JP5713999B2 - アミド化合物、その製造方法及びそれを含む薬学組成物 - Google Patents
アミド化合物、その製造方法及びそれを含む薬学組成物 Download PDFInfo
- Publication number
- JP5713999B2 JP5713999B2 JP2012510756A JP2012510756A JP5713999B2 JP 5713999 B2 JP5713999 B2 JP 5713999B2 JP 2012510756 A JP2012510756 A JP 2012510756A JP 2012510756 A JP2012510756 A JP 2012510756A JP 5713999 B2 JP5713999 B2 JP 5713999B2
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- aminophenyl
- benzamide
- oxoisoindoline
- bromo
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- -1 Amide compound Chemical class 0.000 title claims description 249
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 8
- 238000000034 method Methods 0.000 title description 42
- 230000008569 process Effects 0.000 title description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 292
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 245
- 150000001875 compounds Chemical class 0.000 claims description 221
- ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 claims description 209
- 239000000126 substance Substances 0.000 claims description 39
- 125000001072 heteroaryl group Chemical group 0.000 claims description 31
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 17
- 239000000203 mixture Substances 0.000 claims description 11
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 10
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 8
- 208000020084 Bone disease Diseases 0.000 claims description 8
- 208000001132 Osteoporosis Diseases 0.000 claims description 8
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 7
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 6
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 claims description 5
- 206010017076 Fracture Diseases 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- APSTWUQDOVMXOZ-UHFFFAOYSA-N 4-[[7-(3-acetamidophenyl)-3-oxo-1h-isoindol-2-yl]methyl]-n-(2-aminophenyl)benzamide Chemical compound CC(=O)NC1=CC=CC(C=2C=3CN(CC=4C=CC(=CC=4)C(=O)NC=4C(=CC=CC=4)N)C(=O)C=3C=CC=2)=C1 APSTWUQDOVMXOZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- LYHZVZOXCVEZLV-UHFFFAOYSA-N n-(2-aminophenyl)-4-[(3-oxo-6-pyridin-3-yl-1h-isoindol-2-yl)methyl]benzamide Chemical compound NC1=CC=CC=C1NC(=O)C(C=C1)=CC=C1CN1C(=O)C2=CC=C(C=3C=NC=CC=3)C=C2C1 LYHZVZOXCVEZLV-UHFFFAOYSA-N 0.000 claims description 3
- YFKZHVYJZWLAID-UHFFFAOYSA-N n-(2-aminophenyl)-4-[(3-oxo-6-pyrimidin-5-yl-1h-isoindol-2-yl)methyl]benzamide Chemical compound NC1=CC=CC=C1NC(=O)C(C=C1)=CC=C1CN1C(=O)C2=CC=C(C=3C=NC=NC=3)C=C2C1 YFKZHVYJZWLAID-UHFFFAOYSA-N 0.000 claims description 3
- FADRSVQBYKMIQN-UHFFFAOYSA-N n-(2-aminophenyl)-4-[(3-oxo-7-pyridin-3-yl-1h-isoindol-2-yl)methyl]benzamide Chemical compound NC1=CC=CC=C1NC(=O)C(C=C1)=CC=C1CN1C(=O)C(C=CC=C2C=3C=NC=CC=3)=C2C1 FADRSVQBYKMIQN-UHFFFAOYSA-N 0.000 claims description 3
- CSIHFGREVUCTLK-UHFFFAOYSA-N n-(2-aminophenyl)-4-[(3-oxo-7-pyrimidin-5-yl-1h-isoindol-2-yl)methyl]benzamide Chemical compound NC1=CC=CC=C1NC(=O)C(C=C1)=CC=C1CN1C(=O)C(C=CC=C2C=3C=NC=NC=3)=C2C1 CSIHFGREVUCTLK-UHFFFAOYSA-N 0.000 claims description 3
- KIPJIVDSUCESGM-UHFFFAOYSA-N n-(2-aminophenyl)-4-[[3-oxo-7-(4-phenoxyphenyl)-1h-isoindol-2-yl]methyl]benzamide Chemical compound NC1=CC=CC=C1NC(=O)C(C=C1)=CC=C1CN1C(=O)C(C=CC=C2C=3C=CC(OC=4C=CC=CC=4)=CC=3)=C2C1 KIPJIVDSUCESGM-UHFFFAOYSA-N 0.000 claims description 3
- OZJARHJCNXYKJQ-UHFFFAOYSA-N n-(2-aminophenyl)-4-[[3-oxo-7-(4-phenylphenyl)-1h-isoindol-2-yl]methyl]benzamide Chemical compound NC1=CC=CC=C1NC(=O)C(C=C1)=CC=C1CN1C(=O)C(C=CC=C2C=3C=CC(=CC=3)C=3C=CC=CC=3)=C2C1 OZJARHJCNXYKJQ-UHFFFAOYSA-N 0.000 claims description 3
- LBAHPAGTDLXSBT-UHFFFAOYSA-N n-(2-aminophenyl)-4-[[6-(4-cyanophenyl)-3-oxo-1h-isoindol-2-yl]methyl]benzamide Chemical compound NC1=CC=CC=C1NC(=O)C(C=C1)=CC=C1CN1C(=O)C2=CC=C(C=3C=CC(=CC=3)C#N)C=C2C1 LBAHPAGTDLXSBT-UHFFFAOYSA-N 0.000 claims description 3
- HXRBEWCWHLXIQT-UHFFFAOYSA-N n-(2-aminophenyl)-4-[[7-(4-cyanophenyl)-3-oxo-1h-isoindol-2-yl]methyl]benzamide Chemical compound NC1=CC=CC=C1NC(=O)C(C=C1)=CC=C1CN1C(=O)C(C=CC=C2C=3C=CC(=CC=3)C#N)=C2C1 HXRBEWCWHLXIQT-UHFFFAOYSA-N 0.000 claims description 3
- 208000010191 Osteitis Deformans Diseases 0.000 claims description 2
- 208000027868 Paget disease Diseases 0.000 claims description 2
- 230000008468 bone growth Effects 0.000 claims description 2
- 208000037824 growth disorder Diseases 0.000 claims description 2
- 208000027202 mammary Paget disease Diseases 0.000 claims description 2
- 208000028169 periodontal disease Diseases 0.000 claims description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
- 206010027452 Metastases to bone Diseases 0.000 claims 1
- 230000001548 androgenic effect Effects 0.000 claims 1
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 156
- 238000006243 chemical reaction Methods 0.000 description 59
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 49
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 43
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
- 230000000694 effects Effects 0.000 description 35
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- ALBYIUDWACNRRB-UHFFFAOYSA-N hexanamide Chemical compound CCCCCC(N)=O ALBYIUDWACNRRB-UHFFFAOYSA-N 0.000 description 34
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 239000002904 solvent Substances 0.000 description 26
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 25
- 229910052763 palladium Inorganic materials 0.000 description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 125000003118 aryl group Chemical group 0.000 description 21
- 210000004027 cell Anatomy 0.000 description 20
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 20
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 20
- 239000000243 solution Substances 0.000 description 20
- 206010065687 Bone loss Diseases 0.000 description 19
- 230000011164 ossification Effects 0.000 description 19
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 18
- 235000019439 ethyl acetate Nutrition 0.000 description 18
- 239000012046 mixed solvent Substances 0.000 description 18
- 210000003625 skull Anatomy 0.000 description 18
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- 108010024682 Core Binding Factor Alpha 1 Subunit Proteins 0.000 description 16
- 102000015775 Core Binding Factor Alpha 1 Subunit Human genes 0.000 description 16
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 15
- 150000001408 amides Chemical class 0.000 description 15
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 14
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 14
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 210000000988 bone and bone Anatomy 0.000 description 14
- 125000003107 substituted aryl group Chemical group 0.000 description 14
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 13
- 229910052739 hydrogen Inorganic materials 0.000 description 13
- 230000002829 reductive effect Effects 0.000 description 13
- 210000002997 osteoclast Anatomy 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 12
- 230000035484 reaction time Effects 0.000 description 12
- 239000011734 sodium Substances 0.000 description 12
- 239000005711 Benzoic acid Substances 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- 238000005859 coupling reaction Methods 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 239000012153 distilled water Substances 0.000 description 10
- 238000001727 in vivo Methods 0.000 description 10
- 210000000963 osteoblast Anatomy 0.000 description 10
- ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 10
- 239000007858 starting material Substances 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 102000000589 Interleukin-1 Human genes 0.000 description 9
- 108010002352 Interleukin-1 Proteins 0.000 description 9
- 241000699666 Mus <mouse, genus> Species 0.000 description 9
- 241000700159 Rattus Species 0.000 description 9
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 9
- 229910052736 halogen Inorganic materials 0.000 description 9
- 150000002367 halogens Chemical class 0.000 description 9
- 229910052500 inorganic mineral Inorganic materials 0.000 description 9
- 239000011707 mineral Substances 0.000 description 9
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 9
- 229910000029 sodium carbonate Inorganic materials 0.000 description 9
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 238000006069 Suzuki reaction reaction Methods 0.000 description 8
- GJOQYAQQJLSJTO-UHFFFAOYSA-N n-[6-(2-aminoanilino)-6-oxohexyl]-4-bromo-3-methylbenzamide Chemical compound C1=C(Br)C(C)=CC(C(=O)NCCCCCC(=O)NC=2C(=CC=CC=2)N)=C1 GJOQYAQQJLSJTO-UHFFFAOYSA-N 0.000 description 8
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
- 235000010233 benzoic acid Nutrition 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 7
- 230000001965 increasing effect Effects 0.000 description 7
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 7
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 238000004809 thin layer chromatography Methods 0.000 description 7
- QWQBQRYFWNIDOC-UHFFFAOYSA-N (3,5-difluorophenyl)boronic acid Chemical compound OB(O)C1=CC(F)=CC(F)=C1 QWQBQRYFWNIDOC-UHFFFAOYSA-N 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- IQHSSYROJYPFDV-UHFFFAOYSA-N 2-bromo-1,3-dichloro-5-(trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC(Cl)=C(Br)C(Cl)=C1 IQHSSYROJYPFDV-UHFFFAOYSA-N 0.000 description 6
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- 239000005089 Luciferase Substances 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 6
- 238000010603 microCT Methods 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- DJGHSJBYKIQHIK-UHFFFAOYSA-N (3,5-dimethylphenyl)boronic acid Chemical compound CC1=CC(C)=CC(B(O)O)=C1 DJGHSJBYKIQHIK-UHFFFAOYSA-N 0.000 description 5
- OJWWANDRHLUPDP-UHFFFAOYSA-N 6-[(3-bromo-2-methylbenzoyl)amino]hexanoic acid Chemical compound CC1=C(Br)C=CC=C1C(=O)NCCCCCC(O)=O OJWWANDRHLUPDP-UHFFFAOYSA-N 0.000 description 5
- XZNJOZRVLKMPGH-UHFFFAOYSA-N C1C=2C(Br)=C(OC)C(OC)=CC=2C(=O)N1CNC(=O)C1=CC=CC=C1 Chemical compound C1C=2C(Br)=C(OC)C(OC)=CC=2C(=O)N1CNC(=O)C1=CC=CC=C1 XZNJOZRVLKMPGH-UHFFFAOYSA-N 0.000 description 5
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 208000035896 Twin-reversed arterial perfusion sequence Diseases 0.000 description 5
- ALMFIOZYDASRRC-UHFFFAOYSA-N [4-(trifluoromethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=C(C(F)(F)F)C=C1 ALMFIOZYDASRRC-UHFFFAOYSA-N 0.000 description 5
- 125000004122 cyclic group Chemical group 0.000 description 5
- 230000008034 disappearance Effects 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- GQHPLAGWOKBJEH-UHFFFAOYSA-N methyl 3-bromo-2-(bromomethyl)-4,5-dimethoxybenzoate Chemical compound COC(=O)C1=CC(OC)=C(OC)C(Br)=C1CBr GQHPLAGWOKBJEH-UHFFFAOYSA-N 0.000 description 5
- XVBOZQPOGMIZKG-UHFFFAOYSA-N n-[6-(2-aminoanilino)-6-oxohexyl]-3-bromo-2-methylbenzamide Chemical compound CC1=C(Br)C=CC=C1C(=O)NCCCCCC(=O)NC1=CC=CC=C1N XVBOZQPOGMIZKG-UHFFFAOYSA-N 0.000 description 5
- OPNRMJUNSYQVSW-UHFFFAOYSA-N n-[[4-[(2-aminophenyl)carbamoyl]phenyl]methyl]-3-bromo-2-methylbenzamide Chemical compound CC1=C(Br)C=CC=C1C(=O)NCC1=CC=C(C(=O)NC=2C(=CC=CC=2)N)C=C1 OPNRMJUNSYQVSW-UHFFFAOYSA-N 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 230000002103 transcriptional effect Effects 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- SQTUYFKNCCBFRR-UHFFFAOYSA-N (2,4-dimethoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C(OC)=C1 SQTUYFKNCCBFRR-UHFFFAOYSA-N 0.000 description 4
- RCVDPBFUMYUKPB-UHFFFAOYSA-N (3,4-dimethoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1OC RCVDPBFUMYUKPB-UHFFFAOYSA-N 0.000 description 4
- OADZVXZARJCFMF-UHFFFAOYSA-N 3-bromo-2-methylbenzamide Chemical compound CC1=C(Br)C=CC=C1C(N)=O OADZVXZARJCFMF-UHFFFAOYSA-N 0.000 description 4
- NRBLRDWWLUJKSN-UHFFFAOYSA-N 4-(aminomethyl)-2-methylbenzoic acid;hydrochloride Chemical compound Cl.CC1=CC(CN)=CC=C1C(O)=O NRBLRDWWLUJKSN-UHFFFAOYSA-N 0.000 description 4
- 229940122361 Bisphosphonate Drugs 0.000 description 4
- 108060001084 Luciferase Proteins 0.000 description 4
- 102000004067 Osteocalcin Human genes 0.000 description 4
- 108090000573 Osteocalcin Proteins 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- 102000040945 Transcription factor Human genes 0.000 description 4
- 108091023040 Transcription factor Proteins 0.000 description 4
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 125000005605 benzo group Chemical group 0.000 description 4
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 4
- 150000004663 bisphosphonates Chemical class 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 239000000515 collagen sponge Substances 0.000 description 4
- 230000007547 defect Effects 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 229940011871 estrogen Drugs 0.000 description 4
- 239000000262 estrogen Substances 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- WMILMIDBWBQPAB-UHFFFAOYSA-N methyl 3-bromo-2-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=CC(Br)=C1CBr WMILMIDBWBQPAB-UHFFFAOYSA-N 0.000 description 4
- PZFBVCWBRSVYFV-UHFFFAOYSA-N methyl 6-[(3-bromo-2-methylbenzoyl)amino]hexanoate Chemical compound COC(=O)CCCCCNC(=O)C1=CC=CC(Br)=C1C PZFBVCWBRSVYFV-UHFFFAOYSA-N 0.000 description 4
- 239000011259 mixed solution Substances 0.000 description 4
- QHWLEVLLYKCVAB-UHFFFAOYSA-N n-[[4-[(2-aminophenyl)carbamoyl]phenyl]methyl]-3-bromo-4,5-dimethoxy-2-methylbenzamide Chemical compound BrC1=C(OC)C(OC)=CC(C(=O)NCC=2C=CC(=CC=2)C(=O)NC=2C(=CC=CC=2)N)=C1C QHWLEVLLYKCVAB-UHFFFAOYSA-N 0.000 description 4
- 230000004072 osteoblast differentiation Effects 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 238000002953 preparative HPLC Methods 0.000 description 4
- 230000001737 promoting effect Effects 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 230000001629 suppression Effects 0.000 description 4
- JNJJINIJWXHEQQ-UHFFFAOYSA-N tert-butyl n-(2-amino-4-thiophen-2-ylphenyl)carbamate Chemical compound C1=C(N)C(NC(=O)OC(C)(C)C)=CC=C1C1=CC=CS1 JNJJINIJWXHEQQ-UHFFFAOYSA-N 0.000 description 4
- 239000010409 thin film Substances 0.000 description 4
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 3
- SHAHPWSYJFYMRX-GDLCADMTSA-N (2S)-2-(4-{[(1R,2S)-2-hydroxycyclopentyl]methyl}phenyl)propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C[C@@H]1[C@@H](O)CCC1 SHAHPWSYJFYMRX-GDLCADMTSA-N 0.000 description 3
- VOAAEKKFGLPLLU-UHFFFAOYSA-N (4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1 VOAAEKKFGLPLLU-UHFFFAOYSA-N 0.000 description 3
- IGVKWAAPMVVTFX-BUHFOSPRSA-N (e)-octadec-5-en-7,9-diynoic acid Chemical compound CCCCCCCCC#CC#C\C=C\CCCC(O)=O IGVKWAAPMVVTFX-BUHFOSPRSA-N 0.000 description 3
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 3
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
- IJVLKUUJKWFLNT-UHFFFAOYSA-N 3-(2,4-dimethoxyphenyl)-n-[6-(hydroxyamino)-6-oxohexyl]-2-methylbenzamide Chemical compound COC1=CC(OC)=CC=C1C1=CC=CC(C(=O)NCCCCCC(=O)NO)=C1C IJVLKUUJKWFLNT-UHFFFAOYSA-N 0.000 description 3
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 3
- FZRPPZOGSGRYDE-UHFFFAOYSA-N 4-[(7-bromo-5,6-dimethoxy-3-oxo-1h-isoindol-2-yl)methyl]benzoic acid Chemical compound C1C=2C(Br)=C(OC)C(OC)=CC=2C(=O)N1CC1=CC=C(C(O)=O)C=C1 FZRPPZOGSGRYDE-UHFFFAOYSA-N 0.000 description 3
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
- LPZLDMDIMAIPIG-UHFFFAOYSA-N 6-(7-bromo-3-oxo-1h-isoindol-2-yl)hexanoic acid Chemical compound O=C1N(CCCCCC(=O)O)CC2=C1C=CC=C2Br LPZLDMDIMAIPIG-UHFFFAOYSA-N 0.000 description 3
- DLFWMLVFCAOVOH-UHFFFAOYSA-N 6-amino-2-methylhexanoic acid;hydrochloride Chemical compound Cl.OC(=O)C(C)CCCCN DLFWMLVFCAOVOH-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 208000006386 Bone Resorption Diseases 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 238000006161 Suzuki-Miyaura coupling reaction Methods 0.000 description 3
- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 3
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 230000024279 bone resorption Effects 0.000 description 3
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000006264 debenzylation reaction Methods 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 3
- ZJJQGVOFSMFSJP-UHFFFAOYSA-N n-[6-(hydroxyamino)-6-oxohexyl]-2-methyl-3-phenylbenzamide Chemical compound CC1=C(C(=O)NCCCCCC(=O)NO)C=CC=C1C1=CC=CC=C1 ZJJQGVOFSMFSJP-UHFFFAOYSA-N 0.000 description 3
- IQSVCTXOPFGMPJ-UHFFFAOYSA-N n-[6-(hydroxyamino)-6-oxohexyl]-3-methyl-4-phenylbenzamide Chemical compound CC1=CC(C(=O)NCCCCCC(=O)NO)=CC=C1C1=CC=CC=C1 IQSVCTXOPFGMPJ-UHFFFAOYSA-N 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- BSCCSDNZEIHXOK-UHFFFAOYSA-N phenyl carbamate Chemical compound NC(=O)OC1=CC=CC=C1 BSCCSDNZEIHXOK-UHFFFAOYSA-N 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- XZTLPIUYVNWVTP-UHFFFAOYSA-N tert-butyl n-[6-oxo-6-(phenylmethoxyamino)hexyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCCCC(=O)NOCC1=CC=CC=C1 XZTLPIUYVNWVTP-UHFFFAOYSA-N 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- HBENZIXOGRCSQN-VQWWACLZSA-N (1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylpentan-2-yl]-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol Chemical compound N1([C@@H]2CC=3C4=C(C(=CC=3)O)O[C@H]3[C@@]5(OC)CC[C@@]2([C@@]43CC1)C[C@@H]5[C@](C)(O)C(C)(C)CC)CC1CC1 HBENZIXOGRCSQN-VQWWACLZSA-N 0.000 description 2
- CEBAHYWORUOILU-UHFFFAOYSA-N (4-cyanophenyl)boronic acid Chemical compound OB(O)C1=CC=C(C#N)C=C1 CEBAHYWORUOILU-UHFFFAOYSA-N 0.000 description 2
- WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 2
- HTFXWAOSQODIBI-UHFFFAOYSA-N 2-benzyl-1,3-dihydropyrrolo[3,4-c]pyridine Chemical compound C1C2=CC=NC=C2CN1CC1=CC=CC=C1 HTFXWAOSQODIBI-UHFFFAOYSA-N 0.000 description 2
- WMMGNLLTRCSAFW-UHFFFAOYSA-N 4-[[(3-bromo-4,5-dimethoxy-2-methylbenzoyl)amino]methyl]benzoic acid Chemical compound BrC1=C(OC)C(OC)=CC(C(=O)NCC=2C=CC(=CC=2)C(O)=O)=C1C WMMGNLLTRCSAFW-UHFFFAOYSA-N 0.000 description 2
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 2
- YWEONUUQMOCJOQ-UHFFFAOYSA-N 6-[(2-methyl-3-phenylbenzoyl)amino]hexanoic acid Chemical compound CC1=C(C(=O)NCCCCCC(O)=O)C=CC=C1C1=CC=CC=C1 YWEONUUQMOCJOQ-UHFFFAOYSA-N 0.000 description 2
- AFUWDQAKUSQZRI-UHFFFAOYSA-N 6-[(3-methyl-4-phenylbenzoyl)amino]hexanoic acid Chemical compound CC1=CC(C(=O)NCCCCCC(O)=O)=CC=C1C1=CC=CC=C1 AFUWDQAKUSQZRI-UHFFFAOYSA-N 0.000 description 2
- WDMUDVALAINKTA-UHFFFAOYSA-N 6-[(4-bromo-3-methylbenzoyl)amino]hexanoic acid Chemical compound CC1=CC(C(=O)NCCCCCC(O)=O)=CC=C1Br WDMUDVALAINKTA-UHFFFAOYSA-N 0.000 description 2
- GPRGHRLPSXZHCX-UHFFFAOYSA-N 6-[6-(3,5-difluorophenyl)-3-oxo-1h-isoindol-2-yl]-n-hydroxyhexanamide Chemical compound C=1C=C2C(=O)N(CCCCCC(=O)NO)CC2=CC=1C1=CC(F)=CC(F)=C1 GPRGHRLPSXZHCX-UHFFFAOYSA-N 0.000 description 2
- QZXXPIJAYMKWSC-UHFFFAOYSA-N 6-amino-n-phenylmethoxyhexanamide Chemical compound NCCCCCC(=O)NOCC1=CC=CC=C1 QZXXPIJAYMKWSC-UHFFFAOYSA-N 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- LBNPDSWIFXMPBS-UHFFFAOYSA-N CCCCCCN1CC2=C(C(=C(C=C2C1=O)OC)OC)Br Chemical class CCCCCCN1CC2=C(C(=C(C=C2C1=O)OC)OC)Br LBNPDSWIFXMPBS-UHFFFAOYSA-N 0.000 description 2
- QCMHGCDOZLWPOT-FMNCTDSISA-N COC1=C(CC[C@@H]2CCC3=C(C2)C=CC(=C3)[C@H]2CC[C@](N)(CO)C2)C=CC=C1 Chemical compound COC1=C(CC[C@@H]2CCC3=C(C2)C=CC(=C3)[C@H]2CC[C@](N)(CO)C2)C=CC=C1 QCMHGCDOZLWPOT-FMNCTDSISA-N 0.000 description 2
- 101100297347 Caenorhabditis elegans pgl-3 gene Proteins 0.000 description 2
- 102000055006 Calcitonin Human genes 0.000 description 2
- 108060001064 Calcitonin Proteins 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- 101100477839 Drosophila melanogaster Smurf gene Proteins 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
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 102000003964 Histone deacetylase Human genes 0.000 description 2
- 108090000353 Histone deacetylase Proteins 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- HPKJGHVHQWJOOT-ZJOUEHCJSA-N N-[(2S)-3-cyclohexyl-1-oxo-1-({(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}amino)propan-2-yl]-1H-indole-2-carboxamide Chemical compound C1C(CCCC1)C[C@H](NC(=O)C=1NC2=CC=CC=C2C=1)C(=O)N[C@@H](C[C@H]1C(=O)NCC1)C=O HPKJGHVHQWJOOT-ZJOUEHCJSA-N 0.000 description 2
- 102000003982 Parathyroid hormone Human genes 0.000 description 2
- 108090000445 Parathyroid hormone Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 101150086605 Runx2 gene Proteins 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 102000044159 Ubiquitin Human genes 0.000 description 2
- 108090000848 Ubiquitin Proteins 0.000 description 2
- 229930003316 Vitamin D Natural products 0.000 description 2
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 2
- ZMQBBPRAZLACCW-UHFFFAOYSA-N acetic acid;dichloromethane Chemical compound ClCCl.CC(O)=O ZMQBBPRAZLACCW-UHFFFAOYSA-N 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 229910052796 boron Inorganic materials 0.000 description 2
- SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 description 2
- 125000005997 bromomethyl group Chemical group 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 2
- 229960004015 calcitonin Drugs 0.000 description 2
- 229940037448 calcitonin preparations Drugs 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- PXZQEOJJUGGUIB-UHFFFAOYSA-N isoindolin-1-one Chemical group C1=CC=C2C(=O)NCC2=C1 PXZQEOJJUGGUIB-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- JMZFEHDNIAQMNB-UHFFFAOYSA-N m-aminophenylboronic acid Chemical compound NC1=CC=CC(B(O)O)=C1 JMZFEHDNIAQMNB-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- SGFACFBLUAWICV-UHFFFAOYSA-N methyl 4-bromo-2-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=C(Br)C=C1CBr SGFACFBLUAWICV-UHFFFAOYSA-N 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 2
- ONKPXXLEOCVXSX-UHFFFAOYSA-N n-[6-(2-aminoanilino)-6-oxohexyl]-2-methyl-3-phenylbenzamide Chemical compound CC1=C(C(=O)NCCCCCC(=O)NC=2C(=CC=CC=2)N)C=CC=C1C1=CC=CC=C1 ONKPXXLEOCVXSX-UHFFFAOYSA-N 0.000 description 2
- IYBLDDMWCACMSU-UHFFFAOYSA-N n-[6-(2-aminoanilino)-6-oxohexyl]-2-methyl-3-pyridin-3-ylbenzamide Chemical compound CC1=C(C(=O)NCCCCCC(=O)NC=2C(=CC=CC=2)N)C=CC=C1C1=CC=CN=C1 IYBLDDMWCACMSU-UHFFFAOYSA-N 0.000 description 2
- QXUSPNJEPXHZFJ-UHFFFAOYSA-N n-[6-(2-aminoanilino)-6-oxohexyl]-2-methyl-3-pyridin-4-ylbenzamide Chemical compound CC1=C(C(=O)NCCCCCC(=O)NC=2C(=CC=CC=2)N)C=CC=C1C1=CC=NC=C1 QXUSPNJEPXHZFJ-UHFFFAOYSA-N 0.000 description 2
- UPSIJSSOIMGMRG-UHFFFAOYSA-N n-[6-(2-aminoanilino)-6-oxohexyl]-3-methyl-4-phenylbenzamide Chemical compound CC1=CC(C(=O)NCCCCCC(=O)NC=2C(=CC=CC=2)N)=CC=C1C1=CC=CC=C1 UPSIJSSOIMGMRG-UHFFFAOYSA-N 0.000 description 2
- OTEVANIASIXPMY-UHFFFAOYSA-N n-[6-(2-aminoanilino)-6-oxohexyl]-3-methyl-4-pyridin-3-ylbenzamide Chemical compound CC1=CC(C(=O)NCCCCCC(=O)NC=2C(=CC=CC=2)N)=CC=C1C1=CC=CN=C1 OTEVANIASIXPMY-UHFFFAOYSA-N 0.000 description 2
- PUXLIDVSFRGNKD-UHFFFAOYSA-N n-[6-(2-aminoanilino)-6-oxohexyl]-3-methyl-4-pyridin-4-ylbenzamide Chemical compound CC1=CC(C(=O)NCCCCCC(=O)NC=2C(=CC=CC=2)N)=CC=C1C1=CC=NC=C1 PUXLIDVSFRGNKD-UHFFFAOYSA-N 0.000 description 2
- NDOQOYMXQCHYNP-UHFFFAOYSA-N n-[6-(2-aminoanilino)-6-oxohexyl]-3-methyl-4-pyrimidin-5-ylbenzamide Chemical compound CC1=CC(C(=O)NCCCCCC(=O)NC=2C(=CC=CC=2)N)=CC=C1C1=CN=CN=C1 NDOQOYMXQCHYNP-UHFFFAOYSA-N 0.000 description 2
- XXTLYNLIXHSTNO-UHFFFAOYSA-N n-[6-(2-aminoanilino)-6-oxohexyl]-4-(2,4-dimethoxyphenyl)-3-methylbenzamide Chemical compound COC1=CC(OC)=CC=C1C1=CC=C(C(=O)NCCCCCC(=O)NC=2C(=CC=CC=2)N)C=C1C XXTLYNLIXHSTNO-UHFFFAOYSA-N 0.000 description 2
- DWXYWTQUHQDVML-UHFFFAOYSA-N n-[6-(2-aminoanilino)-6-oxohexyl]-4-(3,5-dimethylphenyl)-3-methylbenzamide Chemical compound CC1=CC(C)=CC(C=2C(=CC(=CC=2)C(=O)NCCCCCC(=O)NC=2C(=CC=CC=2)N)C)=C1 DWXYWTQUHQDVML-UHFFFAOYSA-N 0.000 description 2
- YRCHYHRCBXNYNU-UHFFFAOYSA-N n-[[3-fluoro-4-[2-[5-[(2-methoxyethylamino)methyl]pyridin-2-yl]thieno[3,2-b]pyridin-7-yl]oxyphenyl]carbamothioyl]-2-(4-fluorophenyl)acetamide Chemical compound N1=CC(CNCCOC)=CC=C1C1=CC2=NC=CC(OC=3C(=CC(NC(=S)NC(=O)CC=4C=CC(F)=CC=4)=CC=3)F)=C2S1 YRCHYHRCBXNYNU-UHFFFAOYSA-N 0.000 description 2
- XCCGRSGMQOTYQD-UHFFFAOYSA-N n-[[4-[(2-aminophenyl)carbamoyl]phenyl]methyl]-2-methyl-3-phenylbenzamide Chemical compound CC1=C(C(=O)NCC=2C=CC(=CC=2)C(=O)NC=2C(=CC=CC=2)N)C=CC=C1C1=CC=CC=C1 XCCGRSGMQOTYQD-UHFFFAOYSA-N 0.000 description 2
- PRKAQBQNEYQMQX-UHFFFAOYSA-N n-[[4-[(2-aminophenyl)carbamoyl]phenyl]methyl]-4,5-dimethoxy-2-methyl-3-phenylbenzamide Chemical compound CC=1C(C=2C=CC=CC=2)=C(OC)C(OC)=CC=1C(=O)NCC(C=C1)=CC=C1C(=O)NC1=CC=CC=C1N PRKAQBQNEYQMQX-UHFFFAOYSA-N 0.000 description 2
- AJCQTXMBEDIFOV-UHFFFAOYSA-N n-hydroxy-6-[3-oxo-6-[4-(trifluoromethyl)phenyl]-1h-isoindol-2-yl]hexanamide Chemical compound C=1C=C2C(=O)N(CCCCCC(=O)NO)CC2=CC=1C1=CC=C(C(F)(F)F)C=C1 AJCQTXMBEDIFOV-UHFFFAOYSA-N 0.000 description 2
- IGKUBBOXCUWRIB-UHFFFAOYSA-N n-hydroxy-6-[3-oxo-7-[4-(trifluoromethyl)phenyl]-1h-isoindol-2-yl]hexanamide Chemical compound O=C1N(CCCCCC(=O)NO)CC2=C1C=CC=C2C1=CC=C(C(F)(F)F)C=C1 IGKUBBOXCUWRIB-UHFFFAOYSA-N 0.000 description 2
- KPTRDYONBVUWPD-UHFFFAOYSA-N naphthalen-2-ylboronic acid Chemical compound C1=CC=CC2=CC(B(O)O)=CC=C21 KPTRDYONBVUWPD-UHFFFAOYSA-N 0.000 description 2
- ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluic acid Chemical compound CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 230000001582 osteoblastic effect Effects 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 239000000199 parathyroid hormone Substances 0.000 description 2
- 229960001319 parathyroid hormone Drugs 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- QLULGIRFKAWHOJ-UHFFFAOYSA-N pyridin-4-ylboronic acid Chemical compound OB(O)C1=CC=NC=C1 QLULGIRFKAWHOJ-UHFFFAOYSA-N 0.000 description 2
- HZFPPBMKGYINDF-UHFFFAOYSA-N pyrimidin-5-ylboronic acid Chemical compound OB(O)C1=CN=CN=C1 HZFPPBMKGYINDF-UHFFFAOYSA-N 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000000849 selective androgen receptor modulator Substances 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 239000000725 suspension Substances 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
- 238000005292 vacuum distillation Methods 0.000 description 2
- 235000019166 vitamin D Nutrition 0.000 description 2
- 239000011710 vitamin D Substances 0.000 description 2
- 150000003710 vitamin D derivatives Chemical class 0.000 description 2
- 229940046008 vitamin d Drugs 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
- ZYYANAWVBDFAHY-UHFFFAOYSA-N (2,3-dimethylphenyl)boronic acid Chemical compound CC1=CC=CC(B(O)O)=C1C ZYYANAWVBDFAHY-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- LJIOTBMDLVHTBO-CUYJMHBOSA-N (2s)-2-amino-n-[(1r,2r)-1-cyano-2-[4-[4-(4-methylpiperazin-1-yl)sulfonylphenyl]phenyl]cyclopropyl]butanamide Chemical compound CC[C@H](N)C(=O)N[C@]1(C#N)C[C@@H]1C1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)N2CCN(C)CC2)C=C1 LJIOTBMDLVHTBO-CUYJMHBOSA-N 0.000 description 1
- IBTSWKLSEOGJGJ-UHFFFAOYSA-N (3-acetamidophenyl)boronic acid Chemical compound CC(=O)NC1=CC=CC(B(O)O)=C1 IBTSWKLSEOGJGJ-UHFFFAOYSA-N 0.000 description 1
- WDGWHKRJEBENCE-UHFFFAOYSA-N (3-carbamoylphenyl)boronic acid Chemical compound NC(=O)C1=CC=CC(B(O)O)=C1 WDGWHKRJEBENCE-UHFFFAOYSA-N 0.000 description 1
- WPVBHUUZDFUIJA-UHFFFAOYSA-N (3-fluoro-4-methylphenyl)boronic acid Chemical compound CC1=CC=C(B(O)O)C=C1F WPVBHUUZDFUIJA-UHFFFAOYSA-N 0.000 description 1
- KFXUHRXGLWUOJT-UHFFFAOYSA-N (4-phenoxyphenyl)boronic acid Chemical compound C1=CC(B(O)O)=CC=C1OC1=CC=CC=C1 KFXUHRXGLWUOJT-UHFFFAOYSA-N 0.000 description 1
- XPEIJWZLPWNNOK-UHFFFAOYSA-N (4-phenylphenyl)boronic acid Chemical compound C1=CC(B(O)O)=CC=C1C1=CC=CC=C1 XPEIJWZLPWNNOK-UHFFFAOYSA-N 0.000 description 1
- MNJYZNVROSZZQC-UHFFFAOYSA-N (4-tert-butylphenyl)boronic acid Chemical compound CC(C)(C)C1=CC=C(B(O)O)C=C1 MNJYZNVROSZZQC-UHFFFAOYSA-N 0.000 description 1
- HBZBAMXERPYTFS-SECBINFHSA-N (4S)-2-(6,7-dihydro-5H-pyrrolo[3,2-f][1,3]benzothiazol-2-yl)-4,5-dihydro-1,3-thiazole-4-carboxylic acid Chemical compound OC(=O)[C@H]1CSC(=N1)c1nc2cc3CCNc3cc2s1 HBZBAMXERPYTFS-SECBINFHSA-N 0.000 description 1
- DHADXDMPEUWEAS-UHFFFAOYSA-N (6-methoxypyridin-3-yl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=N1 DHADXDMPEUWEAS-UHFFFAOYSA-N 0.000 description 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
- JNPGUXGVLNJQSQ-BGGMYYEUSA-M (e,3r,5s)-7-[4-(4-fluorophenyl)-1,2-di(propan-2-yl)pyrrol-3-yl]-3,5-dihydroxyhept-6-enoate Chemical compound CC(C)N1C(C(C)C)=C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)C(C=2C=CC(F)=CC=2)=C1 JNPGUXGVLNJQSQ-BGGMYYEUSA-M 0.000 description 1
- VAVHMEQFYYBAPR-ITWZMISCSA-N (e,3r,5s)-7-[4-(4-fluorophenyl)-1-phenyl-2-propan-2-ylpyrrol-3-yl]-3,5-dihydroxyhept-6-enoic acid Chemical compound CC(C)C1=C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)C(C=2C=CC(F)=CC=2)=CN1C1=CC=CC=C1 VAVHMEQFYYBAPR-ITWZMISCSA-N 0.000 description 1
- 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 1
- 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 description 1
- 125000004529 1,2,3-triazinyl group Chemical group N1=NN=C(C=C1)* 0.000 description 1
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
- 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 1
- 125000004530 1,2,4-triazinyl group Chemical group N1=NC(=NC=C1)* 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical class CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- FXNLPFZVSBANLC-UHFFFAOYSA-N 2-bromo-3-methylbenzamide Chemical compound CC1=CC=CC(C(N)=O)=C1Br FXNLPFZVSBANLC-UHFFFAOYSA-N 0.000 description 1
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 1
- BJGKVCKGUBYULR-UHFFFAOYSA-N 3-bromo-2-methylbenzoic acid Chemical compound CC1=C(Br)C=CC=C1C(O)=O BJGKVCKGUBYULR-UHFFFAOYSA-N 0.000 description 1
- LBTVFKZYTAKXAT-UHFFFAOYSA-N 3-bromo-N-hexyl-2-methylbenzamide Chemical compound CCCCCCNC(=O)C1=CC=CC(Br)=C1C LBTVFKZYTAKXAT-UHFFFAOYSA-N 0.000 description 1
- UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- IQKLOQHWKQYTQZ-UHFFFAOYSA-N 4-(aminomethyl)benzoic acid;hydrochloride Chemical compound Cl.NCC1=CC=C(C(O)=O)C=C1 IQKLOQHWKQYTQZ-UHFFFAOYSA-N 0.000 description 1
- YYWCKNXGOMDWRX-UHFFFAOYSA-N 4-[(6-bromo-3-oxo-1h-isoindol-2-yl)methyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1CN1C(=O)C2=CC=C(Br)C=C2C1 YYWCKNXGOMDWRX-UHFFFAOYSA-N 0.000 description 1
- TYRICULVJRGSTL-UHFFFAOYSA-N 4-bromo-2,3-dihydroisoindol-1-one Chemical compound BrC1=CC=CC2=C1CNC2=O TYRICULVJRGSTL-UHFFFAOYSA-N 0.000 description 1
- LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 1
- KUZSBKJSGSKPJH-VXGBXAGGSA-N 5-[(9R)-6-[(3R)-3-methylmorpholin-4-yl]-11-oxa-1,3,5-triazatricyclo[7.4.0.02,7]trideca-2,4,6-trien-4-yl]pyrazin-2-amine Chemical compound C[C@@H]1COCCN1c1nc(nc2N3CCOC[C@H]3Cc12)-c1cnc(N)cn1 KUZSBKJSGSKPJH-VXGBXAGGSA-N 0.000 description 1
- WJNKJYJCWXMBNV-UHFFFAOYSA-N 5-bromo-2,3-dihydroisoindol-1-one Chemical compound BrC1=CC=C2C(=O)NCC2=C1 WJNKJYJCWXMBNV-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- DPJPEMCOHNHLTA-UHFFFAOYSA-N 6-(5,6-dimethoxy-3-oxo-7-phenyl-1h-isoindol-2-yl)hexanoic acid Chemical compound COC=1C(OC)=CC=2C(=O)N(CCCCCC(O)=O)CC=2C=1C1=CC=CC=C1 DPJPEMCOHNHLTA-UHFFFAOYSA-N 0.000 description 1
- MSOABOBTMGOQMV-UHFFFAOYSA-N 6-(5,6-dimethoxy-3-oxo-7-pyridin-3-yl-1h-isoindol-2-yl)hexanoic acid Chemical compound COC=1C(OC)=CC=2C(=O)N(CCCCCC(O)=O)CC=2C=1C1=CC=CN=C1 MSOABOBTMGOQMV-UHFFFAOYSA-N 0.000 description 1
- GZKYLNQSYMQMCN-UHFFFAOYSA-N 6-[3-oxo-7-[4-(trifluoromethyl)phenyl]-1h-isoindol-2-yl]-n-phenylmethoxyhexanamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC2=C1CN(CCCCCC(=O)NOCC=1C=CC=CC=1)C2=O GZKYLNQSYMQMCN-UHFFFAOYSA-N 0.000 description 1
- MPCXJWTVWLWZIO-UHFFFAOYSA-N 6-[5,6-dimethoxy-3-oxo-7-[4-(trifluoromethyl)phenyl]-1h-isoindol-2-yl]hexanoic acid Chemical compound COC=1C(OC)=CC=2C(=O)N(CCCCCC(O)=O)CC=2C=1C1=CC=C(C(F)(F)F)C=C1 MPCXJWTVWLWZIO-UHFFFAOYSA-N 0.000 description 1
- AMEODNRBRYGFEK-UHFFFAOYSA-N 6-[7-(3,5-difluorophenyl)-3-oxo-1h-isoindol-2-yl]-n-hydroxyhexanamide Chemical compound O=C1N(CCCCCC(=O)NO)CC2=C1C=CC=C2C1=CC(F)=CC(F)=C1 AMEODNRBRYGFEK-UHFFFAOYSA-N 0.000 description 1
- UOLFCMTTZVBMDS-UHFFFAOYSA-N 6-[7-(3,5-difluorophenyl)-5,6-dimethoxy-3-oxo-1h-isoindol-2-yl]hexanoic acid Chemical compound COC=1C(OC)=CC=2C(=O)N(CCCCCC(O)=O)CC=2C=1C1=CC(F)=CC(F)=C1 UOLFCMTTZVBMDS-UHFFFAOYSA-N 0.000 description 1
- KCNZDOOHVVXSTR-UHFFFAOYSA-N 6-[7-(3,5-dimethylphenyl)-5,6-dimethoxy-3-oxo-1h-isoindol-2-yl]hexanoic acid Chemical compound COC=1C(OC)=CC=2C(=O)N(CCCCCC(O)=O)CC=2C=1C1=CC(C)=CC(C)=C1 KCNZDOOHVVXSTR-UHFFFAOYSA-N 0.000 description 1
- YLGMYSZZGXFCLZ-UHFFFAOYSA-N 6-[[3-(2,4-dimethoxyphenyl)-2-methylbenzoyl]amino]hexanoic acid Chemical compound COC1=CC(OC)=CC=C1C1=CC=CC(C(=O)NCCCCCC(O)=O)=C1C YLGMYSZZGXFCLZ-UHFFFAOYSA-N 0.000 description 1
- MITGKKFYIJJQGL-UHFFFAOYSA-N 9-(4-chlorobenzoyl)-6-methylsulfonyl-2,3-dihydro-1H-carbazol-4-one Chemical compound ClC1=CC=C(C(=O)N2C3=CC=C(C=C3C=3C(CCCC2=3)=O)S(=O)(=O)C)C=C1 MITGKKFYIJJQGL-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 101000797612 Arabidopsis thaliana Protein MEI2-like 3 Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- IGMAGMMQLGBNJN-UHFFFAOYSA-N C1C2=C(C=CC=C2Br)C(=O)N1CNC(=O)C3=CC=CC=C3 Chemical compound C1C2=C(C=CC=C2Br)C(=O)N1CNC(=O)C3=CC=CC=C3 IGMAGMMQLGBNJN-UHFFFAOYSA-N 0.000 description 1
- UPXMDKVJXIXJDR-UHFFFAOYSA-N CC(C=C(CN(CC(C1=CC(OC)=C2OC)=C2Br)C1=O)C=C1)=C1C(O)=O Chemical compound CC(C=C(CN(CC(C1=CC(OC)=C2OC)=C2Br)C1=O)C=C1)=C1C(O)=O UPXMDKVJXIXJDR-UHFFFAOYSA-N 0.000 description 1
- IVSVGZJQBNZJPW-UHFFFAOYSA-N CC1=CC(=C(C=C1)C2=C3CN(C(=O)C3=CC=C2)CCCCCC(=O)NO)C Chemical compound CC1=CC(=C(C=C1)C2=C3CN(C(=O)C3=CC=C2)CCCCCC(=O)NO)C IVSVGZJQBNZJPW-UHFFFAOYSA-N 0.000 description 1
- INTBYCVYEVHEPM-UHFFFAOYSA-N CCCCCC(=O)NN1Cc2ccccc2C1 Chemical compound CCCCCC(=O)NN1Cc2ccccc2C1 INTBYCVYEVHEPM-UHFFFAOYSA-N 0.000 description 1
- PTDIDDUASZGWJU-UHFFFAOYSA-N CCCCCC(NN(CC(C1=CC=C2)=C2Br)C1=O)=O Chemical compound CCCCCC(NN(CC(C1=CC=C2)=C2Br)C1=O)=O PTDIDDUASZGWJU-UHFFFAOYSA-N 0.000 description 1
- SUZMHIZGALNDCP-UHFFFAOYSA-N CCCCCCCN(CC(C1=C2)=C(C3=CC=CN=C3)C(OC)=C2OC)C1=O Chemical class CCCCCCCN(CC(C1=C2)=C(C3=CC=CN=C3)C(OC)=C2OC)C1=O SUZMHIZGALNDCP-UHFFFAOYSA-N 0.000 description 1
- ONFBNUWZJFIKJJ-UHFFFAOYSA-N CCCCCCCN(CC(C1=CC(OC)=C2OC)=C2Br)C1=O Chemical class CCCCCCCN(CC(C1=CC(OC)=C2OC)=C2Br)C1=O ONFBNUWZJFIKJJ-UHFFFAOYSA-N 0.000 description 1
- ZETXAYGOPXNWDJ-UHFFFAOYSA-N CCCCCCN1CC2=C(C(=C(C=C2C1=O)OC)OC)C3=CC=CC=C3 Chemical class CCCCCCN1CC2=C(C(=C(C=C2C1=O)OC)OC)C3=CC=CC=C3 ZETXAYGOPXNWDJ-UHFFFAOYSA-N 0.000 description 1
- 229940123564 Calcium-sensing receptor antagonist Drugs 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 102000004171 Cathepsin K Human genes 0.000 description 1
- 108090000625 Cathepsin K Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 229940126657 Compound 17 Drugs 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 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
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- RRSNDVCODIMOFX-MPKOGUQCSA-N Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O Chemical compound Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O RRSNDVCODIMOFX-MPKOGUQCSA-N 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 101000857682 Homo sapiens Runt-related transcription factor 2 Proteins 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
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102000016921 Integrin-Binding Sialoprotein Human genes 0.000 description 1
- 108010028750 Integrin-Binding Sialoprotein Proteins 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 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 1
- 241000234435 Lilium Species 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 206010030216 Oesophagitis Diseases 0.000 description 1
- 206010030247 Oestrogen deficiency Diseases 0.000 description 1
- 102000004264 Osteopontin Human genes 0.000 description 1
- 108010081689 Osteopontin Proteins 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 1
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 1
- 229940079156 Proteasome inhibitor Drugs 0.000 description 1
- 102000014128 RANK Ligand Human genes 0.000 description 1
- 108010025832 RANK Ligand Proteins 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
- 102100025368 Runt-related transcription factor 2 Human genes 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 102000013275 Somatomedins Human genes 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 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
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- GLEVLJDDWXEYCO-UHFFFAOYSA-N Trolox Chemical compound O1C(C)(C(O)=O)CCC2=C1C(C)=C(C)C(O)=C2C GLEVLJDDWXEYCO-UHFFFAOYSA-N 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- YVEUWHCSIGXLHM-UHFFFAOYSA-N [3-(fluoromethoxy)phenyl]boronic acid Chemical compound OB(O)C1=CC=CC(OCF)=C1 YVEUWHCSIGXLHM-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 229910001413 alkali metal ion Inorganic materials 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- ILOJFJBXXANEQW-UHFFFAOYSA-N aminooxy(phenyl)borinic acid Chemical compound NOB(O)C1=CC=CC=C1 ILOJFJBXXANEQW-UHFFFAOYSA-N 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- YCOOQFCBEZGPIZ-UHFFFAOYSA-N bis(methylperoxy)-phenylborane Chemical compound COOB(OOC)C1=CC=CC=C1 YCOOQFCBEZGPIZ-UHFFFAOYSA-N 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 239000008004 cell lysis buffer Substances 0.000 description 1
- AEULIVPVIDOLIN-UHFFFAOYSA-N cep-11981 Chemical compound C1=C2C3=C4CNC(=O)C4=C4C5=CN(C)N=C5CCC4=C3N(CC(C)C)C2=CC=C1NC1=NC=CC=N1 AEULIVPVIDOLIN-UHFFFAOYSA-N 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 229960003067 cystine Drugs 0.000 description 1
- 230000006196 deacetylation Effects 0.000 description 1
- 238000003381 deacetylation reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000004821 effect on bone Effects 0.000 description 1
- 208000006881 esophagitis Diseases 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229960002598 fumaric acid Drugs 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 229960005219 gentisic acid Drugs 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 229950006191 gluconic acid Drugs 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000003324 growth hormone secretagogue Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- SRUKOJDGOUUFRB-UHFFFAOYSA-N heptylazanium;chloride Chemical compound Cl.CCCCCCCN SRUKOJDGOUUFRB-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 229940015872 ibandronate Drugs 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 235000014705 isoleucine Nutrition 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- 229940099563 lactobionic acid Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- VMPHSYLJUKZBJJ-UHFFFAOYSA-N lauric acid triglyceride Natural products CCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC)COC(=O)CCCCCCCCCCC VMPHSYLJUKZBJJ-UHFFFAOYSA-N 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- FZRNJOXQNWVMIH-UHFFFAOYSA-N lithium;hydrate Chemical compound [Li].O FZRNJOXQNWVMIH-UHFFFAOYSA-N 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 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
- 239000011976 maleic acid Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- GIZCKBSSWNIUMZ-UHFFFAOYSA-N methyl 4-(aminomethyl)benzoate;hydrochloride Chemical compound Cl.COC(=O)C1=CC=C(CN)C=C1 GIZCKBSSWNIUMZ-UHFFFAOYSA-N 0.000 description 1
- WVCLWLZWACDYHH-UHFFFAOYSA-N methyl 4-[(7-bromo-3-oxo-1h-isoindol-2-yl)methyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CN1C(=O)C(C=CC=C2Br)=C2C1 WVCLWLZWACDYHH-UHFFFAOYSA-N 0.000 description 1
- 229940095102 methyl benzoate Drugs 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
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- KFLQMQGLHYRTGZ-UHFFFAOYSA-N n-(2-aminophenyl)-4-[[7-(3,5-difluorophenyl)-3-oxo-1h-isoindol-2-yl]methyl]benzamide Chemical compound NC1=CC=CC=C1NC(=O)C(C=C1)=CC=C1CN1C(=O)C(C=CC=C2C=3C=C(F)C=C(F)C=3)=C2C1 KFLQMQGLHYRTGZ-UHFFFAOYSA-N 0.000 description 1
- BYKKIOVHGIAXRY-UHFFFAOYSA-N n-(2-aminophenyl)-4-[[7-(3-aminophenyl)-3-oxo-1h-isoindol-2-yl]methyl]benzamide Chemical compound NC1=CC=CC(C=2C=3CN(CC=4C=CC(=CC=4)C(=O)NC=4C(=CC=CC=4)N)C(=O)C=3C=CC=2)=C1 BYKKIOVHGIAXRY-UHFFFAOYSA-N 0.000 description 1
- MKRLOYGAMDADCY-UHFFFAOYSA-N n-(2-aminophenyl)-6-(3-oxo-7-pyridin-3-yl-1h-isoindol-2-yl)hexanamide Chemical compound NC1=CC=CC=C1NC(=O)CCCCCN1C(=O)C(C=CC=C2C=3C=NC=CC=3)=C2C1 MKRLOYGAMDADCY-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- XXPDBLUZJRXNNZ-UHFFFAOYSA-N promethazine hydrochloride Chemical compound Cl.C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 XXPDBLUZJRXNNZ-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 239000003207 proteasome inhibitor Substances 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 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
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
- 229960004622 raloxifene Drugs 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 229940089617 risedronate Drugs 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 235000004400 serine Nutrition 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 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
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 150000003573 thiols Chemical group 0.000 description 1
- 125000005425 toluyl group Chemical group 0.000 description 1
- 230000002463 transducing effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 235000014393 valine Nutrition 0.000 description 1
- JQSHBVHOMNKWFT-DTORHVGOSA-N varenicline Chemical compound C12=CC3=NC=CN=C3C=C2[C@H]2C[C@@H]1CNC2 JQSHBVHOMNKWFT-DTORHVGOSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 125000005023 xylyl group Chemical group 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/46—Iso-indoles; Hydrogenated iso-indoles with an oxygen atom in position 1
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- 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
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Physical Education & Sports Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Engineering & Computer Science (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Oncology (AREA)
- Indole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR10-2009-0042691 | 2009-05-15 | ||
| KR10-2009-0042585 | 2009-05-15 | ||
| KR1020090042691A KR101142053B1 (ko) | 2009-05-15 | 2009-05-15 | 이소인돌리논 유도체, 이의 제조방법 및 이를 포함하는 약학 조성물 |
| KR1020090042585A KR20100123379A (ko) | 2009-05-15 | 2009-05-15 | 벤즈아마이드 유도체, 이의 제조방법 및 이를 포함하는 골 질환의 예방 및 치료용 약학 조성물 |
| PCT/KR2010/003060 WO2010131922A2 (en) | 2009-05-15 | 2010-05-14 | Amide compound, preparation method thereof and pharmaceutical composition comprising same |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2012526803A JP2012526803A (ja) | 2012-11-01 |
| JP2012526803A5 JP2012526803A5 (enExample) | 2014-09-11 |
| JP5713999B2 true JP5713999B2 (ja) | 2015-05-07 |
Family
ID=43085472
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012510756A Expired - Fee Related JP5713999B2 (ja) | 2009-05-15 | 2010-05-14 | アミド化合物、その製造方法及びそれを含む薬学組成物 |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US8716326B2 (enExample) |
| EP (1) | EP2429987A4 (enExample) |
| JP (1) | JP5713999B2 (enExample) |
| WO (1) | WO2010131922A2 (enExample) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2009289649B2 (en) | 2008-09-03 | 2016-05-05 | Biomarin Pharmaceutical Inc. | Compositions including 6-aminohexanoic acid derivatives as HDAC inhibitors |
| PL2526093T3 (pl) | 2010-01-22 | 2017-02-28 | Acetylon Pharmaceuticals, Inc. | Odwrócone związki amidowe jako inhibitory deacetylazy białkowej oraz sposoby ich stosowania |
| US8957066B2 (en) | 2011-02-28 | 2015-02-17 | Biomarin Pharmaceutical Inc. | Histone deacetylase inhibitors |
| US10059723B2 (en) | 2011-02-28 | 2018-08-28 | Biomarin Pharmaceutical Inc. | Histone deacetylase inhibitors |
| WO2012118782A1 (en) | 2011-02-28 | 2012-09-07 | Repligen Corporation | Histone deacetylase inhibitors |
| CN102850236B (zh) * | 2011-06-27 | 2016-05-18 | 国药一心制药有限公司 | 新型苯甲酰胺类组蛋白去乙酰化酶抑制剂及其应用 |
| EP2734500A4 (en) | 2011-07-20 | 2015-04-08 | Gen Hospital Corp | SELECTIVE HISTONDEACETYLASE-6 INHIBITORS FOR THE TREATMENT OF BONE DISORDERS |
| RU2665554C2 (ru) | 2013-03-15 | 2018-08-31 | Байомарин Фармасьютикал Инк. | Ингибиторы hdac |
| EP2801569A1 (en) | 2013-05-09 | 2014-11-12 | Ikerchem, S.L. | Histone deacetylase inhibitors based on derivatives of tricyclic polyhydroacridine and analogs possessing fused saturated five- and seven-membered rings |
| WO2015054099A1 (en) | 2013-10-08 | 2015-04-16 | Acetylon Pharmaceuticals, Inc. | Combinations of histone deacetylase inhibitors and either her2 inhibitors or pi3k inhibitors |
| EP3060217B1 (en) | 2013-10-24 | 2022-06-08 | Mayo Foundation for Medical Education and Research | Treatment of polycystic diseases with an hdac6 inhibitor |
| EP3076973B1 (en) | 2013-12-03 | 2020-04-29 | Acetylon Pharmaceuticals, Inc. | Combinations of histone deacetylase inhibitors and immunomodulatory drugs |
| CN107205988A (zh) | 2014-07-07 | 2017-09-26 | 埃斯泰隆制药公司 | 利用组蛋白脱乙酰酶抑制剂治疗白血病 |
| CN107438436A (zh) | 2014-12-05 | 2017-12-05 | 摩德纳和雷焦艾米利亚大学 | 用于治疗淋巴瘤的组蛋白脱乙酰酶抑制剂和苯达莫司汀的组合 |
| AR104935A1 (es) | 2015-06-08 | 2017-08-23 | Acetylon Pharmaceuticals Inc | Formas cristalinas de un inhibidor de histona deacetilasa |
| TWI706937B (zh) | 2015-06-08 | 2020-10-11 | 美商艾斯特隆製藥公司 | 製備蛋白質去乙醯酶抑制劑之方法 |
| WO2017068412A1 (en) | 2015-10-21 | 2017-04-27 | Otsuka Pharmaceutical Co., Ltd. | Benzolactam compounds as protein kinase inhibitors |
| US11813261B2 (en) | 2016-04-19 | 2023-11-14 | Acetylon Pharmaceuticals, Inc. | HDAC inhibitors, alone or in combination with BTK inhibitors, for treating chronic lymphocytic leukemia |
| JP7100018B2 (ja) | 2016-08-08 | 2022-07-12 | アセチロン ファーマシューティカルズ インコーポレイテッド | ヒストンデアセチラーゼ６阻害剤及びｃｄ２０阻害抗体の薬学的組み合わせならびにその使用 |
| GB201706327D0 (en) | 2017-04-20 | 2017-06-07 | Otsuka Pharma Co Ltd | A pharmaceutical compound |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4077998A (en) * | 1975-10-28 | 1978-03-07 | Morton-Norwich Products, Inc. | Phthaloyl amino acid hydroxamic acids |
| KR100194535B1 (ko) * | 1995-12-27 | 1999-06-15 | 우종일 | 아릴 벤조일 우레아 유도체 및 이를 함유하는 농약조성물 |
| KR100194534B1 (ko) * | 1996-06-29 | 1999-06-15 | 우종일 | 2-클로로-3,5-비스 (트피플루오르메틸) 페닐 벤조일 우레아 유도체 및 이의 제조방법 |
| US6174905B1 (en) * | 1996-09-30 | 2001-01-16 | Mitsui Chemicals, Inc. | Cell differentiation inducer |
| EP1024134A4 (en) * | 1997-10-09 | 2003-05-14 | Ono Pharmaceutical Co | DERIVATIVES OF AMINOBUTANIC ACID |
| CA2423868C (en) * | 2000-09-29 | 2011-06-07 | Prolifix Limited | Carbamic acid compounds comprising an amide linkage as hdac inhibitors |
| WO2002074298A1 (en) * | 2001-03-21 | 2002-09-26 | Ono Pharmaceutical Co., Ltd. | Il-6 production inhibitors |
| US7868204B2 (en) * | 2001-09-14 | 2011-01-11 | Methylgene Inc. | Inhibitors of histone deacetylase |
| US20050215601A1 (en) * | 2002-09-25 | 2005-09-29 | Santen Pharmaceutical Co., Ltd. | Therapeutic agent for rheumatic disease comprising benzamide derivative as active ingredient |
| EP1641458A2 (en) * | 2002-12-27 | 2006-04-05 | Schering Aktiengesellschaft | Pharmaceutical combinations of phthalazine vegf inhibitors and benzamide hdac inhibitors |
| JP4939941B2 (ja) * | 2003-08-26 | 2012-05-30 | 株式會社アモーレパシフィック | ヒドロキサム酸誘導体及びその製造方法 |
| CA2591443A1 (en) * | 2004-12-14 | 2006-06-22 | Biorunx Co. Ltd. | Method to enhance the bone formation activity of bmp by runx2 acetylation |
| WO2007144341A1 (en) * | 2006-06-12 | 2007-12-21 | Vrije Universiteit Brussel | Differentiation of rat liver epithelial cells into hepatocyte-like cells |
| WO2009002495A1 (en) * | 2007-06-27 | 2008-12-31 | Merck & Co., Inc. | 4-carboxybenzylamino derivatives as histone deacetylase inhibitors |
| AU2009289649B2 (en) * | 2008-09-03 | 2016-05-05 | Biomarin Pharmaceutical Inc. | Compositions including 6-aminohexanoic acid derivatives as HDAC inhibitors |
-
2010
- 2010-05-14 US US13/320,117 patent/US8716326B2/en not_active Expired - Fee Related
- 2010-05-14 JP JP2012510756A patent/JP5713999B2/ja not_active Expired - Fee Related
- 2010-05-14 WO PCT/KR2010/003060 patent/WO2010131922A2/en not_active Ceased
- 2010-05-14 EP EP10775124A patent/EP2429987A4/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| US8716326B2 (en) | 2014-05-06 |
| WO2010131922A4 (en) | 2011-05-26 |
| EP2429987A2 (en) | 2012-03-21 |
| JP2012526803A (ja) | 2012-11-01 |
| US20120065396A1 (en) | 2012-03-15 |
| WO2010131922A2 (en) | 2010-11-18 |
| WO2010131922A3 (en) | 2011-03-24 |
| EP2429987A4 (en) | 2012-10-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2012526803A (ja) | アミド化合物、その製造方法及びそれを含む薬学組成物 | |
| ES2401079T3 (es) | Moduladores del asma y de la inflamación alérgica | |
| TWI422579B (zh) | 新化合物 | |
| EP1553075B1 (en) | Lpa receptor antagonists | |
| JP6219882B2 (ja) | ＩＲＥ−１αインヒビター | |
| US7115645B2 (en) | 1,2 diarylbenzimidazoles and their pharmaceutical use | |
| JP2011522865A (ja) | Ｉａ心不全および癌の治療に有用なプロテインキナーゼｄ阻害剤としての２，４’−ビピリジニル化合物 | |
| WO2004058717A1 (en) | Isoquinolinone derivatives and their use as therapeutic agents | |
| CA2602583A1 (en) | Biaryl derived amide modulators of vanilloid vr1 receptor | |
| WO2004002530A1 (ja) | 慢性疾患治療剤 | |
| CA2681979A1 (en) | Indole derivatives having cpla2 inhibiting activity and applications and production methods of the same | |
| CA3057736A1 (en) | Liver x receptors (lxr) modulators | |
| IL288851B1 (en) | Heteroaromatic inhibitors of astacin proteinases | |
| NO326408B1 (no) | Benzimidazoler, farmasoytisk preparat og anvendelse av disse for fremstilling av et medikament for behandling av sykdommer som er tilknyttet en mikrogliaaktivering | |
| KR20110126751A (ko) | Ｋｃｎｑ２／３ 조절제로서의 치환된 2-머캅토-3-아미노피리딘 | |
| JP2011503042A (ja) | ｐ３８ＭＡＰキナーゼ阻害剤 | |
| BRPI0718399A2 (pt) | Derivados heterocíclicos como inibidores de cetp | |
| CN114432301B (zh) | 一种共价抑制剂衍生物及其在治疗病毒感染方面的应用 | |
| WO2005063689A1 (ja) | ベンズアミド誘導体 | |
| KR101969553B1 (ko) | 신규 아미드 화합물 및 이의 용도 | |
| JP4892475B2 (ja) | Ｌｘｒ受容体モジュレーター | |
| JP2008533091A (ja) | ヒストンデアセチラーゼ阻害剤としてのヒドロキサム酸及びこれを含有する医薬組成物 | |
| US7329679B2 (en) | 1,2 Diarylbenzimidazoles and their pharmaceutical use | |
| RU2468020C2 (ru) | Биарилкарбоксиариламиды как модуляторы ванилоидного рецептора типа 1 | |
| KR101142053B1 (ko) | 이소인돌리논 유도체, 이의 제조방법 및 이를 포함하는 약학 조성물 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130319 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140430 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20140501 |
|
| A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20140723 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20150210 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20150310 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5713999 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |