)
Hospice & Palliative Care (AREA)
Pain & Pain Management (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Hematology (AREA)
Oncology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Peptides Or Proteins (AREA)
Plural Heterocyclic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Medicinal Preparation (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Pyridine Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

SK1762-99A 1997-06-19 1998-06-05 New 'beta'-amino and 'beta'-azidocarboxylic acid derivatives, the production thereof and the use thereof as endothelin receptor antagonists SK176299A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE19726146A DE19726146A1 (de)	1997-06-19	1997-06-19	Neue ß-Amino und ß-Azidopcarbonsäurederivate, ihre Herstellung und Verwendung als Endothelinrezeptorantagonisten
PCT/EP1998/003366 WO1998058916A1 (de)	1997-06-19	1998-06-05	NEUE β-AMINO UND β-AZIDOCARBONSÄUREDERIVATE, IHRE HERSTELLUNG UND VERWENDUNG ALS ENDOTHELINREZEPTORANTAGONISTEN

Publications (1)

Publication Number	Publication Date
SK176299A3 true SK176299A3 (en)	2000-06-12

Family

ID=7833081

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1762-99A SK176299A3 (en)	1997-06-19	1998-06-05	New 'beta'-amino and 'beta'-azidocarboxylic acid derivatives, the production thereof and the use thereof as endothelin receptor antagonists

Country Status (22)

Country	Link
EP (1)	EP0994861A1 (de)
JP (1)	JP2002504130A (de)
KR (1)	KR20010013981A (de)
CN (1)	CN1261352A (de)
AR (1)	AR015893A1 (de)
AU (1)	AU8213398A (de)
BG (1)	BG104022A (de)
BR (1)	BR9810182A (de)
CA (1)	CA2294050A1 (de)
CO (1)	CO4950605A1 (de)
DE (1)	DE19726146A1 (de)
HR (1)	HRP980331A2 (de)
HU (1)	HUP0002714A3 (de)
ID (1)	ID24346A (de)
IL (1)	IL133104A0 (de)
NO (1)	NO996268L (de)
NZ (1)	NZ502319A (de)
PL (1)	PL337507A1 (de)
SK (1)	SK176299A3 (de)
TR (1)	TR199903159T2 (de)
WO (1)	WO1998058916A1 (de)
ZA (1)	ZA985277B (de)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE19806438A1 (de) *	1998-02-17	1999-08-19	Basf Ag	Neue Carbonsäurederivate mit 5-substituiertem Pyrimidinring, ihre Herstellung und Verwendung
DE19858779A1 (de) *	1998-12-18	2000-06-21	Basf Ag	Neue ß-Amido und ß-Sulfonamidocarbonsäurederivate, ihre Herstellung und Verwendung als Endothelinrezeptorantagonisten
DE19924892A1 (de) *	1999-06-01	2000-12-07	Basf Ag	Neue Carbonsäurederivate mit arylsubstituierten Stickstoffheterocyclen, ihre Herstellung und Verwendung als Endothelin Rezeptorantagonisten
WO2002064573A1 (de) *	2001-02-14	2002-08-22	Abbott Gmbh & Co. Kg	Neue carbonsäurederivate mit alkylsubstituierten triazinen, ihre herstellung und verwendung als endothelin-rezeptorantagonisten
EP1632821B1 (de)	2004-09-01	2012-05-30	Océ-Technologies B.V.	Zwischenübertragungselement mit einem Reinigungselement
US7790770B2 (en) *	2005-11-23	2010-09-07	Bristol-Myers Squibb Company	Heterocyclic CETP inhibitors
CA2695259C (en)	2007-07-31	2016-05-24	Gilead Colorado, Inc.	Metabolites and derivatives of ambrisentan
CN109422664B (zh) *	2017-08-23	2022-02-18	中国科学院福建物质结构研究所	一类干扰素调节剂及其制备方法和用途

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5136060A (en) *	1989-11-14	1992-08-04	Florida State University	Method for preparation of taxol using an oxazinone
DE4313412A1 (de) *	1993-04-23	1994-10-27	Basf Ag	3-(Het)aryl-Carbonsäurederivate, Verfahren und Zwischenprodukte zu ihrer Herstellung
DE4329911A1 (de) *	1993-09-04	1995-03-09	Basf Ag	Substituierte Milchsäurederivate mit einem N-organischen Rest in beta-Position
DE4411225A1 (de) *	1994-03-31	1995-10-05	Basf Ag	Verwendung von Carbonsäurederivaten als Arzneimittel
DE19614533A1 (de) *	1996-04-12	1997-10-16	Basf Ag	Neue alpha-Hydroxysäurederivate, ihre Herstellung und Verwendung

1997
- 1997-06-19 DE DE19726146A patent/DE19726146A1/de not_active Withdrawn
1998
- 1998-06-05 JP JP50366799A patent/JP2002504130A/ja active Pending
- 1998-06-05 CN CN98806397A patent/CN1261352A/zh active Pending
- 1998-06-05 NZ NZ502319A patent/NZ502319A/en unknown
- 1998-06-05 BR BR9810182-0A patent/BR9810182A/pt not_active IP Right Cessation
- 1998-06-05 SK SK1762-99A patent/SK176299A3/sk unknown
- 1998-06-05 KR KR19997012007A patent/KR20010013981A/ko not_active Withdrawn
- 1998-06-05 HU HU0002714A patent/HUP0002714A3/hu unknown
- 1998-06-05 WO PCT/EP1998/003366 patent/WO1998058916A1/de not_active Ceased
- 1998-06-05 AU AU82133/98A patent/AU8213398A/en not_active Abandoned
- 1998-06-05 IL IL13310498A patent/IL133104A0/xx unknown
- 1998-06-05 ID IDW991614A patent/ID24346A/id unknown
- 1998-06-05 EP EP98932123A patent/EP0994861A1/de not_active Withdrawn
- 1998-06-05 CA CA002294050A patent/CA2294050A1/en not_active Abandoned
- 1998-06-05 TR TR1999/03159T patent/TR199903159T2/xx unknown
- 1998-06-05 PL PL98337507A patent/PL337507A1/xx unknown
- 1998-06-17 HR HR19726146.9A patent/HRP980331A2/hr not_active Application Discontinuation
- 1998-06-17 AR ARP980102873A patent/AR015893A1/es unknown
- 1998-06-18 CO CO98034781A patent/CO4950605A1/es unknown
- 1998-06-18 ZA ZA9805277A patent/ZA985277B/xx unknown
1999
- 1999-12-16 BG BG104022A patent/BG104022A/xx unknown
- 1999-12-17 NO NO996268A patent/NO996268L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
ID24346A (id)	2000-07-13
BR9810182A (pt)	2000-08-08
CA2294050A1 (en)	1998-12-30
IL133104A0 (en)	2001-03-19
JP2002504130A (ja)	2002-02-05
AU8213398A (en)	1999-01-04
CO4950605A1 (es)	2000-09-01
NO996268D0 (no)	1999-12-17
ZA985277B (en)	1999-12-20
AR015893A1 (es)	2001-05-30
CN1261352A (zh)	2000-07-26
NZ502319A (en)	2002-03-01
KR20010013981A (ko)	2001-02-26
EP0994861A1 (de)	2000-04-26
HRP980331A2 (en)	1999-02-28
WO1998058916A1 (de)	1998-12-30
HUP0002714A3 (en)	2001-07-30
PL337507A1 (en)	2000-08-28
DE19726146A1 (de)	1998-12-24
HUP0002714A2 (hu)	2001-05-28
BG104022A (en)	2001-04-30
NO996268L (no)	1999-12-17
TR199903159T2 (xx)	2000-07-21

Publication	Publication Date	Title
CZ113297A3 (cs)	1998-03-18	Derivát karboxylové kyseliny
KR20000068446A (ko)	2000-11-25	아지닐옥시, 및 페녹시-디아릴-카르복실산 유도체, 그의 제조 방법 및 혼합된 ｅｔａ/ｅｔｂ 엔도델린 수용체 길항물질로서의 용도
SK176299A3 (en)	2000-06-12	New 'beta'-amino and 'beta'-azidocarboxylic acid derivatives, the production thereof and the use thereof as endothelin receptor antagonists
HRP980560A2 (en)	1999-08-31	New carboxylic acid derivatives, carrying amido side-chains, their production and use as endothelin receptor antagonists
SK77799A3 (en)	2000-02-14	Heterocyclic carboxylic acid derivatives, the production and use thereof as endothelin receptor antagonists
SK1522000A3 (en)	2000-08-14	Novel carboxylic acid derivatives, their production and their use as mixed eta/etb endothelin-receptor antagonists
TW579376B (en)	2004-03-11	Novel carboxylic acid derivatives having a 5-substituted pyrimidine ring, their preparation and use
SK4932000A3 (en)	2001-02-12	Heterocyclically substituted alpha-hydroxycarboxlic acid derivatives, method for producing the same and their use as endothelin receptor antagonists
AU765345B2 (en)	2003-09-18	Novel carboxylic acid derivatives comprising aryl-substituted nitrogen heterocycles, their production and their use as endothelin receptor antagonists
SK8682001A3 (en)	2002-08-06	New beta-amide and beta-sulfonamide carboxylic acid derivatives, their preparation and their use as endothelin receptor antagonists
SK11752000A3 (sk)	2001-05-10	Nesymetricky substituované deriváty karboxylových kyselín, spôsob ich prípravy a ich použitie ako zmesových antagonistov eta/etb receptora
SK772002A3 (en)	2003-01-09	Novel carboxylic acid derivatives with 5,6 substituted pyrimidine ring, the production and utilization thereof as endothelin receptor antagonists
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