AU2004285972A1 - Preparation of 4,5-dialkyl-3-acyl-pyrrole-2-carboxylic acid derivatives by Fischer-Fink type synthesis and subsequent acylation - Google Patents
Preparation of 4,5-dialkyl-3-acyl-pyrrole-2-carboxylic acid derivatives by Fischer-Fink type synthesis and subsequent acylation Download PDFInfo
- Publication number
- AU2004285972A1 AU2004285972A1 AU2004285972A AU2004285972A AU2004285972A1 AU 2004285972 A1 AU2004285972 A1 AU 2004285972A1 AU 2004285972 A AU2004285972 A AU 2004285972A AU 2004285972 A AU2004285972 A AU 2004285972A AU 2004285972 A1 AU2004285972 A1 AU 2004285972A1
- Authority
- AU
- Australia
- Prior art keywords
- compound
- formula
- process according
- alkyl
- aliphatic
- Prior art date
- Legal status (The legal status 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 status listed.)
- Abandoned
Links
- 230000010933 acylation Effects 0.000 title claims description 8
- 238000005917 acylation reaction Methods 0.000 title claims description 8
- 238000003786 synthesis reaction Methods 0.000 title abstract description 10
- 230000015572 biosynthetic process Effects 0.000 title abstract description 8
- 238000002360 preparation method Methods 0.000 title description 9
- 150000001875 compounds Chemical class 0.000 claims description 84
- 238000000034 method Methods 0.000 claims description 57
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 39
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 37
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 34
- 239000000243 solution Substances 0.000 claims description 27
- 238000006243 chemical reaction Methods 0.000 claims description 25
- 239000000203 mixture Substances 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 239000002904 solvent Substances 0.000 claims description 22
- 125000001931 aliphatic group Chemical group 0.000 claims description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 17
- 239000011701 zinc Substances 0.000 claims description 17
- 229910052725 zinc Inorganic materials 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 239000011541 reaction mixture Substances 0.000 claims description 14
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 238000010992 reflux Methods 0.000 claims description 9
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 8
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 7
- 238000010438 heat treatment Methods 0.000 claims description 7
- 125000001072 heteroaryl group Chemical group 0.000 claims description 7
- 230000007062 hydrolysis Effects 0.000 claims description 7
- 238000006460 hydrolysis reaction Methods 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 239000011734 sodium Substances 0.000 claims description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 229910052700 potassium Inorganic materials 0.000 claims description 4
- 239000011591 potassium Substances 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- 101100323029 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) alc-1 gene Proteins 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
- 230000001476 alcoholic effect Effects 0.000 claims description 2
- 229910052792 caesium Inorganic materials 0.000 claims description 2
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 claims description 2
- 239000011575 calcium Substances 0.000 claims description 2
- 229910052791 calcium Inorganic materials 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- 229910052744 lithium Inorganic materials 0.000 claims description 2
- 239000011777 magnesium Substances 0.000 claims description 2
- 229910052749 magnesium Inorganic materials 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 229940125898 compound 5 Drugs 0.000 claims 1
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 abstract description 9
- 239000002243 precursor Substances 0.000 abstract description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 229960000583 acetic acid Drugs 0.000 description 12
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 12
- 239000000463 material Substances 0.000 description 12
- 239000010410 layer Substances 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 11
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- 230000014759 maintenance of location Effects 0.000 description 10
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 8
- 101100347605 Arabidopsis thaliana VIII-A gene Proteins 0.000 description 7
- 108010050904 Interferons Proteins 0.000 description 6
- 102000014150 Interferons Human genes 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 6
- 235000011167 hydrochloric acid Nutrition 0.000 description 6
- 229940079322 interferon Drugs 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 229940093858 ethyl acetoacetate Drugs 0.000 description 5
- 239000012065 filter cake Substances 0.000 description 5
- 235000010288 sodium nitrite Nutrition 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 229910004373 HOAc Inorganic materials 0.000 description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 125000001151 peptidyl group Chemical group 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000000967 suction filtration Methods 0.000 description 3
- -1 tert-Butyl methyl Chemical group 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 2
- 241000711549 Hepacivirus C Species 0.000 description 2
- 208000005176 Hepatitis C Diseases 0.000 description 2
- 206010019799 Hepatitis viral Diseases 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000029812 viral genome replication Effects 0.000 description 2
- 201000001862 viral hepatitis Diseases 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- 108010017640 Aspartic Acid Proteases Proteins 0.000 description 1
- 102000004580 Aspartic Acid Proteases Human genes 0.000 description 1
- FIPWRIJSWJWJAI-UHFFFAOYSA-N Butyl carbitol 6-propylpiperonyl ether Chemical compound C1=C(CCC)C(COCCOCCOCCCC)=CC2=C1OCO2 FIPWRIJSWJWJAI-UHFFFAOYSA-N 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 238000012369 In process control Methods 0.000 description 1
- 101800001020 Non-structural protein 4A Proteins 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 208000020403 chronic hepatitis C virus infection Diseases 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 235000019439 ethyl acetate Nutrition 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 208000010710 hepatitis C virus infection Diseases 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- 239000004030 hiv protease inhibitor Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000010965 in-process control Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 238000010943 off-gassing Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 229940002988 pegasys Drugs 0.000 description 1
- 108010092853 peginterferon alfa-2a Proteins 0.000 description 1
- 108010092851 peginterferon alfa-2b Proteins 0.000 description 1
- 229940106366 pegintron Drugs 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000020978 protein processing Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- WRHZVMBBRYBTKZ-UHFFFAOYSA-N pyrrole-2-carboxylic acid Chemical compound OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 229960000329 ribavirin Drugs 0.000 description 1
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000005464 sample preparation method Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 150000003385 sodium Chemical class 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000017613 viral reproduction Effects 0.000 description 1
Classifications
-
- 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
- C07D207/30—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 two double bonds between ring members or between ring members and non-ring members
- C07D207/34—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 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
- C07D207/36—Oxygen or sulfur atoms
- C07D207/40—2,5-Pyrrolidine-diones
- C07D207/416—2,5-Pyrrolidine-diones 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 other ring carbon atoms
-
- 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
-
- 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
-
- 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
- C07D207/30—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 two double bonds between ring members or between ring members and non-ring members
- C07D207/34—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 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Pulmonology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2011265547A AU2011265547A1 (en) | 2003-10-28 | 2011-12-23 | Preparation of 4,5-Dialkyl-3-Acyl-Pyrrole-2-Carboxylic Acid Derivatives by Fischer-Fink Type Synthesis and Subsequent Acylation |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US51528303P | 2003-10-28 | 2003-10-28 | |
| US60/515,283 | 2003-10-28 | ||
| PCT/US2004/037985 WO2005042484A1 (en) | 2003-10-28 | 2004-10-28 | Preparation of 4,5-dialkyl-3-acyl-pyrrole-2-carboxylic acid derivatives by fischer-fink type synthesis and subsequent acylation |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2011265547A Division AU2011265547A1 (en) | 2003-10-28 | 2011-12-23 | Preparation of 4,5-Dialkyl-3-Acyl-Pyrrole-2-Carboxylic Acid Derivatives by Fischer-Fink Type Synthesis and Subsequent Acylation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2004285972A1 true AU2004285972A1 (en) | 2005-05-12 |
Family
ID=34549387
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2004285972A Abandoned AU2004285972A1 (en) | 2003-10-28 | 2004-10-28 | Preparation of 4,5-dialkyl-3-acyl-pyrrole-2-carboxylic acid derivatives by Fischer-Fink type synthesis and subsequent acylation |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US7250520B2 (enExample) |
| EP (1) | EP1678134B1 (enExample) |
| JP (2) | JP4942485B2 (enExample) |
| KR (1) | KR20060122872A (enExample) |
| CN (1) | CN1894211A (enExample) |
| AT (1) | ATE442355T1 (enExample) |
| AU (1) | AU2004285972A1 (enExample) |
| DE (1) | DE602004023105D1 (enExample) |
| ES (1) | ES2330944T3 (enExample) |
| IL (1) | IL175253A0 (enExample) |
| WO (1) | WO2005042484A1 (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| UA79749C2 (en) | 1996-10-18 | 2007-07-25 | Vertex Pharma | Inhibitors of serine proteases, particularly hepatitis c virus ns3 protease |
| SV2003000617A (es) | 2000-08-31 | 2003-01-13 | Lilly Co Eli | Inhibidores de la proteasa peptidomimetica ref. x-14912m |
| TWI359147B (en) | 2003-09-05 | 2012-03-01 | Vertex Pharma | Inhibitors of serine proteases, particularly hcv n |
| US8399615B2 (en) | 2005-08-19 | 2013-03-19 | Vertex Pharmaceuticals Incorporated | Processes and intermediates |
| AR055395A1 (es) | 2005-08-26 | 2007-08-22 | Vertex Pharma | Compuestos inhibidores de la actividad de la serina proteasa ns3-ns4a del virus de la hepatitis c |
| US7964624B1 (en) | 2005-08-26 | 2011-06-21 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine proteases |
| AU2007217355B2 (en) | 2006-02-27 | 2012-06-21 | Vertex Pharmaceuticals Incorporated | Co-crystals comprising VX-950 and pharmaceutical compositions comprising the same |
| EP2194039A1 (en) | 2006-03-16 | 2010-06-09 | Vertex Pharmceuticals Incorporated | Process for preparing optically enriched compounds |
| CA2679312A1 (en) | 2007-02-27 | 2008-09-04 | Vertex Pharmaceuticals Incorporated | Co-crystals and pharmaceutical compositions comprising the same |
| CN101903392A (zh) | 2007-02-27 | 2010-12-01 | 弗特克斯药品有限公司 | 丝氨酸蛋白酶的抑制剂 |
| WO2009032198A1 (en) | 2007-08-30 | 2009-03-12 | Vertex Pharmaceuticals Incorporated | Co-crystals and pharmaceutical compositions comprising the same |
| EP2489346A1 (en) | 2011-01-26 | 2012-08-22 | NanotecMARIN GmbH | Food supplement and injectable material for prophylaxis and therapy of osteoporosis and other bone diseases |
| JP2015053226A (ja) | 2013-09-09 | 2015-03-19 | タイコエレクトロニクスジャパン合同会社 | 電気コネクタの端子、及び電気コネクタ |
| US10207974B1 (en) | 2017-12-05 | 2019-02-19 | Chevron Phillips Chemical Company Lp | Synthesis of gamma dicarbonyl and pyrrole compounds |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2481369C (en) | 2002-04-11 | 2012-07-10 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine proteases, particularly hepatitis c virus ns3 - ns4 protease |
| TW200510391A (en) * | 2003-04-11 | 2005-03-16 | Vertex Pharma | Inhibitors of serine proteases, particularly HCV NS3-NS4A protease |
-
2004
- 2004-10-28 AT AT04796917T patent/ATE442355T1/de not_active IP Right Cessation
- 2004-10-28 AU AU2004285972A patent/AU2004285972A1/en not_active Abandoned
- 2004-10-28 JP JP2006538556A patent/JP4942485B2/ja not_active Expired - Fee Related
- 2004-10-28 EP EP04796917A patent/EP1678134B1/en not_active Expired - Lifetime
- 2004-10-28 KR KR1020067010241A patent/KR20060122872A/ko not_active Abandoned
- 2004-10-28 DE DE602004023105T patent/DE602004023105D1/de not_active Expired - Lifetime
- 2004-10-28 ES ES04796917T patent/ES2330944T3/es not_active Expired - Lifetime
- 2004-10-28 CN CNA2004800377619A patent/CN1894211A/zh active Pending
- 2004-10-28 WO PCT/US2004/037985 patent/WO2005042484A1/en not_active Ceased
- 2004-10-28 US US10/978,301 patent/US7250520B2/en not_active Expired - Fee Related
-
2006
- 2006-04-27 IL IL175253A patent/IL175253A0/en unknown
-
2007
- 2007-06-13 US US11/762,274 patent/US20080167480A1/en not_active Abandoned
-
2011
- 2011-06-14 JP JP2011131818A patent/JP2011231117A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP4942485B2 (ja) | 2012-05-30 |
| US7250520B2 (en) | 2007-07-31 |
| DE602004023105D1 (de) | 2009-10-22 |
| ES2330944T3 (es) | 2009-12-17 |
| JP2007509991A (ja) | 2007-04-19 |
| CN1894211A (zh) | 2007-01-10 |
| HK1092134A1 (en) | 2007-02-02 |
| WO2005042484A1 (en) | 2005-05-12 |
| US20050143585A1 (en) | 2005-06-30 |
| IL175253A0 (en) | 2006-09-05 |
| EP1678134A1 (en) | 2006-07-12 |
| EP1678134B1 (en) | 2009-09-09 |
| US20080167480A1 (en) | 2008-07-10 |
| JP2011231117A (ja) | 2011-11-17 |
| ATE442355T1 (de) | 2009-09-15 |
| KR20060122872A (ko) | 2006-11-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK5 | Application lapsed section 142(2)(e) - patent request and compl. specification not accepted |