MXPA06012008A - Compuestos de amida tri(ciclo) sustituidos. - Google Patents
Compuestos de amida tri(ciclo) sustituidos.Info
- Publication number
- MXPA06012008A MXPA06012008A MXPA06012008A MXPA06012008A MXPA06012008A MX PA06012008 A MXPA06012008 A MX PA06012008A MX PA06012008 A MXPA06012008 A MX PA06012008A MX PA06012008 A MXPA06012008 A MX PA06012008A MX PA06012008 A MXPA06012008 A MX PA06012008A
- Authority
- MX
- Mexico
- Prior art keywords
- alkyl
- pharmaceutically acceptable
- acceptable salt
- group
- compound
- Prior art date
Links
- -1 amide compounds Chemical class 0.000 title claims description 138
- 150000001875 compounds Chemical class 0.000 claims abstract description 129
- 150000003839 salts Chemical class 0.000 claims abstract description 65
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 17
- 238000011282 treatment Methods 0.000 claims abstract description 15
- 201000001421 hyperglycemia Diseases 0.000 claims abstract description 14
- 230000000069 prophylactic effect Effects 0.000 claims abstract description 9
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 62
- 238000000034 method Methods 0.000 claims description 38
- 239000001257 hydrogen Substances 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 238000002360 preparation method Methods 0.000 claims description 25
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 13
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
- 150000001408 amides Chemical class 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 10
- 229940080818 propionamide Drugs 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 239000000460 chlorine Substances 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical group 0.000 claims description 9
- 150000002431 hydrogen Chemical group 0.000 claims description 9
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 8
- 230000004913 activation Effects 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 239000003472 antidiabetic agent Substances 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- 101100533890 Hypocrea jecorina (strain QM6a) sor3 gene Chemical group 0.000 claims description 5
- 101100533874 Hypocrea jecorina (strain QM6a) sor5 gene Chemical group 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 208000002705 Glucose Intolerance Diseases 0.000 claims description 4
- 206010018429 Glucose tolerance impaired Diseases 0.000 claims description 4
- 229940125708 antidiabetic agent Drugs 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000005350 hydroxycycloalkyl group Chemical group 0.000 claims description 4
- 201000009104 prediabetes syndrome Diseases 0.000 claims description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 3
- 125000005330 8 membered heterocyclic group Chemical group 0.000 claims description 3
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 3
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical compound [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 2
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 2
- 101000947164 Homo sapiens CAAX box protein 1 Proteins 0.000 claims description 2
- 101000699848 Homo sapiens Retrotransposon Gag-like protein 8C Proteins 0.000 claims description 2
- 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 238000009833 condensation Methods 0.000 claims 2
- 230000005494 condensation Effects 0.000 claims 2
- 102100029439 Retrotransposon Gag-like protein 8C Human genes 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 55
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 37
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- 239000000243 solution Substances 0.000 description 36
- 239000012190 activator Substances 0.000 description 27
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
- 235000019439 ethyl acetate Nutrition 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- 239000002904 solvent Substances 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000004480 active ingredient Substances 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 11
- 239000012267 brine Substances 0.000 description 11
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 239000008280 blood Substances 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 8
- 238000001704 evaporation Methods 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 235000019341 magnesium sulphate Nutrition 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 125000000524 functional group Chemical group 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 231100000252 nontoxic Toxicity 0.000 description 7
- 230000003000 nontoxic effect Effects 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 239000003981 vehicle Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 125000004043 oxo group Chemical group O=* 0.000 description 6
- HUUPNPWVDMNTAH-UHFFFAOYSA-N 5-fluoro-1,3-thiazol-2-amine Chemical compound NC1=NC=C(F)S1 HUUPNPWVDMNTAH-UHFFFAOYSA-N 0.000 description 5
- 102100031126 6-phosphogluconolactonase Human genes 0.000 description 5
- 108010029731 6-phosphogluconolactonase Proteins 0.000 description 5
- 108010018962 Glucosephosphate Dehydrogenase Proteins 0.000 description 5
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 150000001735 carboxylic acids Chemical class 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 4
- 150000002170 ethers Chemical class 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 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
- 235000019260 propionic acid Nutrition 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- LSBDFXRDZJMBSC-UHFFFAOYSA-N 2-phenylacetamide Chemical group NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 description 3
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
- NBSCHQHZLSJFNQ-GASJEMHNSA-N D-Glucose 6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@H]1O NBSCHQHZLSJFNQ-GASJEMHNSA-N 0.000 description 3
- VFRROHXSMXFLSN-UHFFFAOYSA-N Glc6P Natural products OP(=O)(O)OCC(O)C(O)C(O)C(O)C=O VFRROHXSMXFLSN-UHFFFAOYSA-N 0.000 description 3
- 102000051325 Glucagon Human genes 0.000 description 3
- 108060003199 Glucagon Proteins 0.000 description 3
- 102000030595 Glucokinase Human genes 0.000 description 3
- 108010021582 Glucokinase Proteins 0.000 description 3
- 241000282412 Homo Species 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
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 3
- 229960004666 glucagon Drugs 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 229910052757 nitrogen Chemical group 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 150000007530 organic bases Chemical class 0.000 description 3
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000006340 racemization Effects 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 235000017550 sodium carbonate Nutrition 0.000 description 3
- 239000012453 solvate Substances 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 239000011593 sulfur Chemical group 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 3
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- XLULWLRVYSRNCI-UHFFFAOYSA-N 2-(4-cyclopropylsulfanylphenyl)-2-oxoacetic acid Chemical compound C1=CC(C(=O)C(=O)O)=CC=C1SC1CC1 XLULWLRVYSRNCI-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
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- 125000001425 triazolyl group Chemical group 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
- 229960001641 troglitazone Drugs 0.000 description 1
- GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/44—Acylated amino or imino radicals
- C07D277/46—Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US56417104P | 2004-04-21 | 2004-04-21 | |
| US60107704P | 2004-08-12 | 2004-08-12 | |
| PCT/GB2005/050053 WO2005103021A1 (en) | 2004-04-21 | 2005-04-19 | Tri(cyclo) substituted amide compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA06012008A true MXPA06012008A (es) | 2007-01-25 |
Family
ID=34965439
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA06012008A MXPA06012008A (es) | 2004-04-21 | 2005-04-19 | Compuestos de amida tri(ciclo) sustituidos. |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US20080242869A1 (enExample) |
| EP (1) | EP1740560A1 (enExample) |
| JP (1) | JP2007533722A (enExample) |
| KR (1) | KR20060134179A (enExample) |
| AU (1) | AU2005235798A1 (enExample) |
| BR (1) | BRPI0510163A (enExample) |
| CA (1) | CA2563192A1 (enExample) |
| EA (1) | EA012204B1 (enExample) |
| IL (1) | IL178473A0 (enExample) |
| MA (1) | MA28545B1 (enExample) |
| MX (1) | MXPA06012008A (enExample) |
| NO (1) | NO20065260L (enExample) |
| NZ (1) | NZ550567A (enExample) |
| WO (1) | WO2005103021A1 (enExample) |
| ZA (1) | ZA200608489B (enExample) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE0102299D0 (sv) | 2001-06-26 | 2001-06-26 | Astrazeneca Ab | Compounds |
| SE0102764D0 (sv) | 2001-08-17 | 2001-08-17 | Astrazeneca Ab | Compounds |
| RU2005113713A (ru) | 2002-10-03 | 2006-01-20 | Новартис АГ (CH) | Замещенные (тиазол-2-ил)амиды или сульфонамиды в качестве активаторов глюкокиназы, которые могут применяться при лечении диабета типа 2 |
| GB0226931D0 (en) | 2002-11-19 | 2002-12-24 | Astrazeneca Ab | Chemical compounds |
| WO2005095417A1 (en) | 2004-04-02 | 2005-10-13 | Novartis Ag | Thiazolopyridine derivates, pharmaceutical conditions containing them and methods of treating glucokinase mediated conditions |
| ATE524479T1 (de) | 2004-04-02 | 2011-09-15 | Novartis Ag | Sulfonamidthiazolpyridinderivate als zur behandlung von typ-2-diabetes geeignete glucokinaseaktivatoren |
| GB0418058D0 (en) * | 2004-08-12 | 2004-09-15 | Prosidion Ltd | Fluorination process |
| AU2005271016A1 (en) * | 2004-08-12 | 2006-02-16 | Prosidion Limited | Substituted phenylacetamides and their use as glucokinase activators |
| BRPI0622261A2 (pt) | 2005-07-09 | 2011-08-09 | Astrazeneca Ab | composto, composição farmacêutica, uso de um composto ou um sal farmaceuticamente aceitável do mesmo, e, processo para a preparação de um composto |
| RU2008112198A (ru) | 2005-09-29 | 2009-10-10 | Санофи-Авентис (Fr) | Производные фенил-1,2,4-оксадиазолона, способы их получения и их применение в качестве фармацевтических средств |
| GT200600428A (es) | 2005-09-30 | 2007-05-21 | Compuestos organicos | |
| GT200600429A (es) | 2005-09-30 | 2007-04-30 | Compuestos organicos | |
| US20080293741A1 (en) * | 2005-11-03 | 2008-11-27 | Matthew Colin Thor Fyfe | Tricyclo Substituted Amides as Glucokinase Modulators |
| PE20110235A1 (es) | 2006-05-04 | 2011-04-14 | Boehringer Ingelheim Int | Combinaciones farmaceuticas que comprenden linagliptina y metmorfina |
| US7910747B2 (en) | 2006-07-06 | 2011-03-22 | Bristol-Myers Squibb Company | Phosphonate and phosphinate pyrazolylamide glucokinase activators |
| US7888504B2 (en) | 2006-07-06 | 2011-02-15 | Bristol-Myers Squibb Company | Glucokinase activators and methods of using same |
| BRPI0715531A2 (pt) | 2006-07-24 | 2014-06-24 | Hoffmann La Roche | Composto, composição farmacêutica, método para o tratamento de uma enfermidade e/ou distúrbio metabólico, processo para a preparação de compostos e uso do composto |
| US7902248B2 (en) | 2006-12-14 | 2011-03-08 | Hoffmann-La Roche Inc. | Oxime glucokinase activators |
| TW200831081A (en) | 2006-12-25 | 2008-08-01 | Kyorin Seiyaku Kk | Glucokinase activator |
| WO2008111473A1 (ja) * | 2007-03-07 | 2008-09-18 | Kyorin Pharmaceutical Co., Ltd. | グルコキナーゼ活性化物質 |
| CL2009000004A1 (es) * | 2008-01-15 | 2010-02-19 | Lilly Co Eli | Forma cristalina de r-2-(4-ciclopropansulfonil-fenil)-n-pirazin-2-il-3-(tetrahidropiran-4-il)-propionamida; composicion farmaceutica que comprende a dicha forma cristalina; y uso para el tratamiento de diabetes o hiperglicemia. |
| KR20100113518A (ko) | 2008-01-18 | 2010-10-21 | 아스텔라스세이야쿠 가부시키가이샤 | 페닐아세트아미드 유도체 |
| US8258134B2 (en) | 2008-04-16 | 2012-09-04 | Hoffmann-La Roche Inc. | Pyridazinone glucokinase activators |
| US7741327B2 (en) | 2008-04-16 | 2010-06-22 | Hoffmann-La Roche Inc. | Pyrrolidinone glucokinase activators |
| SI2275414T1 (sl) | 2008-04-28 | 2015-10-30 | Kyorin Pharmaceutical Co., Ltd., | Ciklopentilakrilamidni derivat |
| WO2009140624A2 (en) | 2008-05-16 | 2009-11-19 | Takeda San Diego, Inc. | Glucokinase activators |
| CN102245574A (zh) * | 2008-12-08 | 2011-11-16 | 欧洲筛选有限公司 | 用于治疗代谢疾病的化合物、药物组合物以及方法 |
| UA104742C2 (uk) | 2008-12-19 | 2014-03-11 | Эли Лилли Энд Компани | Похідні арилциклопропілацетаміду, застосовні як активатори глюкокінази |
| US8222416B2 (en) | 2009-12-14 | 2012-07-17 | Hoffmann-La Roche Inc. | Azaindole glucokinase activators |
| JP2013522294A (ja) | 2010-03-18 | 2013-06-13 | タケダ カリフォルニア インコーポレイテッド | ２−アミノ−５−フルオロチアゾールの製造プロセス |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6610846B1 (en) * | 1999-03-29 | 2003-08-26 | Hoffman-La Roche Inc. | Heteroaromatic glucokinase activators |
| CN1151140C (zh) * | 1999-03-29 | 2004-05-26 | 霍夫曼-拉罗奇有限公司 | 葡糖激酶活化剂 |
| US6353111B1 (en) * | 1999-12-15 | 2002-03-05 | Hoffmann-La Roche Inc. | Trans olefinic glucokinase activators |
| EP1282611B1 (en) * | 2000-05-08 | 2004-10-20 | F. Hoffmann-La Roche Ag | Substituted phenylacetamides and their use as glucokinase activators |
| ATE297907T1 (de) * | 2000-07-20 | 2005-07-15 | Hoffmann La Roche | Alpha-acyl- und alpha-heteroatom-substituierte benzenacetamide verwendbar als glucokinase- aktivatoren |
| JP4109111B2 (ja) * | 2000-12-06 | 2008-07-02 | エフ．ホフマン−ラ ロシュ アーゲー | 縮合複素環式芳香族グルコキナーゼアクチベーター |
| WO2003095438A1 (en) * | 2002-04-26 | 2003-11-20 | F. Hoffmann-La Roche Ag | Substituted phenylacetamides and their use as glucokinase activators |
| PL378117A1 (pl) * | 2003-02-11 | 2006-03-06 | Prosidion Limited | Tricyklopodstawione związki amidowe |
-
2005
- 2005-04-19 NZ NZ550567A patent/NZ550567A/en not_active IP Right Cessation
- 2005-04-19 WO PCT/GB2005/050053 patent/WO2005103021A1/en not_active Ceased
- 2005-04-19 AU AU2005235798A patent/AU2005235798A1/en not_active Abandoned
- 2005-04-19 KR KR1020067022240A patent/KR20060134179A/ko not_active Ceased
- 2005-04-19 JP JP2007508982A patent/JP2007533722A/ja not_active Withdrawn
- 2005-04-19 MX MXPA06012008A patent/MXPA06012008A/es unknown
- 2005-04-19 EP EP05732317A patent/EP1740560A1/en not_active Withdrawn
- 2005-04-19 CA CA002563192A patent/CA2563192A1/en not_active Abandoned
- 2005-04-19 US US11/578,752 patent/US20080242869A1/en not_active Abandoned
- 2005-04-19 EA EA200601747A patent/EA012204B1/ru not_active IP Right Cessation
- 2005-04-19 BR BRPI0510163-8A patent/BRPI0510163A/pt not_active IP Right Cessation
-
2006
- 2006-10-05 IL IL178473A patent/IL178473A0/en unknown
- 2006-10-11 ZA ZA2006/08489A patent/ZA200608489B/en unknown
- 2006-10-20 MA MA29401A patent/MA28545B1/fr unknown
- 2006-11-15 NO NO20065260A patent/NO20065260L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| NO20065260L (no) | 2006-11-21 |
| EA012204B1 (ru) | 2009-08-28 |
| NZ550567A (en) | 2010-07-30 |
| MA28545B1 (fr) | 2007-04-03 |
| WO2005103021A1 (en) | 2005-11-03 |
| BRPI0510163A (pt) | 2007-10-02 |
| US20080242869A1 (en) | 2008-10-02 |
| EA200601747A1 (ru) | 2007-04-27 |
| AU2005235798A1 (en) | 2005-11-03 |
| CA2563192A1 (en) | 2005-11-03 |
| JP2007533722A (ja) | 2007-11-22 |
| ZA200608489B (en) | 2008-06-25 |
| IL178473A0 (en) | 2007-02-11 |
| EP1740560A1 (en) | 2007-01-10 |
| KR20060134179A (ko) | 2006-12-27 |
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