ES2236485T3 - Derivados de 2h-1-benzopirano, procedimientos para su preparacion y composiciones farmaceuticas de los mismos. - Google Patents
Derivados de 2h-1-benzopirano, procedimientos para su preparacion y composiciones farmaceuticas de los mismos.Info
- Publication number
- ES2236485T3 ES2236485T3 ES02703564T ES02703564T ES2236485T3 ES 2236485 T3 ES2236485 T3 ES 2236485T3 ES 02703564 T ES02703564 T ES 02703564T ES 02703564 T ES02703564 T ES 02703564T ES 2236485 T3 ES2236485 T3 ES 2236485T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- alkanoyl
- aryloyl
- compound
- compounds
- 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.)
- Expired - Lifetime
Links
- 238000002360 preparation method Methods 0.000 title claims description 27
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 5
- 238000000034 method Methods 0.000 title description 10
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 39
- -1 aryloyl Chemical group 0.000 claims abstract description 30
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 125000003118 aryl group Chemical group 0.000 claims abstract description 15
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 15
- 125000005843 halogen group Chemical group 0.000 claims abstract description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 10
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 9
- 125000004429 atom Chemical group 0.000 claims abstract description 9
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 8
- 125000000262 haloalkenyl group Chemical group 0.000 claims abstract description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 7
- 125000001424 substituent group Chemical group 0.000 claims abstract description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 6
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims abstract description 5
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 5
- 150000000463 2H-chromenes Chemical class 0.000 claims abstract description 4
- WPJWYDWRUYBVGA-UHFFFAOYSA-N 4-benzylidene-2,3-dihydrochromene Chemical compound C12=CC=CC=C2OCCC1=CC1=CC=CC=C1 WPJWYDWRUYBVGA-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 3
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims abstract description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 3
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 3
- 239000011737 fluorine Substances 0.000 claims abstract description 3
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 4
- 150000001875 compounds Chemical class 0.000 claims description 136
- 229940011871 estrogen Drugs 0.000 claims description 15
- 239000000262 estrogen Substances 0.000 claims description 15
- 125000001589 carboacyl group Chemical group 0.000 claims description 13
- 150000002148 esters Chemical class 0.000 claims description 10
- KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical compound C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 claims description 5
- 208000001132 Osteoporosis Diseases 0.000 claims description 4
- QKFSKKROTLEPHN-UHFFFAOYSA-N 3-phenyl-4-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]-2h-chromen-7-ol Chemical compound C=1C=CC=CC=1C=1COC2=CC(O)=CC=C2C=1CC(C=C1)=CC=C1OCCN1CCCCC1 QKFSKKROTLEPHN-UHFFFAOYSA-N 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 230000001419 dependent effect Effects 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 230000007170 pathology Effects 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims 2
- 239000004480 active ingredient Substances 0.000 claims 1
- 208000019622 heart disease Diseases 0.000 claims 1
- 125000002252 acyl group Chemical group 0.000 abstract description 9
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 2
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 abstract 1
- IQVYMVBVNVNDLK-UHFFFAOYSA-N C=1COC2=CC=CC=C2C=1CC1=CC=CC=C1 Chemical compound C=1COC2=CC=CC=C2C=1CC1=CC=CC=C1 IQVYMVBVNVNDLK-UHFFFAOYSA-N 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 41
- 239000000243 solution Substances 0.000 description 39
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 35
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 31
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- 239000000203 mixture Substances 0.000 description 24
- 241000700159 Rattus Species 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- 239000007787 solid Substances 0.000 description 19
- 239000002904 solvent Substances 0.000 description 18
- 230000000694 effects Effects 0.000 description 17
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 17
- 229960004622 raloxifene Drugs 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- 235000019439 ethyl acetate Nutrition 0.000 description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- 210000000988 bone and bone Anatomy 0.000 description 11
- XZEUAXYWNKYKPL-WDYNHAJCSA-N levormeloxifene Chemical compound C1([C@H]2[C@@H](C3=CC=C(C=C3OC2(C)C)OC)C=2C=CC(OCCN3CCCC3)=CC=2)=CC=CC=C1 XZEUAXYWNKYKPL-WDYNHAJCSA-N 0.000 description 11
- 229950002728 levormeloxifene Drugs 0.000 description 11
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 10
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 239000000556 agonist Substances 0.000 description 9
- 239000011777 magnesium Substances 0.000 description 9
- 239000003208 petroleum Substances 0.000 description 9
- 229940095743 selective estrogen receptor modulator Drugs 0.000 description 9
- 239000000333 selective estrogen receptor modulator Substances 0.000 description 9
- 239000002585 base Substances 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 7
- 150000001562 benzopyrans Chemical group 0.000 description 7
- 238000009835 boiling Methods 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 210000004291 uterus Anatomy 0.000 description 7
- 206010065687 Bone loss Diseases 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- 230000000638 stimulation Effects 0.000 description 6
- BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 description 5
- 231100000673 dose–response relationship Toxicity 0.000 description 5
- 229910052763 palladium Inorganic materials 0.000 description 5
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 5
- 230000003389 potentiating effect Effects 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000001356 surgical procedure Methods 0.000 description 5
- 229960001603 tamoxifen Drugs 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- 230000003042 antagnostic effect Effects 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 239000000010 aprotic solvent Substances 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 229910052749 magnesium Inorganic materials 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 230000001012 protector Effects 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 238000003747 Grignard reaction Methods 0.000 description 3
- 102000003992 Peroxidases Human genes 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 238000009547 dual-energy X-ray absorptiometry Methods 0.000 description 3
- 230000002327 eosinophilic effect Effects 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 108040007629 peroxidase activity proteins Proteins 0.000 description 3
- 150000002989 phenols Chemical class 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- BFPYWIDHMRZLRN-UHFFFAOYSA-N 17alpha-ethynyl estradiol Natural products OC1=CC=C2C3CCC(C)(C(CC4)(O)C#C)C4C3CCC2=C1 BFPYWIDHMRZLRN-UHFFFAOYSA-N 0.000 description 2
- WMKOZARWBMFKAS-UHFFFAOYSA-N 7-hydroxyisoflavone Chemical compound C=1C(O)=CC=C(C2=O)C=1OC=C2C1=CC=CC=C1 WMKOZARWBMFKAS-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000001266 acyl halides Chemical class 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 230000001833 anti-estrogenic effect Effects 0.000 description 2
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000003821 enantio-separation Methods 0.000 description 2
- 230000001076 estrogenic effect Effects 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 230000009036 growth inhibition Effects 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000015320 potassium carbonate Nutrition 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000008259 solid foam Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 230000001836 utereotrophic effect Effects 0.000 description 2
- NIIVBDSTHWZTJC-UHFFFAOYSA-N (4-oxo-3-phenyl-2,3-dihydrochromen-7-yl) 2,2-dimethylpropanoate Chemical compound C1OC2=CC(OC(=O)C(C)(C)C)=CC=C2C(=O)C1C1=CC=CC=C1 NIIVBDSTHWZTJC-UHFFFAOYSA-N 0.000 description 1
- HBWSXWRFMUSIQF-UHFFFAOYSA-N (4-oxo-3-phenylchromen-7-yl) 2,2-dimethylpropanoate Chemical compound C=1C(OC(=O)C(C)(C)C)=CC=C(C2=O)C=1OC=C2C1=CC=CC=C1 HBWSXWRFMUSIQF-UHFFFAOYSA-N 0.000 description 1
- KEIFWROAQVVDBN-UHFFFAOYSA-N 1,2-dihydronaphthalene Chemical compound C1=CC=C2C=CCCC2=C1 KEIFWROAQVVDBN-UHFFFAOYSA-N 0.000 description 1
- WNRWEBKEQARBKV-UHFFFAOYSA-N 1-(2-chloroethyl)piperidine Chemical compound ClCCN1CCCCC1 WNRWEBKEQARBKV-UHFFFAOYSA-N 0.000 description 1
- VFLQQZCRHPIGJU-UHFFFAOYSA-N 1-(2-chloroethyl)piperidine;hydron;chloride Chemical compound Cl.ClCCN1CCCCC1 VFLQQZCRHPIGJU-UHFFFAOYSA-N 0.000 description 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- HQALDKFFRYFTKP-UHFFFAOYSA-N 2-[4-[4-(2-benzyl-1-benzothiophen-3-yl)phenyl]-2-bromo-6-(3-methoxyphenyl)phenoxy]acetic acid Chemical compound COC1=CC=CC(C=2C(=C(Br)C=C(C=2)C=2C=CC(=CC=2)C=2C3=CC=CC=C3SC=2CC=2C=CC=CC=2)OCC(O)=O)=C1 HQALDKFFRYFTKP-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- IIAVSNKEOMCQBQ-UHFFFAOYSA-N 3,4-dihydro-2H-chromen-2-yl 2,2-dimethylpropanoate Chemical compound C(C(C)(C)C)(=O)OC1OC2=CC=CC=C2CC1 IIAVSNKEOMCQBQ-UHFFFAOYSA-N 0.000 description 1
- SSIMHHUMYMHNID-UHFFFAOYSA-N 4-(chloromethyl)phenol Chemical compound OC1=CC=C(CCl)C=C1 SSIMHHUMYMHNID-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
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- 241000283690 Bos taurus Species 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 229940127406 Estrogen Receptor Agonists Drugs 0.000 description 1
- 101000882584 Homo sapiens Estrogen receptor Proteins 0.000 description 1
- 101001068027 Homo sapiens Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 1
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
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- 102100034464 Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform Human genes 0.000 description 1
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- QCDYQQDYXPDABM-UHFFFAOYSA-N phloroglucinol Chemical compound OC1=CC(O)=CC(O)=C1 QCDYQQDYXPDABM-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/30—Oestrogens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/32—Antioestrogens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrane Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01101521 | 2001-01-24 | ||
| EP01101521A EP1229036B1 (en) | 2001-01-24 | 2001-01-24 | 2H-1-benzopyran derivatives, processes for their preparation and pharmaceutical compositions thereof |
| EP01118682 | 2001-08-03 | ||
| EP01118682A EP1281710A1 (en) | 2001-08-03 | 2001-08-03 | 2H-1-benzopyran derivatives, processes for their preparation and pharmaceutical compositions thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2236485T3 true ES2236485T3 (es) | 2005-07-16 |
Family
ID=26076450
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES02703564T Expired - Lifetime ES2236485T3 (es) | 2001-01-24 | 2002-01-21 | Derivados de 2h-1-benzopirano, procedimientos para su preparacion y composiciones farmaceuticas de los mismos. |
Country Status (26)
| Country | Link |
|---|---|
| US (1) | US6951883B2 (enExample) |
| EP (1) | EP1355906B1 (enExample) |
| JP (1) | JP4332349B2 (enExample) |
| CN (1) | CN1261431C (enExample) |
| AT (1) | ATE286894T1 (enExample) |
| AU (1) | AU2002237282B2 (enExample) |
| BR (1) | BR0207066A (enExample) |
| CA (1) | CA2435775A1 (enExample) |
| CZ (1) | CZ20032014A3 (enExample) |
| DE (1) | DE60202590T2 (enExample) |
| DK (1) | DK1355906T3 (enExample) |
| DZ (1) | DZ3459A1 (enExample) |
| EA (1) | EA006158B1 (enExample) |
| ES (1) | ES2236485T3 (enExample) |
| HU (1) | HUP0401018A3 (enExample) |
| IL (2) | IL157065A0 (enExample) |
| MA (1) | MA26982A1 (enExample) |
| MX (1) | MXPA03006505A (enExample) |
| NO (1) | NO327808B1 (enExample) |
| NZ (1) | NZ527144A (enExample) |
| PL (1) | PL365062A1 (enExample) |
| PT (1) | PT1355906E (enExample) |
| SI (1) | SI1355906T1 (enExample) |
| SK (1) | SK287086B6 (enExample) |
| TN (1) | TNSN03043A1 (enExample) |
| WO (1) | WO2002059113A1 (enExample) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8080675B2 (en) | 2004-09-21 | 2011-12-20 | Marshall Edwards, Inc. | Chroman derivatives, medicaments and use in therapy |
| EP2436680B1 (en) * | 2004-09-21 | 2016-05-18 | Marshall Edwards, Inc. | Chroman derivatives, medicaments and use in therapy |
| CN101056868B (zh) | 2004-09-21 | 2012-05-02 | 马休爱德华兹股份有限公司 | 取代的苯并二氢吡喃衍生物、药物及其在治疗中的应用 |
| AU2005201855B2 (en) * | 2004-09-21 | 2012-03-29 | Marshall Edwards, Inc. | Chroman derived compounds and formulations thereof for use in therapy |
| JP4976649B2 (ja) * | 2004-09-21 | 2012-07-18 | マーシャル エドワーズ，インク． | 化合物 |
| ES2377073T3 (es) * | 2004-09-21 | 2012-03-22 | Marshall Edwards, Inc. | Derivados de cromano sustituidos, medicamentos y utilización en terapia |
| CN101444499B (zh) * | 2007-11-26 | 2012-12-05 | 湘北威尔曼制药股份有限公司 | 一种化合物及其组合物的新用途 |
| WO2012061409A1 (en) | 2010-11-01 | 2012-05-10 | Marshall Edwards, Inc. | Isoflavonoid compounds and methods for the treatment of cancer |
| EA031077B1 (ru) | 2013-06-19 | 2018-11-30 | Серагон Фармасьютикалз, Инк. | Модулятор рецептора эстрогена и его применения |
| PT3253208T (pt) | 2015-02-02 | 2021-06-17 | The Spanish National Cancer Res Centre | Terapêuticas de combinação para utilização no tratamento do cancro da mama |
| EP3541809B1 (en) * | 2016-11-17 | 2025-06-25 | Sanofi | Novel substituted n-(3-fluoropropyl)-pyrrolidine compounds, processes for their preparation and therapeutic uses thereof |
| WO2019051562A1 (en) * | 2017-09-15 | 2019-03-21 | Norbio No. 1 Pty Ltd | TREATMENT OF EXCITOTOXICITY |
| CN112225716A (zh) * | 2020-10-30 | 2021-01-15 | 陕西嘉禾生物科技股份有限公司 | 一种鹰嘴豆牙素a的合成方法 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3374245A (en) * | 1964-04-01 | 1968-03-19 | Ciba Geigy Corp | Unsaturated oxacycles |
| DE1518002C3 (de) * | 1965-01-02 | 1975-01-23 | Merck Patent Gmbh, 6100 Darmstadt | Isoflavane und Isoflavene und Verfahren zu Ihrer Herstellung sowie diese enthaltende Arzneimittel |
| US5280040A (en) * | 1993-03-11 | 1994-01-18 | Zymogenetics, Inc. | Methods for reducing bone loss using centchroman derivatives |
| US5985306A (en) * | 1996-10-28 | 1999-11-16 | Novo Nordisk A/S | (+)-enantiomers of cis-3,4-chroman derivatives useful in prevention or treatment of estrogen diseases or syndromes |
| IL129623A0 (en) * | 1996-10-28 | 2000-02-29 | Novo Nordisk As | Novel trans-3,4-chroman derivatives useful in the prevention or treatment of estrogen related diseases or syndromes |
| ATE225782T1 (de) | 1996-12-13 | 2002-10-15 | Chugai Pharmaceutical Co Ltd | Benzopyranderivate |
| KR20000001793A (ko) | 1998-06-13 | 2000-01-15 | 이경하 | 신규한 벤조피란 또는 티오벤조피란 유도체 |
| ES2207982T3 (es) | 1998-12-30 | 2004-06-01 | Signal Pharmaceuticals, Inc. | Compuestos y metodos para la modulacion de receptores estrogenicos. |
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2002
- 2002-01-21 WO PCT/EP2002/000567 patent/WO2002059113A1/en not_active Ceased
- 2002-01-21 ES ES02703564T patent/ES2236485T3/es not_active Expired - Lifetime
- 2002-01-21 PL PL02365062A patent/PL365062A1/xx not_active IP Right Cessation
- 2002-01-21 JP JP2002559415A patent/JP4332349B2/ja not_active Expired - Fee Related
- 2002-01-21 BR BR0207066-9A patent/BR0207066A/pt not_active IP Right Cessation
- 2002-01-21 CN CNB02804066XA patent/CN1261431C/zh not_active Expired - Fee Related
- 2002-01-21 PT PT02703564T patent/PT1355906E/pt unknown
- 2002-01-21 SI SI200230096T patent/SI1355906T1/xx unknown
- 2002-01-21 DK DK02703564T patent/DK1355906T3/da active
- 2002-01-21 EA EA200300727A patent/EA006158B1/ru not_active IP Right Cessation
- 2002-01-21 CA CA002435775A patent/CA2435775A1/en not_active Abandoned
- 2002-01-21 US US10/466,118 patent/US6951883B2/en not_active Expired - Fee Related
- 2002-01-21 EP EP02703564A patent/EP1355906B1/en not_active Expired - Lifetime
- 2002-01-21 SK SK939-2003A patent/SK287086B6/sk not_active IP Right Cessation
- 2002-01-21 MX MXPA03006505A patent/MXPA03006505A/es active IP Right Grant
- 2002-01-21 AU AU2002237282A patent/AU2002237282B2/en not_active Ceased
- 2002-01-21 NZ NZ527144A patent/NZ527144A/en unknown
- 2002-01-21 DZ DZ023459A patent/DZ3459A1/fr active
- 2002-01-21 IL IL15706502A patent/IL157065A0/xx unknown
- 2002-01-21 CZ CZ20032014A patent/CZ20032014A3/cs unknown
- 2002-01-21 DE DE60202590T patent/DE60202590T2/de not_active Expired - Lifetime
- 2002-01-21 HU HU0401018A patent/HUP0401018A3/hu unknown
- 2002-01-21 AT AT02703564T patent/ATE286894T1/de not_active IP Right Cessation
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2003
- 2003-07-08 TN TNPCT/EP2002/000567A patent/TNSN03043A1/en unknown
- 2003-07-15 MA MA27236A patent/MA26982A1/fr unknown
- 2003-07-23 NO NO20033318A patent/NO327808B1/no not_active IP Right Cessation
- 2003-07-23 IL IL157065A patent/IL157065A/en not_active IP Right Cessation
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