BG107676A - Модулатори на естрогенни рецептори - Google Patents

Модулатори на естрогенни рецептори Download PDF

Info

Publication number: BG107676A
Authority: BG; Bulgaria
Prior art keywords: alkyl; group; ppm; nmr; mhz
Prior art date: 2000-10-19

Application number

BG107676A

Other languages

Bulgarian (bg)

English (en)

Inventor

Frank Dininno

Helen Chen

Seongkon Kim

Jane Wu

Original Assignee

Merck & Co., Inc.

Priority date (The priority date 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 date listed.)

2000-10-19

Filing date

2003-03-26

Publication date

2003-11-28

2003-03-26 Application filed by Merck & Co., Inc. filed Critical Merck & Co., Inc.

2003-11-28 Publication of BG107676A publication Critical patent/BG107676A/bg

Links

239000002834 estrogen receptor modulator Substances 0.000 title abstract 2
150000001875 compounds Chemical class 0.000 claims abstract description 157
125000000217 alkyl group Chemical group 0.000 claims description 216
-1 CF 3 Chemical group 0.000 claims description 48
229910052739 hydrogen Inorganic materials 0.000 claims description 48
239000000460 chlorine Substances 0.000 claims description 42
229910052736 halogen Inorganic materials 0.000 claims description 42
150000002367 halogens Chemical class 0.000 claims description 42
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 40
125000000858 thiocyanato group Chemical group *SC#N 0.000 claims description 40
125000004093 cyano group Chemical group *C#N 0.000 claims description 37
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 37
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 37
125000004414 alkyl thio group Chemical group 0.000 claims description 35
125000000753 cycloalkyl group Chemical group 0.000 claims description 34
239000001257 hydrogen Substances 0.000 claims description 34
229910052799 carbon Inorganic materials 0.000 claims description 32
125000001072 heteroaryl group Chemical group 0.000 claims description 31
125000000623 heterocyclic group Chemical group 0.000 claims description 30
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 30
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 30
150000003839 salts Chemical class 0.000 claims description 27
125000001424 substituent group Chemical group 0.000 claims description 27
229910052757 nitrogen Inorganic materials 0.000 claims description 21
229910052760 oxygen Inorganic materials 0.000 claims description 20
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 19
229920006395 saturated elastomer Polymers 0.000 claims description 19
125000003342 alkenyl group Chemical group 0.000 claims description 18
125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 claims description 18
125000000304 alkynyl group Chemical group 0.000 claims description 17
125000000392 cycloalkenyl group Chemical group 0.000 claims description 16
229910052717 sulfur Inorganic materials 0.000 claims description 16
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 14
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 14
239000001301 oxygen Substances 0.000 claims description 14
239000011593 sulfur Substances 0.000 claims description 14
125000004429 atom Chemical group 0.000 claims description 13
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
125000004432 carbon atom Chemical group C* 0.000 claims description 10
125000005843 halogen group Chemical group 0.000 claims description 10
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
150000003462 sulfoxides Chemical class 0.000 claims description 5
150000003457 sulfones Chemical class 0.000 claims description 4
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 3
229910052801 chlorine Inorganic materials 0.000 claims description 2
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 1
239000000262 estrogen Substances 0.000 abstract description 36
229940011871 estrogen Drugs 0.000 abstract description 34
238000011282 treatment Methods 0.000 abstract description 26
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 25
102000015694 estrogen receptors Human genes 0.000 abstract description 20
108010038795 estrogen receptors Proteins 0.000 abstract description 20
206010065687 Bone loss Diseases 0.000 abstract description 13
208000001132 Osteoporosis Diseases 0.000 abstract description 11
230000015572 biosynthetic process Effects 0.000 abstract description 11
238000003786 synthesis reaction Methods 0.000 abstract description 10
208000024172 Cardiovascular disease Diseases 0.000 abstract description 9
208000035475 disorder Diseases 0.000 abstract description 9
206010028980 Neoplasm Diseases 0.000 abstract description 8
210000004291 uterus Anatomy 0.000 abstract description 8
230000002265 prevention Effects 0.000 abstract description 7
201000009273 Endometriosis Diseases 0.000 abstract description 6
201000011510 cancer Diseases 0.000 abstract description 6
208000010392 Bone Fractures Diseases 0.000 abstract description 5
230000001965 increasing effect Effects 0.000 abstract description 5
239000003446 ligand Substances 0.000 abstract description 5
208000033830 Hot Flashes Diseases 0.000 abstract description 4
206010060800 Hot flush Diseases 0.000 abstract description 4
206010021639 Incontinence Diseases 0.000 abstract description 4
206010046798 Uterine leiomyoma Diseases 0.000 abstract description 4
210000000481 breast Anatomy 0.000 abstract description 4
230000004663 cell proliferation Effects 0.000 abstract description 4
230000002490 cerebral effect Effects 0.000 abstract description 4
230000007850 degeneration Effects 0.000 abstract description 4
230000003412 degenerative effect Effects 0.000 abstract description 4
201000010260 leiomyoma Diseases 0.000 abstract description 4
238000008214 LDL Cholesterol Methods 0.000 abstract description 3
230000006735 deficit Effects 0.000 abstract description 3
210000002307 prostate Anatomy 0.000 abstract description 3
208000010579 uterine corpus leiomyoma Diseases 0.000 abstract description 3
201000007954 uterine fibroid Diseases 0.000 abstract description 3
210000004509 vascular smooth muscle cell Anatomy 0.000 abstract description 3
208000008589 Obesity Diseases 0.000 abstract description 2
235000020824 obesity Nutrition 0.000 abstract description 2
210000000845 cartilage Anatomy 0.000 abstract 1
230000001149 cognitive effect Effects 0.000 abstract 1
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 286
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 250
238000000034 method Methods 0.000 description 215
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 189
239000000047 product Substances 0.000 description 174
239000003480 eluent Substances 0.000 description 128
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 120
235000019439 ethyl acetate Nutrition 0.000 description 120
239000000741 silica gel Substances 0.000 description 118
229910002027 silica gel Inorganic materials 0.000 description 118
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 115
238000011097 chromatography purification Methods 0.000 description 111
239000000203 mixture Substances 0.000 description 51
239000000243 solution Substances 0.000 description 50
239000011541 reaction mixture Substances 0.000 description 36
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 34
KZTWONRVIPPDKH-UHFFFAOYSA-N 2-(piperidin-1-yl)ethanol Chemical compound OCCN1CCCCC1 KZTWONRVIPPDKH-UHFFFAOYSA-N 0.000 description 33
239000000126 substance Substances 0.000 description 33
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 32
MOIPGXQKZSZOQX-UHFFFAOYSA-N carbonyl bromide Chemical class BrC(Br)=O MOIPGXQKZSZOQX-UHFFFAOYSA-N 0.000 description 28
WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
239000003921 oil Substances 0.000 description 27
238000006243 chemical reaction Methods 0.000 description 26
150000002576 ketones Chemical class 0.000 description 26
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 26
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
238000002360 preparation method Methods 0.000 description 23
235000002639 sodium chloride Nutrition 0.000 description 23
239000000543 intermediate Substances 0.000 description 22
238000004587 chromatography analysis Methods 0.000 description 20
239000012044 organic layer Substances 0.000 description 19
125000006239 protecting group Chemical group 0.000 description 19
238000000746 purification Methods 0.000 description 19
210000004027 cell Anatomy 0.000 description 18
230000000694 effects Effects 0.000 description 18
239000008194 pharmaceutical composition Substances 0.000 description 18
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical class SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 18
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 17
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
241000124008 Mammalia Species 0.000 description 16
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 16
239000000463 material Substances 0.000 description 15
BGDOLELXXPTPFX-UHFFFAOYSA-N 3,4-dihydro-2h-1,2-benzoxazine Chemical compound C1=CC=C2ONCCC2=C1 BGDOLELXXPTPFX-UHFFFAOYSA-N 0.000 description 14
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
201000010099 disease Diseases 0.000 description 13
239000003814 drug Substances 0.000 description 13
238000012360 testing method Methods 0.000 description 13
238000006751 Mitsunobu reaction Methods 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
210000000988 bone and bone Anatomy 0.000 description 12
239000011734 sodium Substances 0.000 description 12
238000003756 stirring Methods 0.000 description 12
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Natural products 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 11
229910052731 fluorine Inorganic materials 0.000 description 11
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
241000700159 Rattus Species 0.000 description 10
239000010410 layer Substances 0.000 description 10
230000009467 reduction Effects 0.000 description 10
238000007363 ring formation reaction Methods 0.000 description 10
239000007787 solid Substances 0.000 description 10
239000002904 solvent Substances 0.000 description 10
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
238000004458 analytical method Methods 0.000 description 9
238000003556 assay Methods 0.000 description 9
229940079593 drug Drugs 0.000 description 9
238000010828 elution Methods 0.000 description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
208000006386 Bone Resorption Diseases 0.000 description 8
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 8
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
125000003118 aryl group Chemical group 0.000 description 8
230000024279 bone resorption Effects 0.000 description 8
239000012043 crude product Substances 0.000 description 8
238000005828 desilylation reaction Methods 0.000 description 8
AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 8
229940122361 Bisphosphonate Drugs 0.000 description 7
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 7
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
150000004663 bisphosphonates Chemical class 0.000 description 7
239000003638 chemical reducing agent Substances 0.000 description 7
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 7
229960005309 estradiol Drugs 0.000 description 7
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 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 description 6
108091003079 Bovine Serum Albumin Proteins 0.000 description 6
241001465754 Metazoa Species 0.000 description 6
208000000236 Prostatic Neoplasms Diseases 0.000 description 6
239000002253 acid Substances 0.000 description 6
239000004480 active ingredient Substances 0.000 description 6
239000003795 chemical substances by application Substances 0.000 description 6
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
238000010790 dilution Methods 0.000 description 6
239000012895 dilution Substances 0.000 description 6
230000001076 estrogenic effect Effects 0.000 description 6
239000005457 ice water Substances 0.000 description 6
238000002560 therapeutic procedure Methods 0.000 description 6
210000001519 tissue Anatomy 0.000 description 6
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
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 5
208000026310 Breast neoplasm Diseases 0.000 description 5
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 5
206010060862 Prostate cancer Diseases 0.000 description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
230000002378 acidificating effect Effects 0.000 description 5
229940062527 alendronate Drugs 0.000 description 5
230000003042 antagnostic effect Effects 0.000 description 5
239000002585 base Substances 0.000 description 5
235000012000 cholesterol Nutrition 0.000 description 5
239000003937 drug carrier Substances 0.000 description 5
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238000009164 estrogen replacement therapy Methods 0.000 description 5
239000000284 extract Substances 0.000 description 5
239000012091 fetal bovine serum Substances 0.000 description 5
239000012467 final product Substances 0.000 description 5
150000002989 phenols Chemical class 0.000 description 5
VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 5
102000005962 receptors Human genes 0.000 description 5
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VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 4
CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 4
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LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 4
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239000005557 antagonist Substances 0.000 description 4
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GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 4
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
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KQIADDMXRMTWHZ-UHFFFAOYSA-N chloro-tri(propan-2-yl)silane Chemical compound CC(C)[Si](Cl)(C(C)C)C(C)C KQIADDMXRMTWHZ-UHFFFAOYSA-N 0.000 description 4
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125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
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RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
238000001802 infusion Methods 0.000 description 3
150000007517 lewis acids Chemical class 0.000 description 3
150000002632 lipids Chemical class 0.000 description 3
238000004519 manufacturing process Methods 0.000 description 3
LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 3
239000002480 mineral oil Substances 0.000 description 3
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238000000926 separation method Methods 0.000 description 1
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239000004299 sodium benzoate Substances 0.000 description 1
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235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
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235000019345 sodium thiosulphate Nutrition 0.000 description 1
239000012453 solvate Substances 0.000 description 1
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239000000057 synthetic resin Substances 0.000 description 1
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LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
229940052907 telazol Drugs 0.000 description 1
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 description 1
125000005323 thioketone group Chemical group 0.000 description 1
WZMPOCLULGAHJR-UHFFFAOYSA-N thiophen-2-ol Chemical compound OC1=CC=CS1 WZMPOCLULGAHJR-UHFFFAOYSA-N 0.000 description 1
HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 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
230000037317 transdermal delivery Effects 0.000 description 1
238000002054 transplantation Methods 0.000 description 1
DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
WRTMQOHKMFDUKX-UHFFFAOYSA-N triiodide Chemical compound I[I-]I WRTMQOHKMFDUKX-UHFFFAOYSA-N 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
AKQNYQDSIDKVJZ-UHFFFAOYSA-N triphenylsilane Chemical compound C1=CC=CC=C1[SiH](C=1C=CC=CC=1)C1=CC=CC=C1 AKQNYQDSIDKVJZ-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
QYBXIUDBUIUBHS-UHFFFAOYSA-N tris(methylsulfonyl)methane Chemical group CS(=O)(=O)C(S(C)(=O)=O)S(C)(=O)=O QYBXIUDBUIUBHS-UHFFFAOYSA-N 0.000 description 1
210000000689 upper leg Anatomy 0.000 description 1
230000002485 urinary effect Effects 0.000 description 1
229940070710 valerate Drugs 0.000 description 1
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1
239000003039 volatile agent Substances 0.000 description 1
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239000000230 xanthan gum Substances 0.000 description 1
235000010493 xanthan gum Nutrition 0.000 description 1
229920001285 xanthan gum Polymers 0.000 description 1
229940082509 xanthan gum Drugs 0.000 description 1
XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 description 1
229960004276 zoledronic acid Drugs 0.000 description 1
229930195724 β-lactose Natural products 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D411/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms
- C07D411/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D411/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D411/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms
- C07D411/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D411/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms 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
- 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
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
- 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
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
- 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
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D327/00—Heterocyclic compounds containing rings having oxygen and sulfur atoms as the only ring hetero atoms
- C07D327/02—Heterocyclic compounds containing rings having oxygen and sulfur atoms as the only ring hetero atoms one oxygen atom and one sulfur atom
- C07D327/06—Six-membered rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D339/00—Heterocyclic compounds containing rings having two sulfur atoms as the only ring hetero atoms
- C07D339/08—Six-membered rings

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Diabetes (AREA)
Physical Education & Sports Medicine (AREA)
Endocrinology (AREA)
Orthopedic Medicine & Surgery (AREA)
Neurosurgery (AREA)
Rheumatology (AREA)
Cardiology (AREA)
Hematology (AREA)
Heart & Thoracic Surgery (AREA)
Biomedical Technology (AREA)
Obesity (AREA)
Neurology (AREA)
Child & Adolescent Psychology (AREA)
Psychiatry (AREA)
Hospice & Palliative Care (AREA)
Oncology (AREA)
Vascular Medicine (AREA)
Urology & Nephrology (AREA)
Reproductive Health (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Steroid Compounds (AREA)
Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Plural Heterocyclic Compounds (AREA)

BG107676A 2000-10-19 2003-03-26 Модулатори на естрогенни рецептори BG107676A (bg)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US24158200P	2000-10-19	2000-10-19
PCT/US2001/042735 WO2002032377A2 (en)	2000-10-19	2001-10-15	Estrogen receptor modulators

Publications (1)

Publication Number	Publication Date
BG107676A true BG107676A (bg)	2003-11-28

Family

ID=22911282

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG107676A BG107676A (bg)	2000-10-19	2003-03-26	Модулатори на естрогенни рецептори

Country Status (20)

Country	Link
EP (1)	EP1333827A2 (xx)
JP (1)	JP2004511502A (xx)
KR (1)	KR20030042020A (xx)
CN (1)	CN1469743A (xx)
AU (2)	AU2002232381B2 (xx)
BG (1)	BG107676A (xx)
BR (1)	BR0114689A (xx)
CA (1)	CA2424729A1 (xx)
EA (1)	EA200300474A1 (xx)
EC (1)	ECSP034558A (xx)
EE (1)	EE200300153A (xx)
HU (1)	HUP0303563A2 (xx)
IL (1)	IL154984A0 (xx)
IS (1)	IS6761A (xx)
MX (1)	MXPA03003485A (xx)
NO (1)	NO20031737L (xx)
PE (1)	PE20021083A1 (xx)
PL (1)	PL361053A1 (xx)
SK (1)	SK4772003A3 (xx)
WO (1)	WO2002032377A2 (xx)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US20030225132A1 (en) *	2002-04-11	2003-12-04	Dininno Frank P.	Estrogen receptor modulators
EP1501819B1 (en)	2002-04-24	2010-09-15	Merck Sharp & Dohme Corp.	Estrogen receptor modulators
DE60317061T2 (de)	2002-05-10	2008-07-24	F. Hoffmann-La Roche Ag	Ibandronsäure zur behandlung und vorbeugung von osteoporose
AU2003292625B2 (en) *	2002-12-26	2008-07-24	Eisai R & D Management Co., Ltd.	Selective estrogen receptor modulators
US8410109B2 (en)	2005-07-29	2013-04-02	Resverlogix Corp.	Pharmaceutical compositions for the prevention and treatment of complex diseases and their delivery by insertable medical devices
CA2627139A1 (en) *	2005-10-27	2007-05-03	Banyu Pharmaceutical Co., Ltd.	Novel benzoxathiin derivative
AU2007345526B2 (en)	2007-02-01	2013-02-28	Resverlogix Corp.	Compounds for the prevention and treatment of cardiovascular diseases
AU2010204106B2 (en)	2009-01-08	2014-05-08	Resverlogix Corp.	Compounds for the prevention and treatment of cardiovascular disease
MX392179B (es)	2009-03-18	2025-03-21	Resverlogix Corp	Nuevos agentes anti-inflamatorios.
TR201818390T4 (tr)	2009-04-22	2019-01-21	Resverlogix Corp	Yeni̇ anti̇-i̇nflamatuvar ajanlar
MX2012014431A (es)	2010-06-10	2013-02-26	Aragon Pharmaceuticals Inc	Modulares del receptor de estrogenos y usos de los mismos.
US8853423B2 (en)	2010-06-17	2014-10-07	Seragon Pharmaceuticals, Inc.	Indane estrogen receptor modulators and uses thereof
ES2745471T3 (es)	2011-11-01	2020-03-02	Resverlogix Corp	Formulaciones orales de liberación inmediata para quinazolinonas sustituidas
JP2015500346A (ja)	2011-12-14	2015-01-05	セラゴンファーマシューティカルズ，インク．	エストロゲン受容体モジュレーターおよびその使用
US9073878B2 (en)	2012-11-21	2015-07-07	Zenith Epigenetics Corp.	Cyclic amines as bromodomain inhibitors
US9765039B2 (en)	2012-11-21	2017-09-19	Zenith Epigenetics Ltd.	Biaryl derivatives as bromodomain inhibitors
EP2935253B1 (en)	2012-12-21	2018-08-01	Zenith Epigenetics Ltd.	Novel heterocyclic compounds as bromodomain inhibitors
KR102662814B1 (ko)	2015-03-13	2024-05-03	리스버로직스 코퍼레이션	보체 관련 질환을 치료하기 위한 조성물 및 치료 방법

2001
- 2001-10-15 IL IL15498401A patent/IL154984A0/xx unknown
- 2001-10-15 AU AU2002232381A patent/AU2002232381B2/en not_active Ceased
- 2001-10-15 BR BR0114689-0A patent/BR0114689A/pt not_active Application Discontinuation
- 2001-10-15 EA EA200300474A patent/EA200300474A1/ru unknown
- 2001-10-15 WO PCT/US2001/042735 patent/WO2002032377A2/en not_active Ceased
- 2001-10-15 AU AU3238102A patent/AU3238102A/xx active Pending
- 2001-10-15 MX MXPA03003485A patent/MXPA03003485A/es unknown
- 2001-10-15 CN CNA018176720A patent/CN1469743A/zh active Pending
- 2001-10-15 JP JP2002535616A patent/JP2004511502A/ja not_active Withdrawn
- 2001-10-15 EP EP01987654A patent/EP1333827A2/en not_active Withdrawn
- 2001-10-15 SK SK477-2003A patent/SK4772003A3/sk unknown
- 2001-10-15 EE EEP200300153A patent/EE200300153A/xx unknown
- 2001-10-15 CA CA002424729A patent/CA2424729A1/en not_active Abandoned
- 2001-10-15 KR KR10-2003-7005518A patent/KR20030042020A/ko not_active Withdrawn
- 2001-10-15 HU HU0303563A patent/HUP0303563A2/hu unknown
- 2001-10-15 PL PL01361053A patent/PL361053A1/xx not_active Application Discontinuation
2002
- 2002-04-15 PE PE2002000308A patent/PE20021083A1/es not_active Application Discontinuation
2003
- 2003-03-26 BG BG107676A patent/BG107676A/bg unknown
- 2003-03-27 IS IS6761A patent/IS6761A/is unknown
- 2003-04-15 NO NO20031737A patent/NO20031737L/no unknown
- 2003-04-17 EC EC2003004558A patent/ECSP034558A/es unknown

Also Published As

Publication number	Publication date
IS6761A (is)	2003-03-27
BR0114689A (pt)	2003-07-01
HUP0303563A2 (hu)	2004-03-01
SK4772003A3 (en)	2003-08-05
MXPA03003485A (es)	2003-07-14
CN1469743A (zh)	2004-01-21
PE20021083A1 (es)	2002-12-16
ECSP034558A (es)	2003-06-25
PL361053A1 (en)	2004-09-20
EP1333827A2 (en)	2003-08-13
AU3238102A (en)	2002-04-29
WO2002032377A3 (en)	2002-08-22
WO2002032377A2 (en)	2002-04-25
KR20030042020A (ko)	2003-05-27
NO20031737L (no)	2003-06-19
EA200300474A1 (ru)	2003-10-30
EE200300153A (et)	2003-06-16
IL154984A0 (en)	2003-10-31
CA2424729A1 (en)	2002-04-25
AU2002232381B2 (en)	2004-11-18
JP2004511502A (ja)	2004-04-15
NO20031737D0 (no)	2003-04-15

Publication	Publication Date	Title
BG107676A (bg)	2003-11-28	Модулатори на естрогенни рецептори
AU2003237084B2 (en)	2008-11-20	Estrogen receptor modulators
AU2002232381A1 (en)	2002-07-04	Estrogen receptor modulators
HRP980356A2 (en)	1999-02-28	Prostaglandin agonists
KR102446027B1 (ko)	2022-09-21	함질소 6원환 화합물
JP2002530411A (ja)	2002-09-17	骨疾患の治療または予防のためのプロスタグランジン結合体
US6750213B2 (en)	2004-06-15	Estrogen receptor modulators
WO2004073612A2 (en)	2004-09-02	Estrogen receptor modulators
JP2011516523A (ja)	2011-05-26	新規エストロゲン受容体リガンド
JP2004511501A (ja)	2004-04-15	エストロゲン受容体モジュレーター
BRPI0713743A2 (pt)	2012-11-06	composto ou um sal do mesmo, pró-droga, e, composição farmacêutica
US20030225132A1 (en)	2003-12-04	Estrogen receptor modulators
WO2004091488A2 (en)	2004-10-28	Estrogen receptor modulators
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