JP2003524626A - プロゲステロンレセプタモジュレーターとしてのキナゾリノンおよびベンゾキサジン誘導体 - Google Patents
プロゲステロンレセプタモジュレーターとしてのキナゾリノンおよびベンゾキサジン誘導体Info
- Publication number
- JP2003524626A JP2003524626A JP2000615391A JP2000615391A JP2003524626A JP 2003524626 A JP2003524626 A JP 2003524626A JP 2000615391 A JP2000615391 A JP 2000615391A JP 2000615391 A JP2000615391 A JP 2000615391A JP 2003524626 A JP2003524626 A JP 2003524626A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- substituted
- alkoxy
- aryl
- compound
- 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.)
- Pending
Links
- 150000005130 benzoxazines Chemical class 0.000 title description 4
- AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical compound C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 title description 3
- 239000002379 progesterone receptor modulator Substances 0.000 title description 3
- 229940095745 sex hormone and modulator of the genital system progesterone receptor modulator Drugs 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 126
- 125000003118 aryl group Chemical group 0.000 claims abstract description 50
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 49
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 37
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 36
- 150000002367 halogens Chemical class 0.000 claims abstract description 36
- 150000003839 salts Chemical class 0.000 claims abstract description 34
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 23
- 125000004103 aminoalkyl group Chemical group 0.000 claims abstract description 18
- 229910052760 oxygen Chemical class 0.000 claims abstract description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 18
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 15
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 15
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 14
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 13
- 229910002091 carbon monoxide Inorganic materials 0.000 claims abstract description 11
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 10
- 241000124008 Mammalia Species 0.000 claims abstract description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 8
- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 68
- -1 -OH Chemical group 0.000 claims description 50
- 238000000034 method Methods 0.000 claims description 45
- 239000000126 substance Substances 0.000 claims description 40
- 238000011282 treatment Methods 0.000 claims description 39
- 238000006243 chemical reaction Methods 0.000 claims description 28
- 125000001424 substituent group Chemical group 0.000 claims description 25
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 18
- 125000003107 substituted aryl group Chemical group 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 7
- 229940088597 hormone Drugs 0.000 claims description 7
- 239000005556 hormone Substances 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 201000009273 Endometriosis Diseases 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 206010046798 Uterine leiomyoma Diseases 0.000 claims description 6
- 210000000481 breast Anatomy 0.000 claims description 6
- 201000011510 cancer Diseases 0.000 claims description 6
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- 201000010260 leiomyoma Diseases 0.000 claims description 6
- 210000002307 prostate Anatomy 0.000 claims description 6
- 125000003003 spiro group Chemical group 0.000 claims description 6
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 6
- 210000001072 colon Anatomy 0.000 claims description 5
- 230000001419 dependent effect Effects 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 125000006664 (C1-C3) perfluoroalkyl group Chemical group 0.000 claims description 4
- ISAGHPZBJVZKEI-UHFFFAOYSA-N 2-amino-5-(3-chlorophenyl)benzonitrile Chemical compound C1=C(C#N)C(N)=CC=C1C1=CC=CC(Cl)=C1 ISAGHPZBJVZKEI-UHFFFAOYSA-N 0.000 claims description 4
- 230000002357 endometrial effect Effects 0.000 claims description 4
- 125000005309 thioalkoxy group Chemical group 0.000 claims description 4
- PQIVJXSRWOEROD-UHFFFAOYSA-N 1-[(4-methoxyphenyl)methyl]quinazolin-2-one Chemical compound C1=CC(OC)=CC=C1CN1C(=O)N=CC2=CC=CC=C21 PQIVJXSRWOEROD-UHFFFAOYSA-N 0.000 claims description 3
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 3
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 3
- 208000007913 Pituitary Neoplasms Diseases 0.000 claims description 3
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 230000002611 ovarian Effects 0.000 claims description 3
- 210000001672 ovary Anatomy 0.000 claims description 3
- UOSQTHOCALGTIP-UHFFFAOYSA-N 6-(3-chlorophenyl)-2,2,4,4-tetramethyl-1h-3,1-benzoxazine Chemical compound C1=C2C(C)(C)OC(C)(C)NC2=CC=C1C1=CC=CC(Cl)=C1 UOSQTHOCALGTIP-UHFFFAOYSA-N 0.000 claims description 2
- ANOMVYQZVDOVOK-UHFFFAOYSA-N C1=C2C(C)OC(C)(C)NC2=CC=C1C1=CC=CC([N+]([O-])=O)=C1 Chemical compound C1=C2C(C)OC(C)(C)NC2=CC=C1C1=CC=CC([N+]([O-])=O)=C1 ANOMVYQZVDOVOK-UHFFFAOYSA-N 0.000 claims description 2
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 201000007954 uterine fibroid Diseases 0.000 claims description 2
- MVCFDHLQJVJMDE-UHFFFAOYSA-N 1-methyl-3,4-dihydroquinazolin-2-one Chemical compound C1=CC=C2N(C)C(=O)NCC2=C1 MVCFDHLQJVJMDE-UHFFFAOYSA-N 0.000 claims 1
- ZJKBQAKWOAFRPC-UHFFFAOYSA-N 6-(3-chlorophenyl)-4-cyclopropyl-3h-quinazolin-2-one Chemical compound ClC1=CC=CC(C=2C=C3C(C4CC4)=NC(=O)NC3=CC=2)=C1 ZJKBQAKWOAFRPC-UHFFFAOYSA-N 0.000 claims 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- 201000003908 endometrial adenocarcinoma Diseases 0.000 claims 1
- 208000029382 endometrium adenocarcinoma Diseases 0.000 claims 1
- 239000011737 fluorine Substances 0.000 claims 1
- 230000001939 inductive effect Effects 0.000 claims 1
- 206010027191 meningioma Diseases 0.000 claims 1
- 208000011866 pituitary adenocarcinoma Diseases 0.000 claims 1
- 201000002511 pituitary cancer Diseases 0.000 claims 1
- 208000010579 uterine corpus leiomyoma Diseases 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 abstract description 11
- 229940123788 Progesterone receptor antagonist Drugs 0.000 abstract description 9
- 229940121912 Progesterone receptor agonist Drugs 0.000 abstract 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 172
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 122
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 81
- 239000007787 solid Substances 0.000 description 61
- 235000019439 ethyl acetate Nutrition 0.000 description 59
- 239000000203 mixture Substances 0.000 description 57
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 55
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
- 239000000243 solution Substances 0.000 description 52
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 50
- 238000005160 1H NMR spectroscopy Methods 0.000 description 42
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 40
- 239000012044 organic layer Substances 0.000 description 38
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 36
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- 239000002904 solvent Substances 0.000 description 30
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 26
- 230000000694 effects Effects 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 238000004458 analytical method Methods 0.000 description 23
- 238000002844 melting Methods 0.000 description 23
- 230000008018 melting Effects 0.000 description 23
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 23
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 22
- 239000012298 atmosphere Substances 0.000 description 22
- 239000005557 antagonist Substances 0.000 description 21
- 239000002609 medium Substances 0.000 description 21
- 102000003998 progesterone receptors Human genes 0.000 description 21
- 108090000468 progesterone receptors Proteins 0.000 description 21
- 229910052786 argon Inorganic materials 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- 239000012267 brine Substances 0.000 description 19
- 238000005859 coupling reaction Methods 0.000 description 19
- 239000000186 progesterone Substances 0.000 description 19
- 238000010992 reflux Methods 0.000 description 19
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 19
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- 239000000556 agonist Substances 0.000 description 17
- 231100000673 dose–response relationship Toxicity 0.000 description 16
- 239000000583 progesterone congener Substances 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- 230000000708 anti-progestin effect Effects 0.000 description 14
- 239000003418 antiprogestin Substances 0.000 description 14
- 239000010410 layer Substances 0.000 description 14
- 235000019270 ammonium chloride Nutrition 0.000 description 13
- 230000008878 coupling Effects 0.000 description 13
- 238000010168 coupling process Methods 0.000 description 13
- 238000003818 flash chromatography Methods 0.000 description 13
- 229960003387 progesterone Drugs 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 238000003556 assay Methods 0.000 description 12
- 239000003054 catalyst Substances 0.000 description 11
- 229920006395 saturated elastomer Polymers 0.000 description 11
- 229910000029 sodium carbonate Inorganic materials 0.000 description 11
- 235000017550 sodium carbonate Nutrition 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 10
- 239000005089 Luciferase Substances 0.000 description 9
- 229910052799 carbon Inorganic materials 0.000 description 9
- 239000001963 growth medium Substances 0.000 description 9
- 238000005259 measurement Methods 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 235000019198 oils Nutrition 0.000 description 9
- 229910000104 sodium hydride Inorganic materials 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 102220497176 Small vasohibin-binding protein_T47D_mutation Human genes 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 239000000010 aprotic solvent Substances 0.000 description 8
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- 229910052739 hydrogen Inorganic materials 0.000 description 8
- 239000003446 ligand Substances 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- 239000007818 Grignard reagent Substances 0.000 description 7
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- 229910052763 palladium Inorganic materials 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 6
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- DJYVXBJLHPKUKS-UHFFFAOYSA-N 4-bromothiophene-2-carbonitrile Chemical compound BrC1=CSC(C#N)=C1 DJYVXBJLHPKUKS-UHFFFAOYSA-N 0.000 description 5
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- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 5
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- SDEAGACSNFSZCU-UHFFFAOYSA-N (3-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(Cl)=C1 SDEAGACSNFSZCU-UHFFFAOYSA-N 0.000 description 4
- UWNGZUZXZLSTCT-UHFFFAOYSA-N 6-bromo-2,4,4-trimethyl-1,2-dihydro-3,1-benzoxazine Chemical compound C1=C(Br)C=C2C(C)(C)OC(C)NC2=C1 UWNGZUZXZLSTCT-UHFFFAOYSA-N 0.000 description 4
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
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- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
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- 239000007858 starting material Substances 0.000 description 4
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- CUPOOAWTRIURFT-UHFFFAOYSA-N thiophene-2-carbonitrile Chemical compound N#CC1=CC=CS1 CUPOOAWTRIURFT-UHFFFAOYSA-N 0.000 description 4
- JUNDJWOLDSCTFK-MTZCLOFQSA-N trimegestone Chemical compound C1CC2=CC(=O)CCC2=C2[C@@H]1[C@@H]1CC[C@@](C(=O)[C@@H](O)C)(C)[C@@]1(C)CC2 JUNDJWOLDSCTFK-MTZCLOFQSA-N 0.000 description 4
- 229950008546 trimegestone Drugs 0.000 description 4
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- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- FQZYTYWMLGAPFJ-OQKDUQJOSA-N tamoxifen citrate Chemical compound [H+].[H+].[H+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 FQZYTYWMLGAPFJ-OQKDUQJOSA-N 0.000 description 1
- KUYMVWXKHQSIAS-UHFFFAOYSA-N tert-butyl 2-chloroacetate Chemical compound CC(C)(C)OC(=O)CCl KUYMVWXKHQSIAS-UHFFFAOYSA-N 0.000 description 1
- MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 125000006089 thiamorpholinyl sulfoxide group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30455199A | 1999-05-04 | 1999-05-04 | |
| US09/304,551 | 1999-05-04 | ||
| US09/552,629 | 2000-04-19 | ||
| US09/552,629 US6358948B1 (en) | 1999-05-04 | 2000-04-19 | Quinazolinone and benzoxazine derivatives as progesterone receptor modulators |
| PCT/US2000/011835 WO2000066560A1 (en) | 1999-05-04 | 2000-05-01 | Quinazolinone and benzoxazine derivatives as progesterone receptor modulators |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2003524626A true JP2003524626A (ja) | 2003-08-19 |
Family
ID=56290017
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000615391A Pending JP2003524626A (ja) | 1999-05-04 | 2000-05-01 | プロゲステロンレセプタモジュレーターとしてのキナゾリノンおよびベンゾキサジン誘導体 |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP1175404A1 (zh) |
| JP (1) | JP2003524626A (zh) |
| AU (1) | AU4814000A (zh) |
| CA (1) | CA2371651A1 (zh) |
| HK (1) | HK1043991A1 (zh) |
| MX (1) | MXPA01011310A (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007534767A (ja) * | 2004-04-27 | 2007-11-29 | ワイス | シアノピロール含有環式カルバメートおよびチオカルバメートビアリール、およびこれらの製造方法 |
-
2000
- 2000-05-01 CA CA002371651A patent/CA2371651A1/en not_active Abandoned
- 2000-05-01 AU AU48140/00A patent/AU4814000A/en not_active Abandoned
- 2000-05-01 MX MXPA01011310A patent/MXPA01011310A/es unknown
- 2000-05-01 EP EP00930288A patent/EP1175404A1/en not_active Withdrawn
- 2000-05-01 JP JP2000615391A patent/JP2003524626A/ja active Pending
-
2002
- 2002-06-28 HK HK02104857.2A patent/HK1043991A1/zh unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007534767A (ja) * | 2004-04-27 | 2007-11-29 | ワイス | シアノピロール含有環式カルバメートおよびチオカルバメートビアリール、およびこれらの製造方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1175404A1 (en) | 2002-01-30 |
| CA2371651A1 (en) | 2000-11-09 |
| MXPA01011310A (es) | 2003-07-14 |
| AU4814000A (en) | 2000-11-17 |
| HK1043991A1 (zh) | 2002-10-04 |
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