OA11503A - Antipicornaviral compounds, their preparation and use. - Google Patents

Antipicornaviral compounds, their preparation and use. Download PDF

Info

Publication number: OA11503A
Authority: OA; OAPI
Prior art keywords: group; compound; prodrug; solvaté; pharmaceutically active
Prior art date: 1998-04-30

Application number

OA1200000288A

Other languages

English (en)

Inventor

Peter Scott Dragovich

Theodore O Johnson

Joseph Timothy Marakovits

Thomas Jay Prins

Jayashree Girish Tikhe

Stephen Evan Webber

Ru Zhou

Original Assignee

Agouron Pharma

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.)

1998-04-30

Filing date

2000-10-20

Publication date

2004-05-10

2000-10-20 Application filed by Agouron Pharma filed Critical Agouron Pharma

2004-05-10 Publication of OA11503A publication Critical patent/OA11503A/en

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 258
238000002360 preparation method Methods 0.000 title description 3
239000004365 Protease Substances 0.000 claims abstract description 23
108091005804 Peptidases Proteins 0.000 claims abstract description 19
102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims abstract description 18
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
229910052739 hydrogen Inorganic materials 0.000 claims description 111
125000000217 alkyl group Chemical group 0.000 claims description 102
229910052757 nitrogen Inorganic materials 0.000 claims description 101
229910052799 carbon Inorganic materials 0.000 claims description 87
239000000651 prodrug Substances 0.000 claims description 85
229940002612 prodrug Drugs 0.000 claims description 85
125000003118 aryl group Chemical group 0.000 claims description 73
-1 2-methyl-l-propyl Chemical group 0.000 claims description 66
125000000753 cycloalkyl group Chemical group 0.000 claims description 56
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 45
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 40
125000001072 heteroaryl group Chemical group 0.000 claims description 40
125000001424 substituent group Chemical group 0.000 claims description 33
229910052731 fluorine Inorganic materials 0.000 claims description 30
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 30
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
125000006239 protecting group Chemical group 0.000 claims description 29
125000004429 atom Chemical group 0.000 claims description 26
125000002252 acyl group Chemical group 0.000 claims description 23
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 23
230000000694 effects Effects 0.000 claims description 21
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 20
150000002367 halogens Chemical class 0.000 claims description 18
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238000003556 assay Methods 0.000 claims description 14
230000002401 inhibitory effect Effects 0.000 claims description 14
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QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
125000005842 heteroatom Chemical group 0.000 claims description 11
125000000623 heterocyclic group Chemical group 0.000 claims description 11
238000004113 cell culture Methods 0.000 claims description 10
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 9
125000003545 alkoxy group Chemical group 0.000 claims description 8
125000005002 aryl methyl group Chemical group 0.000 claims description 8
239000001257 hydrogen Substances 0.000 claims description 8
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238000004519 manufacturing process Methods 0.000 claims description 7
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125000003441 thioacyl group Chemical group 0.000 claims description 6
125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 claims description 5
150000001408 amides Chemical class 0.000 claims description 5
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
239000003795 chemical substances by application Substances 0.000 claims description 5
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125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 claims 6
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 3
SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 2
238000007821 culture assay Methods 0.000 claims 1
239000000543 intermediate Substances 0.000 abstract description 123
239000000816 peptidomimetic Substances 0.000 abstract description 4
238000010189 synthetic method Methods 0.000 abstract description 4
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XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 192
239000000243 solution Substances 0.000 description 126
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 92
235000019439 ethyl acetate Nutrition 0.000 description 92
239000000203 mixture Substances 0.000 description 77
239000000047 product Substances 0.000 description 59
239000011541 reaction mixture Substances 0.000 description 58
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VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 46
238000000034 method Methods 0.000 description 46
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239000007787 solid Substances 0.000 description 45
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CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 40
238000003818 flash chromatography Methods 0.000 description 40
239000012044 organic layer Substances 0.000 description 39
230000002829 reductive effect Effects 0.000 description 36
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239000002904 solvent Substances 0.000 description 30
239000012267 brine Substances 0.000 description 29
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 29
239000007832 Na2SO4 Substances 0.000 description 27
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 27
239000006260 foam Substances 0.000 description 27
229910052938 sodium sulfate Inorganic materials 0.000 description 27
235000011152 sodium sulphate Nutrition 0.000 description 27
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 26
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
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LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 22
238000010828 elution Methods 0.000 description 22
239000000463 material Substances 0.000 description 21
229910052943 magnesium sulfate Inorganic materials 0.000 description 20
235000019341 magnesium sulphate Nutrition 0.000 description 20
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 19
241000430519 Human rhinovirus sp. Species 0.000 description 19
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 19
150000001412 amines Chemical class 0.000 description 19
150000001413 amino acids Chemical class 0.000 description 19
239000003039 volatile agent Substances 0.000 description 19
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
229940024606 amino acid Drugs 0.000 description 18
235000001014 amino acid Nutrition 0.000 description 18
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
238000003756 stirring Methods 0.000 description 17
239000000725 suspension Substances 0.000 description 17
125000006355 carbonyl methylene group Chemical group [H]C([H])([*:2])C([*:1])=O 0.000 description 16
238000007429 general method Methods 0.000 description 16
239000002253 acid Substances 0.000 description 15
239000012074 organic phase Substances 0.000 description 15
150000001732 carboxylic acid derivatives Chemical class 0.000 description 14
150000003839 salts Chemical class 0.000 description 13
229920006395 saturated elastomer Polymers 0.000 description 13
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
239000003921 oil Substances 0.000 description 12
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150000001252 acrylic acid derivatives Chemical class 0.000 description 11
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 11
238000012360 testing method Methods 0.000 description 11
231100001274 therapeutic index Toxicity 0.000 description 11
108010091324 3C proteases Proteins 0.000 description 10
YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 10
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239000000706 filtrate Substances 0.000 description 10
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 10
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 10
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 9
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241000282414 Homo sapiens Species 0.000 description 8
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BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 6
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
XMVNMWDLOGSUSM-UHFFFAOYSA-N 5-methyl-1,2-oxazole-3-carbonyl chloride Chemical compound CC1=CC(C(Cl)=O)=NO1 XMVNMWDLOGSUSM-UHFFFAOYSA-N 0.000 description 5
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
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230000003612 virological effect Effects 0.000 description 5
VNDWQCSOSCCWIP-UHFFFAOYSA-N 2-tert-butyl-9-fluoro-1,6-dihydrobenzo[h]imidazo[4,5-f]isoquinolin-7-one Chemical compound C1=2C=CNC(=O)C=2C2=CC(F)=CC=C2C2=C1NC(C(C)(C)C)=N2 VNDWQCSOSCCWIP-UHFFFAOYSA-N 0.000 description 4
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241000283891 Kobus Species 0.000 description 4
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239000000126 substance Substances 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
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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
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DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical class CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
XUYJLQHKOGNDPB-UHFFFAOYSA-N phosphonoacetic acid Chemical compound OC(=O)CP(O)(O)=O XUYJLQHKOGNDPB-UHFFFAOYSA-N 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
125000005498 phthalate group Chemical group 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
230000004962 physiological condition Effects 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
239000000843 powder Substances 0.000 description 1
150000003138 primary alcohols Chemical class 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
230000008569 process Effects 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
UORVCLMRJXCDCP-UHFFFAOYSA-N propynoic acid Chemical class OC(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-N 0.000 description 1
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
235000018102 proteins Nutrition 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
230000002797 proteolythic effect Effects 0.000 description 1
230000006337 proteolytic cleavage Effects 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
229940107700 pyruvic acid Drugs 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
230000007017 scission Effects 0.000 description 1
CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical class OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 1
DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
238000004513 sizing Methods 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
239000012418 sodium perborate tetrahydrate Substances 0.000 description 1
239000001476 sodium potassium tartrate Substances 0.000 description 1
235000011006 sodium potassium tartrate Nutrition 0.000 description 1
HJHVQCXHVMGZNC-JCJNLNMISA-M sodium;(2z)-2-[(3r,4s,5s,8s,9s,10s,11r,13r,14s,16s)-16-acetyloxy-3,11-dihydroxy-4,8,10,14-tetramethyl-2,3,4,5,6,7,9,11,12,13,15,16-dodecahydro-1h-cyclopenta[a]phenanthren-17-ylidene]-6-methylhept-5-enoate Chemical compound [Na+].O[C@@H]([C@@H]12)C[C@H]3\C(=C(/CCC=C(C)C)C([O-])=O)[C@@H](OC(C)=O)C[C@]3(C)[C@@]2(C)CC[C@@H]2[C@]1(C)CC[C@@H](O)[C@H]2C HJHVQCXHVMGZNC-JCJNLNMISA-M 0.000 description 1
IBDSNZLUHYKHQP-UHFFFAOYSA-N sodium;3-oxidodioxaborirane;tetrahydrate Chemical compound O.O.O.O.[Na+].[O-]B1OO1 IBDSNZLUHYKHQP-UHFFFAOYSA-N 0.000 description 1
238000003797 solvolysis reaction Methods 0.000 description 1
230000003595 spectral effect Effects 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
239000011550 stock solution Substances 0.000 description 1
TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical class OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 description 1
150000003890 succinate salts Chemical class 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
150000003871 sulfonates Chemical class 0.000 description 1
UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide-pyridine complex Substances O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 description 1
239000000829 suppository Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
DGQOCLATAPFASR-UHFFFAOYSA-N tetrahydroxy-1,4-benzoquinone Chemical compound OC1=C(O)C(=O)C(O)=C(O)C1=O DGQOCLATAPFASR-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
229910052719 titanium Inorganic materials 0.000 description 1
238000012546 transfer Methods 0.000 description 1
FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
GDJZZWYLFXAGFH-UHFFFAOYSA-M xylenesulfonate group Chemical group C1(C(C=CC=C1)C)(C)S(=O)(=O)[O-] GDJZZWYLFXAGFH-UHFFFAOYSA-M 0.000 description 1
229910052727 yttrium Inorganic materials 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1
150000003953 γ-lactams Chemical class 0.000 description 1
150000003954 δ-lactams Chemical class 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D261/18—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0205—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)3-C(=0)-, e.g. statine or derivatives thereof
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Virology (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Genetics & Genomics (AREA)
Biophysics (AREA)
Biochemistry (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Veterinary Medicine (AREA)
Crystallography & Structural Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Pharmacology & Pharmacy (AREA)
Pulmonology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Pyridine Compounds (AREA)
Enzymes And Modification Thereof (AREA)
Hydrogenated Pyridines (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Plural Heterocyclic Compounds (AREA)
Pyrrole Compounds (AREA)
Medicines Containing Plant Substances (AREA)

OA1200000288A 1998-04-30 2000-10-20 Antipicornaviral compounds, their preparation and use. OA11503A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US8382898P	1998-04-30	1998-04-30
US9835898P	1998-08-28	1998-08-28

Publications (1)

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OA11503A true OA11503A (en)	2004-05-10

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ID=26769788

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OA1200000288A OA11503A (en)	1998-04-30	2000-10-20	Antipicornaviral compounds, their preparation and use.

Country Status (33)

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US (3)	US6531452B1 (is)
EP (1)	EP1073672B1 (is)
JP (1)	JP2003526600A (is)
KR (1)	KR20010043004A (is)
CN (1)	CN1198838C (is)
AP (1)	AP2000001934A0 (is)
AT (2)	ATE308557T1 (is)
AU (1)	AU768539B2 (is)
BG (1)	BG104899A (is)
BR (1)	BR9910573A (is)
CA (1)	CA2326763A1 (is)
DE (2)	DE69910762T2 (is)
DK (1)	DK1073672T3 (is)
EA (1)	EA003856B1 (is)
EE (1)	EE200000621A (is)
ES (1)	ES2205760T3 (is)
GE (1)	GEP20022824B (is)
HR (1)	HRP20000623A2 (is)
HU (1)	HUP0400624A2 (is)
IL (1)	IL138609A0 (is)
IS (1)	IS5633A (is)
LT (1)	LT4846B (is)
LV (1)	LV12666B (is)
NO (1)	NO20005411L (is)
NZ (1)	NZ507633A (is)
OA (1)	OA11503A (is)
PL (1)	PL351250A1 (is)
PT (1)	PT1073672E (is)
SI (1)	SI20428A (is)
SK (1)	SK284714B6 (is)
TR (1)	TR200003159T2 (is)
WO (1)	WO1999057135A1 (is)
YU (1)	YU66000A (is)

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DK1073672T3 (da)	1998-04-30	2003-12-08	Agouron Pharma	Antipicornavirale forbindelser, deres fremstilling og anvendelse
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AU779321B2 (en)	1999-08-04	2005-01-20	Agouron Pharmaceuticals, Inc.	Antipicornaviral compounds and compositions, their pharmaceutical uses, and materials for their synthesis
PE20010517A1 (es)	1999-08-24	2001-05-16	Agouron Pharma	Las rutas sinteticas eficientes para la preparacion de los inhibidores de la proteasa del rinovirus y los intermedios claves
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PE20020157A1 (es)	1999-12-03	2002-02-22	Agouron Pharma	Compuestos derivados de piridona como inhibidores de proteasas de picornaviral 3c, composiciones, sus usos farmaceuticos y materiales para su sintesis

1999
- 1999-01-05 DK DK99900780T patent/DK1073672T3/da active
- 1999-01-05 LT LT2000109A patent/LT4846B/lt not_active IP Right Cessation
- 1999-01-05 DE DE69910762T patent/DE69910762T2/de not_active Expired - Fee Related
- 1999-01-05 AP APAP/P/2000/001934A patent/AP2000001934A0/en unknown
- 1999-01-05 NZ NZ507633A patent/NZ507633A/en unknown
- 1999-01-05 PT PT99900780T patent/PT1073672E/pt unknown
- 1999-01-05 YU YU66000A patent/YU66000A/sh unknown
- 1999-01-05 IL IL13860999A patent/IL138609A0/xx unknown
- 1999-01-05 EA EA200001133A patent/EA003856B1/ru not_active IP Right Cessation
- 1999-01-05 WO PCT/US1999/000260 patent/WO1999057135A1/en not_active Ceased
- 1999-01-05 AU AU20287/99A patent/AU768539B2/en not_active Ceased
- 1999-01-05 SI SI9920041A patent/SI20428A/sl not_active IP Right Cessation
- 1999-01-05 DE DE69928140T patent/DE69928140D1/de not_active Expired - Lifetime
- 1999-01-05 CA CA002326763A patent/CA2326763A1/en not_active Abandoned
- 1999-01-05 KR KR1020007011851A patent/KR20010043004A/ko not_active Ceased
- 1999-01-05 GE GEAP19995606A patent/GEP20022824B/en unknown
- 1999-01-05 HR HR20000623A patent/HRP20000623A2/hr not_active Application Discontinuation
- 1999-01-05 ES ES99900780T patent/ES2205760T3/es not_active Expired - Lifetime
- 1999-01-05 AT AT03009409T patent/ATE308557T1/de not_active IP Right Cessation
- 1999-01-05 AT AT99900780T patent/ATE248186T1/de not_active IP Right Cessation
- 1999-01-05 EE EEP200000621A patent/EE200000621A/xx unknown
- 1999-01-05 PL PL99351250A patent/PL351250A1/xx not_active Application Discontinuation
- 1999-01-05 CN CNB998056278A patent/CN1198838C/zh not_active Expired - Fee Related
- 1999-01-05 TR TR2000/03159T patent/TR200003159T2/xx unknown
- 1999-01-05 SK SK1604-2000A patent/SK284714B6/sk unknown
- 1999-01-05 EP EP99900780A patent/EP1073672B1/en not_active Expired - Lifetime
- 1999-01-05 JP JP2000547104A patent/JP2003526600A/ja not_active Withdrawn
- 1999-01-05 HU HU0400624A patent/HUP0400624A2/hu unknown
- 1999-01-05 BR BR9910573-0A patent/BR9910573A/pt not_active IP Right Cessation
- 1999-04-29 US US09/301,977 patent/US6531452B1/en not_active Expired - Fee Related
2000
- 2000-09-22 IS IS5633A patent/IS5633A/is unknown
- 2000-10-20 OA OA1200000288A patent/OA11503A/en unknown
- 2000-10-27 NO NO20005411A patent/NO20005411L/no not_active Application Discontinuation
- 2000-11-01 BG BG104899A patent/BG104899A/xx unknown
- 2000-12-19 LV LV000162A patent/LV12666B/xx unknown
2002
- 2002-11-06 US US10/289,982 patent/US6995142B2/en not_active Expired - Fee Related
2005
- 2005-08-24 US US11/210,717 patent/US20060046966A1/en not_active Abandoned

Also Published As

Publication number	Publication date
NZ507633A (en)	2003-10-31
EP1073672B1 (en)	2003-08-27
EP1073672A1 (en)	2001-02-07
TR200003159T2 (tr)	2001-09-21
LV12666B (lv)	2001-11-20
LV12666A (en)	2001-05-20
DE69910762D1 (de)	2003-10-02
ES2205760T3 (es)	2004-05-01
GEP20022824B (en)	2002-10-25
DK1073672T3 (da)	2003-12-08
JP2003526600A (ja)	2003-09-09
HK1034722A1 (en)	2001-11-02
ATE308557T1 (de)	2005-11-15
US6531452B1 (en)	2003-03-11
US20060046966A1 (en)	2006-03-02
CA2326763A1 (en)	1999-11-11
NO20005411D0 (no)	2000-10-27
US20030130204A1 (en)	2003-07-10
DE69910762T2 (de)	2004-03-11
CN1311793A (zh)	2001-09-05
DE69928140D1 (de)	2005-12-08
US6995142B2 (en)	2006-02-07
PL351250A1 (en)	2003-04-07
ATE248186T1 (de)	2003-09-15
HRP20000623A2 (en)	2001-04-30
AP2000001934A0 (en)	2000-12-31
EA200001133A1 (ru)	2001-08-27
PT1073672E (pt)	2004-01-30
WO1999057135A1 (en)	1999-11-11
YU66000A (sh)	2003-12-31
EE200000621A (et)	2002-06-17
AU768539B2 (en)	2003-12-18
BR9910573A (pt)	2001-01-16
BG104899A (en)	2001-08-31
NO20005411L (no)	2000-10-27
SI20428A (sl)	2001-06-30
SK16042000A3 (sk)	2001-05-10
HUP0400624A2 (hu)	2004-06-28
LT2000109A (en)	2001-05-25
IS5633A (is)	2000-09-22
CN1198838C (zh)	2005-04-27
KR20010043004A (ko)	2001-05-25
AU2028799A (en)	1999-11-23
LT4846B (lt)	2001-10-25
EA003856B1 (ru)	2003-10-30
IL138609A0 (en)	2001-10-31
SK284714B6 (sk)	2005-09-08

Publication	Publication Date	Title
OA11503A (en)	2004-05-10	Antipicornaviral compounds, their preparation and use.
AU779321B2 (en)	2005-01-20	Antipicornaviral compounds and compositions, their pharmaceutical uses, and materials for their synthesis
NZ505034A (en)	2003-07-25	Substituted propanoic acid derivatives useful as antipicornaviral compounds
US6514997B2 (en)	2003-02-04	Antipicornaviral compounds and compositions, their pharmaceutical uses, and materials for their synthesis
AU736550B2 (en)	2001-08-02	Antipicornaviral compounds, compositions containing them, and methods for their use
US6906198B1 (en)	2005-06-14	Antipicornaviral compounds, their preparation and use
EP1329457B1 (en)	2005-11-02	Antipicornaviral compounds, their preparation and use
CZ20003986A3 (cs)	2001-06-13	Antipicornavirální součeniny a kompozice, jejich farmaceutické použití a materiály pro jejich syntézu
HK1034722B (en)	2003-11-28	Antipicornaviral compounds, their preparation and use
MXPA00010406A (en)	2001-07-31	Antipicornaviral compounds, their preparation and use