KR20060054189A - 벤조(4,5)티에노(2,3-ｄ)피리미딘-4-온즈 및 치료용으로의이들의 사용 - Google Patents
벤조(4,5)티에노(2,3-ｄ)피리미딘-4-온즈 및 치료용으로의이들의 사용 Download PDFInfo
- Publication number
- KR20060054189A KR20060054189A KR1020057022958A KR20057022958A KR20060054189A KR 20060054189 A KR20060054189 A KR 20060054189A KR 1020057022958 A KR1020057022958 A KR 1020057022958A KR 20057022958 A KR20057022958 A KR 20057022958A KR 20060054189 A KR20060054189 A KR 20060054189A
- Authority
- KR
- South Korea
- Prior art keywords
- alkyl
- group
- benzo
- optionally substituted
- aryl
- 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.)
- Abandoned
Links
- 238000002560 therapeutic procedure Methods 0.000 title claims description 6
- 125000005605 benzo group Chemical group 0.000 title 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 89
- 201000010099 disease Diseases 0.000 claims abstract description 54
- 230000001419 dependent effect Effects 0.000 claims abstract description 43
- 238000011282 treatment Methods 0.000 claims abstract description 43
- 208000035475 disorder Diseases 0.000 claims abstract description 35
- 102000004190 Enzymes Human genes 0.000 claims abstract description 30
- 108090000790 Enzymes Proteins 0.000 claims abstract description 30
- 239000003270 steroid hormone Substances 0.000 claims abstract description 27
- 239000003098 androgen Substances 0.000 claims abstract description 17
- 201000010260 leiomyoma Diseases 0.000 claims abstract description 17
- 230000005764 inhibitory process Effects 0.000 claims abstract description 15
- 150000003431 steroids Chemical class 0.000 claims abstract description 15
- 206010060862 Prostate cancer Diseases 0.000 claims abstract description 11
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims abstract description 11
- 206010006187 Breast cancer Diseases 0.000 claims abstract description 9
- 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 9
- 206010046798 Uterine leiomyoma Diseases 0.000 claims abstract description 8
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims abstract description 7
- 206010014733 Endometrial cancer Diseases 0.000 claims abstract description 7
- 206010014759 Endometrial neoplasm Diseases 0.000 claims abstract description 7
- 206010033128 Ovarian cancer Diseases 0.000 claims abstract description 7
- 206010061535 Ovarian neoplasm Diseases 0.000 claims abstract description 7
- 208000002193 Pain Diseases 0.000 claims abstract description 7
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims abstract description 7
- 208000002874 Acne Vulgaris Diseases 0.000 claims abstract description 6
- 201000004384 Alopecia Diseases 0.000 claims abstract description 6
- 208000005171 Dysmenorrhea Diseases 0.000 claims abstract description 6
- 206010013935 Dysmenorrhoea Diseases 0.000 claims abstract description 6
- 201000009273 Endometriosis Diseases 0.000 claims abstract description 6
- 206010020112 Hirsutism Diseases 0.000 claims abstract description 6
- 208000002495 Uterine Neoplasms Diseases 0.000 claims abstract description 6
- 206010046788 Uterine haemorrhage Diseases 0.000 claims abstract description 6
- 206010000496 acne Diseases 0.000 claims abstract description 6
- 206010046766 uterine cancer Diseases 0.000 claims abstract description 6
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 5
- 206010039792 Seborrhoea Diseases 0.000 claims abstract description 5
- 231100000360 alopecia Toxicity 0.000 claims abstract description 5
- 230000004064 dysfunction Effects 0.000 claims abstract description 5
- 201000010065 polycystic ovary syndrome Diseases 0.000 claims abstract description 5
- 201000007094 prostatitis Diseases 0.000 claims abstract description 5
- 208000008742 seborrheic dermatitis Diseases 0.000 claims abstract description 5
- 230000002485 urinary effect Effects 0.000 claims abstract description 5
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 4
- 208000002177 Cataract Diseases 0.000 claims abstract description 4
- 206010009944 Colon cancer Diseases 0.000 claims abstract description 4
- 206010014756 Endometrial hypertrophy Diseases 0.000 claims abstract description 4
- 206010020880 Hypertrophy Diseases 0.000 claims abstract description 4
- 230000001919 adrenal effect Effects 0.000 claims abstract description 4
- 208000029742 colonic neoplasm Diseases 0.000 claims abstract description 4
- 201000006417 multiple sclerosis Diseases 0.000 claims abstract description 4
- 210000002307 prostate Anatomy 0.000 claims abstract description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 4
- 208000037816 tissue injury Diseases 0.000 claims abstract description 4
- 230000037303 wrinkles Effects 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 521
- -1 dioxolyl Chemical group 0.000 claims description 241
- 125000001424 substituent group Chemical group 0.000 claims description 148
- 229910052736 halogen Inorganic materials 0.000 claims description 132
- 125000003118 aryl group Chemical group 0.000 claims description 129
- 229910052739 hydrogen Inorganic materials 0.000 claims description 129
- 239000001257 hydrogen Substances 0.000 claims description 129
- 238000000034 method Methods 0.000 claims description 126
- 150000002367 halogens Chemical class 0.000 claims description 116
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 106
- 125000001072 heteroaryl group Chemical group 0.000 claims description 96
- 125000000217 alkyl group Chemical group 0.000 claims description 93
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 62
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 62
- 125000004122 cyclic group Chemical group 0.000 claims description 61
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 51
- 125000004043 oxo group Chemical group O=* 0.000 claims description 45
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 42
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 41
- 125000001544 thienyl group Chemical group 0.000 claims description 38
- 125000004076 pyridyl group Chemical group 0.000 claims description 35
- 125000002541 furyl group Chemical group 0.000 claims description 34
- 150000002825 nitriles Chemical class 0.000 claims description 29
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 28
- 125000004104 aryloxy group Chemical group 0.000 claims description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
- 125000001624 naphthyl group Chemical group 0.000 claims description 27
- 125000004432 carbon atom Chemical group C* 0.000 claims description 26
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 24
- 108010070743 3(or 17)-beta-hydroxysteroid dehydrogenase Proteins 0.000 claims description 23
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 23
- 125000002252 acyl group Chemical group 0.000 claims description 21
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 20
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 20
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 20
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical group O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 claims description 19
- 125000005843 halogen group Chemical group 0.000 claims description 18
- 125000003368 amide group Chemical group 0.000 claims description 17
- 150000002430 hydrocarbons Chemical group 0.000 claims description 17
- 125000002757 morpholinyl group Chemical group 0.000 claims description 17
- 125000003386 piperidinyl group Chemical group 0.000 claims description 17
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 17
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 17
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 17
- 125000004642 (C1-C12) alkoxy group Chemical group 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 15
- 125000001246 bromo group Chemical group Br* 0.000 claims description 15
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 15
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 15
- 230000002265 prevention Effects 0.000 claims description 14
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 14
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 13
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 13
- 125000000335 thiazolyl group Chemical group 0.000 claims description 13
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims description 12
- 125000004423 acyloxy group Chemical group 0.000 claims description 12
- 125000004414 alkyl thio group Chemical group 0.000 claims description 12
- 239000004305 biphenyl Substances 0.000 claims description 12
- 235000010290 biphenyl Nutrition 0.000 claims description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 12
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 12
- 125000003107 substituted aryl group Chemical group 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 11
- 125000005110 aryl thio group Chemical group 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 125000003725 azepanyl group Chemical group 0.000 claims description 10
- 125000002393 azetidinyl group Chemical group 0.000 claims description 10
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 10
- 125000005959 diazepanyl group Chemical group 0.000 claims description 10
- 125000002883 imidazolyl group Chemical group 0.000 claims description 10
- 125000001041 indolyl group Chemical group 0.000 claims description 10
- 125000000160 oxazolidinyl group Chemical group 0.000 claims description 10
- 125000004193 piperazinyl group Chemical group 0.000 claims description 10
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 10
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 claims description 10
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 claims description 10
- 125000001984 thiazolidinyl group Chemical group 0.000 claims description 10
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 9
- 102100034067 Dehydrogenase/reductase SDR family member 11 Human genes 0.000 claims description 9
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 9
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 9
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 9
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- 125000002971 oxazolyl group Chemical group 0.000 claims description 9
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 9
- 229920006395 saturated elastomer Polymers 0.000 claims description 9
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 9
- 239000004480 active ingredient Substances 0.000 claims description 8
- 125000005251 aryl acyl group Chemical group 0.000 claims description 8
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 125000001680 trimethoxyphenyl group Chemical group 0.000 claims description 7
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 6
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- XPTDTOFYTCYHSF-UHFFFAOYSA-N 3-benzyl-8-hydroxy-2-thiophen-2-yl-[1]benzothiolo[2,3-d]pyrimidin-4-one Chemical compound OC1=CC=CC(C=2C(=O)N3CC=4C=CC=CC=4)=C1SC=2N=C3C1=CC=CS1 XPTDTOFYTCYHSF-UHFFFAOYSA-N 0.000 claims description 4
- FBFTVBPTKNXUJZ-UHFFFAOYSA-N 7-bromo-3-(2-methylbutyl)-2-(3,4,5-trimethoxyphenyl)-6,7-dihydro-5h-[1]benzothiolo[2,3-d]pyrimidine-4,8-dione Chemical compound N=1C=2SC(C(C(Br)CC3)=O)=C3C=2C(=O)N(CC(C)CC)C=1C1=CC(OC)=C(OC)C(OC)=C1 FBFTVBPTKNXUJZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 4
- DRJKOQOGSXDPKO-UHFFFAOYSA-N 2-(2-chloro-3,4,5-trimethoxyphenyl)-8-hydroxy-3-(2-methylbutyl)-[1]benzothiolo[2,3-d]pyrimidin-4-one Chemical compound N=1C=2SC3=C(O)C=CC=C3C=2C(=O)N(CC(C)CC)C=1C1=CC(OC)=C(OC)C(OC)=C1Cl DRJKOQOGSXDPKO-UHFFFAOYSA-N 0.000 claims description 3
- QCKAVYPIXVSRIP-UHFFFAOYSA-N 2-(2-chloro-3,4,5-trimethoxyphenyl)-8-hydroxy-3-(oxolan-2-ylmethyl)-[1]benzothiolo[2,3-d]pyrimidin-4-one Chemical compound COC1=C(OC)C(OC)=CC(C=2N(C(=O)C=3C4=CC=CC(O)=C4SC=3N=2)CC2OCCC2)=C1Cl QCKAVYPIXVSRIP-UHFFFAOYSA-N 0.000 claims description 3
- BLRNHMUGGSGEFC-UHFFFAOYSA-N 2-(8-hydroxy-4-oxo-2-thiophen-2-yl-[1]benzothiolo[2,3-d]pyrimidin-3-yl)ethyl thiophene-2-carboxylate Chemical compound OC1=CC=CC(C=2C(=O)N3CCOC(=O)C=4SC=CC=4)=C1SC=2N=C3C1=CC=CS1 BLRNHMUGGSGEFC-UHFFFAOYSA-N 0.000 claims description 3
- DCLCVMZXAZXDIA-UHFFFAOYSA-N 3-[(5-bromofuran-2-yl)methyl]-8-hydroxy-2-propyl-[1]benzothiolo[2,3-d]pyrimidin-4-one Chemical compound CCCC1=NC=2SC3=C(O)C=CC=C3C=2C(=O)N1CC1=CC=C(Br)O1 DCLCVMZXAZXDIA-UHFFFAOYSA-N 0.000 claims description 3
- BYLUGBTVNKWOOP-UHFFFAOYSA-N 3-benzyl-2-(2-chloro-3,4,5-trimethoxyphenyl)-8-hydroxy-[1]benzothiolo[2,3-d]pyrimidin-4-one Chemical compound COC1=C(OC)C(OC)=CC(C=2N(C(=O)C=3C4=CC=CC(O)=C4SC=3N=2)CC=2C=CC=CC=2)=C1Cl BYLUGBTVNKWOOP-UHFFFAOYSA-N 0.000 claims description 3
- IHFCTBYGNJBHLU-UHFFFAOYSA-N 3-benzyl-2-(4-methoxyphenyl)-4-oxo-[1]benzothiolo[2,3-d]pyrimidine-7-carbaldehyde Chemical compound C1=CC(OC)=CC=C1C(N(C1=O)CC=2C=CC=CC=2)=NC2=C1C1=CC=C(C=O)C=C1S2 IHFCTBYGNJBHLU-UHFFFAOYSA-N 0.000 claims description 3
- PLMIWUYUHDKIOU-UHFFFAOYSA-N 3-benzyl-8-ethylsulfanyl-2-(4-methoxyphenyl)-4-oxo-5,6-dihydro-[1]benzothiolo[2,3-d]pyrimidine-7-carbaldehyde Chemical compound CCSC1=C(C=O)CCC(C=2C(=O)N3CC=4C=CC=CC=4)=C1SC=2N=C3C1=CC=C(OC)C=C1 PLMIWUYUHDKIOU-UHFFFAOYSA-N 0.000 claims description 3
- GOBGXFNVRDORKE-UHFFFAOYSA-N 3-benzyl-8-ethylsulfanyl-2-(4-methoxyphenyl)-4-oxo-[1]benzothiolo[2,3-d]pyrimidine-7-carbaldehyde Chemical compound CCSC1=C(C=O)C=CC(C=2C(=O)N3CC=4C=CC=CC=4)=C1SC=2N=C3C1=CC=C(OC)C=C1 GOBGXFNVRDORKE-UHFFFAOYSA-N 0.000 claims description 3
- XQSDTRVRYXPNAZ-UHFFFAOYSA-N 3-butyl-2-(2,4-difluorophenyl)-8-hydroxy-[1]benzothiolo[2,3-d]pyrimidin-4-one Chemical compound N=1C=2SC3=C(O)C=CC=C3C=2C(=O)N(CCCC)C=1C1=CC=C(F)C=C1F XQSDTRVRYXPNAZ-UHFFFAOYSA-N 0.000 claims description 3
- CMIPVAHJRMGCEL-UHFFFAOYSA-N 3-butyl-8-hydroxy-2-(2-methoxyphenyl)-[1]benzothiolo[2,3-d]pyrimidin-4-one Chemical compound N=1C=2SC3=C(O)C=CC=C3C=2C(=O)N(CCCC)C=1C1=CC=CC=C1OC CMIPVAHJRMGCEL-UHFFFAOYSA-N 0.000 claims description 3
- HHBJKZCQWKMHNL-UHFFFAOYSA-N 3-butyl-8-hydroxy-2-(3,4,5-trimethoxyphenyl)-[1]benzothiolo[2,3-d]pyrimidin-4-one Chemical compound N=1C=2SC3=C(O)C=CC=C3C=2C(=O)N(CCCC)C=1C1=CC(OC)=C(OC)C(OC)=C1 HHBJKZCQWKMHNL-UHFFFAOYSA-N 0.000 claims description 3
- FVCXLTHFQRFWJY-UHFFFAOYSA-N 5-bromo-3-(2-methylpropyl)-2-(3,4,5-trimethoxyphenyl)-6,7-dihydro-5h-[1]benzothiolo[2,3-d]pyrimidine-4,8-dione Chemical compound COC1=C(OC)C(OC)=CC(C=2N(C(=O)C=3C4=C(C(CCC4Br)=O)SC=3N=2)CC(C)C)=C1 FVCXLTHFQRFWJY-UHFFFAOYSA-N 0.000 claims description 3
- RSKOJBUMOCXXJN-UHFFFAOYSA-N 7-bromo-8-hydroxy-3-(2-methoxyethyl)-2-thiophen-2-yl-[1]benzothiolo[2,3-d]pyrimidin-4-one Chemical compound N=1C=2SC3=C(O)C(Br)=CC=C3C=2C(=O)N(CCOC)C=1C1=CC=CS1 RSKOJBUMOCXXJN-UHFFFAOYSA-N 0.000 claims description 3
- IERNYVIIHPXXCC-UHFFFAOYSA-N 8-hydroxy-3-(2-methylbutyl)-2-(3,4,5-trimethoxyphenyl)-[1]benzothiolo[2,3-d]pyrimidin-4-one Chemical compound N=1C=2SC3=C(O)C=CC=C3C=2C(=O)N(CC(C)CC)C=1C1=CC(OC)=C(OC)C(OC)=C1 IERNYVIIHPXXCC-UHFFFAOYSA-N 0.000 claims description 3
- IWWPVLAMLDKZCY-UHFFFAOYSA-N [3-[(5-bromofuran-2-yl)methyl]-4-oxo-2-propyl-[1]benzothiolo[2,3-d]pyrimidin-8-yl] acetate Chemical class CCCC1=NC=2SC3=C(OC(C)=O)C=CC=C3C=2C(=O)N1CC1=CC=C(Br)O1 IWWPVLAMLDKZCY-UHFFFAOYSA-N 0.000 claims description 3
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000004494 ethyl ester group Chemical group 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- DRTQHLFDZIQYNT-UHFFFAOYSA-N methyl 2-(3-benzyl-7-tert-butyl-4-oxo-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-2-yl)acetate Chemical compound COC(=O)CC1=NC=2SC=3CC(C(C)(C)C)CCC=3C=2C(=O)N1CC1=CC=CC=C1 DRTQHLFDZIQYNT-UHFFFAOYSA-N 0.000 claims description 3
- 238000011321 prophylaxis Methods 0.000 claims description 3
- 238000006467 substitution reaction Methods 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- JZGZKRJVTIRPOK-UHFFFAOYSA-N ethyl thiophene-2-carboxylate Chemical compound CCOC(=O)C1=CC=CS1 JZGZKRJVTIRPOK-UHFFFAOYSA-N 0.000 claims description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 37
- 125000003396 thiol group Chemical class [H]S* 0.000 claims 8
- 125000005961 oxazepanyl group Chemical group 0.000 claims 3
- 125000006219 1-ethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 claims 1
- XHHYIAWXOGUEII-UHFFFAOYSA-N 2-(2-bromo-3,4,5-trimethoxyphenyl)-8-hydroxy-3-(2-methylpropyl)-[1]benzothiolo[2,3-d]pyrimidin-4-one Chemical compound COC1=C(OC)C(OC)=CC(C=2N(C(=O)C=3C4=CC=CC(O)=C4SC=3N=2)CC(C)C)=C1Br XHHYIAWXOGUEII-UHFFFAOYSA-N 0.000 claims 1
- 125000006512 3,4-dichlorobenzyl group Chemical group [H]C1=C(Cl)C(Cl)=C([H])C(=C1[H])C([H])([H])* 0.000 claims 1
- BGNGWHSBYQYVRX-UHFFFAOYSA-N 4-(dimethylamino)benzaldehyde Chemical compound CN(C)C1=CC=C(C=O)C=C1 BGNGWHSBYQYVRX-UHFFFAOYSA-N 0.000 claims 1
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims 1
- 101710088194 Dehydrogenase Proteins 0.000 claims 1
- 208000032843 Hemorrhage Diseases 0.000 claims 1
- 230000000740 bleeding effect Effects 0.000 claims 1
- 125000004802 cyanophenyl group Chemical group 0.000 claims 1
- 125000000950 dibromo group Chemical group Br* 0.000 claims 1
- 125000004188 dichlorophenyl group Chemical group 0.000 claims 1
- 125000004212 difluorophenyl group Chemical group 0.000 claims 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 1
- 125000001207 fluorophenyl group Chemical group 0.000 claims 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 1
- 125000006513 pyridinyl methyl group Chemical group 0.000 claims 1
- 238000011285 therapeutic regimen Methods 0.000 claims 1
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Classifications
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Landscapes
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- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Plural Heterocyclic Compounds (AREA)
- Joining Of Glass To Other Materials (AREA)
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| US47704703P | 2003-06-10 | 2003-06-10 | |
| US60/477,047 | 2003-06-10 |
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| KR20060054189A true KR20060054189A (ko) | 2006-05-22 |
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| KR1020057022958A Abandoned KR20060054189A (ko) | 2003-06-10 | 2004-06-09 | 벤조(4,5)티에노(2,3-ｄ)피리미딘-4-온즈 및 치료용으로의이들의 사용 |
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| EP (1) | EP1635839B1 (enExample) |
| JP (1) | JP4605800B2 (enExample) |
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| AT (1) | ATE479437T1 (enExample) |
| AU (1) | AU2004277311B8 (enExample) |
| BR (1) | BRPI0411295A (enExample) |
| CA (1) | CA2527617A1 (enExample) |
| DE (1) | DE602004028934D1 (enExample) |
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| ES (2) | ES2352552T3 (enExample) |
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| MX (1) | MXPA05012745A (enExample) |
| NO (1) | NO20060123L (enExample) |
| PL (1) | PL1635839T3 (enExample) |
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| SA (1) | SA04250159B1 (enExample) |
| SI (1) | SI1635839T1 (enExample) |
| TW (1) | TWI349551B (enExample) |
| WO (1) | WO2005032527A2 (enExample) |
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| US7524853B2 (en) | 2003-06-10 | 2009-04-28 | Solvay Pharmaceuticals B.V. | Compounds and their use in therapy |
| WO2005108376A1 (en) * | 2004-05-06 | 2005-11-17 | Smithkline Beecham Corporation | Calcilytic compounds |
| WO2006044826A2 (en) * | 2004-10-20 | 2006-04-27 | Compass Pharmaceuticals Llc | Thiophens and their use as anti-tumor agents |
| BRPI0419229A (pt) * | 2004-12-13 | 2007-12-18 | Solvay Pharm Gmbh | derivados de tiofenopirimidinona substituìdos como inibidores de 17beta-hidroxiesteróide-desidrogenase, uso e composição farmacêutica |
| FR2904000A1 (fr) * | 2006-07-19 | 2008-01-25 | Galderma Res & Dev S N C Snc | Modulateurs de hsd17b7 dans le traitement de l'acne ou de l'hyperseborrhee |
| FR2904318B1 (fr) * | 2006-07-27 | 2011-02-25 | Scras | Derives de pyrimidinone et leur utilisation comme medicament |
| US8080540B2 (en) | 2006-09-19 | 2011-12-20 | Abbott Products Gmbh | Therapeutically active triazoles and their use |
| US8288367B2 (en) | 2006-11-30 | 2012-10-16 | Solvay Pharmaceuticals Gmbh | Substituted estratriene derivatives as 17BETA HSD inhibitors |
| DE102007015169A1 (de) | 2007-03-27 | 2008-10-02 | Universität des Saarlandes Campus Saarbrücken | 17Beta-Hydroxysteroid-Dehydrogenase-Typ1-Inhibitoren zur Behandlung hormonabhängiger Erkrankungen |
| WO2009001214A2 (en) * | 2007-06-28 | 2008-12-31 | Pfizer Products Inc. | Thieno[2,3-d]pyrimidin-4(3h)-one, isoxazolo[5,4-d]pyrimidin-4(5h)-one and isothiazolo[5,4-d]pyrimidin-4(5h)-one derivatives as calcium receptor antagonists |
| DE102007040243A1 (de) * | 2007-08-25 | 2009-02-26 | Universität des Saarlandes | 17Beta-Hydroxysteriod-Dehydrogenase Typ1 Inhibitoren zur Behandlung hormonabhängiger Erkrankungen |
| EP2381775A4 (en) * | 2008-12-23 | 2012-08-15 | Harvard College | INHIBITORS OF NECROPTOSIS OF SMALL MOLECULAR SIZE |
| EP2609089A1 (en) | 2010-08-27 | 2013-07-03 | Universität des Saarlandes | Selective 17beta-hydroxysteroid dehydrogenase type 1 inhibitors |
| WO2012119605A1 (en) * | 2011-03-10 | 2012-09-13 | Akar Yahya Ahmed Abdellhafeez Salem | New disperse dye with potent anticancer activity |
| TW201520219A (zh) * | 2013-03-12 | 2015-06-01 | Lilly Co Eli | 咪唑並吡啶化合物 |
| EP2968276A4 (en) | 2013-03-15 | 2017-02-15 | President and Fellows of Harvard College | Hybrid necroptosis inhibitors |
| AR096728A1 (es) | 2013-06-25 | 2016-01-27 | Forendo Pharma Ltd | Derivados de estratrieno-tiazol terapéuticamente activos |
| AR096729A1 (es) | 2013-06-25 | 2016-01-27 | Forendo Pharma Ltd | Derivados terapéuticamente activos de estratien-tiazol |
| JP6456373B2 (ja) | 2013-06-25 | 2019-01-23 | フォレンド ファーマ リミテッド | １７β−ヒドロキシステロイドデヒドロゲナーゼ タイプ１の阻害剤として治療活性のあるエストラトリエンチアゾール誘導体 |
| EP3089969A2 (en) | 2014-01-03 | 2016-11-09 | Elexopharm GmbH | Inhibitors of 17beta-hydroxysteroid dehydrogenases type 1 and type 2 |
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| CN109503572B (zh) * | 2017-09-15 | 2021-10-08 | 上海交通大学 | 一种合成吲哚喹啉类化合物的方法 |
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| WO1989008113A1 (en) | 1988-03-02 | 1989-09-08 | Yoshitomi Pharmaceutical Industries, Ltd. | 3,4-DIHYDROTHIENO[2,3-d]PYRIMIDINE COMPOUNDS AND PHARMACEUTICAL APPLICATION THEREOF |
| US5597823A (en) * | 1995-01-27 | 1997-01-28 | Abbott Laboratories | Tricyclic substituted hexahydrobenz [e]isoindole alpha-1 adrenergic antagonists |
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| JPH10273467A (ja) | 1997-01-29 | 1998-10-13 | Snow Brand Milk Prod Co Ltd | 新規テトラロン又はベンゾピラノン誘導体及びその製造方法 |
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| US6291505B1 (en) | 1998-08-07 | 2001-09-18 | Chiron Corporation | Estrogen receptor modulators |
| GB9929302D0 (en) | 1999-12-11 | 2000-02-02 | Univ Cardiff | Benzyl tetralins compositions and uses thereof |
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| US6750248B2 (en) | 2001-11-09 | 2004-06-15 | National University Of Singapore | Methods for preparing an estrogenic preparation and isolated estrogenic compounds from a plant and uses thereof |
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- 2004-06-09 DE DE602004028934T patent/DE602004028934D1/de not_active Expired - Lifetime
- 2004-06-09 AU AU2004277311A patent/AU2004277311B8/en not_active Ceased
- 2004-06-09 AT AT04803089T patent/ATE479437T1/de active
- 2004-06-09 PL PL04803089T patent/PL1635839T3/pl unknown
- 2004-06-09 JP JP2006515869A patent/JP4605800B2/ja not_active Expired - Fee Related
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Also Published As
| Publication number | Publication date |
|---|---|
| US7465739B2 (en) | 2008-12-16 |
| RU2006100033A (ru) | 2007-07-20 |
| MXPA05012745A (es) | 2006-05-17 |
| TW200509937A (en) | 2005-03-16 |
| AU2004277311B8 (en) | 2010-05-27 |
| WO2005032527A3 (en) | 2005-08-04 |
| AU2004277311A1 (en) | 2005-04-14 |
| TWI349551B (en) | 2011-10-01 |
| WO2005032527B1 (en) | 2005-09-22 |
| ZA200508296B (en) | 2007-01-31 |
| AR044650A1 (es) | 2005-09-21 |
| EP1635839B1 (en) | 2010-09-01 |
| AU2004277311B2 (en) | 2010-04-29 |
| PT1635839E (pt) | 2010-10-12 |
| SA04250159B1 (ar) | 2008-06-21 |
| CN1791412A (zh) | 2006-06-21 |
| ATE479437T1 (de) | 2010-09-15 |
| BRPI0411295A (pt) | 2006-08-01 |
| NO20060123L (no) | 2006-03-09 |
| EP1635839A2 (en) | 2006-03-22 |
| ES2352552T3 (es) | 2011-02-21 |
| DK1635839T3 (da) | 2011-01-03 |
| PL1635839T3 (pl) | 2011-02-28 |
| RU2412190C2 (ru) | 2011-02-20 |
| DE602004028934D1 (de) | 2010-10-14 |
| IL172316A0 (en) | 2011-08-01 |
| JP4605800B2 (ja) | 2011-01-05 |
| US20050038053A1 (en) | 2005-02-17 |
| CA2527617A1 (en) | 2005-04-14 |
| JP2006527226A (ja) | 2006-11-30 |
| SI1635839T1 (sl) | 2010-12-31 |
| ES2352554T3 (es) | 2011-02-21 |
| WO2005032527A2 (en) | 2005-04-14 |
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