TW200848036A - Novel oxycarbonyl compound - Google Patents
Novel oxycarbonyl compound Download PDFInfo
- Publication number
- TW200848036A TW200848036A TW096147687A TW96147687A TW200848036A TW 200848036 A TW200848036 A TW 200848036A TW 096147687 A TW096147687 A TW 096147687A TW 96147687 A TW96147687 A TW 96147687A TW 200848036 A TW200848036 A TW 200848036A
- Authority
- TW
- Taiwan
- Prior art keywords
- phenoxy
- esi
- propyl
- nmr
- preparation
- Prior art date
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- -1 oxycarbonyl compound Chemical class 0.000 title claims description 191
- 150000001875 compounds Chemical class 0.000 claims abstract description 134
- 150000003839 salts Chemical class 0.000 claims abstract description 28
- 239000003814 drug Substances 0.000 claims abstract description 8
- 208000006673 asthma Diseases 0.000 claims abstract description 6
- 206010039085 Rhinitis allergic Diseases 0.000 claims abstract description 5
- 201000010105 allergic rhinitis Diseases 0.000 claims abstract description 5
- 201000008937 atopic dermatitis Diseases 0.000 claims abstract description 5
- 208000010668 atopic eczema Diseases 0.000 claims abstract description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 5
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims abstract description 4
- 206010012434 Dermatitis allergic Diseases 0.000 claims abstract description 4
- 208000004262 Food Hypersensitivity Diseases 0.000 claims abstract description 4
- 235000020932 food allergy Nutrition 0.000 claims abstract description 4
- 201000006417 multiple sclerosis Diseases 0.000 claims abstract description 4
- 206010065563 Eosinophilic bronchitis Diseases 0.000 claims abstract description 3
- 206010016946 Food allergy Diseases 0.000 claims abstract description 3
- 206010061218 Inflammation Diseases 0.000 claims abstract 3
- 230000004054 inflammatory process Effects 0.000 claims abstract 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 259
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 219
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 124
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 115
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 101
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 81
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 66
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 66
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 44
- 125000001424 substituent group Chemical group 0.000 claims description 37
- 125000000217 alkyl group Chemical group 0.000 claims description 31
- 235000019260 propionic acid Nutrition 0.000 claims description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims description 29
- 239000002585 base Substances 0.000 claims description 27
- 229910052736 halogen Inorganic materials 0.000 claims description 27
- 150000002367 halogens Chemical class 0.000 claims description 26
- 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 claims description 26
- 125000002947 alkylene group Chemical group 0.000 claims description 17
- 125000003118 aryl group Chemical group 0.000 claims description 17
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 15
- 239000004305 biphenyl Substances 0.000 claims description 14
- 239000000651 prodrug Substances 0.000 claims description 14
- 229940002612 prodrug Drugs 0.000 claims description 14
- 125000001072 heteroaryl group Chemical group 0.000 claims description 11
- 229910052783 alkali metal Inorganic materials 0.000 claims description 10
- 235000010290 biphenyl Nutrition 0.000 claims description 9
- 125000001624 naphthyl group Chemical group 0.000 claims description 9
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 210000004241 Th2 cell Anatomy 0.000 claims description 8
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 7
- 125000001544 thienyl group Chemical group 0.000 claims description 7
- 238000011282 treatment Methods 0.000 claims description 7
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 6
- 150000001340 alkali metals Chemical class 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 6
- 125000002883 imidazolyl group Chemical group 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 6
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 5
- 150000002923 oximes Chemical class 0.000 claims description 5
- 238000006467 substitution reaction Methods 0.000 claims description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 4
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 150000001336 alkenes Chemical class 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 230000027455 binding Effects 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 229920002554 vinyl polymer Chemical group 0.000 claims description 4
- 206010010741 Conjunctivitis Diseases 0.000 claims description 3
- 206010047115 Vasculitis Diseases 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 3
- 201000009890 sinusitis Diseases 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- 206010027654 Allergic conditions Diseases 0.000 claims description 2
- 102000011652 Formyl peptide receptors Human genes 0.000 claims description 2
- 108010076288 Formyl peptide receptors Proteins 0.000 claims description 2
- 229910052786 argon Inorganic materials 0.000 claims description 2
- 238000009739 binding Methods 0.000 claims description 2
- 230000002327 eosinophilic effect Effects 0.000 claims description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims description 2
- 210000002784 stomach Anatomy 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- 201000005505 Measles Diseases 0.000 claims 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 claims 2
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 claims 1
- 235000001258 Cinchona calisaya Nutrition 0.000 claims 1
- 230000003266 anti-allergic effect Effects 0.000 claims 1
- 210000000621 bronchi Anatomy 0.000 claims 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 claims 1
- 125000004122 cyclic group Chemical group 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 claims 1
- 229960000948 quinine Drugs 0.000 claims 1
- 210000003979 eosinophil Anatomy 0.000 abstract description 8
- 208000035475 disorder Diseases 0.000 abstract 2
- 229940124003 CRTH2 antagonist Drugs 0.000 abstract 1
- 208000024780 Urticaria Diseases 0.000 abstract 1
- 230000000172 allergic effect Effects 0.000 abstract 1
- 210000003695 paranasal sinus Anatomy 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 583
- 238000002360 preparation method Methods 0.000 description 372
- 238000005481 NMR spectroscopy Methods 0.000 description 350
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 278
- 239000011734 sodium Substances 0.000 description 211
- 235000019439 ethyl acetate Nutrition 0.000 description 202
- 239000000203 mixture Substances 0.000 description 180
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 126
- 239000000243 solution Substances 0.000 description 126
- 101150041968 CDC13 gene Proteins 0.000 description 113
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 113
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 93
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 86
- 235000011054 acetic acid Nutrition 0.000 description 83
- 238000005160 1H NMR spectroscopy Methods 0.000 description 78
- 239000012044 organic layer Substances 0.000 description 73
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
- 239000012267 brine Substances 0.000 description 70
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 70
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 68
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 67
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 67
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 62
- 239000011541 reaction mixture Substances 0.000 description 59
- 238000004440 column chromatography Methods 0.000 description 54
- 238000000034 method Methods 0.000 description 54
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 51
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 44
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 41
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 37
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- 238000006243 chemical reaction Methods 0.000 description 35
- 206010057190 Respiratory tract infections Diseases 0.000 description 34
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 34
- 239000007864 aqueous solution Substances 0.000 description 31
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 31
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 23
- OBNCKNCVKJNDBV-UHFFFAOYSA-N ethyl butyrate Chemical group CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 description 23
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- 238000001914 filtration Methods 0.000 description 21
- 239000002253 acid Substances 0.000 description 18
- 238000001816 cooling Methods 0.000 description 18
- 229910000027 potassium carbonate Inorganic materials 0.000 description 18
- 235000011181 potassium carbonates Nutrition 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- 238000003756 stirring Methods 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 17
- 239000012230 colorless oil Substances 0.000 description 17
- 229910052757 nitrogen Inorganic materials 0.000 description 17
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 17
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 16
- 235000017557 sodium bicarbonate Nutrition 0.000 description 16
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 15
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 15
- 238000001704 evaporation Methods 0.000 description 15
- 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 15
- 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 15
- 229920006395 saturated elastomer Polymers 0.000 description 15
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 13
- WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 13
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N o-biphenylenemethane Natural products C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 12
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 12
- 230000008020 evaporation Effects 0.000 description 12
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 12
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 11
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 11
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 11
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 11
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 11
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 11
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 10
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 239000013078 crystal Substances 0.000 description 10
- 150000002148 esters Chemical class 0.000 description 10
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 10
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 9
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- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
- JAWMENYCRQKKJY-UHFFFAOYSA-N [3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-ylmethyl)-1-oxa-2,8-diazaspiro[4.5]dec-2-en-8-yl]-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]methanone Chemical compound N1N=NC=2CN(CCC=21)CC1=NOC2(C1)CCN(CC2)C(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F JAWMENYCRQKKJY-UHFFFAOYSA-N 0.000 description 9
- 238000001035 drying Methods 0.000 description 9
- 229910000103 lithium hydride Inorganic materials 0.000 description 9
- 239000012299 nitrogen atmosphere Substances 0.000 description 9
- 229910000029 sodium carbonate Inorganic materials 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 235000019198 oils Nutrition 0.000 description 8
- 125000003396 thiol group Chemical group [H]S* 0.000 description 8
- 229940086542 triethylamine Drugs 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 7
- 102000009389 Prostaglandin D receptors Human genes 0.000 description 7
- 108050000258 Prostaglandin D receptors Proteins 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 150000002576 ketones Chemical class 0.000 description 7
- 239000012046 mixed solvent Substances 0.000 description 7
- 150000002762 monocarboxylic acid derivatives Chemical class 0.000 description 7
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- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
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- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
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- SNJIJYKMYQRHRC-UHFFFAOYSA-M sodium;2-[4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]phenoxy]acetate Chemical compound [Na+].C=1C=CC(Cl)=CC=1C(O)CNC(C)CC1=CC=C(OCC([O-])=O)C=C1 SNJIJYKMYQRHRC-UHFFFAOYSA-M 0.000 description 1
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- ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
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- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
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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
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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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
- A61P37/08—Antiallergic agents
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- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (1)
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| US87001406P | 2006-12-14 | 2006-12-14 |
Publications (1)
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| TW200848036A true TW200848036A (en) | 2008-12-16 |
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| TW096147687A TW200848036A (en) | 2006-12-14 | 2007-12-13 | Novel oxycarbonyl compound |
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| EP (1) | EP2094662B1 (enExample) |
| JP (1) | JP5278318B2 (enExample) |
| KR (1) | KR20090096690A (enExample) |
| CN (2) | CN102442941A (enExample) |
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| AT (1) | ATE553084T1 (enExample) |
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| PT (1) | PT2094662E (enExample) |
| TW (1) | TW200848036A (enExample) |
| WO (1) | WO2008072784A1 (enExample) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
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| AU2008219166B2 (en) * | 2007-02-16 | 2013-05-16 | Amgen Inc. | Nitrogen-containing heterocyclyl ketones and their use as c-Met inhibitors |
| US8304413B2 (en) | 2008-06-03 | 2012-11-06 | Intermune, Inc. | Compounds and methods for treating inflammatory and fibrotic disorders |
| MX2011012155A (es) | 2009-05-13 | 2012-02-28 | Enanta Pharm Inc | Compuestos macrociclicos como inhibidores del virus de hepatitis c. |
| EP2590944B1 (en) | 2010-07-05 | 2015-09-30 | Actelion Pharmaceuticals Ltd. | 1-phenyl-substituted heterocyclyl derivatives and their use as prostaglandin d2 receptor modulators |
| US9255090B2 (en) | 2011-12-21 | 2016-02-09 | Actelion Pharmaceuticals Ltd. | Heterocyclyl derivatives and their use as prostaglandin D2 receptor modulators |
| MX2014015156A (es) | 2012-06-12 | 2015-08-06 | Abbvie Inc | Derivados de piridinona y piridazinona. |
| US9169270B2 (en) | 2012-07-05 | 2015-10-27 | Actelion Pharmaceuticals Ltd. | 1-phenyl-substituted heterocyclyl derivatives and their use as prostaglandin D2 receptor modulators |
| WO2014047427A2 (en) | 2012-09-21 | 2014-03-27 | Vanderbilt University | Substituted benzofuran, benzothiophene and indole mcl-1 inhibitors |
| AR092742A1 (es) | 2012-10-02 | 2015-04-29 | Intermune Inc | Piridinonas antifibroticas |
| WO2014080290A2 (en) | 2012-11-21 | 2014-05-30 | Rvx Therapeutics Inc. | Cyclic amines as bromodomain inhibitors |
| WO2014080291A2 (en) | 2012-11-21 | 2014-05-30 | Rvx Therapeutics Inc. | Biaryl derivatives as bromodomain inhibitors |
| AU2013365926B9 (en) * | 2012-12-21 | 2019-01-17 | Zenith Epigenetics Ltd. | Novel heterocyclic compounds as bromodomain inhibitors |
| ES2661437T3 (es) | 2013-06-21 | 2018-04-02 | Zenith Epigenetics Corp. | Nuevos compuestos bicíclicos sustituidos como inhibidores de bromodominio |
| SI3010503T1 (sl) | 2013-06-21 | 2020-07-31 | Zenith Epigenetics Ltd. | Novi biciklični inhibitorji bromodomene |
| CN105593224B (zh) | 2013-07-31 | 2021-05-25 | 恒元生物医药科技(苏州)有限公司 | 作为溴结构域抑制剂的新型喹唑啉酮类化合物 |
| US10005728B2 (en) | 2013-08-28 | 2018-06-26 | Vanderbilt University | Substituted indole Mcl-1 inhibitors |
| CA2943815C (en) | 2014-03-27 | 2023-04-04 | Vanderbilt University | Substituted indole mcl-1 inhibitors |
| KR102373700B1 (ko) | 2014-04-02 | 2022-03-11 | 인터뮨, 인크. | 항섬유성 피리디논 |
| US9949965B2 (en) | 2014-10-17 | 2018-04-24 | Vanderbilt University | Tricyclic indole Mcl-1 inhibitors and uses thereof |
| US10710992B2 (en) | 2014-12-01 | 2020-07-14 | Zenith Epigenetics Ltd. | Substituted pyridinones as bromodomain inhibitors |
| EP3227280B1 (en) | 2014-12-01 | 2019-04-24 | Zenith Epigenetics Ltd. | Substituted pyridines as bromodomain inhibitors |
| US10292968B2 (en) | 2014-12-11 | 2019-05-21 | Zenith Epigenetics Ltd. | Substituted heterocycles as bromodomain inhibitors |
| CA2966450A1 (en) | 2014-12-17 | 2016-06-23 | Olesya KHARENKO | Inhibitors of bromodomains |
| CN105353095B (zh) * | 2015-11-16 | 2017-10-20 | 华南农业大学 | 一种西地那非及其结构类似物的免疫检测方法 |
| WO2017104728A1 (ja) * | 2015-12-16 | 2017-06-22 | 国立大学法人東京大学 | 食物アレルギー治療薬 |
| WO2017126635A1 (ja) * | 2016-01-22 | 2017-07-27 | 武田薬品工業株式会社 | 複素環化合物およびその用途 |
| EP4292662A3 (en) | 2016-03-04 | 2024-02-21 | Vanderbilt University | Substituted indole mcl-1 inhibitors |
| US11608320B2 (en) | 2020-02-02 | 2023-03-21 | Kuwait University | Oxazolidinone hydroxamic acid derivatives |
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| JP3245864B2 (ja) | 1994-03-10 | 2002-01-15 | 藤沢薬品工業株式会社 | プロスタグランジンi2アゴニストとしてのナフタレン誘導体 |
| AU3387895A (en) * | 1994-09-10 | 1996-03-27 | Basf Aktiengesellschaft | Phenylacetic acid alkyl esters |
| AU691673B2 (en) | 1994-11-14 | 1998-05-21 | Dow Agrosciences Llc | Pyridazinones and their use as fungicides |
| DE19514568A1 (de) * | 1995-04-20 | 1996-10-24 | Merck Patent Gmbh | Arylalkyl-pyridazinone |
| KR20020014797A (ko) * | 1999-05-17 | 2002-02-25 | 한센 핀 베네드, 안네 제헤르, 웨이콥 마리안느 | 글루카곤 길항제/역 아고니스트 |
| CA2437932A1 (en) * | 2001-02-12 | 2002-09-19 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Use of type 4 phosphodiesterase inhibitors in myocardial diseases |
| TW200400930A (en) * | 2002-06-26 | 2004-01-16 | Ono Pharmaceutical Co | Therapeutic agent for chronic disease |
| US7820682B2 (en) * | 2002-10-03 | 2010-10-26 | Ono Pharmaceutical Co., Ltd. | LPA receptor antagonist |
| EP2336113A1 (en) | 2004-05-29 | 2011-06-22 | 7TM Pharma A/S | CRTH2 Receptor Ligands for Medical Use |
| DE102005057924A1 (de) | 2005-12-05 | 2007-06-06 | Merck Patent Gmbh | Pyridazinonderivate |
| DE102006037478A1 (de) * | 2006-08-10 | 2008-02-14 | Merck Patent Gmbh | 2-(Heterocyclylbenzyl)-pyridazinonderivate |
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- 2007-12-13 KR KR1020097008871A patent/KR20090096690A/ko not_active Withdrawn
- 2007-12-13 WO PCT/JP2007/074475 patent/WO2008072784A1/en not_active Ceased
- 2007-12-13 US US12/518,280 patent/US8273745B2/en not_active Expired - Fee Related
- 2007-12-13 AT AT07859872T patent/ATE553084T1/de active
- 2007-12-13 ES ES07859872T patent/ES2383239T3/es active Active
- 2007-12-13 TW TW096147687A patent/TW200848036A/zh unknown
- 2007-12-13 EP EP07859872A patent/EP2094662B1/en not_active Not-in-force
- 2007-12-13 MX MX2009006312A patent/MX2009006312A/es active IP Right Grant
- 2007-12-13 CN CN2011102832598A patent/CN102442941A/zh active Pending
- 2007-12-13 CN CN200780046458A patent/CN101636386A/zh active Pending
- 2007-12-13 CA CA002672601A patent/CA2672601A1/en not_active Abandoned
- 2007-12-13 AR ARP070105614A patent/AR064346A1/es unknown
- 2007-12-13 JP JP2009524246A patent/JP5278318B2/ja not_active Expired - Fee Related
- 2007-12-13 PT PT07859872T patent/PT2094662E/pt unknown
Also Published As
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| MX2009006312A (es) | 2009-08-07 |
| JP2010513224A (ja) | 2010-04-30 |
| JP5278318B2 (ja) | 2013-09-04 |
| US20100009991A1 (en) | 2010-01-14 |
| PL2094662T3 (pl) | 2012-09-28 |
| CA2672601A1 (en) | 2008-06-19 |
| ES2383239T3 (es) | 2012-06-19 |
| CN102442941A (zh) | 2012-05-09 |
| PT2094662E (pt) | 2012-07-02 |
| EP2094662A1 (en) | 2009-09-02 |
| AR064346A1 (es) | 2009-04-01 |
| CN101636386A (zh) | 2010-01-27 |
| ATE553084T1 (de) | 2012-04-15 |
| WO2008072784A1 (en) | 2008-06-19 |
| US8273745B2 (en) | 2012-09-25 |
| KR20090096690A (ko) | 2009-09-14 |
| EP2094662B1 (en) | 2012-04-11 |
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