CA2608678A1 - Organic compounds - Google Patents
Organic compounds Download PDFInfo
- Publication number
- CA2608678A1 CA2608678A1 CA002608678A CA2608678A CA2608678A1 CA 2608678 A1 CA2608678 A1 CA 2608678A1 CA 002608678 A CA002608678 A CA 002608678A CA 2608678 A CA2608678 A CA 2608678A CA 2608678 A1 CA2608678 A1 CA 2608678A1
- Authority
- CA
- Canada
- Prior art keywords
- chloro
- alkyl
- phenoxy
- acetic acid
- benzyl
- 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
- 150000002894 organic compounds Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 91
- 150000003839 salts Chemical group 0.000 claims abstract description 31
- 230000002757 inflammatory effect Effects 0.000 claims abstract description 20
- 208000027771 Obstructive airways disease Diseases 0.000 claims abstract description 10
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 10
- 230000001404 mediated effect Effects 0.000 claims abstract 2
- 229910052799 carbon Inorganic materials 0.000 claims description 58
- 238000002360 preparation method Methods 0.000 claims description 49
- -1 carboxy-C1-C8-alkyl Chemical group 0.000 claims description 43
- 125000002837 carbocyclic group Chemical group 0.000 claims description 32
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 27
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 20
- 201000010099 disease Diseases 0.000 claims description 17
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 15
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 14
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 239000001301 oxygen Substances 0.000 claims description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
- 239000005864 Sulphur Chemical group 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 8
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 7
- LQHAONOJEMFNCP-UHFFFAOYSA-N 2-[2-[[2-(carboxymethoxy)-5-methylphenyl]methyl]-4-methylphenoxy]acetic acid Chemical compound CC1=CC=C(OCC(O)=O)C(CC=2C(=CC=C(C)C=2)OCC(O)=O)=C1 LQHAONOJEMFNCP-UHFFFAOYSA-N 0.000 claims description 6
- 206010027654 Allergic conditions Diseases 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- BOIZYIQPIXHURV-UHFFFAOYSA-N 2-[2-[[2-(carboxymethoxy)-5-fluorophenyl]methyl]-4-fluorophenoxy]acetic acid Chemical compound OC(=O)COC1=CC=C(F)C=C1CC1=CC(F)=CC=C1OCC(O)=O BOIZYIQPIXHURV-UHFFFAOYSA-N 0.000 claims description 5
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- KGRVJHAUYBGFFP-UHFFFAOYSA-N 2,2'-Methylenebis(4-methyl-6-tert-butylphenol) Chemical compound CC(C)(C)C1=CC(C)=CC(CC=2C(=C(C=C(C)C=2)C(C)(C)C)O)=C1O KGRVJHAUYBGFFP-UHFFFAOYSA-N 0.000 claims description 4
- 125000004185 ester group Chemical group 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- OGIQZJALYXINPX-UHFFFAOYSA-N 2-[2-[2-(carboxymethoxy)-5-chlorobenzoyl]-4-chlorophenoxy]acetic acid Chemical compound OC(=O)COC1=CC=C(Cl)C=C1C(=O)C1=CC(Cl)=CC=C1OCC(O)=O OGIQZJALYXINPX-UHFFFAOYSA-N 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- BOCZNUWTUHOLLZ-UHFFFAOYSA-N 2-[2-[1-carboxyethoxy-(3-chloro-5-methylphenyl)methyl]-4-chloro-6-methylphenoxy]propanoic acid Chemical compound C=1C(Cl)=CC(C)=C(OC(C)C(O)=O)C=1C(OC(C)C(O)=O)C1=CC(C)=CC(Cl)=C1 BOCZNUWTUHOLLZ-UHFFFAOYSA-N 0.000 claims description 2
- HPFHAUZDNSPEKD-UHFFFAOYSA-N 2-[2-[2-(carboxymethoxy)-5-chlorophenyl]sulfanyl-4-chlorophenoxy]acetic acid Chemical compound OC(=O)COC1=CC=C(Cl)C=C1SC1=CC(Cl)=CC=C1OCC(O)=O HPFHAUZDNSPEKD-UHFFFAOYSA-N 0.000 claims description 2
- CBYKCRPSWLZBMW-UHFFFAOYSA-N 2-[2-[[2-(2-carboxypropan-2-yloxy)-5-chlorophenyl]methyl]-4-chlorophenoxy]-2-methylpropanoic acid Chemical compound OC(=O)C(C)(C)OC1=CC=C(Cl)C=C1CC1=CC(Cl)=CC=C1OC(C)(C)C(O)=O CBYKCRPSWLZBMW-UHFFFAOYSA-N 0.000 claims description 2
- PWVRTSVTEBDMJG-UHFFFAOYSA-N 2-[2-[[2-(carboxymethoxy)-3,5,6-trichlorophenyl]methyl]-3,4,6-trichlorophenoxy]acetic acid Chemical compound OC(=O)COC1=C(Cl)C=C(Cl)C(Cl)=C1CC1=C(Cl)C(Cl)=CC(Cl)=C1OCC(O)=O PWVRTSVTEBDMJG-UHFFFAOYSA-N 0.000 claims description 2
- SJTYWYNVLFFTSD-UHFFFAOYSA-N 2-[2-[[2-(carboxymethoxy)-5-chlorophenyl]methyl]-4-chlorophenoxy]acetic acid Chemical compound OC(=O)COC1=CC=C(Cl)C=C1CC1=CC(Cl)=CC=C1OCC(O)=O SJTYWYNVLFFTSD-UHFFFAOYSA-N 0.000 claims description 2
- FJMQTBUJTXVGPH-UHFFFAOYSA-N 2-[2-[[2-(carboxymethoxy)-5-chlorophenyl]methyl]-4-methylsulfonylphenoxy]acetic acid Chemical compound CS(=O)(=O)C1=CC=C(OCC(O)=O)C(CC=2C(=CC=C(Cl)C=2)OCC(O)=O)=C1 FJMQTBUJTXVGPH-UHFFFAOYSA-N 0.000 claims description 2
- UYGNLQGEKJMMPW-UHFFFAOYSA-N 2-[2-[[2-(carboxymethoxy)-5-chlorophenyl]methyl]-4-nitrophenoxy]acetic acid Chemical compound OC(=O)COC1=CC=C(Cl)C=C1CC1=CC([N+]([O-])=O)=CC=C1OCC(O)=O UYGNLQGEKJMMPW-UHFFFAOYSA-N 0.000 claims description 2
- LFNZZMDJWLNDON-UHFFFAOYSA-N 2-[2-[[2-(carboxymethoxy)phenyl]methyl]-4-chlorophenoxy]acetic acid Chemical compound OC(=O)COC1=CC=CC=C1CC1=CC(Cl)=CC=C1OCC(O)=O LFNZZMDJWLNDON-UHFFFAOYSA-N 0.000 claims description 2
- BKEAWZNCCQSEAT-UHFFFAOYSA-N 2-[4-bromo-2-[[5-bromo-2-(carboxymethoxy)phenyl]methyl]phenoxy]acetic acid Chemical compound OC(=O)COC1=CC=C(Br)C=C1CC1=CC(Br)=CC=C1OCC(O)=O BKEAWZNCCQSEAT-UHFFFAOYSA-N 0.000 claims description 2
- WNHRQTWQPKYCQK-UHFFFAOYSA-N 2-[4-chloro-2-[(4-chloro-2-hydroxyphenyl)methyl]phenoxy]acetic acid Chemical compound OC(=O)COC1=CC=C(Cl)C=C1CC1=CC=C(Cl)C=C1O WNHRQTWQPKYCQK-UHFFFAOYSA-N 0.000 claims description 2
- KORWLPVXXKRQFU-UHFFFAOYSA-N 2-[4-chloro-2-[[5-chloro-2-(2-ethoxy-2-oxoethoxy)phenyl]methyl]phenoxy]acetic acid Chemical compound CCOC(=O)COC1=CC=C(Cl)C=C1CC1=CC(Cl)=CC=C1OCC(O)=O KORWLPVXXKRQFU-UHFFFAOYSA-N 0.000 claims description 2
- GYQTXISSJAMIFO-UHFFFAOYSA-N 2-[4-chloro-2-[[5-chloro-2-(2-methoxy-2-oxoethoxy)phenyl]methyl]phenoxy]acetic acid Chemical compound COC(=O)COC1=CC=C(Cl)C=C1CC1=CC(Cl)=CC=C1OCC(O)=O GYQTXISSJAMIFO-UHFFFAOYSA-N 0.000 claims description 2
- URICLRSVMYKICO-UHFFFAOYSA-N 2-[4-chloro-2-[[5-chloro-2-[2-(2-methylpropoxy)-2-oxoethoxy]phenyl]methyl]phenoxy]acetic acid Chemical compound CC(C)COC(=O)COC1=CC=C(Cl)C=C1CC1=CC(Cl)=CC=C1OCC(O)=O URICLRSVMYKICO-UHFFFAOYSA-N 0.000 claims description 2
- GXVYQCSRLFWPPJ-UHFFFAOYSA-N 2-[4-tert-butyl-2-[[5-tert-butyl-2-(carboxymethoxy)phenyl]methyl]phenoxy]acetic acid Chemical compound CC(C)(C)C1=CC=C(OCC(O)=O)C(CC=2C(=CC=C(C=2)C(C)(C)C)OCC(O)=O)=C1 GXVYQCSRLFWPPJ-UHFFFAOYSA-N 0.000 claims description 2
- IWFJOZWHVNWUOT-UHFFFAOYSA-N 3-[2-[[2-(2-carboxyethoxy)-3,4,6-trichlorophenyl]methyl]-3,5,6-trichlorophenoxy]propanoic acid Chemical compound OC(=O)CCOC1=C(Cl)C(Cl)=CC(Cl)=C1CC1=C(Cl)C=C(Cl)C(Cl)=C1OCCC(O)=O IWFJOZWHVNWUOT-UHFFFAOYSA-N 0.000 claims description 2
- DEXJMKACDOXYPA-UHFFFAOYSA-N 3-[2-[[2-(carboxymethoxy)-5-chlorophenyl]methyl]phenyl]propanoic acid Chemical compound OC(=O)CCC1=CC=CC=C1CC1=CC(Cl)=CC=C1OCC(O)=O DEXJMKACDOXYPA-UHFFFAOYSA-N 0.000 claims description 2
- DLLGIZACHUEAHT-UHFFFAOYSA-N 4-[2-[[2-(carboxymethoxy)-5-chlorophenyl]methyl]-4-chlorophenoxy]butanoic acid Chemical compound OC(=O)CCCOC1=CC=C(Cl)C=C1CC1=CC(Cl)=CC=C1OCC(O)=O DLLGIZACHUEAHT-UHFFFAOYSA-N 0.000 claims description 2
- SMDNCSKZPGUUDI-UHFFFAOYSA-N 4-[4-chloro-2-[(5-chloro-2-hydroxyphenyl)methyl]phenoxy]butanoic acid Chemical compound OC(=O)CCCOC1=CC=C(Cl)C=C1CC1=CC(Cl)=CC=C1O SMDNCSKZPGUUDI-UHFFFAOYSA-N 0.000 claims description 2
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims description 2
- 150000001721 carbon Chemical group 0.000 claims 3
- OZWFWSMTJXJBKD-UHFFFAOYSA-N 2-[2-[[2-(carboxymethoxy)-5-chlorophenyl]methyl]-4-chlorophenoxy]-2-methylpropanoic acid Chemical compound OC(=O)C(C)(C)OC1=CC=C(Cl)C=C1CC1=CC(Cl)=CC=C1OCC(O)=O OZWFWSMTJXJBKD-UHFFFAOYSA-N 0.000 claims 1
- JXDMMCNWSZMSAQ-UHFFFAOYSA-N 2-[4-chloro-2-[[5-chloro-2-(2-oxo-2-propan-2-yloxyethoxy)phenyl]methyl]phenoxy]acetic acid Chemical compound CC(C)OC(=O)COC1=CC=C(Cl)C=C1CC1=CC(Cl)=CC=C1OCC(O)=O JXDMMCNWSZMSAQ-UHFFFAOYSA-N 0.000 claims 1
- ZXYOIXJYHSSPNZ-UHFFFAOYSA-N 2-[4-chloro-2-[[5-chloro-2-[2-(cyclopropylamino)-2-oxoethoxy]phenyl]methyl]phenoxy]acetic acid Chemical compound OC(=O)COC1=CC=C(Cl)C=C1CC1=CC(Cl)=CC=C1OCC(=O)NC1CC1 ZXYOIXJYHSSPNZ-UHFFFAOYSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 62
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 38
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
- 239000011541 reaction mixture Substances 0.000 description 34
- 239000000203 mixture Substances 0.000 description 32
- 235000019439 ethyl acetate Nutrition 0.000 description 31
- 238000006243 chemical reaction Methods 0.000 description 27
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 25
- 239000000243 solution Substances 0.000 description 23
- 208000006673 asthma Diseases 0.000 description 22
- 239000003795 chemical substances by application Substances 0.000 description 20
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 19
- 235000019341 magnesium sulphate Nutrition 0.000 description 19
- 238000003818 flash chromatography Methods 0.000 description 18
- 238000003556 assay Methods 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 239000012267 brine Substances 0.000 description 15
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 239000005557 antagonist Substances 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 125000004432 carbon atom Chemical group C* 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
- 239000012044 organic layer Substances 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 229940002612 prodrug Drugs 0.000 description 9
- 239000000651 prodrug Substances 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- 125000001424 substituent group Chemical group 0.000 description 9
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 125000005843 halogen group Chemical group 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
- 230000003110 anti-inflammatory effect Effects 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 210000003979 eosinophil Anatomy 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 239000000556 agonist Substances 0.000 description 5
- 238000005804 alkylation reaction Methods 0.000 description 5
- 239000012298 atmosphere Substances 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 230000003182 bronchodilatating effect Effects 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 239000011737 fluorine Substances 0.000 description 5
- 229910052731 fluorine Inorganic materials 0.000 description 5
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 5
- BHMBVRSPMRCCGG-OUTUXVNYSA-N prostaglandin D2 Chemical compound CCCCC[C@H](O)\C=C\[C@@H]1[C@@H](C\C=C/CCCC(O)=O)[C@@H](O)CC1=O BHMBVRSPMRCCGG-OUTUXVNYSA-N 0.000 description 5
- BHMBVRSPMRCCGG-UHFFFAOYSA-N prostaglandine D2 Natural products CCCCCC(O)C=CC1C(CC=CCCCC(O)=O)C(O)CC1=O BHMBVRSPMRCCGG-UHFFFAOYSA-N 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 230000009466 transformation Effects 0.000 description 5
- 238000000844 transformation Methods 0.000 description 5
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- 239000007832 Na2SO4 Substances 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 229940124623 antihistamine drug Drugs 0.000 description 4
- 239000000739 antihistaminic agent Substances 0.000 description 4
- 230000001363 autoimmune Effects 0.000 description 4
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 4
- JHVLLYQQQYIWKX-UHFFFAOYSA-N benzyl 2-bromoacetate Chemical compound BrCC(=O)OCC1=CC=CC=C1 JHVLLYQQQYIWKX-UHFFFAOYSA-N 0.000 description 4
- 206010006451 bronchitis Diseases 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 229940088679 drug related substance Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 238000002821 scintillation proximity assay Methods 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 235000017550 sodium carbonate Nutrition 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 3
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 3
- 206010014950 Eosinophilia Diseases 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 3
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- 206010047924 Wheezing Diseases 0.000 description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/67—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids
- C07C69/708—Ethers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/16—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C317/22—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
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- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/27—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups
- C07C205/35—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups having nitro groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C205/36—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups having nitro groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton to carbon atoms of the same non-condensed six-membered aromatic ring or to carbon atoms of six-membered aromatic rings being part of the same condensed ring system
- C07C205/37—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups having nitro groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton to carbon atoms of the same non-condensed six-membered aromatic ring or to carbon atoms of six-membered aromatic rings being part of the same condensed ring system the oxygen atom of at least one of the etherified hydroxy groups being further bound to an acyclic carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C235/18—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having at least one of the singly-bound oxygen atoms further bound to a carbon atom of a six-membered aromatic ring, e.g. phenoxyacetamides
- C07C235/22—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having at least one of the singly-bound oxygen atoms further bound to a carbon atom of a six-membered aromatic ring, e.g. phenoxyacetamides having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/10—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C323/18—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
- C07C323/20—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton with singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
- C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
- C07C59/66—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings
- C07C59/68—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings the oxygen atom of the ether group being bound to a non-condensed six-membered aromatic ring
- C07C59/70—Ethers of hydroxy-acetic acid, e.g. substitutes on the ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/67—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids
- C07C69/708—Ethers
- C07C69/712—Ethers the hydroxy group of the ester being etherified with a hydroxy compound having the hydroxy group bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (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)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0510585.3A GB0510585D0 (en) | 2005-05-24 | 2005-05-24 | Organic compounds |
| GB0510585.3 | 2005-05-24 | ||
| PCT/EP2006/004844 WO2006125593A1 (en) | 2005-05-24 | 2006-05-22 | Organic compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2608678A1 true CA2608678A1 (en) | 2006-11-30 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002608678A Abandoned CA2608678A1 (en) | 2005-05-24 | 2006-05-22 | Organic compounds |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US20080312322A1 (enExample) |
| EP (1) | EP1888505A1 (enExample) |
| JP (1) | JP2008545672A (enExample) |
| KR (1) | KR20080009214A (enExample) |
| CN (1) | CN101180260A (enExample) |
| AU (1) | AU2006251393A1 (enExample) |
| BR (1) | BRPI0610303A2 (enExample) |
| CA (1) | CA2608678A1 (enExample) |
| GB (1) | GB0510585D0 (enExample) |
| MX (1) | MX2007014785A (enExample) |
| RU (1) | RU2007147429A (enExample) |
| WO (1) | WO2006125593A1 (enExample) |
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| DK2327693T3 (da) | 2007-12-14 | 2012-08-13 | Pulmagen Therapeutics Asthma Ltd | Indoler og terapeutisk anvendelse deraf |
| EP2590944B1 (en) | 2010-07-05 | 2015-09-30 | Actelion Pharmaceuticals Ltd. | 1-phenyl-substituted heterocyclyl derivatives and their use as prostaglandin d2 receptor modulators |
| EP2457900A1 (en) | 2010-11-25 | 2012-05-30 | Almirall, S.A. | New pyrazole derivatives having CRTh2 antagonistic behaviour |
| CN104114169A (zh) | 2011-12-16 | 2014-10-22 | 阿托佩斯治疗有限公司 | 用于治疗嗜酸细胞性食管炎的crth2拮抗剂和质子泵抑制剂的组合物 |
| US9255090B2 (en) | 2011-12-21 | 2016-02-09 | Actelion Pharmaceuticals Ltd. | Heterocyclyl derivatives and their use as prostaglandin D2 receptor modulators |
| US9169270B2 (en) | 2012-07-05 | 2015-10-27 | Actelion Pharmaceuticals Ltd. | 1-phenyl-substituted heterocyclyl derivatives and their use as prostaglandin D2 receptor modulators |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2565171A (en) * | 1950-06-26 | 1951-08-21 | Allied Lab Inc | 2,2'-methylenebis (4-chlorophenoxyacetic acid) and a method for its production |
| ZA765075B (en) * | 1975-09-25 | 1977-08-31 | American Cyanamid Co | Hypolipemic compounds and method of treatment |
| FR2428629A1 (fr) * | 1978-06-14 | 1980-01-11 | Hexachimie | Nouveaux composes bis(aryloxycarboxyliques), leur preparation et leur utilisation en therapeutique |
| US5387600A (en) * | 1992-07-30 | 1995-02-07 | Fuji Photo Film Co., Ltd. | Treating arteriosclerosis using benzimidazole compositions |
| US7355074B2 (en) * | 2003-02-05 | 2008-04-08 | The University Of Maryland | Compounds having aromatic rings and side-chain amide-functionality and a method for transporting monovalent anions across biological membranes using the same |
| SE0301010D0 (sv) * | 2003-04-07 | 2003-04-07 | Astrazeneca Ab | Novel compounds |
| SA04250253B1 (ar) * | 2003-08-21 | 2009-11-10 | استرازينيكا ايه بي | احماض فينوكسي اسيتيك مستبدلة باعتبارها مركبات صيدلانية لعلاج الامراض التنفسية مثل الربو ومرض الانسداد الرئوي المزمن |
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2005
- 2005-05-24 GB GBGB0510585.3A patent/GB0510585D0/en not_active Ceased
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2006
- 2006-05-22 AU AU2006251393A patent/AU2006251393A1/en not_active Abandoned
- 2006-05-22 MX MX2007014785A patent/MX2007014785A/es not_active Application Discontinuation
- 2006-05-22 JP JP2008512750A patent/JP2008545672A/ja active Pending
- 2006-05-22 RU RU2007147429/04A patent/RU2007147429A/ru not_active Application Discontinuation
- 2006-05-22 BR BRPI0610303-0A patent/BRPI0610303A2/pt not_active IP Right Cessation
- 2006-05-22 CA CA002608678A patent/CA2608678A1/en not_active Abandoned
- 2006-05-22 CN CNA2006800179674A patent/CN101180260A/zh active Pending
- 2006-05-22 KR KR1020077027360A patent/KR20080009214A/ko not_active Withdrawn
- 2006-05-22 EP EP06753777A patent/EP1888505A1/en not_active Withdrawn
- 2006-05-22 WO PCT/EP2006/004844 patent/WO2006125593A1/en not_active Ceased
- 2006-05-22 US US11/915,091 patent/US20080312322A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP1888505A1 (en) | 2008-02-20 |
| BRPI0610303A2 (pt) | 2010-06-08 |
| US20080312322A1 (en) | 2008-12-18 |
| MX2007014785A (es) | 2008-02-15 |
| CN101180260A (zh) | 2008-05-14 |
| RU2007147429A (ru) | 2009-06-27 |
| WO2006125593A1 (en) | 2006-11-30 |
| JP2008545672A (ja) | 2008-12-18 |
| KR20080009214A (ko) | 2008-01-25 |
| AU2006251393A1 (en) | 2006-11-30 |
| GB0510585D0 (en) | 2005-06-29 |
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| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |