HUP0303563A2 - Ösztrogén receptor modulátorok - Google Patents

Info

Publication number

HUP0303563A2

HUP0303563A2 HU0303563A HUP0303563A HUP0303563A2 HU P0303563 A2 HUP0303563 A2 HU P0303563A2 HU 0303563 A HU0303563 A HU 0303563A HU P0303563 A HUP0303563 A HU P0303563A HU P0303563 A2 HUP0303563 A2 HU P0303563A2

Authority

HU

Hungary

Prior art keywords

alkyl

ppm

mhz

nmr

halogen

Prior art date

2000-10-19

Links

• Espacenet
• Global Dossier
• Discuss

• 239000002834 estrogen receptor modulator Substances 0.000 title abstract description 5
• 150000001875 compounds Chemical class 0.000 claims abstract description 197
• 239000000262 estrogen Substances 0.000 claims abstract description 43
• 229940011871 estrogen Drugs 0.000 claims abstract description 41
• 238000011282 treatment Methods 0.000 claims abstract description 30
• 102000015694 estrogen receptors Human genes 0.000 claims abstract description 24
• 108010038795 estrogen receptors Proteins 0.000 claims abstract description 24
• 206010006187 Breast cancer Diseases 0.000 claims abstract description 8
• 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 8
• 206010046798 Uterine leiomyoma Diseases 0.000 claims abstract description 6
• 201000010260 leiomyoma Diseases 0.000 claims abstract description 6
• 208000037803 restenosis Diseases 0.000 claims abstract description 6
• 208000004145 Endometritis Diseases 0.000 claims abstract description 5
• 238000000034 method Methods 0.000 claims description 159
• 125000000217 alkyl group Chemical group 0.000 claims description 92
• -1 cyano, carboxyl Chemical group 0.000 claims description 84
• 229910052739 hydrogen Inorganic materials 0.000 claims description 64
• 239000001257 hydrogen Substances 0.000 claims description 63
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 50
• 229910052736 halogen Inorganic materials 0.000 claims description 47
• 150000002367 halogens Chemical class 0.000 claims description 47
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 41
• 125000000858 thiocyanato group Chemical group *SC#N 0.000 claims description 39
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 38
• 125000004414 alkyl thio group Chemical group 0.000 claims description 36
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 36
• 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 35
• 150000003839 salts Chemical class 0.000 claims description 32
• 125000001072 heteroaryl group Chemical group 0.000 claims description 31
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 30
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 29
• 125000000623 heterocyclic group Chemical group 0.000 claims description 29
• 230000000694 effects Effects 0.000 claims description 23
• 229910052757 nitrogen Inorganic materials 0.000 claims description 22
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 20
• 229910052799 carbon Inorganic materials 0.000 claims description 20
• 229910052717 sulfur Inorganic materials 0.000 claims description 20
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 19
• 239000008194 pharmaceutical composition Substances 0.000 claims description 19
• 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 claims description 19
• 241000124008 Mammalia Species 0.000 claims description 18
• 229910052760 oxygen Inorganic materials 0.000 claims description 18
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 16
• 239000011593 sulfur Substances 0.000 claims description 16
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
• 239000001301 oxygen Substances 0.000 claims description 15
• 125000003342 alkenyl group Chemical group 0.000 claims description 14
• 125000000304 alkynyl group Chemical group 0.000 claims description 14
• 125000004432 carbon atom Chemical group C* 0.000 claims description 14
• 239000003814 drug Substances 0.000 claims description 14
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
• 229920006395 saturated elastomer Polymers 0.000 claims description 12
• 108010007005 Estrogen Receptor alpha Proteins 0.000 claims description 10
• 102000007594 Estrogen Receptor alpha Human genes 0.000 claims description 10
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 10
• 239000003937 drug carrier Substances 0.000 claims description 9
• 238000004519 manufacturing process Methods 0.000 claims description 9
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
• 125000005843 halogen group Chemical group 0.000 claims description 7
• 239000003795 chemical substances by application Substances 0.000 claims description 5
• 150000003462 sulfoxides Chemical class 0.000 claims description 5
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
• 230000001419 dependent effect Effects 0.000 claims description 4
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
• 150000003457 sulfones Chemical class 0.000 claims description 4
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
• 238000002156 mixing Methods 0.000 claims description 3
• 208000001685 postmenopausal osteoporosis Diseases 0.000 claims description 3
• 125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims description 2
• 125000006730 (C2-C5) alkynyl group Chemical group 0.000 claims description 2
• 208000031226 Hyperlipidaemia Diseases 0.000 claims description 2
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
• 238000002360 preparation method Methods 0.000 abstract description 30
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 15
• 206010065687 Bone loss Diseases 0.000 abstract description 13
• 208000001132 Osteoporosis Diseases 0.000 abstract description 11
• 208000024172 Cardiovascular disease Diseases 0.000 abstract description 9
• 206010060862 Prostate cancer Diseases 0.000 abstract description 8
• 208000000236 Prostatic Neoplasms Diseases 0.000 abstract description 8
• 230000002265 prevention Effects 0.000 abstract description 7
• 208000010392 Bone Fractures Diseases 0.000 abstract description 6
• 208000033830 Hot Flashes Diseases 0.000 abstract description 6
• 206010060800 Hot flush Diseases 0.000 abstract description 6
• 206010028980 Neoplasm Diseases 0.000 abstract description 6
• 208000002495 Uterine Neoplasms Diseases 0.000 abstract description 6
• 239000003446 ligand Substances 0.000 abstract description 6
• 206010046766 uterine cancer Diseases 0.000 abstract description 6
• 201000011510 cancer Diseases 0.000 abstract description 5
• 230000006870 function Effects 0.000 abstract description 5
• 206010021639 Incontinence Diseases 0.000 abstract description 4
• 210000000845 cartilage Anatomy 0.000 abstract description 4
• 230000004663 cell proliferation Effects 0.000 abstract description 4
• 230000003412 degenerative effect Effects 0.000 abstract description 4
• 210000004509 vascular smooth muscle cell Anatomy 0.000 abstract description 4
• 238000008214 LDL Cholesterol Methods 0.000 abstract description 3
• 208000008589 Obesity Diseases 0.000 abstract description 3
• 230000009471 action Effects 0.000 abstract description 3
• 201000000079 gynecomastia Diseases 0.000 abstract description 3
• 235000020824 obesity Nutrition 0.000 abstract description 3
• 208000010579 uterine corpus leiomyoma Diseases 0.000 abstract description 3
• 201000007954 uterine fibroid Diseases 0.000 abstract description 3
• 201000010099 disease Diseases 0.000 abstract description 2
• 208000014644 Brain disease Diseases 0.000 abstract 1
• 210000000481 breast Anatomy 0.000 abstract 1
• 230000006735 deficit Effects 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 342
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 269
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 234
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 183
• 239000000047 product Substances 0.000 description 183
• 238000005160 1H NMR spectroscopy Methods 0.000 description 179
• 239000000203 mixture Substances 0.000 description 97
• 238000000746 purification Methods 0.000 description 77
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 76
• 239000000741 silica gel Substances 0.000 description 72
• 229910002027 silica gel Inorganic materials 0.000 description 72
• 238000004587 chromatography analysis Methods 0.000 description 71
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
• 238000010898 silica gel chromatography Methods 0.000 description 47
• 239000000243 solution Substances 0.000 description 46
• 150000002431 hydrogen Chemical class 0.000 description 38
• 239000007787 solid Substances 0.000 description 35
• KZTWONRVIPPDKH-UHFFFAOYSA-N 2-(piperidin-1-yl)ethanol Chemical compound OCCN1CCCCC1 KZTWONRVIPPDKH-UHFFFAOYSA-N 0.000 description 33
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
• MOIPGXQKZSZOQX-UHFFFAOYSA-N carbonyl bromide Chemical class BrC(Br)=O MOIPGXQKZSZOQX-UHFFFAOYSA-N 0.000 description 29
• 239000011541 reaction mixture Substances 0.000 description 29
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 28
• 150000002576 ketones Chemical class 0.000 description 26
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
• 238000002474 experimental method Methods 0.000 description 25
• 239000003921 oil Substances 0.000 description 25
• 235000019198 oils Nutrition 0.000 description 25
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
• 235000002639 sodium chloride Nutrition 0.000 description 23
• 239000000543 intermediate Substances 0.000 description 21
• 239000012074 organic phase Substances 0.000 description 21
• RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 21
• CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 20
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 19
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
• 238000006243 chemical reaction Methods 0.000 description 17
• 125000006239 protecting group Chemical group 0.000 description 17
• 210000004027 cell Anatomy 0.000 description 16
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
• 125000001424 substituent group Chemical group 0.000 description 15
• 238000012360 testing method Methods 0.000 description 15
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 13
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
• 210000000988 bone and bone Anatomy 0.000 description 13
• 239000000460 chlorine Substances 0.000 description 13
• 229910052801 chlorine Inorganic materials 0.000 description 13
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 13
• 239000002904 solvent Substances 0.000 description 13
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 12
• 241000700159 Rattus Species 0.000 description 12
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
• 229910052731 fluorine Inorganic materials 0.000 description 12
• 239000011737 fluorine Substances 0.000 description 12
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 11
• 229910052938 sodium sulfate Inorganic materials 0.000 description 11
• 235000011152 sodium sulphate Nutrition 0.000 description 11
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-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
• 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
• 208000035475 disorder Diseases 0.000 description 10
• 239000003480 eluent Substances 0.000 description 10
• 239000005457 ice water Substances 0.000 description 10
• ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 10
• 208000006386 Bone Resorption Diseases 0.000 description 9
• 108010041356 Estrogen Receptor beta Proteins 0.000 description 9
• 230000024279 bone resorption Effects 0.000 description 9
• 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 9
• 238000010828 elution Methods 0.000 description 9
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
• 235000019341 magnesium sulphate Nutrition 0.000 description 9
• 229940122361 Bisphosphonate Drugs 0.000 description 8
• 102000000509 Estrogen Receptor beta Human genes 0.000 description 8
• 150000004663 bisphosphonates Chemical class 0.000 description 8
• 238000005828 desilylation reaction Methods 0.000 description 8
• 239000000463 material Substances 0.000 description 8
• 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 7
• 241001465754 Metazoa Species 0.000 description 7
• 238000006751 Mitsunobu reaction Methods 0.000 description 7
• 230000002378 acidificating effect Effects 0.000 description 7
• 239000002585 base Substances 0.000 description 7
• 230000015572 biosynthetic process Effects 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
• 210000001519 tissue Anatomy 0.000 description 7
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 6
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 6
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
• 125000003118 aryl group Chemical group 0.000 description 6
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
• 238000003821 enantio-separation Methods 0.000 description 6
• 102000005962 receptors Human genes 0.000 description 6
• 108020003175 receptors Proteins 0.000 description 6
• 230000009467 reduction Effects 0.000 description 6
• 238000006722 reduction reaction Methods 0.000 description 6
• 238000003756 stirring Methods 0.000 description 6
• 238000003786 synthesis reaction Methods 0.000 description 6
• 238000004809 thin layer chromatography Methods 0.000 description 6
• AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 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
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 5
• 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 5
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 5
• OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 description 5
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 5
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
• 239000002253 acid Substances 0.000 description 5
• 239000004480 active ingredient Substances 0.000 description 5
• 239000000556 agonist Substances 0.000 description 5
• 229940062527 alendronate Drugs 0.000 description 5
• 230000008485 antagonism Effects 0.000 description 5
• 239000008346 aqueous phase Substances 0.000 description 5
• 239000012043 crude product Substances 0.000 description 5
• 238000010790 dilution Methods 0.000 description 5
• 239000012895 dilution Substances 0.000 description 5
• 229940079593 drug Drugs 0.000 description 5
• 229930182833 estradiol Natural products 0.000 description 5
• 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
• 239000002609 medium Substances 0.000 description 5
• 230000011164 ossification Effects 0.000 description 5
• 238000006476 reductive cyclization reaction Methods 0.000 description 5
• 238000000926 separation method Methods 0.000 description 5
• 235000017557 sodium bicarbonate Nutrition 0.000 description 5
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
• 125000004434 sulfur atom Chemical group 0.000 description 5
• 229960001603 tamoxifen Drugs 0.000 description 5
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 5
• 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
• 125000006553 (C3-C8) cycloalkenyl group Chemical group 0.000 description 4
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
• 208000029725 Metabolic bone disease Diseases 0.000 description 4
• LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 4
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
• 238000004113 cell culture Methods 0.000 description 4
• 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
• 235000012000 cholesterol Nutrition 0.000 description 4
• 239000000706 filtrate Substances 0.000 description 4
• 239000012467 final product Substances 0.000 description 4
• 238000001727 in vivo Methods 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 239000012299 nitrogen atmosphere Substances 0.000 description 4
• 231100000252 nontoxic Toxicity 0.000 description 4
• 230000003000 nontoxic effect Effects 0.000 description 4
• 125000004430 oxygen atom Chemical group O* 0.000 description 4
• 239000012071 phase Substances 0.000 description 4
• 150000002989 phenols Chemical class 0.000 description 4
• 239000000651 prodrug Substances 0.000 description 4
• 229940002612 prodrug Drugs 0.000 description 4
• 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 4
• 238000007363 ring formation reaction Methods 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 4
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
• KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 3
• 239000004215 Carbon black (E152) Substances 0.000 description 3
• 206010049088 Osteopenia Diseases 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
• DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 3
• 229920002472 Starch Polymers 0.000 description 3
• 125000002015 acyclic group Chemical group 0.000 description 3
• 230000002152 alkylating effect Effects 0.000 description 3
• 239000003098 androgen Substances 0.000 description 3
• 230000003042 antagnostic effect Effects 0.000 description 3
• 230000001833 anti-estrogenic effect Effects 0.000 description 3
• 238000013459 approach Methods 0.000 description 3
• 230000009286 beneficial effect Effects 0.000 description 3
• 210000004369 blood Anatomy 0.000 description 3
• 239000008280 blood Substances 0.000 description 3
• 230000037396 body weight Effects 0.000 description 3
• 210000004556 brain Anatomy 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 125000005518 carboxamido group Chemical group 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 239000013058 crude material Substances 0.000 description 3
• 239000012228 culture supernatant Substances 0.000 description 3
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
• 239000000328 estrogen antagonist Substances 0.000 description 3
• 230000001076 estrogenic effect Effects 0.000 description 3
• 238000003818 flash chromatography Methods 0.000 description 3
• 239000001963 growth medium Substances 0.000 description 3
• 229930195733 hydrocarbon Natural products 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 238000001802 infusion Methods 0.000 description 3
• 201000003723 learning disability Diseases 0.000 description 3
• 150000002632 lipids Chemical class 0.000 description 3
• 230000007774 longterm Effects 0.000 description 3
• 238000005259 measurement 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
• 235000010446 mineral oil Nutrition 0.000 description 3
• 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 3
• 239000002953 phosphate buffered saline Substances 0.000 description 3
• 239000000583 progesterone congener Substances 0.000 description 3
• 239000012312 sodium hydride Substances 0.000 description 3
• 229910000104 sodium hydride Inorganic materials 0.000 description 3
• 239000008107 starch Substances 0.000 description 3
• 235000019698 starch Nutrition 0.000 description 3
• 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 3
• 239000003826 tablet Substances 0.000 description 3
• 238000002560 therapeutic procedure Methods 0.000 description 3
• ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 3
• 210000004291 uterus Anatomy 0.000 description 3
• GVFQGRCUTLOVAN-UHFFFAOYSA-N (4-hydroxy-2-pyridin-3-ylphenyl)-phenylmethanone Chemical compound C=1C=CN=CC=1C1=CC(O)=CC=C1C(=O)C1=CC=CC=C1 GVFQGRCUTLOVAN-UHFFFAOYSA-N 0.000 description 2
• YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 2
• BJVASRMDOMQXRQ-UHFFFAOYSA-N 2,4-dimethylpentane-3-thione Chemical compound CC(C)C(=S)C(C)C BJVASRMDOMQXRQ-UHFFFAOYSA-N 0.000 description 2
• FXAGNYAEKGJADI-UHFFFAOYSA-N 2-bromo-1-(4-hydroxyphenyl)-3-methylbutan-1-one Chemical compound CC(C)C(Br)C(=O)C1=CC=C(O)C=C1 FXAGNYAEKGJADI-UHFFFAOYSA-N 0.000 description 2
• ITQTTZVARXURQS-UHFFFAOYSA-N 3-methylpyridine Chemical compound CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 description 2
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
• FKNQCJSGGFJEIZ-UHFFFAOYSA-N 4-methylpyridine Chemical compound CC1=CC=NC=C1 FKNQCJSGGFJEIZ-UHFFFAOYSA-N 0.000 description 2
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
• 201000009273 Endometriosis Diseases 0.000 description 2
• 229940122880 Estrogen receptor agonist Drugs 0.000 description 2
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
• 206010017076 Fracture Diseases 0.000 description 2
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
• 239000002841 Lewis acid Substances 0.000 description 2
• 206010027514 Metrorrhagia Diseases 0.000 description 2
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
• 238000011887 Necropsy Methods 0.000 description 2
• 235000019502 Orange oil Nutrition 0.000 description 2
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
• WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• 230000003187 abdominal effect Effects 0.000 description 2
• 230000001270 agonistic effect Effects 0.000 description 2
• 125000002877 alkyl aryl group Chemical group 0.000 description 2
• RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
• 125000003710 aryl alkyl group Chemical group 0.000 description 2
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• 230000036760 body temperature Effects 0.000 description 2
• 239000012267 brine Substances 0.000 description 2
• 230000031709 bromination Effects 0.000 description 2
• 238000005893 bromination reaction Methods 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 150000001649 bromium compounds Chemical class 0.000 description 2
• GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• 239000001506 calcium phosphate Substances 0.000 description 2
• 150000001721 carbon Chemical group 0.000 description 2
• 239000001569 carbon dioxide Substances 0.000 description 2
• 229910002092 carbon dioxide Inorganic materials 0.000 description 2
• 239000003054 catalyst Substances 0.000 description 2
• YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 2
• 230000010261 cell growth Effects 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
• RHJFFGNEVCBBPP-UHFFFAOYSA-N dicyclopentylmethanethione Chemical compound C1CCCC1C(=S)C1CCCC1 RHJFFGNEVCBBPP-UHFFFAOYSA-N 0.000 description 2
• 229940043279 diisopropylamine Drugs 0.000 description 2
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
• 239000007884 disintegrant Substances 0.000 description 2
• 238000009547 dual-energy X-ray absorptiometry Methods 0.000 description 2
• 150000002081 enamines Chemical class 0.000 description 2
• 230000002357 endometrial effect Effects 0.000 description 2
• 210000004696 endometrium Anatomy 0.000 description 2
• 230000003628 erosive effect Effects 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 230000008020 evaporation Effects 0.000 description 2
• 239000007789 gas Substances 0.000 description 2
• 239000008103 glucose Substances 0.000 description 2
• 235000011187 glycerol Nutrition 0.000 description 2
• KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
• 230000012010 growth Effects 0.000 description 2
• 125000005842 heteroatom Chemical group 0.000 description 2
• 238000009802 hysterectomy Methods 0.000 description 2
• 230000002401 inhibitory effect Effects 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 238000002350 laparotomy Methods 0.000 description 2
• 150000007517 lewis acids Chemical class 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• 239000002502 liposome Substances 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• 230000001404 mediated effect Effects 0.000 description 2
• 230000009245 menopause Effects 0.000 description 2
• 229920000609 methyl cellulose Polymers 0.000 description 2
• 239000001923 methylcellulose Substances 0.000 description 2
• 235000010981 methylcellulose Nutrition 0.000 description 2
• 239000010502 orange oil Substances 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 239000007800 oxidant agent Substances 0.000 description 2
• 239000008188 pellet Substances 0.000 description 2
• 229920000642 polymer Polymers 0.000 description 2
• 239000002244 precipitate Substances 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• KJRCEJOSASVSRA-UHFFFAOYSA-N propane-2-thiol Chemical compound CC(C)S KJRCEJOSASVSRA-UHFFFAOYSA-N 0.000 description 2
• AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
• 239000012429 reaction media Substances 0.000 description 2
• 230000002829 reductive effect Effects 0.000 description 2
• 238000010992 reflux Methods 0.000 description 2
• 210000003491 skin Anatomy 0.000 description 2
• 239000012279 sodium borohydride Substances 0.000 description 2
• 229910000033 sodium borohydride Inorganic materials 0.000 description 2
• 238000012453 sprague-dawley rat model Methods 0.000 description 2
• 238000010561 standard procedure Methods 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 239000000725 suspension Substances 0.000 description 2
• 238000013268 sustained release Methods 0.000 description 2
• 239000012730 sustained-release form Substances 0.000 description 2
• 239000006188 syrup Substances 0.000 description 2
• 235000020357 syrup Nutrition 0.000 description 2
• 150000003512 tertiary amines Chemical class 0.000 description 2
• HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• PRXNKYBFWAWBNZ-UHFFFAOYSA-N trimethylphenylammonium tribromide Chemical compound Br[Br-]Br.C[N+](C)(C)C1=CC=CC=C1 PRXNKYBFWAWBNZ-UHFFFAOYSA-N 0.000 description 2
• 230000004614 tumor growth Effects 0.000 description 2
• 239000002691 unilamellar liposome Substances 0.000 description 2
• 229930195735 unsaturated hydrocarbon Natural products 0.000 description 2
• VEPOHXYIFQMVHW-PVJVQHJQSA-N (2r,3r)-2,3-dihydroxybutanedioic acid;(2s,3s)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.O1CCN(C)[C@@H](C)[C@@H]1C1=CC=CC=C1 VEPOHXYIFQMVHW-PVJVQHJQSA-N 0.000 description 1
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
• SVKQGRNDYAFBPL-UHFFFAOYSA-N (4-hydroxy-2-propan-2-ylphenyl)-phenylmethanone Chemical compound CC(C)C1=CC(O)=CC=C1C(=O)C1=CC=CC=C1 SVKQGRNDYAFBPL-UHFFFAOYSA-N 0.000 description 1
• RCGVQXAUBIVNSJ-UHFFFAOYSA-N (4-hydroxy-2-pyridin-4-ylphenyl)-phenylmethanone Chemical compound C=1C=NC=CC=1C1=CC(O)=CC=C1C(=O)C1=CC=CC=C1 RCGVQXAUBIVNSJ-UHFFFAOYSA-N 0.000 description 1
• GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
• JRNVQLOKVMWBFR-UHFFFAOYSA-N 1,2-benzenedithiol Chemical compound SC1=CC=CC=C1S JRNVQLOKVMWBFR-UHFFFAOYSA-N 0.000 description 1
• OTKCEEWUXHVZQI-UHFFFAOYSA-N 1,2-diphenylethanone Chemical compound C=1C=CC=CC=1C(=O)CC1=CC=CC=C1 OTKCEEWUXHVZQI-UHFFFAOYSA-N 0.000 description 1
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
• XYHKNCXZYYTLRG-UHFFFAOYSA-N 1h-imidazole-2-carbaldehyde Chemical compound O=CC1=NC=CN1 XYHKNCXZYYTLRG-UHFFFAOYSA-N 0.000 description 1
• XYPISWUKQGWYGX-UHFFFAOYSA-N 2,2,2-trifluoroethaneperoxoic acid Chemical compound OOC(=O)C(F)(F)F XYPISWUKQGWYGX-UHFFFAOYSA-N 0.000 description 1
• GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
• SCVJRXQHFJXZFZ-KVQBGUIXSA-N 2-amino-9-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purine-6-thione Chemical compound C1=2NC(N)=NC(=S)C=2N=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 SCVJRXQHFJXZFZ-KVQBGUIXSA-N 0.000 description 1
• DEVGUROIDMOYIZ-UHFFFAOYSA-N 2-bromo-2-cyclohexyl-1-[4-tri(propan-2-yl)silyloxyphenyl]ethanone Chemical compound C1=CC(O[Si](C(C)C)(C(C)C)C(C)C)=CC=C1C(=O)C(Br)C1CCCCC1 DEVGUROIDMOYIZ-UHFFFAOYSA-N 0.000 description 1
• FQOMGYJZIACVND-UHFFFAOYSA-N 2-bromo-2-cyclopentyl-1-[4-tri(propan-2-yl)silyloxyphenyl]ethanone Chemical compound C1=CC(O[Si](C(C)C)(C(C)C)C(C)C)=CC=C1C(=O)C(Br)C1CCCC1 FQOMGYJZIACVND-UHFFFAOYSA-N 0.000 description 1
• AZAKDTJEAYHRPM-UHFFFAOYSA-N 2-bromo-2-pyridin-3-yl-1-[4-tri(propan-2-yl)silyloxyphenyl]ethanone Chemical compound C1=CC(O[Si](C(C)C)(C(C)C)C(C)C)=CC=C1C(=O)C(Br)C1=CC=CN=C1 AZAKDTJEAYHRPM-UHFFFAOYSA-N 0.000 description 1
• CFCHABCVJCYQEK-UHFFFAOYSA-N 2-bromo-2-pyridin-4-yl-1-[4-tri(propan-2-yl)silyloxyphenyl]ethanone Chemical compound C1=CC(O[Si](C(C)C)(C(C)C)C(C)C)=CC=C1C(=O)C(Br)C1=CC=NC=C1 CFCHABCVJCYQEK-UHFFFAOYSA-N 0.000 description 1
• OZUQBIVVKGATPZ-UHFFFAOYSA-N 2-cyclohexyl-1-(4-hydroxyphenyl)ethanone Chemical compound C1=CC(O)=CC=C1C(=O)CC1CCCCC1 OZUQBIVVKGATPZ-UHFFFAOYSA-N 0.000 description 1
• MKVXMOMMVIXHAB-UHFFFAOYSA-N 2-cyclohexyl-1-[4-tri(propan-2-yl)silyloxyphenyl]ethanone Chemical compound C1=CC(O[Si](C(C)C)(C(C)C)C(C)C)=CC=C1C(=O)CC1CCCCC1 MKVXMOMMVIXHAB-UHFFFAOYSA-N 0.000 description 1
• ATWBJCDOAKUIBQ-UHFFFAOYSA-N 2-cyclopentyl-1-(4-hydroxyphenyl)ethanone Chemical compound C1=CC(O)=CC=C1C(=O)CC1CCCC1 ATWBJCDOAKUIBQ-UHFFFAOYSA-N 0.000 description 1
• BEJMTMWWBQEFQL-UHFFFAOYSA-N 2-cyclopentyl-1-[4-tri(propan-2-yl)silyloxyphenyl]ethanone Chemical compound C1=CC(O[Si](C(C)C)(C(C)C)C(C)C)=CC=C1C(=O)CC1CCCC1 BEJMTMWWBQEFQL-UHFFFAOYSA-N 0.000 description 1
• CHZCERSEMVWNHL-UHFFFAOYSA-N 2-hydroxybenzonitrile Chemical compound OC1=CC=CC=C1C#N CHZCERSEMVWNHL-UHFFFAOYSA-N 0.000 description 1
• ZNIBUZCEEWLYPN-UHFFFAOYSA-N 2-pyridin-3-yl-1-[4-tri(propan-2-yl)silyloxyphenyl]ethanone Chemical compound C1=CC(O[Si](C(C)C)(C(C)C)C(C)C)=CC=C1C(=O)CC1=CC=CN=C1 ZNIBUZCEEWLYPN-UHFFFAOYSA-N 0.000 description 1
• ZFQJFYYGUOXGRF-UHFFFAOYSA-N 2-sulfanylbenzene-1,4-diol Chemical compound OC1=CC=C(O)C(S)=C1 ZFQJFYYGUOXGRF-UHFFFAOYSA-N 0.000 description 1
• VMKYTRPNOVFCGZ-UHFFFAOYSA-N 2-sulfanylphenol Chemical compound OC1=CC=CC=C1S VMKYTRPNOVFCGZ-UHFFFAOYSA-N 0.000 description 1
• AJYXPNIENRLELY-UHFFFAOYSA-N 2-thiophen-2-ylacetyl chloride Chemical compound ClC(=O)CC1=CC=CS1 AJYXPNIENRLELY-UHFFFAOYSA-N 0.000 description 1
• GWYFCOCPABKNJV-UHFFFAOYSA-M 3-Methylbutanoic acid Natural products CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
• ALKYHXVLJMQRLQ-UHFFFAOYSA-M 3-carboxynaphthalen-2-olate Chemical compound C1=CC=C2C=C(C([O-])=O)C(O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-M 0.000 description 1
• KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
• JVVRCYWZTJLJSG-UHFFFAOYSA-N 4-dimethylaminophenol Chemical compound CN(C)C1=CC=C(O)C=C1 JVVRCYWZTJLJSG-UHFFFAOYSA-N 0.000 description 1
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
• YPRTZLQGVTVHBN-UHFFFAOYSA-N 4-phenylmethoxybenzenethiol Chemical compound C1=CC(S)=CC=C1OCC1=CC=CC=C1 YPRTZLQGVTVHBN-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 208000002874 Acne Vulgaris Diseases 0.000 description 1
• 229920001817 Agar Polymers 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• 229930185605 Bisphenol Natural products 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
• 208000020084 Bone disease Diseases 0.000 description 1
• BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
• ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 229940122156 Cathepsin K inhibitor Drugs 0.000 description 1
• 241001432959 Chernes Species 0.000 description 1
• XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 1
• 238000008620 Cholesterol Assay Methods 0.000 description 1
• 101150065749 Churc1 gene Proteins 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
• ZAHDXEIQWWLQQL-IHRRRGAJSA-N Deoxypyridinoline Chemical compound OC(=O)[C@@H](N)CCCC[N+]1=CC(O)=C(C[C@H](N)C([O-])=O)C(CC[C@H](N)C(O)=O)=C1 ZAHDXEIQWWLQQL-IHRRRGAJSA-N 0.000 description 1
• 229920002307 Dextran Polymers 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
• 206010013908 Dysfunctional uterine bleeding Diseases 0.000 description 1
• 206010014733 Endometrial cancer Diseases 0.000 description 1
• 206010014759 Endometrial neoplasm Diseases 0.000 description 1
• 102100038595 Estrogen receptor Human genes 0.000 description 1
• 101710196141 Estrogen receptor Proteins 0.000 description 1
• 102100029951 Estrogen receptor beta Human genes 0.000 description 1
• DBVJJBKOTRCVKF-UHFFFAOYSA-N Etidronic acid Chemical compound OP(=O)(O)C(O)(C)P(O)(O)=O DBVJJBKOTRCVKF-UHFFFAOYSA-N 0.000 description 1
• 244000165918 Eucalyptus papuana Species 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 102000006771 Gonadotropins Human genes 0.000 description 1
• 108010086677 Gonadotropins Proteins 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 241000380126 Gymnosteris Species 0.000 description 1
• 229910004373 HOAc Inorganic materials 0.000 description 1
• 206010019044 Hair growth abnormal Diseases 0.000 description 1
• 206010020100 Hip fracture Diseases 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101000882584 Homo sapiens Estrogen receptor Proteins 0.000 description 1
• 206010020584 Hypercalcaemia of malignancy Diseases 0.000 description 1
• 206010020850 Hyperthyroidism Diseases 0.000 description 1
• MPBVHIBUJCELCL-UHFFFAOYSA-N Ibandronate Chemical compound CCCCCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O MPBVHIBUJCELCL-UHFFFAOYSA-N 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
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 206010027304 Menopausal symptoms Diseases 0.000 description 1
• 208000019255 Menstrual disease Diseases 0.000 description 1
• 206010027452 Metastases to bone Diseases 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
• 208000010191 Osteitis Deformans Diseases 0.000 description 1
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
• UQCNKQCJZOAFTQ-ISWURRPUSA-N Oxymorphone Chemical compound O([C@H]1C(CC[C@]23O)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O UQCNKQCJZOAFTQ-ISWURRPUSA-N 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 208000027868 Paget disease Diseases 0.000 description 1
• BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 102100038239 Protein Churchill Human genes 0.000 description 1
• 241000700157 Rattus norvegicus Species 0.000 description 1
• IIDJRNMFWXDHID-UHFFFAOYSA-N Risedronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=CN=C1 IIDJRNMFWXDHID-UHFFFAOYSA-N 0.000 description 1
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
• BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 229920002253 Tannate Polymers 0.000 description 1
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 208000027418 Wounds and injury Diseases 0.000 description 1
• 240000008042 Zea mays Species 0.000 description 1
• 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
• 241001507534 Zora Species 0.000 description 1
• OGQICQVSFDPSEI-UHFFFAOYSA-N Zorac Chemical compound N1=CC(C(=O)OCC)=CC=C1C#CC1=CC=C(SCCC2(C)C)C2=C1 OGQICQVSFDPSEI-UHFFFAOYSA-N 0.000 description 1
• 210000001015 abdomen Anatomy 0.000 description 1
• 210000003489 abdominal muscle Anatomy 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• 239000003377 acid catalyst Substances 0.000 description 1
• 239000003929 acidic solution Substances 0.000 description 1
• 206010000496 acne Diseases 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 235000010419 agar Nutrition 0.000 description 1
• 230000008484 agonism Effects 0.000 description 1
• DCSBSVSZJRSITC-UHFFFAOYSA-M alendronate sodium trihydrate Chemical compound O.O.O.[Na+].NCCCC(O)(P(O)(O)=O)P(O)([O-])=O DCSBSVSZJRSITC-UHFFFAOYSA-M 0.000 description 1
• 229960004343 alendronic acid Drugs 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 125000003545 alkoxy group Chemical group 0.000 description 1
• 150000001356 alkyl thiols Chemical class 0.000 description 1
• VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 1
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 239000005557 antagonist Substances 0.000 description 1
• 229940046836 anti-estrogen Drugs 0.000 description 1
• 239000006286 aqueous extract Substances 0.000 description 1
• OISFUZRUIGGTSD-LJTMIZJLSA-N azane;(2r,3r,4r,5s)-6-(methylamino)hexane-1,2,3,4,5-pentol Chemical compound N.CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO OISFUZRUIGGTSD-LJTMIZJLSA-N 0.000 description 1
• 125000002393 azetidinyl group Chemical group 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 239000000440 bentonite Substances 0.000 description 1
• 229910000278 bentonite Inorganic materials 0.000 description 1
• 235000012216 bentonite Nutrition 0.000 description 1
• SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
• 229940077388 benzenesulfonate Drugs 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical class C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• GWYFCOCPABKNJV-UHFFFAOYSA-N beta-methyl-butyric acid Natural products CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
• 229960003237 betaine Drugs 0.000 description 1
• 125000002619 bicyclic group Chemical group 0.000 description 1
• 230000002146 bilateral effect Effects 0.000 description 1
• 230000008512 biological response Effects 0.000 description 1
• IISBACLAFKSPIT-UHFFFAOYSA-N bisphenol A Chemical compound C=1C=C(O)C=CC=1C(C)(C)C1=CC=C(O)C=C1 IISBACLAFKSPIT-UHFFFAOYSA-N 0.000 description 1
• 229920001400 block copolymer Polymers 0.000 description 1
• 230000008416 bone turnover Effects 0.000 description 1
• 229910052796 boron Inorganic materials 0.000 description 1
• 229940098773 bovine serum albumin Drugs 0.000 description 1
• 201000008274 breast adenocarcinoma Diseases 0.000 description 1
• DEGAKNSWVGKMLS-UHFFFAOYSA-N calcein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(O)=O)CC(O)=O)=C(O)C=C1OC1=C2C=C(CN(CC(O)=O)CC(=O)O)C(O)=C1 DEGAKNSWVGKMLS-UHFFFAOYSA-N 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
• JYYOBHFYCIDXHH-UHFFFAOYSA-N carbonic acid;hydrate Chemical compound O.OC(O)=O JYYOBHFYCIDXHH-UHFFFAOYSA-N 0.000 description 1
• SKOLWUPSYHWYAM-UHFFFAOYSA-N carbonodithioic O,S-acid Chemical compound SC(S)=O SKOLWUPSYHWYAM-UHFFFAOYSA-N 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 229940105329 carboxymethylcellulose Drugs 0.000 description 1
• 230000000747 cardiac effect Effects 0.000 description 1
• 230000036996 cardiovascular health Effects 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 150000005829 chemical entities Chemical class 0.000 description 1
• 238000002512 chemotherapy Methods 0.000 description 1
• 125000004803 chlorobenzyl group Chemical group 0.000 description 1
• 229940061627 chloromethyl methyl ether Drugs 0.000 description 1
• 229940090805 clavulanate Drugs 0.000 description 1
• HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 1
• ACSIXWWBWUQEHA-UHFFFAOYSA-N clodronic acid Chemical compound OP(O)(=O)C(Cl)(Cl)P(O)(O)=O ACSIXWWBWUQEHA-UHFFFAOYSA-N 0.000 description 1
• 229960002286 clodronic acid Drugs 0.000 description 1
• 230000011382 collagen catabolic process Effects 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 239000012230 colorless oil Substances 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 229920001577 copolymer Polymers 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 239000003246 corticosteroid Substances 0.000 description 1
• 229960001334 corticosteroids Drugs 0.000 description 1
• 229940109239 creatinine Drugs 0.000 description 1
• 238000004132 cross linking Methods 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• HBLUJTHFXFVJRN-UHFFFAOYSA-N cyclopentylmethanethiol Chemical class SCC1CCCC1 HBLUJTHFXFVJRN-UHFFFAOYSA-N 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 238000006264 debenzylation reaction Methods 0.000 description 1
• 230000007812 deficiency Effects 0.000 description 1
• 239000007857 degradation product Substances 0.000 description 1
• 230000001934 delay Effects 0.000 description 1
• 230000008021 deposition Effects 0.000 description 1
• 238000001212 derivatisation Methods 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
• 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
• 229940038472 dicalcium phosphate Drugs 0.000 description 1
• RUHCATDGSSLXPZ-UHFFFAOYSA-N dicarboxyazaniumylideneazanide Chemical compound OC(=O)[N+](=[N-])C(O)=O RUHCATDGSSLXPZ-UHFFFAOYSA-N 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• SPCNPOWOBZQWJK-UHFFFAOYSA-N dimethoxy-(2-propan-2-ylsulfanylethylsulfanyl)-sulfanylidene-$l^{5}-phosphane Chemical compound COP(=S)(OC)SCCSC(C)C SPCNPOWOBZQWJK-UHFFFAOYSA-N 0.000 description 1
• FFHWGQQFANVOHV-UHFFFAOYSA-N dimethyldioxirane Chemical compound CC1(C)OO1 FFHWGQQFANVOHV-UHFFFAOYSA-N 0.000 description 1
• 150000002012 dioxanes Chemical class 0.000 description 1
• 239000001177 diphosphate Substances 0.000 description 1
• XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
• 235000011180 diphosphates Nutrition 0.000 description 1
• ZZFKAZHZSSJSSE-UHFFFAOYSA-L disodium;[(cycloheptylamino)-[hydroxy(oxido)phosphoryl]methyl]-hydroxyphosphinate;hydrate Chemical compound O.[Na+].[Na+].OP(O)(=O)C(P([O-])([O-])=O)NC1CCCCCC1 ZZFKAZHZSSJSSE-UHFFFAOYSA-L 0.000 description 1
• POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 239000006196 drop Substances 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 229940009662 edetate Drugs 0.000 description 1
• 229950008913 edisilate Drugs 0.000 description 1
• 229950005627 embonate Drugs 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 230000002124 endocrine Effects 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• 229950000206 estolate Drugs 0.000 description 1
• 239000003687 estradiol congener Substances 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• 239000002024 ethyl acetate extract Substances 0.000 description 1
• 229940009626 etidronate Drugs 0.000 description 1
• 239000003889 eye drop Substances 0.000 description 1
• 229940012356 eye drops Drugs 0.000 description 1
• 210000003195 fascia Anatomy 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 125000004175 fluorobenzyl group Chemical group 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 238000009472 formulation Methods 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 239000012737 fresh medium Substances 0.000 description 1
• 229940050411 fumarate Drugs 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 229960001731 gluceptate Drugs 0.000 description 1
• 201000003617 glucocorticoid-induced osteoporosis Diseases 0.000 description 1
• KWMLJOLKUYYJFJ-VFUOTHLCSA-N glucoheptonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C(O)=O KWMLJOLKUYYJFJ-VFUOTHLCSA-N 0.000 description 1
• 229940050410 gluconate Drugs 0.000 description 1
• 235000001727 glucose Nutrition 0.000 description 1
• 229930195712 glutamate Natural products 0.000 description 1
• 229940049906 glutamate Drugs 0.000 description 1
• 208000002566 gonadal dysgenesis Diseases 0.000 description 1
• 239000002622 gonadotropin Substances 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
• GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 208000008750 humoral hypercalcemia of malignancy Diseases 0.000 description 1
• XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 150000004678 hydrides Chemical class 0.000 description 1
• 239000000017 hydrogel Substances 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 229940015872 ibandronate Drugs 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 229950006971 incadronic acid Drugs 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 230000000968 intestinal effect Effects 0.000 description 1
• 210000000936 intestine Anatomy 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 230000003907 kidney function Effects 0.000 description 1
• 238000002372 labelling Methods 0.000 description 1
• 229940001447 lactate Drugs 0.000 description 1
• 229940099584 lactobionate Drugs 0.000 description 1
• JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
• 229940070765 laurate Drugs 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 230000003908 liver function Effects 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 229940049920 malate Drugs 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 208000027202 mammary Paget disease Diseases 0.000 description 1
• 238000007726 management method Methods 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000000691 measurement method Methods 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
• 229940102396 methyl bromide Drugs 0.000 description 1
• LRMHVVPPGGOAJQ-UHFFFAOYSA-N methyl nitrate Chemical compound CO[N+]([O-])=O LRMHVVPPGGOAJQ-UHFFFAOYSA-N 0.000 description 1
• JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• VMMKGHQPQIEGSQ-UHFFFAOYSA-N minodronic acid Chemical compound C1=CC=CN2C(CC(O)(P(O)(O)=O)P(O)(O)=O)=CN=C21 VMMKGHQPQIEGSQ-UHFFFAOYSA-N 0.000 description 1
• 229950011129 minodronic acid Drugs 0.000 description 1
• 239000011259 mixed solution Substances 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 230000000897 modulatory effect Effects 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• 210000003205 muscle Anatomy 0.000 description 1
• 210000000754 myometrium Anatomy 0.000 description 1
• PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
• 229950006327 napsilate Drugs 0.000 description 1
• PUUSSSIBPPTKTP-UHFFFAOYSA-N neridronic acid Chemical compound NCCCCCC(O)(P(O)(O)=O)P(O)(O)=O PUUSSSIBPPTKTP-UHFFFAOYSA-N 0.000 description 1
• 229950010733 neridronic acid Drugs 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• 229960002378 oftasceine Drugs 0.000 description 1
• 229940049964 oleate Drugs 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 239000006186 oral dosage form Substances 0.000 description 1
• 229940126701 oral medication Drugs 0.000 description 1
• 239000007935 oral tablet Substances 0.000 description 1
• 239000013110 organic ligand Substances 0.000 description 1
• 210000000963 osteoblast Anatomy 0.000 description 1
• 210000002997 osteoclast Anatomy 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 125000005646 oximino group Chemical group 0.000 description 1
• 125000000466 oxiranyl group Chemical group 0.000 description 1
• 229960005118 oxymorphone Drugs 0.000 description 1
• WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 description 1
• 229940046231 pamidronate Drugs 0.000 description 1
• 229940014662 pantothenate Drugs 0.000 description 1
• 235000019161 pantothenic acid Nutrition 0.000 description 1
• 239000011713 pantothenic acid Substances 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 208000028169 periodontal disease Diseases 0.000 description 1
• 239000008024 pharmaceutical diluent Substances 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
• 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004344 phenylpropyl group Chemical group 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
• 150000003904 phospholipids Chemical class 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 239000004417 polycarbonate Substances 0.000 description 1
• 229920000515 polycarbonate Polymers 0.000 description 1
• 229920002721 polycyanoacrylate Polymers 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 229920006324 polyoxymethylene Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 239000013641 positive control Substances 0.000 description 1
• XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
• 239000001103 potassium chloride Substances 0.000 description 1
• 235000011164 potassium chloride Nutrition 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 230000035755 proliferation Effects 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 239000008213 purified water Substances 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000004076 pyridyl group Chemical group 0.000 description 1
• 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
• 239000000700 radioactive tracer Substances 0.000 description 1
• 230000009257 reactivity Effects 0.000 description 1
• 238000001525 receptor binding assay Methods 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 238000001223 reverse osmosis Methods 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 229940089617 risedronate Drugs 0.000 description 1
• YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
• 229960001860 salicylate Drugs 0.000 description 1
• 229920006298 saran Polymers 0.000 description 1
• 229930195734 saturated hydrocarbon Natural products 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
• 238000006884 silylation reaction Methods 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 235000015424 sodium Nutrition 0.000 description 1
• 239000001632 sodium acetate Substances 0.000 description 1
• 235000017281 sodium acetate Nutrition 0.000 description 1
• 235000010413 sodium alginate Nutrition 0.000 description 1
• 239000000661 sodium alginate Substances 0.000 description 1
• 229940005550 sodium alginate Drugs 0.000 description 1
• WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
• 239000004299 sodium benzoate Substances 0.000 description 1
• 235000010234 sodium benzoate Nutrition 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 229940079827 sodium hydrogen sulfite Drugs 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
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
• 235000019345 sodium thiosulphate Nutrition 0.000 description 1
• 239000012453 solvate Substances 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 235000010356 sorbitol Nutrition 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 206010041569 spinal fracture Diseases 0.000 description 1
• 238000013223 sprague-dawley female rat Methods 0.000 description 1
• 229910001220 stainless steel Inorganic materials 0.000 description 1
• 239000010935 stainless steel Substances 0.000 description 1
• KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 1
• 229910000080 stannane Inorganic materials 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 239000011550 stock solution Substances 0.000 description 1
• 238000010254 subcutaneous injection Methods 0.000 description 1
• 239000007929 subcutaneous injection Substances 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 229940095064 tartrate Drugs 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
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 230000004797 therapeutic response Effects 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 125000001544 thienyl group Chemical group 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
• 229940098465 tincture Drugs 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
• 125000005425 toluyl group Chemical group 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
• 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
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
• PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-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
• 230000007306 turnover Effects 0.000 description 1
• 210000000689 upper leg Anatomy 0.000 description 1
• 230000002485 urinary effect Effects 0.000 description 1
• 238000003828 vacuum filtration Methods 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
• 230000000304 vasodilatating effect Effects 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• 238000010626 work up procedure Methods 0.000 description 1
• 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