CN1312806A - 质子泵抑制剂的前药 - Google Patents
质子泵抑制剂的前药 Download PDFInfo
- Publication number
- CN1312806A CN1312806A CN99809512A CN99809512A CN1312806A CN 1312806 A CN1312806 A CN 1312806A CN 99809512 A CN99809512 A CN 99809512A CN 99809512 A CN99809512 A CN 99809512A CN 1312806 A CN1312806 A CN 1312806A
- Authority
- CN
- China
- Prior art keywords
- pyridyl
- benzoglyoxaline
- methyl
- methoxyl group
- group
- 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.)
- Granted
Links
- 229940126409 proton pump inhibitor Drugs 0.000 title claims abstract description 40
- 239000000612 proton pump inhibitor Substances 0.000 title claims abstract description 40
- 229940002612 prodrug Drugs 0.000 title claims abstract description 30
- 239000000651 prodrug Substances 0.000 title claims abstract description 30
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims abstract description 289
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 314
- -1 Guanidine radicals Chemical class 0.000 claims description 205
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 139
- 229910052799 carbon Inorganic materials 0.000 claims description 133
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 124
- 150000001875 compounds Chemical class 0.000 claims description 116
- 125000003545 alkoxy group Chemical group 0.000 claims description 90
- 125000000217 alkyl group Chemical group 0.000 claims description 89
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 69
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 64
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 54
- 239000000460 chlorine Substances 0.000 claims description 52
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 49
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 47
- 150000001721 carbon Chemical group 0.000 claims description 44
- 229910052801 chlorine Inorganic materials 0.000 claims description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims description 40
- 239000001257 hydrogen Substances 0.000 claims description 38
- 239000000203 mixture Substances 0.000 claims description 30
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical group C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 24
- 229910052760 oxygen Inorganic materials 0.000 claims description 24
- 239000002253 acid Substances 0.000 claims description 23
- 239000004202 carbamide Substances 0.000 claims description 22
- 125000001072 heteroaryl group Chemical group 0.000 claims description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- 150000004303 annulenes Chemical class 0.000 claims description 17
- 125000005842 heteroatom Chemical group 0.000 claims description 16
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 14
- 125000003368 amide group Chemical group 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- 229910052731 fluorine Inorganic materials 0.000 claims description 12
- 125000002757 morpholinyl group Chemical group 0.000 claims description 12
- 125000001624 naphthyl group Chemical group 0.000 claims description 12
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 10
- ZRALSGWEFCBTJO-UHFFFAOYSA-N anhydrous guanidine Natural products NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 10
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Substances ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 10
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 10
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims description 10
- RDOXTESZEPMUJZ-UHFFFAOYSA-N methyl phenyl ether Natural products COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims description 10
- GQHWSLKNULCZGI-UHFFFAOYSA-N trifluoromethoxybenzene Chemical compound FC(F)(F)OC1=CC=CC=C1 GQHWSLKNULCZGI-UHFFFAOYSA-N 0.000 claims description 10
- 125000003282 alkyl amino group Chemical group 0.000 claims description 9
- 229910052794 bromium Inorganic materials 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- UBOOKRVGOBKDMM-UHFFFAOYSA-N 3h-imidazo[4,5-c]pyridine Chemical compound C1=NC=C2NC=NC2=C1 UBOOKRVGOBKDMM-UHFFFAOYSA-N 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 8
- 125000005936 piperidyl group Chemical group 0.000 claims description 8
- 239000011734 sodium Substances 0.000 claims description 8
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- HCXJFMDOHDNDCC-UHFFFAOYSA-N 5-$l^{1}-oxidanyl-3,4-dihydropyrrol-2-one Chemical group O=C1CCC(=O)[N]1 HCXJFMDOHDNDCC-UHFFFAOYSA-N 0.000 claims description 4
- 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
- 241000124008 Mammalia Species 0.000 claims description 4
- 229960001413 acetanilide Drugs 0.000 claims description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 claims description 4
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 4
- 125000001326 naphthylalkyl group Chemical group 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 229940124531 pharmaceutical excipient Drugs 0.000 claims description 4
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- 125000005118 N-alkylcarbamoyl group Chemical group 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 150000003983 crown ethers Chemical group 0.000 claims description 3
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 150000002460 imidazoles Chemical class 0.000 claims description 3
- 150000003014 phosphoric acid esters Chemical class 0.000 claims description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 2
- 125000001118 alkylidene group Chemical group 0.000 claims description 2
- 230000008859 change Effects 0.000 claims description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
- 125000002971 oxazolyl group Chemical group 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000004646 sulfenyl group Chemical group S(*)* 0.000 claims description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims 1
- 239000011593 sulfur Substances 0.000 claims 1
- 125000001544 thienyl group Chemical group 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 50
- 229940079593 drug Drugs 0.000 abstract description 15
- 238000011282 treatment Methods 0.000 abstract description 15
- 201000010099 disease Diseases 0.000 abstract description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 11
- 230000027119 gastric acid secretion Effects 0.000 abstract description 8
- 125000004391 aryl sulfonyl group Chemical group 0.000 abstract description 6
- 230000004962 physiological condition Effects 0.000 abstract description 5
- HBDKFZNDMVLSHM-UHFFFAOYSA-N 2-(pyridin-2-ylmethylsulfinyl)-1h-benzimidazole Chemical compound N=1C2=CC=CC=C2NC=1S(=O)CC1=CC=CC=N1 HBDKFZNDMVLSHM-UHFFFAOYSA-N 0.000 abstract description 2
- 230000036470 plasma concentration Effects 0.000 abstract description 2
- JJZPWCVHSLZLQC-UHFFFAOYSA-N [N].C1=CC=C2NC=NC2=C1 Chemical group [N].C1=CC=C2NC=NC2=C1 JJZPWCVHSLZLQC-UHFFFAOYSA-N 0.000 abstract 2
- 230000002459 sustained effect Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 260
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 132
- 239000011541 reaction mixture Substances 0.000 description 76
- 238000002360 preparation method Methods 0.000 description 71
- 239000000047 product Substances 0.000 description 69
- 239000000243 solution Substances 0.000 description 51
- 238000005481 NMR spectroscopy Methods 0.000 description 47
- 238000001035 drying Methods 0.000 description 47
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 42
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 38
- 239000012044 organic layer Substances 0.000 description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
- 239000010410 layer Substances 0.000 description 33
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 32
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 28
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 26
- SBQLYHNEIUGQKH-UHFFFAOYSA-N omeprazole Chemical compound N1=C2[CH]C(OC)=CC=C2N=C1S(=O)CC1=NC=C(C)C(OC)=C1C SBQLYHNEIUGQKH-UHFFFAOYSA-N 0.000 description 25
- 229960000381 omeprazole Drugs 0.000 description 25
- 239000007787 solid Substances 0.000 description 25
- 238000005406 washing Methods 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 239000002585 base Substances 0.000 description 20
- 238000001704 evaporation Methods 0.000 description 20
- 230000008020 evaporation Effects 0.000 description 20
- 210000002784 stomach Anatomy 0.000 description 20
- 238000000354 decomposition reaction Methods 0.000 description 19
- 230000002829 reductive effect Effects 0.000 description 19
- 235000017557 sodium bicarbonate Nutrition 0.000 description 19
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 19
- 230000000694 effects Effects 0.000 description 18
- 238000000034 method Methods 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- XTHPWXDJESJLNJ-UHFFFAOYSA-N sulfurochloridic acid Chemical compound OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 17
- 230000007062 hydrolysis Effects 0.000 description 16
- 238000006460 hydrolysis reaction Methods 0.000 description 16
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- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
- 210000002381 plasma Anatomy 0.000 description 12
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- 230000005764 inhibitory process Effects 0.000 description 11
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- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
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- 238000001816 cooling Methods 0.000 description 8
- 210000004211 gastric acid Anatomy 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N methyl alcohol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 8
- QROKOTBWFZITJZ-UHFFFAOYSA-N n-pyridin-2-ylacetamide Chemical compound CC(=O)NC1=CC=CC=N1 QROKOTBWFZITJZ-UHFFFAOYSA-N 0.000 description 8
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 8
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- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 7
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- 235000017550 sodium carbonate Nutrition 0.000 description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 description 7
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 7
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- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- SIXIIKVOZAGHPV-UHFFFAOYSA-N lansoprazole Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=C[CH]C2=N1 SIXIIKVOZAGHPV-UHFFFAOYSA-N 0.000 description 6
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- PWWDEIMGEBPTJL-UHFFFAOYSA-N 1-(pyridin-2-ylmethylsulfinyl)benzimidazole Chemical class C1=NC2=CC=CC=C2N1S(=O)CC1=CC=CC=N1 PWWDEIMGEBPTJL-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
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- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 5
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
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- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
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- MFZUXRKTKZKWSS-UHFFFAOYSA-N benzene;sulfuryl dichloride Chemical class ClS(Cl)(=O)=O.C1=CC=CC=C1 MFZUXRKTKZKWSS-UHFFFAOYSA-N 0.000 description 3
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- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 3
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- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles 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 in position 2
- C07D235/28—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Steroid Compounds (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
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- Pyridine Compounds (AREA)
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Abstract
Description
# | R6 * | R1 * | R2 * | R3 * | R17 * | 产率(%) | m.p.(℃) |
2 | 5-OCH3 1 | -CH3 | -OCH3 | -CH3 | 4-Cl | 81 | 76-78 |
3 | 5-OCH3 1 | -CH3 | -OCH3 | -CH3 | 4-Br | 73 | 84-86 |
4 | 5-OCH3 1 | -CH3 | -OCH3 | -CH3 | 4-F | 85 | 70-72 |
5 | 5-OCH3 1 | -CH3 | -OCH3 | -CH3 | 4-CH3 | 79 | 64-66 |
6 | 5-OCH3 1 | -CH3 | -OCH3 | -CH3 | 4-OCH3 | 83 | 85-87 |
7 | 5-OCH3 1 | -CH3 | -OCH3 | -CH3 | 3-CF3 | 67 | 65-67 |
8 | 5-OCH3 1 | -CH3 | -OCH3 | -CH3 | 4-OCF3 | 78 | 63-64 |
9 | H | -CH3 | OCH2CF3 | H | H | 78 | 80-83 |
10 | H | -CH3 | OCH2CF3 | H | 4-Cl | 79 | 90-92 |
11 | H | -CH3 | OCH2CF3 | H | 4-Br | 71 | 105-107 |
12 | H | -CH3 | OCH2CF3 | H | 4-F | 73 | 85-87 |
13 | H | -CH3 | OCH2CF3 | H | 4-CH3 | 67 | 125-126 |
14 | H | -CH3 | OCH2CF3 | H | 4-OCH3 | 78 | 94-95 |
15 | H | -CH3 | OCH2CF3 | H | 3-CF3 | 67 | 123-125 |
16 | H | -CH3 | OCH2CF3 | H | 4-OCF3 | 78 | 125-126 |
172 | 5-OCHF2 | OCH3 | OCH3 | H | H | 92 | 51-54 |
182 | 5-OCHF2 | OCH3 | OCH3 | H | 4-OCH3 | 87 | 67-69 |
192 | 5-OCHF2 | OCH3 | OCH3 | H | 4-OCF3 | 87 | 61-63 |
# | R6 * | R1 * | R2 * | R3 * | R17 * | 产率(%) | m.p.(℃) |
211 | 5-OCHF2 | OCH3 | OCH3 | H | 4-Br | 87 | 80-82 |
221 | 5-OCHF2 | OCH3 | OCH3 | H | 4-F | 78 | 67-70 |
231 | 5-OCHF2 | OCH3 | OCH3 | H | 4-CH3 | 88 | 73-75 |
241 | 5-OCHF2 | OCH3 | OCH3 | H | 3-CF3 | 83 | 62-66 |
Claims (26)
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/131,481 | 1998-08-10 | ||
US09/131,481 US6093734A (en) | 1998-08-10 | 1998-08-10 | Prodrugs of proton pump inhibitors |
US36438199A | 1999-07-29 | 1999-07-29 | |
US09/364,381 | 1999-07-29 |
Publications (2)
Publication Number | Publication Date |
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CN1312806A true CN1312806A (zh) | 2001-09-12 |
CN100396675C CN100396675C (zh) | 2008-06-25 |
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CNB998095125A Expired - Fee Related CN100396675C (zh) | 1998-08-10 | 1999-08-09 | 质子泵抑制剂的前药 |
Country Status (28)
Country | Link |
---|---|
US (1) | US6559167B1 (zh) |
EP (1) | EP1105387B1 (zh) |
JP (1) | JP4346243B2 (zh) |
KR (1) | KR100472126B1 (zh) |
CN (1) | CN100396675C (zh) |
AT (1) | ATE231857T1 (zh) |
AU (1) | AU752292B2 (zh) |
BG (1) | BG64870B1 (zh) |
BR (1) | BR9912937A (zh) |
CA (1) | CA2338311C (zh) |
DE (1) | DE69905171T2 (zh) |
DK (1) | DK1105387T3 (zh) |
ES (1) | ES2192394T3 (zh) |
FI (1) | FI20010248A (zh) |
HK (1) | HK1035368A1 (zh) |
HR (1) | HRP20010106A2 (zh) |
HU (1) | HUP0103464A3 (zh) |
ID (1) | ID28273A (zh) |
IL (2) | IL141083A0 (zh) |
IS (1) | IS5826A (zh) |
MX (1) | MXPA01001464A (zh) |
NO (1) | NO322490B1 (zh) |
NZ (1) | NZ510180A (zh) |
PL (1) | PL346000A1 (zh) |
TR (1) | TR200100431T2 (zh) |
UA (1) | UA67788C2 (zh) |
WO (1) | WO2000009498A1 (zh) |
YU (1) | YU10101A (zh) |
Cited By (1)
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CN101497622B (zh) * | 2008-01-30 | 2011-04-27 | 山东轩竹医药科技有限公司 | 吡啶甲基亚磺酰基咪唑并吡啶衍生物 |
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JP2006188432A (ja) * | 2003-02-25 | 2006-07-20 | Zeria Pharmaceut Co Ltd | 四環系スルフェンアミド化合物 |
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CA2537182A1 (en) * | 2003-08-29 | 2005-03-10 | Dynogen Pharmaceuticals, Inc. | Compositions useful for treating gastrointestinal motility disorders |
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US20050075371A1 (en) * | 2003-10-03 | 2005-04-07 | Allergan, Inc. | Methods and compositions for the oral administration of prodrugs of proton pump inhibitors |
WO2005039640A1 (en) * | 2003-10-03 | 2005-05-06 | Allergan Inc. | Compositions comprising trefoil factor family peptides and/or mucoadhesives and proton pump inhibitor prodrugs |
US20070161679A1 (en) * | 2004-02-18 | 2007-07-12 | Allergan, Inc. | Method and compositions for the intravenous administration of compounds related to proton pump inhibitors |
EP1715861A2 (en) * | 2004-02-18 | 2006-11-02 | Allergan, Inc. | Compositions comprising prodrugs of proton pump inhibitors |
JP2007532677A (ja) * | 2004-04-16 | 2007-11-15 | サンタラス インコーポレイティッド | プロトンポンプ阻害剤、緩衝剤、および運動促進薬の組み合わせ |
PT1740571E (pt) * | 2004-04-28 | 2009-09-02 | Hetero Drugs Ltd | Processo para preparar compostos de piridinilmetil-1hbenzimidazol na forma enantiomericamente enriquecida ou como enantiómeros únicos |
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US7534796B2 (en) * | 2005-02-18 | 2009-05-19 | Wyeth | Imidazo[4,5-b]pyridine antagonists of gonadotropin releasing hormone receptor |
US7538113B2 (en) * | 2005-02-18 | 2009-05-26 | Wyeth | 4-substituted imidazo[4,5-c]pyridine antagonists of gonadotropin releasing hormone receptor |
US7582634B2 (en) * | 2005-02-18 | 2009-09-01 | Wyeth | 7-substituted imidazo[4,5-c]pyridine antagonists of gonadotropin releasing hormone receptor |
US20060189619A1 (en) * | 2005-02-24 | 2006-08-24 | Wyeth | 3-({4-[2-(4-Tert-butylphenyl)-1h-benzimidazol-4-yl]piperazin-1-yl}methyl)pyrido[2,3-b]]pyrazi ne compounds |
US20070015782A1 (en) | 2005-04-15 | 2007-01-18 | Eisai Co., Ltd. | Benzimidazole compound |
US9040564B2 (en) | 2005-04-28 | 2015-05-26 | Eisai R&D Management Co., Ltd. | Stabilized composition |
US7531542B2 (en) | 2005-05-18 | 2009-05-12 | Wyeth | Benzooxazole and benzothiazole antagonists of gonadotropin releasing hormone receptor |
US7582636B2 (en) * | 2005-05-26 | 2009-09-01 | Wyeth | Piperazinylimidazopyridine and piperazinyltriazolopyridine antagonists of Gonadotropin Releasing Hormone receptor |
WO2006134877A1 (ja) * | 2005-06-13 | 2006-12-21 | Takeda Pharmaceutical Company Limited | 注射剤 |
WO2007073301A1 (en) * | 2005-12-23 | 2007-06-28 | Astrazeneca Ab | Benzoimidazole derivatives as prodrugs of proton pump inhibitors |
WO2008036211A1 (en) * | 2006-09-19 | 2008-03-27 | Alevium Pharmaceuticals, Inc. | Prodrugs of proton pump inhibitors including the (1h-pyrrol-1-yl)-1h-benzimidazole moiety |
WO2008036201A1 (en) * | 2006-09-19 | 2008-03-27 | Alevium Pharmaceuticals, Inc. | Prodrugs of proton pump inhibitors including the 1h-imidazo[4,5-b] pyridine moiety |
US20080103169A1 (en) | 2006-10-27 | 2008-05-01 | The Curators Of The University Of Missouri | Compositions comprising acid labile proton pump inhibiting agents, at least one other pharmaceutically active agent and methods of using same |
AU2009215514B9 (en) | 2008-02-20 | 2014-01-30 | The Curators Of The University Of Missouri | Composition comprising a combination of omeprazole and lansoprazole, and a buffering agent, and methods of using same |
UA100192C2 (en) * | 2008-11-11 | 2012-11-26 | УАЙТ ЭлЭлСи | 1-(arylsulfonyl)-4-(piperazin-1-yl)-1h-benzimidazoles as 5-hydroxytryptamine-6 ligands |
CA2891523A1 (en) * | 2012-11-19 | 2014-05-22 | Jiangsu Hansoh Pharmaceutical Co., Ltd. | Pyrrole sulfonamide derivative, preparation method for same, and medical application thereof |
US9487485B2 (en) | 2013-02-28 | 2016-11-08 | Takeda Pharmaceutical Company Limited | Method for producing sulfonyl chloride compound |
PT3762368T (pt) | 2018-03-08 | 2022-05-06 | Incyte Corp | Compostos de aminopirazina diol como inibidores de pi3k-y |
WO2020010003A1 (en) | 2018-07-02 | 2020-01-09 | Incyte Corporation | AMINOPYRAZINE DERIVATIVES AS PI3K-γ INHIBITORS |
JP2023527155A (ja) | 2020-05-20 | 2023-06-27 | エフ. ホフマン-ラ ロシュ アーゲー | 質量分析のための試薬 |
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SE416649B (sv) * | 1974-05-16 | 1981-01-26 | Haessle Ab | Forfarande for framstellning av foreningar som paverkar magsyrasekretionen |
SE7804231L (sv) * | 1978-04-14 | 1979-10-15 | Haessle Ab | Magsyrasekretionsmedel |
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IL76839A (en) * | 1984-10-31 | 1988-08-31 | Byk Gulden Lomberg Chem Fab | Picoline derivatives,processes for the preparation thereof and pharmaceutical compositions containing the same |
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SE9602442D0 (sv) | 1996-06-20 | 1996-06-20 | Astra Ab | Administration of pharmaceuticals |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101497622B (zh) * | 2008-01-30 | 2011-04-27 | 山东轩竹医药科技有限公司 | 吡啶甲基亚磺酰基咪唑并吡啶衍生物 |
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