CN1145618C - 作为黄体酮受体调节剂的环氨基甲酸酯衍生物 - Google Patents

Info

Publication number

CN1145618C

CN1145618C CNB008071004A CN00807100A CN1145618C CN 1145618 C CN1145618 C CN 1145618C CN B008071004 A CNB008071004 A CN B008071004A CN 00807100 A CN00807100 A CN 00807100A CN 1145618 C CN1145618 C CN 1145618C

Authority

CN

China

Prior art keywords

dihydro

benzo

dimethyl

oxazin

phenyl

Prior art date

1999-05-04

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.)

Expired - Fee Related

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• 239000002379 progesterone receptor modulator Substances 0.000 title description 4
• 229940095745 sex hormone and modulator of the genital system progesterone receptor modulator Drugs 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 141
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 62
• 150000003839 salts Chemical class 0.000 claims abstract description 46
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 43
• 150000002367 halogens Chemical class 0.000 claims abstract description 43
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 34
• 125000003342 alkenyl group Chemical group 0.000 claims abstract description 26
• 125000000304 alkynyl group Chemical group 0.000 claims abstract description 22
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 20
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 14
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 13
• 229910052717 sulfur Inorganic materials 0.000 claims abstract description 10
• 125000001424 substituent group Chemical group 0.000 claims abstract description 9
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 83
• -1 diethoxymethyl Chemical group 0.000 claims description 70
• 229910052799 carbon Inorganic materials 0.000 claims description 57
• LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 claims description 56
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 42
• 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 claims description 36
• 229910052739 hydrogen Inorganic materials 0.000 claims description 34
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 18
• 239000000186 progesterone Substances 0.000 claims description 18
• 229960003387 progesterone Drugs 0.000 claims description 18
• UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 17
• 229920006395 saturated elastomer Polymers 0.000 claims description 15
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
• 206010028980 Neoplasm Diseases 0.000 claims description 10
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 10
• 239000003814 drug Substances 0.000 claims description 10
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 9
• 230000015572 biosynthetic process Effects 0.000 claims description 9
• 239000001301 oxygen Substances 0.000 claims description 9
• 125000006697 (C1-C3) aminoalkyl group Chemical group 0.000 claims description 8
• 230000001419 dependent effect Effects 0.000 claims description 8
• 229940088597 hormone Drugs 0.000 claims description 8
• 239000005556 hormone Substances 0.000 claims description 8
• 201000011510 cancer Diseases 0.000 claims description 6
• 201000009273 Endometriosis Diseases 0.000 claims description 5
• 206010016629 fibroma Diseases 0.000 claims description 5
• 229930192474 thiophene Natural products 0.000 claims description 5
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
• GRRPAAFLOYWEHA-UHFFFAOYSA-N 3-(4,4-dimethyl-2-oxo-1h-3,1-benzoxazin-6-yl)-5-methylbenzonitrile Chemical compound CC1=CC(C#N)=CC(C=2C=C3C(C)(C)OC(=O)NC3=CC=2)=C1 GRRPAAFLOYWEHA-UHFFFAOYSA-N 0.000 claims description 3
• 206010062767 Hypophysitis Diseases 0.000 claims description 3
• 210000001072 colon Anatomy 0.000 claims description 3
• 210000004907 gland Anatomy 0.000 claims description 3
• 238000002657 hormone replacement therapy Methods 0.000 claims description 3
• 210000005075 mammary gland Anatomy 0.000 claims description 3
• 206010027191 meningioma Diseases 0.000 claims description 3
• 210000004877 mucosa Anatomy 0.000 claims description 3
• 210000000754 myometrium Anatomy 0.000 claims description 3
• 210000001672 ovary Anatomy 0.000 claims description 3
• 210000002307 prostate Anatomy 0.000 claims description 3
• 150000004867 thiadiazoles Chemical class 0.000 claims description 3
• HVXMMYUSBANZAI-UHFFFAOYSA-N 3-(4,4-dimethyl-2-oxo-1h-3,1-benzoxazin-6-yl)benzonitrile Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC=CC(C#N)=C1 HVXMMYUSBANZAI-UHFFFAOYSA-N 0.000 claims description 2
• NTBMICWLTLYFGW-UHFFFAOYSA-N 3-chloro-5-(4,4-dimethyl-2-oxo-1h-3,1-benzoxazin-6-yl)benzonitrile Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC(Cl)=CC(C#N)=C1 NTBMICWLTLYFGW-UHFFFAOYSA-N 0.000 claims description 2
• BGHLZYDCBNMWCU-UHFFFAOYSA-N 5-(4,4-dimethyl-2-oxo-1h-3,1-benzoxazin-6-yl)thiophene-3-carbonitrile Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC(C#N)=CS1 BGHLZYDCBNMWCU-UHFFFAOYSA-N 0.000 claims description 2
• 230000001105 regulatory effect Effects 0.000 claims description 2
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
• 239000003981 vehicle Substances 0.000 claims description 2
• JVTRZJXFAOQMRA-UHFFFAOYSA-N 1,3-oxazin-2-one Chemical compound O=C1N=CC=CO1 JVTRZJXFAOQMRA-UHFFFAOYSA-N 0.000 claims 5
• 150000003233 pyrroles Chemical class 0.000 claims 3
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 2
• HGGWGNQSJYSEIC-UHFFFAOYSA-N 1-propyl-4H-3,1-benzoxazin-2-one Chemical compound C(CC)N1C(OCC2=C1C=CC=C2)=O HGGWGNQSJYSEIC-UHFFFAOYSA-N 0.000 claims 2
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims 2
• 208000009956 adenocarcinoma Diseases 0.000 claims 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 2
• 230000012173 estrus Effects 0.000 claims 2
• 150000002240 furans Chemical class 0.000 claims 2
• 239000001257 hydrogen Substances 0.000 claims 2
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 2
• 201000006823 malignant adenoma Diseases 0.000 claims 2
• 150000002825 nitriles Chemical class 0.000 claims 2
• YGTAZGSLCXNBQL-UHFFFAOYSA-N 1,2,4-thiadiazole Chemical compound C=1N=CSN=1 YGTAZGSLCXNBQL-UHFFFAOYSA-N 0.000 claims 1
• BFQJUSXZOJUPLO-UHFFFAOYSA-N 2-methyl-4h-3,1-benzoxazine Chemical compound C1=CC=C2COC(C)=NC2=C1 BFQJUSXZOJUPLO-UHFFFAOYSA-N 0.000 claims 1
• FTBBGQKRYUTLMP-UHFFFAOYSA-N 2-nitro-1h-pyrrole Chemical compound [O-][N+](=O)C1=CC=CN1 FTBBGQKRYUTLMP-UHFFFAOYSA-N 0.000 claims 1
• GZOJTRITAZODJV-UHFFFAOYSA-N 3,1-benzoxazin-2-one Chemical compound C1=CC=CC2=COC(=O)N=C21 GZOJTRITAZODJV-UHFFFAOYSA-N 0.000 claims 1
• 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims 1
• JROQAKHICNOXFO-UHFFFAOYSA-N 3-(3-fluorophenyl)thiophene Chemical compound FC1=CC=CC(C2=CSC=C2)=C1 JROQAKHICNOXFO-UHFFFAOYSA-N 0.000 claims 1
• KVMSWMUZFCLLFV-UHFFFAOYSA-N 3-(4,4-dimethyl-2-oxo-1h-3,1-benzoxazin-6-yl)-5-fluorobenzonitrile Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC(F)=CC(C#N)=C1 KVMSWMUZFCLLFV-UHFFFAOYSA-N 0.000 claims 1
• JGYMUYVJOIEFFQ-UHFFFAOYSA-N 3-(4,4-dimethyl-2-oxo-1h-3,1-benzoxazin-6-yl)-5-methoxybenzonitrile Chemical compound COC1=CC(C#N)=CC(C=2C=C3C(C)(C)OC(=O)NC3=CC=2)=C1 JGYMUYVJOIEFFQ-UHFFFAOYSA-N 0.000 claims 1
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims 1
• QRNMAUBTQDBSSM-UHFFFAOYSA-N 3-fluoro-5-(2-oxospiro[1h-3,1-benzoxazine-4,1'-cyclohexane]-6-yl)benzonitrile Chemical compound FC1=CC(C#N)=CC(C=2C=C3C4(CCCCC4)OC(=O)NC3=CC=2)=C1 QRNMAUBTQDBSSM-UHFFFAOYSA-N 0.000 claims 1
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 1
• MEIWUXZPJSPWJO-UHFFFAOYSA-N 4,4-diethyl-6-(3-nitrophenyl)-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(CC)(CC)OC(=O)NC2=CC=C1C1=CC=CC([N+]([O-])=O)=C1 MEIWUXZPJSPWJO-UHFFFAOYSA-N 0.000 claims 1
• AXVHYEZJTTVOJH-UHFFFAOYSA-N 4,4-dimethyl-6-(3-nitrophenyl)-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC=CC([N+]([O-])=O)=C1 AXVHYEZJTTVOJH-UHFFFAOYSA-N 0.000 claims 1
• CHSVPWMJSJAVAI-UHFFFAOYSA-N 4,4-dimethyl-6-[3-(1,3-thiazol-2-yl)phenyl]-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C(C=1)=CC=CC=1C1=NC=CS1 CHSVPWMJSJAVAI-UHFFFAOYSA-N 0.000 claims 1
• DZRIKLQQKVBDJJ-UHFFFAOYSA-N 4,4-dimethyl-6-[3-(2-trimethylsilylethynyl)phenyl]-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC=CC(C#C[Si](C)(C)C)=C1 DZRIKLQQKVBDJJ-UHFFFAOYSA-N 0.000 claims 1
• RHSCGZFJZHKZNC-UHFFFAOYSA-N 4,4-dimethyl-6-[3-(2h-tetrazol-5-yl)phenyl]-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C(C=1)=CC=CC=1C1=NN=NN1 RHSCGZFJZHKZNC-UHFFFAOYSA-N 0.000 claims 1
• QHHQRGUMAXRMAY-UHFFFAOYSA-N 4-(2-oxospiro[1h-3,1-benzoxazine-4,1'-cyclohexane]-6-yl)thiophene-2-carbonitrile Chemical compound O1C(=O)NC2=CC=C(C=3C=C(SC=3)C#N)C=C2C21CCCCC2 QHHQRGUMAXRMAY-UHFFFAOYSA-N 0.000 claims 1
• IJSGDARRCNDONL-UHFFFAOYSA-N 4-(4,4-dimethyl-2-oxo-1h-3,1-benzoxazin-6-yl)furan-2-carbonitrile Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=COC(C#N)=C1 IJSGDARRCNDONL-UHFFFAOYSA-N 0.000 claims 1
• DNRMTRMFSKNGIV-UHFFFAOYSA-N 4-butyl-5-(4,4-dimethyl-2-oxo-1h-3,1-benzoxazin-6-yl)thiophene-2-carbonitrile Chemical compound C1=C(C#N)SC(C=2C=C3C(C)(C)OC(=O)NC3=CC=2)=C1CCCC DNRMTRMFSKNGIV-UHFFFAOYSA-N 0.000 claims 1
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
• NOKYGJVHBGKMNZ-UHFFFAOYSA-N 4-methyl-5-(2-oxospiro[1h-3,1-benzoxazine-4,1'-cyclohexane]-6-yl)thiophene-2-carbonitrile Chemical compound C1=C(C#N)SC(C=2C=C3C4(CCCCC4)OC(=O)NC3=CC=2)=C1C NOKYGJVHBGKMNZ-UHFFFAOYSA-N 0.000 claims 1
• SVVIWFMTYDOJQX-UHFFFAOYSA-N 5-(2-oxospiro[1h-3,1-benzoxazine-4,1'-cyclohexane]-6-yl)thiophene-2-carbonitrile Chemical compound O1C(=O)NC2=CC=C(C=3SC(=CC=3)C#N)C=C2C21CCCCC2 SVVIWFMTYDOJQX-UHFFFAOYSA-N 0.000 claims 1
• MGCPANQAGXWBFT-UHFFFAOYSA-N 6-(2-chlorophenyl)-4,4-dimethyl-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC=CC=C1Cl MGCPANQAGXWBFT-UHFFFAOYSA-N 0.000 claims 1
• RGFZPIHTBCRGJA-UHFFFAOYSA-N 6-(2-fluorophenyl)-4,4-dimethyl-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC=CC=C1F RGFZPIHTBCRGJA-UHFFFAOYSA-N 0.000 claims 1
• GRPMNBASJAVOAN-UHFFFAOYSA-N 6-(3,5-dichlorophenyl)-4,4-dimethyl-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC(Cl)=CC(Cl)=C1 GRPMNBASJAVOAN-UHFFFAOYSA-N 0.000 claims 1
• COCHTGRDEIHWSU-UHFFFAOYSA-N 6-(3-bromo-5-fluorophenyl)-1,4,4-trimethyl-3,1-benzoxazin-2-one Chemical compound C=1C=C2N(C)C(=O)OC(C)(C)C2=CC=1C1=CC(F)=CC(Br)=C1 COCHTGRDEIHWSU-UHFFFAOYSA-N 0.000 claims 1
• UWIIXWIVGXAFAN-UHFFFAOYSA-N 6-(3-bromo-5-fluorophenyl)-4,4-dimethyl-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC(F)=CC(Br)=C1 UWIIXWIVGXAFAN-UHFFFAOYSA-N 0.000 claims 1
• PPDYGKBOJSGKBD-UHFFFAOYSA-N 6-(3-bromophenyl)-4,4-dimethyl-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC=CC(Br)=C1 PPDYGKBOJSGKBD-UHFFFAOYSA-N 0.000 claims 1
• PRCXSDHAGJJCKC-UHFFFAOYSA-N 6-(3-chloro-4-fluorophenyl)-4,4-dimethyl-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC=C(F)C(Cl)=C1 PRCXSDHAGJJCKC-UHFFFAOYSA-N 0.000 claims 1
• QFJFPUFDMQGULL-UHFFFAOYSA-N 6-(3-chloro-5-fluorophenyl)-4,4-dimethyl-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC(F)=CC(Cl)=C1 QFJFPUFDMQGULL-UHFFFAOYSA-N 0.000 claims 1
• ZFMGZMLOROWZPV-UHFFFAOYSA-N 6-(3-chlorophenyl)-4,4-diethyl-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(CC)(CC)OC(=O)NC2=CC=C1C1=CC=CC(Cl)=C1 ZFMGZMLOROWZPV-UHFFFAOYSA-N 0.000 claims 1
• VMPIROWONHUKCP-UHFFFAOYSA-N 6-(3-chlorophenyl)-4,4-dimethyl-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC=CC(Cl)=C1 VMPIROWONHUKCP-UHFFFAOYSA-N 0.000 claims 1
• CPDGATVXBVRXCW-UHFFFAOYSA-N 6-(3-chlorophenyl)-4-cyclopropyl-4-methyl-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)(C3CC3)OC(=O)NC2=CC=C1C1=CC=CC(Cl)=C1 CPDGATVXBVRXCW-UHFFFAOYSA-N 0.000 claims 1
• UNTRVRJHIUBUIT-UHFFFAOYSA-N 6-(3-chlorophenyl)-4-methyl-1,4-dihydro-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)OC(=O)NC2=CC=C1C1=CC=CC(Cl)=C1 UNTRVRJHIUBUIT-UHFFFAOYSA-N 0.000 claims 1
• YTLKMKKTJYVGCW-UHFFFAOYSA-N 6-(3-chlorophenyl)-4-methyl-4-phenyl-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)(C=3C=CC=CC=3)OC(=O)NC2=CC=C1C1=CC=CC(Cl)=C1 YTLKMKKTJYVGCW-UHFFFAOYSA-N 0.000 claims 1
• RTYILLPPQLHABM-UHFFFAOYSA-N 6-(3-chlorophenyl)-4-phenyl-1,4-dihydro-3,1-benzoxazin-2-one Chemical compound ClC1=CC=CC(C=2C=C3C(C=4C=CC=CC=4)OC(=O)NC3=CC=2)=C1 RTYILLPPQLHABM-UHFFFAOYSA-N 0.000 claims 1
• UOARKAQAGLVLOK-UHFFFAOYSA-N 6-(3-chlorophenyl)spiro[1h-3,1-benzoxazine-4,1'-cyclohexane]-2-one Chemical compound ClC1=CC=CC(C=2C=C3C4(CCCCC4)OC(=O)NC3=CC=2)=C1 UOARKAQAGLVLOK-UHFFFAOYSA-N 0.000 claims 1
• GKEMTHTTWRREOR-UHFFFAOYSA-N 6-(3-chlorophenyl)spiro[1h-3,1-benzoxazine-4,1'-cyclopentane]-2-one Chemical compound ClC1=CC=CC(C=2C=C3C4(CCCC4)OC(=O)NC3=CC=2)=C1 GKEMTHTTWRREOR-UHFFFAOYSA-N 0.000 claims 1
• VOXOVWZYJPEBBX-UHFFFAOYSA-N 6-(3-fluoro-5-nitrophenyl)-4,4-dimethyl-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC(F)=CC([N+]([O-])=O)=C1 VOXOVWZYJPEBBX-UHFFFAOYSA-N 0.000 claims 1
• ZFFAAIRKIJZJRS-UHFFFAOYSA-N 6-(4-chlorophenyl)-4,4-dimethyl-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC=C(Cl)C=C1 ZFFAAIRKIJZJRS-UHFFFAOYSA-N 0.000 claims 1
• QBIGFWOGRAVJFF-UHFFFAOYSA-N 6-[3-bromo-5-(trifluoromethoxy)phenyl]-4,4-dimethyl-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC(Br)=CC(OC(F)(F)F)=C1 QBIGFWOGRAVJFF-UHFFFAOYSA-N 0.000 claims 1
• LBLQYBYBFGZIGA-UHFFFAOYSA-N 6-[3-fluoro-5-(trifluoromethyl)phenyl]-4,4-dimethyl-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC(F)=CC(C(F)(F)F)=C1 LBLQYBYBFGZIGA-UHFFFAOYSA-N 0.000 claims 1
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 1
• UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical compound C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 claims 1
• MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims 1
• UPBFDSIZJMPINP-UHFFFAOYSA-N ethoxyethane;phosphoric acid Chemical compound CCOCC.OP(O)(O)=O UPBFDSIZJMPINP-UHFFFAOYSA-N 0.000 claims 1
• 125000000168 pyrrolyl group Chemical group 0.000 claims 1
• 239000000779 smoke Substances 0.000 claims 1
• RWZWZULHLIFOAI-UHFFFAOYSA-N tert-butyl 6-(3-cyano-5-fluorophenyl)-4,4-dimethyl-2-oxo-3,1-benzoxazine-1-carboxylate Chemical compound C=1C=C2N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C2=CC=1C1=CC(F)=CC(C#N)=C1 RWZWZULHLIFOAI-UHFFFAOYSA-N 0.000 claims 1
• 125000003831 tetrazolyl group Chemical group 0.000 claims 1
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 136
• 125000003118 aryl group Chemical group 0.000 abstract description 38
• 102000003998 progesterone receptors Human genes 0.000 abstract description 25
• 108090000468 progesterone receptors Proteins 0.000 abstract description 25
• 239000005557 antagonist Substances 0.000 abstract description 22
• 125000004103 aminoalkyl group Chemical group 0.000 abstract description 9
• 125000005842 heteroatom Chemical group 0.000 abstract description 7
• 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 abstract 4
• 125000004426 substituted alkynyl group Chemical group 0.000 abstract 2
• 125000003107 substituted aryl group Chemical group 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 326
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 156
• 238000005160 1H NMR spectroscopy Methods 0.000 description 154
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 145
• 239000007787 solid Substances 0.000 description 127
• 230000008569 process Effects 0.000 description 114
• 235000019439 ethyl acetate Nutrition 0.000 description 112
• 238000002360 preparation method Methods 0.000 description 90
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 86
• 239000000243 solution Substances 0.000 description 79
• 239000000203 mixture Substances 0.000 description 78
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 78
• 229910052757 nitrogen Inorganic materials 0.000 description 75
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 70
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