JP2015503615A - 卵胞刺激ホルモンの調節因子としてのベンズアミド誘導体 - Google Patents
卵胞刺激ホルモンの調節因子としてのベンズアミド誘導体 Download PDFInfo
- Publication number
- JP2015503615A JP2015503615A JP2014552261A JP2014552261A JP2015503615A JP 2015503615 A JP2015503615 A JP 2015503615A JP 2014552261 A JP2014552261 A JP 2014552261A JP 2014552261 A JP2014552261 A JP 2014552261A JP 2015503615 A JP2015503615 A JP 2015503615A
- Authority
- JP
- Japan
- Prior art keywords
- atoms
- mmol
- het
- hal
- cyc
- 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.)
- Granted
Links
- 150000003936 benzamides Chemical class 0.000 title abstract description 9
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 title description 37
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 title description 37
- 229940028334 follicle stimulating hormone Drugs 0.000 title description 36
- 108010060374 FSH Receptors Proteins 0.000 claims abstract description 56
- 238000011282 treatment Methods 0.000 claims abstract description 39
- 102000008175 FSH Receptors Human genes 0.000 claims abstract description 16
- 208000021267 infertility disease Diseases 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 188
- 125000004432 carbon atom Chemical group C* 0.000 claims description 69
- 150000003839 salts Chemical class 0.000 claims description 64
- 238000000034 method Methods 0.000 claims description 55
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 51
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 40
- 125000001424 substituent group Chemical group 0.000 claims description 39
- 239000004480 active ingredient Substances 0.000 claims description 37
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 29
- 125000004434 sulfur atom Chemical group 0.000 claims description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims description 25
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 25
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 22
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 15
- 238000000338 in vitro Methods 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 14
- 229910052801 chlorine Inorganic materials 0.000 claims description 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
- 229910052731 fluorine Inorganic materials 0.000 claims description 13
- 230000001225 therapeutic effect Effects 0.000 claims description 13
- 241000124008 Mammalia Species 0.000 claims description 12
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 12
- 229910052794 bromium Inorganic materials 0.000 claims description 11
- 230000004720 fertilization Effects 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- 230000000069 prophylactic effect Effects 0.000 claims description 11
- 125000002619 bicyclic group Chemical group 0.000 claims description 10
- 238000012544 monitoring process Methods 0.000 claims description 10
- 229910052727 yttrium Inorganic materials 0.000 claims description 10
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 8
- 229910052740 iodine Inorganic materials 0.000 claims description 7
- 125000002950 monocyclic group Chemical group 0.000 claims description 7
- 239000002671 adjuvant Substances 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 239000008186 active pharmaceutical agent Substances 0.000 claims description 4
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
- 230000003281 allosteric effect Effects 0.000 abstract description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 258
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 219
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 213
- 239000000243 solution Substances 0.000 description 155
- 238000006243 chemical reaction Methods 0.000 description 141
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 120
- -1 β-2-adrenergic Proteins 0.000 description 114
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 110
- 239000007787 solid Substances 0.000 description 93
- 239000000203 mixture Substances 0.000 description 80
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 75
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 69
- 239000000047 product Substances 0.000 description 67
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 66
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 60
- 229910052757 nitrogen Inorganic materials 0.000 description 57
- 230000002829 reductive effect Effects 0.000 description 44
- 150000003254 radicals Chemical class 0.000 description 42
- 102000018343 Follicle stimulating hormone receptors Human genes 0.000 description 40
- 238000003756 stirring Methods 0.000 description 38
- 239000011541 reaction mixture Substances 0.000 description 37
- 238000005481 NMR spectroscopy Methods 0.000 description 36
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 35
- BDAWHHUYCSZZAG-UHFFFAOYSA-N 2-cyclopropyl-1,3-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=COC(C2CC2)=N1 BDAWHHUYCSZZAG-UHFFFAOYSA-N 0.000 description 34
- 239000012267 brine Substances 0.000 description 33
- 238000000746 purification Methods 0.000 description 33
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 33
- 201000010099 disease Diseases 0.000 description 31
- 239000002904 solvent Substances 0.000 description 31
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 26
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 26
- 239000010410 layer Substances 0.000 description 26
- 229920006395 saturated elastomer Polymers 0.000 description 26
- 239000011734 sodium Substances 0.000 description 26
- 239000007821 HATU Substances 0.000 description 25
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 230000000694 effects Effects 0.000 description 24
- 239000012043 crude product Substances 0.000 description 23
- 239000012074 organic phase Substances 0.000 description 23
- 210000004027 cell Anatomy 0.000 description 22
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
- 239000003921 oil Substances 0.000 description 18
- 229910052938 sodium sulfate Inorganic materials 0.000 description 18
- 235000011152 sodium sulphate Nutrition 0.000 description 18
- 230000015572 biosynthetic process Effects 0.000 description 17
- 239000012299 nitrogen atmosphere Substances 0.000 description 17
- 235000019198 oils Nutrition 0.000 description 17
- 238000010898 silica gel chromatography Methods 0.000 description 17
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 16
- 239000003153 chemical reaction reagent Substances 0.000 description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
- 239000007864 aqueous solution Substances 0.000 description 15
- 125000003118 aryl group Chemical group 0.000 description 14
- 239000001257 hydrogen Substances 0.000 description 14
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- 239000000460 chlorine Substances 0.000 description 13
- 238000004440 column chromatography Methods 0.000 description 13
- 238000003786 synthesis reaction Methods 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 12
- 238000009472 formulation Methods 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 238000002953 preparative HPLC Methods 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- 125000001072 heteroaryl group Chemical group 0.000 description 10
- 239000012071 phase Substances 0.000 description 10
- 102000005962 receptors Human genes 0.000 description 10
- 108020003175 receptors Proteins 0.000 description 10
- 230000019491 signal transduction Effects 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- HJORCZCMNWLHMB-UHFFFAOYSA-N 1-(3-aminopropyl)pyrrolidin-2-one Chemical compound NCCCN1CCCC1=O HJORCZCMNWLHMB-UHFFFAOYSA-N 0.000 description 9
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 230000001404 mediated effect Effects 0.000 description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 9
- 239000000556 agonist Substances 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 208000035475 disorder Diseases 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 8
- 230000003993 interaction Effects 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 230000016087 ovulation Effects 0.000 description 8
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 8
- 239000000651 prodrug Substances 0.000 description 8
- 229940002612 prodrug Drugs 0.000 description 8
- 239000012453 solvate Substances 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- 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 7
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 7
- 239000012298 atmosphere Substances 0.000 description 7
- 230000008878 coupling Effects 0.000 description 7
- 238000010168 coupling process Methods 0.000 description 7
- 238000005859 coupling reaction Methods 0.000 description 7
- 235000019253 formic acid Nutrition 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000012047 saturated solution Substances 0.000 description 7
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 6
- LHOBBLRQUGRJOJ-UHFFFAOYSA-N 2-chloro-4-[4-(2-methylphenyl)piperazin-1-yl]-5-nitro-n-[3-(2-oxopyrrolidin-1-yl)propyl]benzamide Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=C(Cl)C=2)C(=O)NCCCN2C(CCC2)=O)[N+]([O-])=O)CC1 LHOBBLRQUGRJOJ-UHFFFAOYSA-N 0.000 description 6
- SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 6
- NZDXSXLYLMHYJA-UHFFFAOYSA-M 4-[(1,3-dimethylimidazol-1-ium-2-yl)diazenyl]-n,n-dimethylaniline;chloride Chemical compound [Cl-].C1=CC(N(C)C)=CC=C1N=NC1=[N+](C)C=CN1C NZDXSXLYLMHYJA-UHFFFAOYSA-M 0.000 description 6
- 0 C*(C)(*)N(*)C(c(c(*)c1)cc(NC(*)=O)c1N(CC1)CCN1[Al])=O Chemical compound C*(C)(*)N(*)C(c(c(*)c1)cc(NC(*)=O)c1N(CC1)CCN1[Al])=O 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 239000003039 volatile agent Substances 0.000 description 6
- MOYXEZPVUAWWOE-UHFFFAOYSA-N 2-chloro-4-[4-(2-methylphenyl)piperazin-1-yl]-5-nitrobenzoic acid Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=C(Cl)C=2)C(O)=O)[N+]([O-])=O)CC1 MOYXEZPVUAWWOE-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 238000006254 arylation reaction Methods 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 230000003197 catalytic effect Effects 0.000 description 5
- 238000004113 cell culture Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 5
- 229940088597 hormone Drugs 0.000 description 5
- 239000005556 hormone Substances 0.000 description 5
- 125000002883 imidazolyl group Chemical group 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 4
- SYZKAFCPWNFONG-UHFFFAOYSA-N 2-chloro-4-fluoro-5-nitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=C(F)C=C1Cl SYZKAFCPWNFONG-UHFFFAOYSA-N 0.000 description 4
- OFTKFKYVSBNYEC-UHFFFAOYSA-N 2-furoyl chloride Chemical compound ClC(=O)C1=CC=CO1 OFTKFKYVSBNYEC-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 4
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 4
- 102000009151 Luteinizing Hormone Human genes 0.000 description 4
- 108010073521 Luteinizing Hormone Proteins 0.000 description 4
- 206010033266 Ovarian Hyperstimulation Syndrome Diseases 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- YMWUJEATGCHHMB-DICFDUPASA-N dichloromethane-d2 Chemical compound [2H]C([2H])(Cl)Cl YMWUJEATGCHHMB-DICFDUPASA-N 0.000 description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 239000011737 fluorine Substances 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- 230000014509 gene expression Effects 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
- 229940040129 luteinizing hormone Drugs 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 4
- 150000007524 organic acids Chemical class 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- 125000003367 polycyclic group Chemical group 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 238000004007 reversed phase HPLC Methods 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- WICKLEOONJPMEQ-UHFFFAOYSA-N 1-(2-methylphenyl)piperazine Chemical compound CC1=CC=CC=C1N1CCNCC1 WICKLEOONJPMEQ-UHFFFAOYSA-N 0.000 description 3
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-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
- FODXFYUFJKVAKU-UHFFFAOYSA-N 5-amino-2-ethoxy-4-[4-(2-methylphenyl)piperazin-1-yl]-n-[3-(2-oxopyrrolidin-1-yl)propyl]benzamide Chemical compound NC=1C=C(C(=O)NCCCN2C(CCC2)=O)C(OCC)=CC=1N(CC1)CCN1C1=CC=CC=C1C FODXFYUFJKVAKU-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- VOVDYPSBXVIIAH-UHFFFAOYSA-N [3-[(dimethylamino)methyl]phenyl]methanamine Chemical compound CN(C)CC1=CC=CC(CN)=C1 VOVDYPSBXVIIAH-UHFFFAOYSA-N 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 239000003708 ampul Substances 0.000 description 3
- 150000005840 aryl radicals Chemical class 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 125000005488 carboaryl group Chemical group 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000012154 double-distilled water Substances 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- 125000002541 furyl group Chemical group 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- TXZLZNRQOKJMOI-UHFFFAOYSA-N methyl 2-chloro-4-[4-(2-methylphenyl)piperazin-1-yl]-5-nitrobenzoate Chemical compound C1=C(Cl)C(C(=O)OC)=CC([N+]([O-])=O)=C1N1CCN(C=2C(=CC=CC=2)C)CC1 TXZLZNRQOKJMOI-UHFFFAOYSA-N 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
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 150000007530 organic bases Chemical class 0.000 description 3
- 230000002611 ovarian Effects 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 3
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 125000005412 pyrazyl group Chemical group 0.000 description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 125000006413 ring segment Chemical group 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- 229940062627 tribasic potassium phosphate Drugs 0.000 description 3
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 3
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 3
- YRIFWVMRUFKWLM-UHFFFAOYSA-N 1-(2,5-dimethylphenyl)piperazine Chemical compound CC1=CC=C(C)C(N2CCNCC2)=C1 YRIFWVMRUFKWLM-UHFFFAOYSA-N 0.000 description 2
- RTYUZFTYDVDLHW-UHFFFAOYSA-N 1-(5-fluoro-2-methylphenyl)piperazine Chemical compound CC1=CC=C(F)C=C1N1CCNCC1 RTYUZFTYDVDLHW-UHFFFAOYSA-N 0.000 description 2
- BOMIVPQLEHJRLO-UHFFFAOYSA-N 2-(dimethylamino)-4-[4-(2-methylphenyl)piperazin-1-yl]-5-nitro-n-[3-(2-oxopyrrolidin-1-yl)propyl]benzamide Chemical compound [O-][N+](=O)C=1C=C(C(=O)NCCCN2C(CCC2)=O)C(N(C)C)=CC=1N(CC1)CCN1C1=CC=CC=C1C BOMIVPQLEHJRLO-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical group COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 2
- UOAUUOAPMZUMFF-UHFFFAOYSA-N 2-[[3-[(dimethylamino)methyl]phenyl]methyl]-6-[4-(2-methylphenyl)piperazin-1-yl]-7-nitro-3,4-dihydroisoquinolin-1-one Chemical compound CN(C)CC1=CC=CC(CN2C(C3=CC(=C(N4CCN(CC4)C=4C(=CC=CC=4)C)C=C3CC2)[N+]([O-])=O)=O)=C1 UOAUUOAPMZUMFF-UHFFFAOYSA-N 0.000 description 2
- OFROTXYKYNYRBB-UHFFFAOYSA-N 2-chloro-4-[4-(2,5-dimethylphenyl)piperazin-1-yl]-5-nitro-n-[3-(2-oxopyrrolidin-1-yl)propyl]benzamide Chemical compound CC1=CC=C(C)C(N2CCN(CC2)C=2C(=CC(=C(Cl)C=2)C(=O)NCCCN2C(CCC2)=O)[N+]([O-])=O)=C1 OFROTXYKYNYRBB-UHFFFAOYSA-N 0.000 description 2
- DENOGFKAKZMABS-UHFFFAOYSA-N 2-chloro-4-[4-(2-methylphenyl)piperazin-1-yl]-5-nitro-n-[3-(2-oxo-1,3-oxazolidin-3-yl)propyl]benzamide Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=C(Cl)C=2)C(=O)NCCCN2C(OCC2)=O)[N+]([O-])=O)CC1 DENOGFKAKZMABS-UHFFFAOYSA-N 0.000 description 2
- QORRVTJHFXXFGB-UHFFFAOYSA-N 2-chloro-4-[4-(5-fluoro-2-methylphenyl)piperazin-1-yl]-5-nitro-n-[3-(2-oxopyrrolidin-1-yl)propyl]benzamide Chemical compound CC1=CC=C(F)C=C1N1CCN(C=2C(=CC(=C(Cl)C=2)C(=O)NCCCN2C(CCC2)=O)[N+]([O-])=O)CC1 QORRVTJHFXXFGB-UHFFFAOYSA-N 0.000 description 2
- UYUBWTRITSPBLW-UHFFFAOYSA-N 2-chloro-n-[[3-[(dimethylamino)methyl]phenyl]methyl]-4-[4-(2,5-dimethylphenyl)piperazin-1-yl]-5-nitrobenzamide Chemical compound CN(C)CC1=CC=CC(CNC(=O)C=2C(=CC(=C(C=2)[N+]([O-])=O)N2CCN(CC2)C=2C(=CC=C(C)C=2)C)Cl)=C1 UYUBWTRITSPBLW-UHFFFAOYSA-N 0.000 description 2
- ZDMCIFQECPDSCH-UHFFFAOYSA-N 2-cyclopropyl-4-[4-(2-methylphenyl)piperazin-1-yl]-5-nitro-n-[3-(2-oxopyrrolidin-1-yl)propyl]benzamide Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=C(C3CC3)C=2)C(=O)NCCCN2C(CCC2)=O)[N+]([O-])=O)CC1 ZDMCIFQECPDSCH-UHFFFAOYSA-N 0.000 description 2
- WQADKJKJIYSENW-UHFFFAOYSA-N 2-cyclopropyl-n-[2-[4-(2-methylphenyl)piperazin-1-yl]-5-[3-(2-oxopyrrolidin-1-yl)propylcarbamoyl]-4-(trifluoromethyl)phenyl]-1,3-oxazole-4-carboxamide Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=C(C=2)C(F)(F)F)C(=O)NCCCN2C(CCC2)=O)NC(=O)C=2N=C(OC=2)C2CC2)CC1 WQADKJKJIYSENW-UHFFFAOYSA-N 0.000 description 2
- SPDUQMGTCKBJPF-UHFFFAOYSA-N 2-cyclopropyl-n-[4-ethoxy-2-[4-(2-methylphenyl)piperazin-1-yl]-5-[3-(2-oxopyrrolidin-1-yl)propylcarbamoyl]phenyl]-1,3-oxazole-4-carboxamide Chemical compound C=1OC(C2CC2)=NC=1C(=O)NC=1C=C(C(=O)NCCCN2C(CCC2)=O)C(OCC)=CC=1N(CC1)CCN1C1=CC=CC=C1C SPDUQMGTCKBJPF-UHFFFAOYSA-N 0.000 description 2
- KOQCOMLKXZTTMU-UHFFFAOYSA-N 2-cyclopropyl-n-[4-methoxy-2-[4-(2-methylphenyl)piperazin-1-yl]-5-[3-(2-oxopyrrolidin-1-yl)propylcarbamoyl]phenyl]-1,3-oxazole-4-carboxamide Chemical compound C=1OC(C2CC2)=NC=1C(=O)NC=1C=C(C(=O)NCCCN2C(CCC2)=O)C(OC)=CC=1N(CC1)CCN1C1=CC=CC=C1C KOQCOMLKXZTTMU-UHFFFAOYSA-N 0.000 description 2
- WCGMNTQPXRVEFJ-UHFFFAOYSA-N 2-cyclopropyl-n-[6-[4-(2-methylphenyl)piperazin-1-yl]-1-oxo-2-[3-(2-oxopyrrolidin-1-yl)propyl]-3,4-dihydroisoquinolin-7-yl]-1,3-oxazole-4-carboxamide Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC=3C(=O)N(CCCN4C(CCC4)=O)CCC=3C=2)NC(=O)C=2N=C(OC=2)C2CC2)CC1 WCGMNTQPXRVEFJ-UHFFFAOYSA-N 0.000 description 2
- JENULOQGZZGJJR-UHFFFAOYSA-N 2-ethenyl-4-[4-(2-methylphenyl)piperazin-1-yl]-5-nitro-n-[3-(2-oxopyrrolidin-1-yl)propyl]benzamide Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=C(C=C)C=2)C(=O)NCCCN2C(CCC2)=O)[N+]([O-])=O)CC1 JENULOQGZZGJJR-UHFFFAOYSA-N 0.000 description 2
- HNFSEKOYCOCYHA-UHFFFAOYSA-N 2-methyl-4-[4-(2-methylphenyl)piperazin-1-yl]-5-nitrobenzamide Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=C(C)C=2)C(N)=O)[N+]([O-])=O)CC1 HNFSEKOYCOCYHA-UHFFFAOYSA-N 0.000 description 2
- XNTGRHMIKOJWKL-UHFFFAOYSA-N 2-methyl-4-[4-(2-methylphenyl)piperazin-1-yl]-5-nitrobenzoic acid Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=C(C)C=2)C(O)=O)[N+]([O-])=O)CC1 XNTGRHMIKOJWKL-UHFFFAOYSA-N 0.000 description 2
- OVUSZVOVNZLPCO-UHFFFAOYSA-N 3-(3-bromopropyl)-1,3-oxazolidin-2-one Chemical compound BrCCCN1CCOC1=O OVUSZVOVNZLPCO-UHFFFAOYSA-N 0.000 description 2
- PPQVUQWAQGUBGL-UHFFFAOYSA-N 4-[4-(2-methylphenyl)piperazin-1-yl]benzamide Chemical compound Cc1ccccc1N1CCN(CC1)c1ccc(cc1)C(N)=O PPQVUQWAQGUBGL-UHFFFAOYSA-N 0.000 description 2
- IBZJPGGBZMXXCE-UHFFFAOYSA-N 4-fluoro-2-methyl-5-nitrobenzoic acid Chemical compound CC1=CC(F)=C([N+]([O-])=O)C=C1C(O)=O IBZJPGGBZMXXCE-UHFFFAOYSA-N 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- BTWABPAASCRZFG-UHFFFAOYSA-N 5-amino-2-chloro-4-[4-(2-methylphenyl)piperazin-1-yl]benzoic acid Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=C(Cl)C=2)C(O)=O)N)CC1 BTWABPAASCRZFG-UHFFFAOYSA-N 0.000 description 2
- FODVBHKCLUTSSO-UHFFFAOYSA-N 5-amino-2-chloro-n-[[3-[(dimethylamino)methyl]phenyl]methyl]-4-[4-(2,5-dimethylphenyl)piperazin-1-yl]benzamide Chemical compound CN(C)CC1=CC=CC(CNC(=O)C=2C(=CC(=C(N)C=2)N2CCN(CC2)C=2C(=CC=C(C)C=2)C)Cl)=C1 FODVBHKCLUTSSO-UHFFFAOYSA-N 0.000 description 2
- FDPZWPCURUZRRT-UHFFFAOYSA-N 5-amino-2-cyclopropyl-4-[4-(2-methylphenyl)piperazin-1-yl]-n-[3-(2-oxopyrrolidin-1-yl)propyl]benzamide Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=C(C3CC3)C=2)C(=O)NCCCN2C(CCC2)=O)N)CC1 FDPZWPCURUZRRT-UHFFFAOYSA-N 0.000 description 2
- JFCXSTIMWSBLIQ-UHFFFAOYSA-N 5-amino-2-ethyl-4-[4-(2-methylphenyl)piperazin-1-yl]-n-[3-(2-oxopyrrolidin-1-yl)propyl]benzamide Chemical compound NC=1C=C(C(=O)NCCCN2C(CCC2)=O)C(CC)=CC=1N(CC1)CCN1C1=CC=CC=C1C JFCXSTIMWSBLIQ-UHFFFAOYSA-N 0.000 description 2
- BDIJOZZSTXALHN-UHFFFAOYSA-N 6-[4-(2-methylphenyl)piperazin-1-yl]-7-nitro-2h-isoquinolin-1-one Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC=3C(=O)NC=CC=3C=2)[N+]([O-])=O)CC1 BDIJOZZSTXALHN-UHFFFAOYSA-N 0.000 description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
- DWOMEVHYSMDXKC-UHFFFAOYSA-N CN(C)c1cc(N2CCN(CC2)c2ccccc2C)c(N)cc1C(=O)NCCCN1CCCC1=O Chemical compound CN(C)c1cc(N2CCN(CC2)c2ccccc2C)c(N)cc1C(=O)NCCCN1CCCC1=O DWOMEVHYSMDXKC-UHFFFAOYSA-N 0.000 description 2
- ANZBFABRIQSXLE-UHFFFAOYSA-N CN(C1=CC(=C(C=C1C(NCCCN1C(CCC1)=O)=O)NC(=O)C=1OC=CC1)N1CCN(CC1)C1=C(C=CC=C1)C)C Chemical compound CN(C1=CC(=C(C=C1C(NCCCN1C(CCC1)=O)=O)NC(=O)C=1OC=CC1)N1CCN(CC1)C1=C(C=CC=C1)C)C ANZBFABRIQSXLE-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 102000011022 Chorionic Gonadotropin Human genes 0.000 description 2
- 108010062540 Chorionic Gonadotropin Proteins 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 102000006771 Gonadotropins Human genes 0.000 description 2
- 108010086677 Gonadotropins Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 208000007466 Male Infertility Diseases 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- WWBMXNZWWQMBIO-RUHGTMQNSA-N N-[2-[(3aR,4S,7aS)-2,2-dimethyl-3a,4,5,6,7,7a-hexahydro-1,3-benzodioxol-4-yl]-6-[4-(2-methylphenyl)piperazin-1-yl]-1-oxo-3,4-dihydroisoquinolin-7-yl]-2-cyclopropyl-1,3-oxazole-4-carboxamide Chemical compound Cc1ccccc1N1CCN(CC1)c1cc2CCN([C@H]3CCC[C@@H]4OC(C)(C)O[C@H]34)C(=O)c2cc1NC(=O)c1coc(n1)C1CC1 WWBMXNZWWQMBIO-RUHGTMQNSA-N 0.000 description 2
- QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 239000004264 Petrolatum Substances 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 102000011923 Thyrotropin Human genes 0.000 description 2
- 108010061174 Thyrotropin Proteins 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 229940072056 alginate Drugs 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 2
- AEMOLEFTQBMNLQ-BKBMJHBISA-N alpha-D-galacturonic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-BKBMJHBISA-N 0.000 description 2
- DXUUXWKFVDVHIK-UHFFFAOYSA-N ambenonium chloride Chemical group [Cl-].[Cl-].C=1C=CC=C(Cl)C=1C[N+](CC)(CC)CCNC(=O)C(=O)NCC[N+](CC)(CC)CC1=CC=CC=C1Cl DXUUXWKFVDVHIK-UHFFFAOYSA-N 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 150000001448 anilines Chemical class 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 2
- 229910001863 barium hydroxide Inorganic materials 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 235000010290 biphenyl Nutrition 0.000 description 2
- 239000004305 biphenyl Substances 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 2
- 239000000920 calcium hydroxide Substances 0.000 description 2
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 229940015047 chorionic gonadotropin Drugs 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000009260 cross reactivity Effects 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 229940011871 estrogen Drugs 0.000 description 2
- 239000000262 estrogen Substances 0.000 description 2
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 2
- 201000003585 eunuchism Diseases 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 230000003325 follicular Effects 0.000 description 2
- 230000008217 follicular development Effects 0.000 description 2
- 239000002622 gonadotropin Substances 0.000 description 2
- 229940094892 gonadotropins Drugs 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 210000002503 granulosa cell Anatomy 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 125000002632 imidazolidinyl group Chemical group 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 208000000509 infertility Diseases 0.000 description 2
- 230000036512 infertility Effects 0.000 description 2
- 231100000535 infertility Toxicity 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 208000037106 male hypogonadism Diseases 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 2
- GQJCAQADCPTHKN-UHFFFAOYSA-N methyl 2,2-difluoro-2-fluorosulfonylacetate Chemical compound COC(=O)C(F)(F)S(F)(=O)=O GQJCAQADCPTHKN-UHFFFAOYSA-N 0.000 description 2
- MSCTVIYGZJCWDV-NTEUORMPSA-N methyl 2-[(e)-2-ethoxyethenyl]-4-[4-(2-methylphenyl)piperazin-1-yl]-5-nitrobenzoate Chemical compound C1=C(C(=O)OC)C(/C=C/OCC)=CC(N2CCN(CC2)C=2C(=CC=CC=2)C)=C1[N+]([O-])=O MSCTVIYGZJCWDV-NTEUORMPSA-N 0.000 description 2
- KULZGQCGJDBQSK-UHFFFAOYSA-N methyl 4-[4-(2-methylphenyl)piperazin-1-yl]-5-nitro-2-(trifluoromethyl)benzoate Chemical compound C1=C(C(F)(F)F)C(C(=O)OC)=CC([N+]([O-])=O)=C1N1CCN(C=2C(=CC=CC=2)C)CC1 KULZGQCGJDBQSK-UHFFFAOYSA-N 0.000 description 2
- JUOLUXRGVFKAJA-UHFFFAOYSA-N methyl 5-amino-4-[4-(2-methylphenyl)piperazin-1-yl]-2-(trifluoromethyl)benzoate Chemical compound C1=C(C(F)(F)F)C(C(=O)OC)=CC(N)=C1N1CCN(C=2C(=CC=CC=2)C)CC1 JUOLUXRGVFKAJA-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- FAFXDDISJICQMQ-UHFFFAOYSA-N n-[4-chloro-5-[[3-[(dimethylamino)methyl]phenyl]methylcarbamoyl]-2-[4-(2-methylphenyl)piperazin-1-yl]phenyl]furan-2-carboxamide Chemical compound CN(C)CC1=CC=CC(CNC(=O)C=2C(=CC(=C(NC(=O)C=3OC=CC=3)C=2)N2CCN(CC2)C=2C(=CC=CC=2)C)Cl)=C1 FAFXDDISJICQMQ-UHFFFAOYSA-N 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- 125000001715 oxadiazolyl group Chemical group 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 125000000160 oxazolidinyl group Chemical group 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 229940066842 petrolatum Drugs 0.000 description 2
- 235000019271 petrolatum Nutrition 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 125000003386 piperidinyl group Chemical group 0.000 description 2
- 210000002826 placenta Anatomy 0.000 description 2
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 210000000717 sertoli cell Anatomy 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 238000005556 structure-activity relationship Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- QFVIEJSGAGMGOY-UHFFFAOYSA-N tert-butyl 3-[[5-[(2-cyclopropyl-1,3-oxazole-4-carbonyl)amino]-2-fluoro-4-[4-(2-methylphenyl)piperazin-1-yl]benzoyl]amino]cyclohexane-1-carboxylate Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=C(F)C=2)C(=O)NC2CC(CCC2)C(=O)OC(C)(C)C)NC(=O)C=2N=C(OC=2)C2CC2)CC1 QFVIEJSGAGMGOY-UHFFFAOYSA-N 0.000 description 2
- HDDNFOIPZIUWMF-UHFFFAOYSA-N tert-butyl 4-(5-fluoro-2-methylphenyl)piperazine-1-carboxylate Chemical compound CC1=CC=C(F)C=C1N1CCN(C(=O)OC(C)(C)C)CC1 HDDNFOIPZIUWMF-UHFFFAOYSA-N 0.000 description 2
- 230000002381 testicular Effects 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 125000001984 thiazolidinyl group Chemical group 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- 238000000825 ultraviolet detection Methods 0.000 description 2
- LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 1
- GKCKZPVVUMMCMU-FCHUYYIVSA-N (1s,3r)-3-[[5-[(2-cyclopropyl-1,3-oxazole-4-carbonyl)amino]-2-fluoro-4-[4-(2-methylphenyl)piperazin-1-yl]benzoyl]amino]cyclohexane-1-carboxylic acid Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=C(F)C=2)C(=O)N[C@H]2C[C@H](CCC2)C(O)=O)NC(=O)C=2N=C(OC=2)C2CC2)CC1 GKCKZPVVUMMCMU-FCHUYYIVSA-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
- DRHZYJAUECRAJM-DWSYSWFDSA-N (2s,3s,4s,5r,6r)-6-[[(3s,4s,4ar,6ar,6bs,8r,8ar,12as,14ar,14br)-8a-[(2s,3r,4s,5r,6r)-3-[(2s,3r,4s,5r,6s)-5-[(2s,3r,4s,5r)-4-[(2s,3r,4r)-3,4-dihydroxy-4-(hydroxymethyl)oxolan-2-yl]oxy-3,5-dihydroxyoxan-2-yl]oxy-3,4-dihydroxy-6-methyloxan-2-yl]oxy-5-[(3s,5s, Chemical compound O([C@H]1[C@H](O)[C@H](O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O1)O)O[C@H]1CC[C@]2(C)[C@H]3CC=C4[C@@H]5CC(C)(C)CC[C@@]5([C@@H](C[C@@]4(C)[C@]3(C)CC[C@H]2[C@@]1(C=O)C)O)C(=O)O[C@@H]1O[C@H](C)[C@@H]([C@@H]([C@H]1O[C@H]1[C@@H]([C@H](O)[C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@](O)(CO)CO3)O)[C@H](O)CO2)O)[C@H](C)O1)O)O)OC(=O)C[C@@H](O)C[C@H](OC(=O)C[C@@H](O)C[C@@H]([C@@H](C)CC)O[C@H]1[C@@H]([C@@H](O)[C@H](CO)O1)O)[C@@H](C)CC)C(O)=O)[C@@H]1OC[C@@H](O)[C@H](O)[C@H]1O DRHZYJAUECRAJM-DWSYSWFDSA-N 0.000 description 1
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
- APJSHECCIRQQDV-ZRDIBKRKSA-N (e)-3-[4-hydroxy-3-(5,5,8,8-tetramethyl-3-pentoxy-6,7-dihydronaphthalen-2-yl)phenyl]prop-2-enoic acid Chemical compound CCCCCOC1=CC(C(CCC2(C)C)(C)C)=C2C=C1C1=CC(\C=C\C(O)=O)=CC=C1O APJSHECCIRQQDV-ZRDIBKRKSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- 125000005919 1,2,2-trimethylpropyl group Chemical group 0.000 description 1
- VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 1
- NCENNBIPRYOJSP-UHFFFAOYSA-N 1-(2-methylphenyl)piperazine-1,4-diium;dichloride Chemical compound Cl.Cl.CC1=CC=CC=C1N1CCNCC1 NCENNBIPRYOJSP-UHFFFAOYSA-N 0.000 description 1
- OGLZSMPGMUDNKR-UHFFFAOYSA-N 1-(2-methylphenyl)piperidine Chemical compound CC1=CC=CC=C1N1CCCCC1 OGLZSMPGMUDNKR-UHFFFAOYSA-N 0.000 description 1
- 125000006218 1-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- NCYCYZXNIZJOKI-IOUUIBBYSA-N 11-cis-retinal Chemical compound O=C/C=C(\C)/C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-IOUUIBBYSA-N 0.000 description 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
- 125000005808 2,4,6-trimethoxyphenyl group Chemical group [H][#6]-1=[#6](-[#8]C([H])([H])[H])-[#6](-*)=[#6](-[#8]C([H])([H])[H])-[#6]([H])=[#6]-1-[#8]C([H])([H])[H] 0.000 description 1
- MDFSGDMPHMKKGB-UHFFFAOYSA-N 2,4-difluoro-5-nitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=C(F)C=C1F MDFSGDMPHMKKGB-UHFFFAOYSA-N 0.000 description 1
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 1
- ATUVFSDKFXGMHL-DOEKTCAHSA-N 2-[(3ar,4s,7as)-2,2-dimethyl-3a,4,5,6,7,7a-hexahydro-1,3-benzodioxol-4-yl]-7-amino-6-[4-(2-methylphenyl)piperazin-1-yl]-3,4-dihydroisoquinolin-1-one Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC=3C(=O)N([C@@H]4[C@H]5OC(C)(C)O[C@H]5CCC4)CCC=3C=2)N)CC1 ATUVFSDKFXGMHL-DOEKTCAHSA-N 0.000 description 1
- MRAYNLYCQPAZJN-BQYQJAHWSA-N 2-[(e)-2-ethoxyethenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound CCO\C=C\B1OC(C)(C)C(C)(C)O1 MRAYNLYCQPAZJN-BQYQJAHWSA-N 0.000 description 1
- PYTMYKVIJXPNBD-OQKDUQJOSA-N 2-[4-[(z)-2-chloro-1,2-diphenylethenyl]phenoxy]-n,n-diethylethanamine;hydron;2-hydroxypropane-1,2,3-tricarboxylate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(/Cl)C1=CC=CC=C1 PYTMYKVIJXPNBD-OQKDUQJOSA-N 0.000 description 1
- SFGFOJPGCOYQJK-UHFFFAOYSA-N 2-bromo-4-fluoro-1-methylbenzene Chemical compound CC1=CC=C(F)C=C1Br SFGFOJPGCOYQJK-UHFFFAOYSA-N 0.000 description 1
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
- ZWEPNQQEVVTYGE-UHFFFAOYSA-N 2-chloro-4-[4-(5-fluoro-2-methylphenyl)piperazin-1-yl]-5-nitrobenzoic acid Chemical compound CC1=CC=C(F)C=C1N1CCN(C=2C(=CC(=C(Cl)C=2)C(O)=O)[N+]([O-])=O)CC1 ZWEPNQQEVVTYGE-UHFFFAOYSA-N 0.000 description 1
- GRPWQLDSGNZEQE-UHFFFAOYSA-N 2-chloro-4-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1Cl GRPWQLDSGNZEQE-UHFFFAOYSA-N 0.000 description 1
- SGQKSVSTXPKBDW-UHFFFAOYSA-N 2-chloro-5-(furan-2-carbonylamino)-4-[4-(2-methylphenyl)piperazin-1-yl]benzoic acid Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=C(Cl)C=2)C(O)=O)NC(=O)C=2OC=CC=2)CC1 SGQKSVSTXPKBDW-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- VUZWGHAVVOOTOM-LOAGWBBBSA-N 2-cyclopropyl-N-[2-[(1S,2R,3S)-2,3-dihydroxycyclohexyl]-6-[4-(2-methylphenyl)piperazin-1-yl]-1-oxo-3,4-dihydroisoquinolin-7-yl]-1,3-oxazole-4-carboxamide Chemical compound Cc1ccccc1N1CCN(CC1)c1cc2CCN([C@H]3CCC[C@H](O)[C@@H]3O)C(=O)c2cc1NC(=O)c1coc(n1)C1CC1 VUZWGHAVVOOTOM-LOAGWBBBSA-N 0.000 description 1
- IBHANJRCDCBGJR-UHFFFAOYSA-N 2-cyclopropyl-n-[2-[4-(2-methylphenyl)piperazin-1-yl]-5-[3-(2-oxopyrrolidin-1-yl)propylcarbamoyl]-3-(trifluoromethyl)phenyl]-1,3-oxazole-4-carboxamide Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=CC=2NC(=O)C=2N=C(OC=2)C2CC2)C(=O)NCCCN2C(CCC2)=O)C(F)(F)F)CC1 IBHANJRCDCBGJR-UHFFFAOYSA-N 0.000 description 1
- GYILBRYIUZXBER-UHFFFAOYSA-N 2-cyclopropyl-n-[4-cyclopropyl-2-[4-(2-methylphenyl)piperazin-1-yl]-5-[3-(2-oxopyrrolidin-1-yl)propylcarbamoyl]phenyl]-1,3-oxazole-4-carboxamide Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=C(C3CC3)C=2)C(=O)NCCCN2C(CCC2)=O)NC(=O)C=2N=C(OC=2)C2CC2)CC1 GYILBRYIUZXBER-UHFFFAOYSA-N 0.000 description 1
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- ISVXTORXPPVUQV-UHFFFAOYSA-N 2-fluoro-4-[4-(2-methylphenyl)piperazin-1-yl]-5-nitro-n-[3-(2-oxopyrrolidin-1-yl)propyl]benzamide Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=C(F)C=2)C(=O)NCCCN2C(CCC2)=O)[N+]([O-])=O)CC1 ISVXTORXPPVUQV-UHFFFAOYSA-N 0.000 description 1
- FBKJKGDLJUHSIR-UHFFFAOYSA-N 2-fluoro-4-[4-(2-methylphenyl)piperazin-1-yl]-5-nitrobenzoic acid Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=C(F)C=2)C(O)=O)[N+]([O-])=O)CC1 FBKJKGDLJUHSIR-UHFFFAOYSA-N 0.000 description 1
- RKXIVXQXOONSCY-UHFFFAOYSA-N 2-methoxy-4-[4-(2-methylphenyl)piperazin-1-yl]-5-nitro-n-[3-(2-oxopyrrolidin-1-yl)propyl]benzamide Chemical compound [O-][N+](=O)C=1C=C(C(=O)NCCCN2C(CCC2)=O)C(OC)=CC=1N(CC1)CCN1C1=CC=CC=C1C RKXIVXQXOONSCY-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 1
- 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- SLAMLWHELXOEJZ-UHFFFAOYSA-N 2-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1[N+]([O-])=O SLAMLWHELXOEJZ-UHFFFAOYSA-N 0.000 description 1
- 125000004362 3,4,5-trichlorophenyl group Chemical group [H]C1=C(Cl)C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 description 1
- CGWMNQRJDFNOCF-UHFFFAOYSA-N 3-(3-aminopropyl)-1,3-oxazolidin-2-one Chemical compound NCCCN1CCOC1=O CGWMNQRJDFNOCF-UHFFFAOYSA-N 0.000 description 1
- OYIVHKGIRRMZLT-UHFFFAOYSA-N 3-[3-[6-[4-(2-methylphenyl)piperazin-1-yl]-7-nitro-1-oxoisoquinolin-2-yl]propyl]-1,3-oxazolidin-2-one Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC=3C(=O)N(CCCN4C(OCC4)=O)C=CC=3C=2)[N+]([O-])=O)CC1 OYIVHKGIRRMZLT-UHFFFAOYSA-N 0.000 description 1
- RJEULMPKXDNOGE-UHFFFAOYSA-N 3-[3-[7-amino-6-[4-(2-methylphenyl)piperazin-1-yl]-1-oxoisoquinolin-2-yl]propyl]-1,3-oxazolidin-2-one Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC=3C(=O)N(CCCN4C(OCC4)=O)C=CC=3C=2)N)CC1 RJEULMPKXDNOGE-UHFFFAOYSA-N 0.000 description 1
- GKCKZPVVUMMCMU-UHFFFAOYSA-N 3-[[5-[(2-cyclopropyl-1,3-oxazole-4-carbonyl)amino]-2-fluoro-4-[4-(2-methylphenyl)piperazin-1-yl]benzoyl]amino]cyclohexane-1-carboxylic acid Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=C(F)C=2)C(=O)NC2CC(CCC2)C(O)=O)NC(=O)C=2N=C(OC=2)C2CC2)CC1 GKCKZPVVUMMCMU-UHFFFAOYSA-N 0.000 description 1
- CDDXEBLDMSEIPK-UHFFFAOYSA-N 3-amino-4-[4-(2-methylphenyl)piperazin-1-yl]-n-[3-(2-oxopyrrolidin-1-yl)propyl]-5-(trifluoromethyl)benzamide Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=CC=2N)C(=O)NCCCN2C(CCC2)=O)C(F)(F)F)CC1 CDDXEBLDMSEIPK-UHFFFAOYSA-N 0.000 description 1
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
- IRBQIHAJILTUPX-UHFFFAOYSA-N 4-[4-(2-methylphenyl)piperazin-1-yl]-3-nitro-5-(trifluoromethyl)benzoic acid Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=CC=2[N+]([O-])=O)C(O)=O)C(F)(F)F)CC1 IRBQIHAJILTUPX-UHFFFAOYSA-N 0.000 description 1
- DHYKSPGVZJQCKT-UHFFFAOYSA-N 4-[4-(2-methylphenyl)piperazin-1-yl]-3-nitro-n-[3-(2-oxopyrrolidin-1-yl)propyl]-5-(trifluoromethyl)benzamide Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=CC=2[N+]([O-])=O)C(=O)NCCCN2C(CCC2)=O)C(F)(F)F)CC1 DHYKSPGVZJQCKT-UHFFFAOYSA-N 0.000 description 1
- MWODXWCZJBKPAE-UHFFFAOYSA-N 4-[[2-chloro-5-[(2-cyclopropyl-1,3-oxazole-4-carbonyl)amino]-4-[4-(2-methylphenyl)piperazin-1-yl]benzoyl]amino]-2,2-dimethylbutanoic acid Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=C(Cl)C=2)C(=O)NCCC(C)(C)C(O)=O)NC(=O)C=2N=C(OC=2)C2CC2)CC1 MWODXWCZJBKPAE-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- KDXOONIQRUZGSY-UHFFFAOYSA-N 4-fluoro-2-methylbenzoic acid Chemical compound CC1=CC(F)=CC=C1C(O)=O KDXOONIQRUZGSY-UHFFFAOYSA-N 0.000 description 1
- XCZRYPKVIJEHSU-UHFFFAOYSA-N 4-fluoro-3-nitro-5-(trifluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=C(F)C(C(F)(F)F)=C1 XCZRYPKVIJEHSU-UHFFFAOYSA-N 0.000 description 1
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- QRAOZQGIUIDZQZ-UHFFFAOYSA-N 4-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1,4-benzoxazine Chemical compound C=1C=C2N(C)CCOC2=CC=1B1OC(C)(C)C(C)(C)O1 QRAOZQGIUIDZQZ-UHFFFAOYSA-N 0.000 description 1
- OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 1
- XCCUXCDIUNHINI-UHFFFAOYSA-N 5-amino-2-(2-methoxyethoxy)-4-[4-(2-methylphenyl)piperazin-1-yl]-N-[3-(2-oxopyrrolidin-1-yl)propyl]benzamide Chemical compound COCCOc1cc(N2CCN(CC2)c2ccccc2C)c(N)cc1C(=O)NCCCN1CCCC1=O XCCUXCDIUNHINI-UHFFFAOYSA-N 0.000 description 1
- KAPLJOWGXNHIBD-UHFFFAOYSA-N 5-amino-2-chloro-4-[4-(2,5-dimethylphenyl)piperazin-1-yl]-n-[3-(2-oxopyrrolidin-1-yl)propyl]benzamide Chemical compound CC1=CC=C(C)C(N2CCN(CC2)C=2C(=CC(=C(Cl)C=2)C(=O)NCCCN2C(CCC2)=O)N)=C1 KAPLJOWGXNHIBD-UHFFFAOYSA-N 0.000 description 1
- LMGDFDOYABVJCW-UHFFFAOYSA-N 5-amino-2-chloro-4-[4-(2-methylphenyl)piperazin-1-yl]-n-[3-(2-oxo-1,3-oxazolidin-3-yl)propyl]benzamide Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=C(Cl)C=2)C(=O)NCCCN2C(OCC2)=O)N)CC1 LMGDFDOYABVJCW-UHFFFAOYSA-N 0.000 description 1
- WXHFKIFDXQPLNH-UHFFFAOYSA-N 5-amino-2-chloro-4-[4-(5-fluoro-2-methylphenyl)piperazin-1-yl]-n-[3-(2-oxopyrrolidin-1-yl)propyl]benzamide Chemical compound CC1=CC=C(F)C=C1N1CCN(C=2C(=CC(=C(Cl)C=2)C(=O)NCCCN2C(CCC2)=O)N)CC1 WXHFKIFDXQPLNH-UHFFFAOYSA-N 0.000 description 1
- QMUXACXRPFVYLW-UHFFFAOYSA-N 5-amino-2-methoxy-4-[4-(2-methylphenyl)piperazin-1-yl]-n-[3-(2-oxopyrrolidin-1-yl)propyl]benzamide Chemical compound NC=1C=C(C(=O)NCCCN2C(CCC2)=O)C(OC)=CC=1N(CC1)CCN1C1=CC=CC=C1C QMUXACXRPFVYLW-UHFFFAOYSA-N 0.000 description 1
- XOFDQZPINNTGLC-UHFFFAOYSA-N 5-amino-4-[4-(2-methylphenyl)piperazin-1-yl]-2-(trifluoromethyl)benzoic acid Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=C(C=2)C(F)(F)F)C(O)=O)N)CC1 XOFDQZPINNTGLC-UHFFFAOYSA-N 0.000 description 1
- CZJLCYHOJNYHCO-UHFFFAOYSA-N 6-[4-(2-methylphenyl)piperazin-1-yl]-7-nitro-2-[3-(2-oxopyrrolidin-1-yl)propyl]-3,4-dihydroisoquinolin-1-one Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC=3C(=O)N(CCCN4C(CCC4)=O)CCC=3C=2)[N+]([O-])=O)CC1 CZJLCYHOJNYHCO-UHFFFAOYSA-N 0.000 description 1
- APKFPKLTEJAOJI-UHFFFAOYSA-N 6-butyldec-5-en-5-ylstannane Chemical compound CCCCC([SnH3])=C(CCCC)CCCC APKFPKLTEJAOJI-UHFFFAOYSA-N 0.000 description 1
- DFWHFWQINUVYDV-UHFFFAOYSA-N 7-amino-2-[[3-[(dimethylamino)methyl]phenyl]methyl]-6-[4-(2-methylphenyl)piperazin-1-yl]-3,4-dihydroisoquinolin-1-one Chemical compound CN(C)CC1=CC=CC(CN2C(C3=CC(N)=C(N4CCN(CC4)C=4C(=CC=CC=4)C)C=C3CC2)=O)=C1 DFWHFWQINUVYDV-UHFFFAOYSA-N 0.000 description 1
- DMYHJOLXMIRWHX-UHFFFAOYSA-N 7-amino-6-[4-(2-methylphenyl)piperazin-1-yl]-2-[3-(2-oxopyrrolidin-1-yl)propyl]-3,4-dihydroisoquinolin-1-one Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC=3C(=O)N(CCCN4C(CCC4)=O)CCC=3C=2)N)CC1 DMYHJOLXMIRWHX-UHFFFAOYSA-N 0.000 description 1
- 108010042708 Acetylmuramyl-Alanyl-Isoglutamine Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- 102100028990 C-X-C chemokine receptor type 3 Human genes 0.000 description 1
- ATUVFSDKFXGMHL-CUBVPSHMSA-N CC(C)(O[C@H]1CCC2)O[C@@H]1C2N(CCc(cc1N(CC2)CCN2c2c(C)cccc2)c2cc1N)C2=O Chemical compound CC(C)(O[C@H]1CCC2)O[C@@H]1C2N(CCc(cc1N(CC2)CCN2c2c(C)cccc2)c2cc1N)C2=O ATUVFSDKFXGMHL-CUBVPSHMSA-N 0.000 description 1
- HJNYCKGEZZSGPP-UHFFFAOYSA-N CN(C)Cc1cccc(CN2CCc3cc(N4CCN(CC4)c4ccccc4C)c(NC(=O)c4ccco4)cc3C2=O)c1 Chemical compound CN(C)Cc1cccc(CN2CCc3cc(N4CCN(CC4)c4ccccc4C)c(NC(=O)c4ccco4)cc3C2=O)c1 HJNYCKGEZZSGPP-UHFFFAOYSA-N 0.000 description 1
- RTDSIWKQCKISPU-UHFFFAOYSA-N CN(C)c1cc(N2CCN(CC2)c2ccccc2C)c(NC(=O)c2coc(n2)C2CC2)cc1C(=O)NCCCN1CCCC1=O Chemical compound CN(C)c1cc(N2CCN(CC2)c2ccccc2C)c(NC(=O)c2coc(n2)C2CC2)cc1C(=O)NCCCN1CCCC1=O RTDSIWKQCKISPU-UHFFFAOYSA-N 0.000 description 1
- BMIWITFMNYQGMZ-UHFFFAOYSA-N COCCOc1cc(N2CCN(CC2)c2ccccc2C)c(NC(=O)c2coc(n2)C2CC2)cc1C(=O)NCCCN1CCCC1=O Chemical compound COCCOc1cc(N2CCN(CC2)c2ccccc2C)c(NC(=O)c2coc(n2)C2CC2)cc1C(=O)NCCCN1CCCC1=O BMIWITFMNYQGMZ-UHFFFAOYSA-N 0.000 description 1
- 101150004010 CXCR3 gene Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- YTGXAYNPRPQJQE-UHFFFAOYSA-N Cc1cc(N(CC2)CCN2c(c([N+]([O-])=O)c2)cc(Cl)c2C(O)=O)c(C)cc1 Chemical compound Cc1cc(N(CC2)CCN2c(c([N+]([O-])=O)c2)cc(Cl)c2C(O)=O)c(C)cc1 YTGXAYNPRPQJQE-UHFFFAOYSA-N 0.000 description 1
- VMPFONGYOLBXGM-UHFFFAOYSA-N Cc1ccccc1NCCNc(c(NC(c1c[o]c(C2CC2)n1)=O)c1)cc(O)c1C(NCCCN(CCC1)C1=O)=O Chemical compound Cc1ccccc1NCCNc(c(NC(c1c[o]c(C2CC2)n1)=O)c1)cc(O)c1C(NCCCN(CCC1)C1=O)=O VMPFONGYOLBXGM-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- 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
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- DSLZVSRJTYRBFB-UHFFFAOYSA-N Galactaric acid Natural products OC(=O)C(O)C(O)C(O)C(O)C(O)=O DSLZVSRJTYRBFB-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000017357 Glycoprotein hormone receptor Human genes 0.000 description 1
- 108050005395 Glycoprotein hormone receptor Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000916050 Homo sapiens C-X-C chemokine receptor type 3 Proteins 0.000 description 1
- 101000772267 Homo sapiens Thyrotropin receptor Proteins 0.000 description 1
- 206010062767 Hypophysitis Diseases 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
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 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
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- 102000023108 LH Receptors Human genes 0.000 description 1
- 108010011942 LH Receptors Proteins 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- ONXPDKGXOOORHB-BYPYZUCNSA-N N(5)-methyl-L-glutamine Chemical compound CNC(=O)CC[C@H](N)C(O)=O ONXPDKGXOOORHB-BYPYZUCNSA-N 0.000 description 1
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 1
- 238000006411 Negishi coupling reaction Methods 0.000 description 1
- 108010040722 Neurokinin-2 Receptors Proteins 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 101150003085 Pdcl gene Proteins 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102100040756 Rhodopsin Human genes 0.000 description 1
- 108090000820 Rhodopsin Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 102100037342 Substance-K receptor Human genes 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 238000006161 Suzuki-Miyaura coupling reaction Methods 0.000 description 1
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 102000003911 Thyrotropin Receptors Human genes 0.000 description 1
- 108090000253 Thyrotropin Receptors Proteins 0.000 description 1
- 102100029337 Thyrotropin receptor Human genes 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 238000005411 Van der Waals force Methods 0.000 description 1
- NELWQUQCCZMRPB-UBPLGANQSA-N [(2r,3r,4r,5r)-4-acetyloxy-5-(4-amino-5-ethenyl-2-oxopyrimidin-1-yl)-2-methyloxolan-3-yl] acetate Chemical compound CC(=O)O[C@@H]1[C@H](OC(C)=O)[C@@H](C)O[C@H]1N1C(=O)N=C(N)C(C=C)=C1 NELWQUQCCZMRPB-UBPLGANQSA-N 0.000 description 1
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 1
- IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 239000012042 active reagent Substances 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 102000030621 adenylate cyclase Human genes 0.000 description 1
- 108060000200 adenylate cyclase Proteins 0.000 description 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 238000010640 amide synthesis reaction Methods 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 210000004198 anterior pituitary gland Anatomy 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 150000001543 aryl boronic acids Chemical class 0.000 description 1
- 150000001500 aryl chlorides Chemical class 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 239000003637 basic solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
- 125000002527 bicyclic carbocyclic group Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000012867 bioactive agent Substances 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 125000005997 bromomethyl group Chemical group 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 238000003763 carbonization Methods 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000001413 cellular effect Effects 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
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- BJDCWCLMFKKGEE-CMDXXVQNSA-N chembl252518 Chemical compound C([C@@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2O[C@H](O)[C@@H]4C BJDCWCLMFKKGEE-CMDXXVQNSA-N 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- KVSASDOGYIBWTA-UHFFFAOYSA-N chloro benzoate Chemical compound ClOC(=O)C1=CC=CC=C1 KVSASDOGYIBWTA-UHFFFAOYSA-N 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229940046989 clomiphene citrate Drugs 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 238000002288 cocrystallisation Methods 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 125000006448 cycloalkyl cycloalkyl group Chemical group 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- WLVKDFJTYKELLQ-UHFFFAOYSA-N cyclopropylboronic acid Chemical compound OB(O)C1CC1 WLVKDFJTYKELLQ-UHFFFAOYSA-N 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000105 evaporative light scattering detection Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 230000003176 fibrotic effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000009093 first-line therapy Methods 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- PTCGDEVVHUXTMP-UHFFFAOYSA-N flutolanil Chemical compound CC(C)OC1=CC=CC(NC(=O)C=2C(=CC=CC=2)C(F)(F)F)=C1 PTCGDEVVHUXTMP-UHFFFAOYSA-N 0.000 description 1
- 108010006578 follitropin alfa Proteins 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- DSLZVSRJTYRBFB-DUHBMQHGSA-N galactaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O DSLZVSRJTYRBFB-DUHBMQHGSA-N 0.000 description 1
- 230000006543 gametophyte development Effects 0.000 description 1
- 229940044627 gamma-interferon Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000009395 genetic defect Effects 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 1
- 229940035638 gonadotropin-releasing hormone Drugs 0.000 description 1
- 229940057854 gonal f Drugs 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000002868 homogeneous time resolved fluorescence Methods 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 238000002169 hydrotherapy Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229940030980 inova Drugs 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 102000027411 intracellular receptors Human genes 0.000 description 1
- 108091008582 intracellular receptors Proteins 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 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
- 150000002576 ketones Chemical class 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 102000014650 luteinizing hormone receptor activity proteins Human genes 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 1
- 229910001623 magnesium bromide Inorganic materials 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229940127554 medical product Drugs 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910044991 metal oxide Inorganic materials 0.000 description 1
- 150000004706 metal oxides Chemical class 0.000 description 1
- 125000005341 metaphosphate group Chemical group 0.000 description 1
- DKGDZEOHNBBRJM-UHFFFAOYSA-N methyl 3-[[5-[(2-cyclopropyl-1,3-oxazole-4-carbonyl)amino]-2-fluoro-4-[4-(2-methylphenyl)piperazin-1-yl]benzoyl]amino]cyclohexane-1-carboxylate Chemical compound C1C(C(=O)OC)CCCC1NC(=O)C1=CC(NC(=O)C=2N=C(OC=2)C2CC2)=C(N2CCN(CC2)C=2C(=CC=CC=2)C)C=C1F DKGDZEOHNBBRJM-UHFFFAOYSA-N 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- BSOQXXWZTUDTEL-ZUYCGGNHSA-N muramyl dipeptide Chemical compound OC(=O)CC[C@H](C(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](C)O[C@H]1[C@H](O)[C@@H](CO)O[C@@H](O)[C@@H]1NC(C)=O BSOQXXWZTUDTEL-ZUYCGGNHSA-N 0.000 description 1
- 125000001446 muramyl group Chemical group N[C@@H](C=O)[C@@H](O[C@@H](C(=O)*)C)[C@H](O)[C@H](O)CO 0.000 description 1
- MIGAVRUXPZDYSZ-UHFFFAOYSA-N n,n-diethylethanamine;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound CCN(CC)CC.OC(=O)CC(O)(C(O)=O)CC(O)=O MIGAVRUXPZDYSZ-UHFFFAOYSA-N 0.000 description 1
- QCUKOSKYQVGDOS-UHFFFAOYSA-N n-[3-(2-oxopyrrolidin-1-yl)propyl]benzamide Chemical compound C=1C=CC=CC=1C(=O)NCCCN1CCCC1=O QCUKOSKYQVGDOS-UHFFFAOYSA-N 0.000 description 1
- MUJNAWXXOJRNGK-UHFFFAOYSA-N n-[3-(6-methyl-1,2,3,4-tetrahydrocarbazol-9-yl)propyl]cyclohexanamine Chemical compound C1=2CCCCC=2C2=CC(C)=CC=C2N1CCCNC1CCCCC1 MUJNAWXXOJRNGK-UHFFFAOYSA-N 0.000 description 1
- WQBWJIKEBRHMIR-UHFFFAOYSA-N n-[4-chloro-2-[4-(2,5-dimethylphenyl)piperazin-1-yl]-5-[3-(2-oxopyrrolidin-1-yl)propylcarbamoyl]phenyl]-2-cyclopropyl-1,3-oxazole-4-carboxamide Chemical compound CC1=CC=C(C)C(N2CCN(CC2)C=2C(=CC(=C(Cl)C=2)C(=O)NCCCN2C(CCC2)=O)NC(=O)C=2N=C(OC=2)C2CC2)=C1 WQBWJIKEBRHMIR-UHFFFAOYSA-N 0.000 description 1
- FQIWFEBIZLOEQB-UHFFFAOYSA-N n-[4-chloro-2-[4-(2-methylphenyl)piperazin-1-yl]-5-[3-(2-oxo-1,3-oxazolidin-3-yl)propylcarbamoyl]phenyl]-2-cyclopropyl-1,3-oxazole-4-carboxamide Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=C(Cl)C=2)C(=O)NCCCN2C(OCC2)=O)NC(=O)C=2N=C(OC=2)C2CC2)CC1 FQIWFEBIZLOEQB-UHFFFAOYSA-N 0.000 description 1
- ADSKFCOWAQNUDH-UHFFFAOYSA-N n-[4-chloro-2-[4-(5-fluoro-2-methylphenyl)piperazin-1-yl]-5-[3-(2-oxopyrrolidin-1-yl)propylcarbamoyl]phenyl]-2-cyclopropyl-1,3-oxazole-4-carboxamide Chemical compound CC1=CC=C(F)C=C1N1CCN(C=2C(=CC(=C(Cl)C=2)C(=O)NCCCN2C(CCC2)=O)NC(=O)C=2N=C(OC=2)C2CC2)CC1 ADSKFCOWAQNUDH-UHFFFAOYSA-N 0.000 description 1
- IWSXRDFNOMZPPX-UHFFFAOYSA-N n-[4-chloro-5-[[3-[(dimethylamino)methyl]phenyl]methylcarbamoyl]-2-[4-(2,5-dimethylphenyl)piperazin-1-yl]phenyl]-2-cyclopropyl-1,3-oxazole-4-carboxamide Chemical compound CN(C)CC1=CC=CC(CNC(=O)C=2C(=CC(=C(NC(=O)C=3N=C(OC=3)C3CC3)C=2)N2CCN(CC2)C=2C(=CC=C(C)C=2)C)Cl)=C1 IWSXRDFNOMZPPX-UHFFFAOYSA-N 0.000 description 1
- FMXXFOACBOOBDH-UHFFFAOYSA-N n-[4-cyclopropyl-2-[4-(2-methylphenyl)piperazin-1-yl]-5-[3-(2-oxopyrrolidin-1-yl)propylcarbamoyl]phenyl]furan-2-carboxamide Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=C(C3CC3)C=2)C(=O)NCCCN2C(CCC2)=O)NC(=O)C=2OC=CC=2)CC1 FMXXFOACBOOBDH-UHFFFAOYSA-N 0.000 description 1
- HTNOREGOSBWNAW-UHFFFAOYSA-N n-[4-ethoxy-2-[4-(2-methylphenyl)piperazin-1-yl]-5-[3-(2-oxopyrrolidin-1-yl)propylcarbamoyl]phenyl]furan-2-carboxamide Chemical compound C=1C=COC=1C(=O)NC=1C=C(C(=O)NCCCN2C(CCC2)=O)C(OCC)=CC=1N(CC1)CCN1C1=CC=CC=C1C HTNOREGOSBWNAW-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
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 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
- KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 210000000287 oocyte Anatomy 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 150000001282 organosilanes Chemical class 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 210000004681 ovum Anatomy 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 125000005475 oxolanyl group Chemical group 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 229940049953 phenylacetate Drugs 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 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
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical group OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 230000027272 reproductive process Effects 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 235000017709 saponins Nutrition 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- RCOSUMRTSQULBK-UHFFFAOYSA-N sodium;propan-1-olate Chemical compound [Na+].CCC[O-] RCOSUMRTSQULBK-UHFFFAOYSA-N 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000000920 spermatogeneic effect Effects 0.000 description 1
- 230000021595 spermatogenesis Effects 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 230000028016 temperature homeostasis Effects 0.000 description 1
- QFVIEJSGAGMGOY-RPBOFIJWSA-N tert-butyl (1r,3s)-3-[[5-[(2-cyclopropyl-1,3-oxazole-4-carbonyl)amino]-2-fluoro-4-[4-(2-methylphenyl)piperazin-1-yl]benzoyl]amino]cyclohexane-1-carboxylate Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=C(F)C=2)C(=O)N[C@@H]2C[C@@H](CCC2)C(=O)OC(C)(C)C)NC(=O)C=2N=C(OC=2)C2CC2)CC1 QFVIEJSGAGMGOY-RPBOFIJWSA-N 0.000 description 1
- QFVIEJSGAGMGOY-LOSJGSFVSA-N tert-butyl (1s,3r)-3-[[5-[(2-cyclopropyl-1,3-oxazole-4-carbonyl)amino]-2-fluoro-4-[4-(2-methylphenyl)piperazin-1-yl]benzoyl]amino]cyclohexane-1-carboxylate Chemical compound CC1=CC=CC=C1N1CCN(C=2C(=CC(=C(F)C=2)C(=O)N[C@H]2C[C@H](CCC2)C(=O)OC(C)(C)C)NC(=O)C=2N=C(OC=2)C2CC2)CC1 QFVIEJSGAGMGOY-LOSJGSFVSA-N 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000011820 transgenic animal model Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- JDLDTRXYGQMDRV-UHFFFAOYSA-N tricesium;borate Chemical compound [Cs+].[Cs+].[Cs+].[O-]B([O-])[O-] JDLDTRXYGQMDRV-UHFFFAOYSA-N 0.000 description 1
- UBOXGVDOUJQMTN-UHFFFAOYSA-N trichloroethylene Natural products ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 1
- 125000000165 tricyclic carbocycle group Chemical group 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
- UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/42—Gynaecological or obstetrical instruments or methods
- A61B17/425—Gynaecological or obstetrical instruments or methods for reproduction or fertilisation
- A61B17/435—Gynaecological or obstetrical instruments or methods for reproduction or fertilisation for embryo or ova transplantation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61D—VETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
- A61D19/00—Instruments or methods for reproduction or fertilisation
- A61D19/02—Instruments or methods for reproduction or fertilisation for artificial insemination
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61D—VETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
- A61D19/00—Instruments or methods for reproduction or fertilisation
- A61D19/04—Instruments or methods for reproduction or fertilisation for embryo transplantation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D405/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Reproductive Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Transplantation (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Surgery (AREA)
- Pregnancy & Childbirth (AREA)
- Gynecology & Obstetrics (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Molecular Biology (AREA)
- Medical Informatics (AREA)
- Biomedical Technology (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Furan Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pyrrole Compounds (AREA)
Abstract
Description
本出願は、2012年1月10日に出願された米国仮特許出願第61/585,077号の優先権の利益を主張し、参照により本明細書に援用する。
W1、W2は、互いに独立してNまたはCHを表し、
但し、W1またはW2の少なくとも1つはNを表し;
R1は、−(CY2)n−E−Het3、−(CY2)n−Cyc−Het3、−(CY2)n−Het1、−(CY2)n−CONH−Het1、−(CY2)n−NHCO−Het1、−(CY2)n−Ar、−(CY2)n−Cyc、−(CY2)n−Cyc−COOY、−(CY2)n−CONH−Cyc、−(CY2)n−NHCO−Cyc、A、−(CYR8)n−OY、−(CY2)n−COOY、−(CY2)n−SO2Y、−(CYR8)n−CONY2、−(CYR8)n−NY2、−(CYR8)n−NYCOY、−(CY2)n−NYCOOY、−(CY2)n−NYCONY2または−(CY2)n−NHCO−CH=CH2を表し:
R1、R2は、また、一緒になって−(CY2)p−NH−(CY2)p−、−(CY2)p−NHCO−(CY2)p−、−(CY2)p−CONH−(CY2)p−、−(CY2)p−N(COA)−(CY2)p−、−(CY2)p−N(COOA)−(CY2)p−、
R3は、−(CY2)n−Het1、−(CY2)n−Het3、−(CY2)n−Ar、H、Aまたは−(CY2)n−Cycを表し;
R4、R9は、互いに独立してYを表し;
R5は、E−Ar、H、A、COOY、SO2Y、Het1またはHet3を表し;
R2、R6、R7は、互いに独立してHを表し;
R6、R7は、また、一緒になって−(CY2)p−を表し;
R8は、YまたはArを表し;
R10は、Hal、Y、OY、−O(CY2)n−OY、NY2、Cyc、COOY、CONH2、NHCOYまたはCNを表し;
但し、R9およびR10が同時にHである場合は除かれ;
R2、R10は、また、一緒になって−(CY2)p−または−(CY)2−を表し;
X、Eは、互いに独立して−(CY2)m−、O、CO、−COO−またはSO2を表し;
YはHまたはAを表し;
Aは、1〜10個のC原子を有する非分岐または分岐アルキルを表し、
ここで1〜7個のH原子は、互いに独立してHalおよび/または=Oに置換されてもよく;
Cycは、3〜7個のC原子を有するシクロアルキルを表し、
ここで1〜4個のH原子は、互いに独立してHal、OHまたはCOOYに置換されてもよく;
Arは、3〜10個のC原子を有する不飽和または芳香族単環式または二環式炭素環を表し、
これは、A、Hal、OY、COOY、CONH2、NHCOY、−(CY2)n−NY2、NO2、SO2Y、CNおよびHet2からなる群より選択される少なくとも1つの置換基により置換されてもよく、あるいは、これは、Cycに縮合していてもよく;
Het1は、1〜10個のC原子ならびに1〜4個のN、Oおよび/またはS原子を有する不飽和または芳香族単環式または二環式複素環を表し、
これは、Hal、A、Cyc、OY、COOY、CONH2、NHCOY、NY2、SO2Y、SO2NY2、NHSO2Y、CNおよびArからなる群より選択される少なくとも1つの置換基により置換されてもよく;
Het2は、1〜3個のC原子ならびに2〜4個のNおよび/またはS原子を有する不飽和単環式5員複素環を表し、
これは、Aにより置換されてもよく;
Het3は、3〜7個のC原子ならびに1〜4個のN、Oおよび/またはS原子を有する飽和単環式または二環式複素環を表し、
これは、=O、A、Hal、−(CY2)n−Cyc、−(CY2)n−OY、COY、COOY、CONY2、NHCOY、NY2、CN、SO2Yおよび−(CY2)n−Arからなる群より選択される少なくとも1つの置換基により置換されてもよく;
HalはF、Cl、BrまたはIを表し;
m、nは、互いに独立して0、1、2、3、4、5または6を表し;そして
pは1、2または3を表す)
の化合物および/またはそれらの生理学的に許容される塩に関する。
R1は、−(CY2)n−E−Het3、−(CY2)n−Cyc−Het3、−(CY2)n−Het1、−(CY2)n−NHCO−Het1、−(CY2)n−Ar、−(CY2)n−Cyc、−(CY2)n−CONH−Cyc、A、−(CYR8)n−OY、−(CY2)n−COOY、−(CYR8)n−NY2、−(CYR8)n−NYCOY、−(CY2)n−NYCOOYまたは−(CY2)n−NHCO−CH=CH2を表し;
R2は、Hを表し;
R3は、Het1、Het3、Ar、H、AまたはCycを表し;
R5は、E−Ar、H、A、COOAまたはHet1を表し;
R8、R9、Yは、互いに独立してHまたはAを表し;
R10は、Hal、Y、OY、−O(CY2)n−OY、NY2またはCycを表し;
但し、R9およびR10が同時にHである場合は除かれ;
R2、R10は、また、一緒になって−(CY2)p−または−(CY)2−を表し;
Eは、−(CY2)m−、CO、−COO−またはSO2を表し;
Aは、1〜10個のC原子を有する非分岐または分岐アルキルを表し、ここで1〜7個のH原子は、互いに独立してHalおよび/または=Oに置換されてもよく;
Cycは、3〜7個のC原子を有するシクロアルキルを表し、ここで1〜4個のH原子は、互いに独立してHal、OHまたはCOOYに置換されてもよく;
Arは、5〜10個のC原子を有する不飽和または芳香族単環式または二環式炭素環を表し、これは、A、Hal、OY、COOY、CONH2、NHCOY、−(CY2)n−NY2、NO2、CNおよびHet2からなる群より選択される少なくとも1つの置換基により置換されてもよく;
Het1は、1〜9個のC原子ならびに1〜4個のN、Oおよび/またはS原子を有する不飽和または芳香族単環式または二環式複素環を表し、これは、Hal、A、Cyc、OY、CONH2、NHCOY、NY2、SO2NY2、NHSO2Y、CNおよびArからなる群より選択される少なくとも1つの置換基により一もしくは二置換されてもよく;
Het2は、イミダゾリル、ピラジル、チアジルまたはテトラジルを表し、これは、メチルにより一置換されてもよく;
Het3は、3〜6個のC原子ならびに1〜3個のN、Oおよび/またはS原子を有する飽和単環式複素環を表し、これは、=O、A、Hal、−(CY2)n−Cyc、−(CY2)n−OY、COY、COOY、CONY2、NHCOY、NY2、CN、SO2Yおよび−(CY2)n−Arからなる群より選択される少なくとも1つの置換基により一、二もしくは三置換されてもよく;
Halは、F、Cl、BrまたはIを表し;
m、nは、互いに独立して0、1、2または3を表し;そして
pは、2または3を表す)
のベンズアミド誘導体および/またはそれらの生理学的に許容される塩が提供される。
R1は、Het3、Het1、ArまたはCycを表し;
R2は、Hを表し;
R5は、ArまたはHet1を表し;
R9は、HまたはCF3を表し;
R10は、Hal、Y、OY、−O(CY2)n−OY、NY2またはCycを表し;
但し、R9およびR10が同時にHを表す場合は除かれ;
R2、R10は、また、一緒になって−(CY2)2−または−(CY)2−を表し;
Yは、HまたはAを表し;
Aは、1〜6個のC原子を有する非分岐または分岐アルキルを表し、ここで1〜4個のH原子は、互いに独立してHalおよび/または=Oに置換されてもよく;
Cycは、3〜6個のC原子を有するシクロアルキルシクロアルキルを表し、ここで1〜3個のH原子は、互いに独立してOHまたはCOOYに置換されてもよく;
Arは、6〜8個のC原子を有する芳香族単環式炭素環を表し、これは、A、Hal、OA、CONH2、−(CY2)n−NY2、NO2およびCNからなる群より選択される少なくとも1つの置換基により一もしくは二置換されてもよく;
Het1は、1〜6個のC原子ならびに1〜4個のN、Oおよび/またはS原子を有する不飽和または芳香族単環式複素環を表し、これは、Hal、A、Cyc、OA、CONH2、NHCOA、NHA、SO2NH2およびCNからなる群より選択される少なくとも1つの置換基により一もしくは二置換されてもよい,あるいは6〜9個のC原子ならびに1〜3個のNおよび/またはS原子を有する芳香族二環式複素環を表し、これは、Aにより一置換されてもよく;
Het3は、3〜6個のC原子ならびに1〜3個のN、Oおよび/またはS原子を有する飽和単環式複素環を表し、これは、=O、A、Cyc、OY、COA、COOA、CONHAおよびSO2Aからなる群より選択される少なくとも1つの置換基により一もしくは二置換されてもよく;
Halは、F、Cl、BrまたはIを表し;そして
nは、0、1、2または3を表す)
のベンズアミド誘導体および/またはそれらの生理学的に許容される塩が提供される。
R1は、Het3またはCycを表し;
R2は、Hを表し;
R10は、Hal、A、OA、−O(CY2)n−OA、NA2またはCycを表し;
R2、R10は、また、一緒になって−(CH2)2−または−(CH)2−を表し;
Yは、HまたはAを表し;
Aは、1〜6個のC原子を有する非分岐または分岐アルキルを表し、ここで1〜4個のH原子は、互いに独立してHalに置換されてもよく;
Cycは、3〜6個のC原子を有するシクロアルキルを表し、ここで1〜3個のH原子は、互いに独立してOHまたはCOOHに置換されてもよく;
Arは、6〜8個のC原子を有する芳香族単環式炭素環を表し、これは、AまたはHalにより一もしくは二置換されてもよく;
Het1は、1〜6個のC原子ならびに1〜3個のN、Oおよび/またはS原子を有する不飽和または芳香族単環式複素環を表し、これは、Cyc、AまたはHalからなる群より選択される少なくとも1つの置換基により一もしくは二置換されてもよく;
Het3は、3〜6個のC原子ならびに1〜3個のN、Oおよび/またはS原子を有する飽和単環式複素環を表し、これは、=O、AまたはHalからなる群より選択される少なくとも1つの置換基により一もしくは二置換されてもよく;
Halは、F、ClまたはBrを表し;そして
nは、0、1、2または3を表す)
のベンズアミド誘導体および/またはそれらの生理学的に許容される塩が提供される。
(a)式(II)
式(III)
式(I)
そして場合により
(b)式(I)の化合物の塩基または酸をその塩に変換する:工程を含む、
式(I)の化合物の製造方法に関する。
R1は、Het3またはArを表し;
R2は、Hを表し;
R10は、Hal、A、OA、−O(CY2)n−OA、NA2またはCycを表し;
R2、R10は、また、一緒になって−(CH2)2−または−(CH)2−を表し;
Yは、HまたはAを表し;
Aは、1〜6個のC原子を有する非分岐または分岐アルキルを表し、ここで1〜4個のH原子は、互いに独立してHalに置換されてもよく;
Cycは、3〜6個のC原子を有するシクロアルキルを表し、ここで1〜3個のH原子は、互いに独立してOHに置換されてもよく;
Arは、6〜8個のC原子を有する芳香族単環式炭素環を表し、これは、A、Halまたは−(CY2)n−NY2により一もしくは二置換されてもよく;
Het3は、3〜6個のC原子ならびに1〜3個のN、Oおよび/またはS原子を有する飽和単環式複素環を表し、これは、=O、AまたはHalからなる群より選択される少なくとも1つの置換基により一もしくは二置換されてもよく;
Halは、F、ClまたはBrを表し;そしてnは、0、1、2または3を表す)
の中間体化合物を提供することである。
(a)式(IV)
式(V)
式(I)
そして場合により
(b)式(I)の化合物の塩基または酸をその塩に変換する:工程を含む、
式(I)の化合物の別の製造方法に関する。
NMRスペクトルは、Automation Triple Broadband(ATB)プローブを備えるVarianUnityInova 400 MHz NMR分光計で得た。ATBプローブは、同時に、1H、19Fおよび13Cに調整した。典型的な1H NMRスペクトルは、パルス角を45度とし、8スキャンを合計し、そしてスペクトル幅を16ppm(−2ppm〜14ppm)とした。合計32768個の複合点を、5.1秒の取得時間中に収集し、待ち時間(recycle delay)を1秒に設定した。スペクトルは25℃で収集した。1H NMRスペクトルは典型的には、フーリエ変換前に0.2Hzの線幅拡大(line broadening)、および131072個の点のゼロ埋め(zero−filling)により処理した。
2500Cho−FSHR−LUC−1−1−43細胞中を、ウェルあたり5μlのフェノールレッド非含有のDMEM/F12+1%FBSを含むプレートに投入した。細胞はマルチドロップを用いて384ウェルの固形で白色の低容量プレート(Greiner784075)に播種した。細胞をマルチドロップを用いて100μlの2×EC20FSH/IBMXをDMEM/F12+0.1%BSAに加え、2μlの検査化合物を384ウェルプレートにスタンプする(化合物は、1:50に希釈)ことによりアッセイした。最終FSH濃度は0.265pMで、最終IBMX濃度は200μMであった。プレートにおける化合物の位置は次の通りであった:カラム1:2μlのDMSO;カラム2:2μlのDMSO;カラム3〜12および13〜24:2μlの検査化合物、100%DMSOで1:4に希釈、または2μlのFSH、DMEM/F12+0.1%BSAで1:4に希釈。FSHの出発濃度は50nMであった(最終濃度は0.5nM)。さらに、カラム23は、最終濃度が0.5nMの2μlのEC100FSH標準液(100×)(DMEM/F12+0.1%BSAで希釈)を含み、カラム24は、2μlの1mM AS707664/2標準化合物を含み、2.5μlの化合物+EC20FSH混合物を細胞プレートに移した(5μlの細胞培地で1:2に希釈)。プレートは37℃で1時間インキュベートした。ウェルあたり10μlの混合HTRF(CisBio#62AM4PEC)試薬を加え、室温で1時間インキュベートした。プレートは、cAMP HTRF−低用量384ウェルプロトコルを用いてEnvision上で読み取った。読み取り値を、蛍光比(665nm/620nm)で算出した。パーセント(%)で示した値は、ある濃度におけるアゴニストの標準FSHの最大応答に対する効果(応答)の百分率を示す。結果を表1に示す。
このアッセイは、参照により本発明の開示に援用するYanofsky et al.(2006)Allosteric activation of the follicle−stimulating hormone(FSH)receptor by selective,nonpeptide agonits.JBC 281(19):13226−13233の教示に従って実施した。結果を表1に示す。
(A)注射バイアル:100gの本発明に係る活性成分および5gのリン酸水素二ナトリウムを3lの再蒸留水に含む溶液を、2N塩酸を用いてpH6.5に調整し、滅菌ろ過して、注射バイアルに移し、滅菌条件下で凍結乾燥し、そして滅菌条件下で密封した。各注射バイアルは、5mgの活性成分を含有していた。
Claims (15)
- 式(I)
W1、W2は、互いに独立してNまたはCHを表し、
但し、W1またはW2の少なくとも1つはNを表し;
R1は、−(CY2)n−E−Het3、−(CY2)n−Cyc−Het3、−(CY2)n−Het1、−(CY2)n−CONH−Het1、−(CY2)n−NHCO−Het1、−(CY2)n−Ar、−(CY2)n−Cyc、−(CY2)n−CONH−Cyc、−(CY2)n−NHCO−Cyc、A、−(CYR8)n−OY、−(CY2)n−COOY、−(CY2)n−SO2Y、−(CYR8)n−CONY2、−(CYR8)n−NY2、−(CYR8)n−NYCOY、−(CY2)n−NYCOOY、−(CY2)n−NYCONY2または−(CY2)n−NHCO−CH=CH2を表し;
R1、R2は、また、一緒になって−(CY2)p−NH−(CY2)p−、−(CY2)p−NHCO−(CY2)p−、−(CY2)p−CONH−(CY2)p−、−(CY2)p−N(COA)−(CY2)p−、−(CY2)p−N(COOA)−(CY2)p−、
R3は、−(CY2)n−Het1、−(CY2)n−Het3、−(CY2)n−Ar、H、Aまたは−(CY2)n−Cycを表し;
R4、R9は、互いに独立してYを表し;
R5は、E−Ar、H、A、COOY、SO2Y、Het1またはHet3を表し;
R2、R6、R7は、互いに独立してHを表し;
R6、R7は、また、一緒になって−(CY2)p−を表し;
R8は、YまたはArを表し;
R10は、Hal、Y、OY、−O(CY2)n−OY、NY2、Cyc、COOY、CONH2、NHCOYまたはCNを表し;
但し、R9およびR10が同時にHを表す場合は除かれ;
R2、R10は、また、一緒になって−(CY2)p−または−(CY)2−を表し;
X、Eは、互いに独立して−(CY2)m−、O、CO、−COO−またはSO2を表し;
Yは、HまたはAを表し;
Aは、1〜10個のC原子を有する非分岐または分岐アルキルを表し、
ここで1〜7個のH原子は、互いに独立してHalおよび/または=Oに置換されてもよく;
Cycは、3〜7個のC原子を有するシクロアルキルを表し、
ここで1〜4個のH原子は、互いに独立してHal、OHまたはCOOYに置換されてもよく;
Arは、3〜10個のC原子を有する不飽和または芳香族単環式または二環式炭素環を表し、
これは、A、Hal、OY、COOY、CONH2、NHCOY、−(CY2)n−NY2、NO2、SO2Y、CNおよびHet2からなる群より選択される少なくとも1つの置換基により置換されてもよく、あるいは、これは、Cycに縮合していてもよく;
Het1は、1〜10個のC原子ならびに1〜4個のN、Oおよび/またはS原子を有する不飽和または芳香族単環式または二環式複素環を表し、
これは、Hal、A、Cyc、OY、COOY、CONH2、NHCOY、NY2、SO2Y、SO2NY2、NHSO2Y、CNおよびArからなる群より選択される少なくとも1つの置換基により置換されてもよく;
Het2は、1〜3個のC原子ならびに2〜4個のNおよび/またはS原子を有する不飽和単環式5員複素環を表し、
これは、Aにより置換されてもよく;
Het3は、3〜7個のC原子ならびに1〜4個のN、Oおよび/またはS原子を有する飽和単環式または二環式複素環を表し、
これは、=O、A、Hal、−(CY2)n−Cyc、−(CY2)n−OY、COY、COOY、CONY2、NHCOY、NY2、CN、SO2Yおよび−(CY2)n−Arからなる群より選択される少なくとも1つの置換基により置換されてもよく;
HalはF、Cl、BrまたはIを表し;
m、nは、互いに独立して0、1、2、3、4、5または6を表し;そして
pは1、2または3を表す)
の化合物および/またはそれらの生理学的に許容される塩。 - W1、W2は、Nを表し;
R6、R7は、一緒になって−(CY2)p−を表し;そして
pは、2を表す、請求項1に記載の化合物。 - Xは、COを表す、請求項1または2に記載の化合物。
- R9は、Hを表し;そして
R10は、Hal、A、OY、−O(CY2)n−OY、NY2またはCycを表し;あるいは
R2、R10は、また、一緒になって−(CY2)2−または−(CY)2−を表す、請求項1〜3のいずれか1項に記載の化合物。 - サブ式(I−B)
R1は、Het3、Het1、ArまたはCycを表し;
R2は、Hを表し;
R5は、ArまたはHet1を表し;
R9は、HまたはCF3を表し;
R10は、Hal、Y、OY、−O(CY2)n−OY、NY2またはCycを表し;
但し、R9およびR10が同時にHを表す場合は除かれ;
R2、R10は、また、一緒になって−(CY2)2−または−(CY)2−を表し;
Yは、HまたはAを表し;
Aは、1〜6個のC原子を有する非分岐または分岐アルキルを表し、ここで1〜4個のH原子は、互いに独立してHalおよび/または=Oに置換されてもよく;
Cycは、3〜6個のC原子を有するシクロアルキルを表し、ここで1〜3個のH原子は、互いに独立してOHまたはCOOYに置換されてもよく;
Arは、6〜8個のC原子を有する芳香族単環式炭素環を表し、これは、A、Hal、OA、CONH2、−(CY2)n−NY2、NO2およびCNからなる群より選択される少なくとも1つの置換基により一もしくは二置換されてもよく;
Het1は、1〜6個のC原子ならびに1〜4個のN、Oおよび/またはS原子を有する不飽和または芳香族単環式複素環を表し、これは、Hal、A、Cyc、OA、CONH2、NHCOA、NHA、SO2NH2およびCNからなる群より選択される少なくとも1つの置換基により一もしくは二置換されてもよく、あるいは6〜9個のC原子ならびに1〜3個のNおよび/またはS原子を有する芳香族二環式複素環を表し、これは、Aにより一置換されてもよく;
Het3は、3〜6個のC原子ならびに1〜3個のN、Oおよび/またはS原子を有する飽和単環式複素環を表し、これは、=O、A、Cyc、OY、COA、COOA、CONHAおよびSO2Aからなる群より選択される少なくとも1つの置換基により一もしくは二置換されてもよく;
Halは、F、Cl、BrまたはIを表し;そして
nは、0、1、2または3を表す)
を有する、請求項1〜3のいずれか1項に記載の化合物および/またはそれらの生理学的に許容される塩。 - サブ式(I−C)
R1は、Het3またはCycを表し;
R2は、Hを表し;
R10は、Hal、A、OA、−O(CY2)n−OA、NA2またはCycを表し;
R2、R10は、また、一緒になって−(CH2)2−または−(CH)2−を表し;
Yは、HまたはAを表し;
Aは、1〜6個のC原子を有する非分岐または分岐アルキルを表し、ここで1〜4個のH原子は、互いに独立してHalに置換されてもよく;
Cycは、3〜6個のC原子を有するシクロアルキル、ここで1〜3個のH原子は、互いに独立してOHまたはCOOHに置換されてもよく;
Arは、6〜8個のC原子を有する芳香族単環式炭素環を表し、これは、AまたはHalに一もしくは二置換されてもよく;
Het1は、1〜6個のC原子ならびに1〜3個のN、Oおよび/またはS原子を有する不飽和または芳香族単環式複素環を表し、これは、Cyc、AまたはHalからなる群より選択される少なくとも1つの置換基により一もしくは二置換されてもよく;
Het3は、3〜6個のC原子ならびに1〜3個のN、Oおよび/またはS原子を有する飽和単環式複素環を表し、これは、=O、AまたはHalからなる群より選択される少なくとも1つの置換基により一もしくは二置換されてもよく;
Halは、F、ClまたはBrを表し;そして
nは、0、1、2または3を表す)
を有する、請求項1〜5のいずれか1項に記載の化合物および/またはそれらの生理学的に許容される塩。 - 式(II−A)
R1は、Het3またはArを表し;
R2は、Hを表し;
R10は、Hal、A、OA、−O(CY2)n−OA、NA2またはCycを表し;
R2、R10 は、また、一緒になって−(CH2)2−または−(CH)2−を表し;
Yは、HまたはAを表し;
Aは、1〜6個のC原子を有する非分岐または分岐アルキルを表し、ここで1〜4個のH原子は、互いに独立してHalに置換されてもよく;
Cycは、3〜6個のC原子を有するシクロアルキル、ここで1〜3個のH原子は、互いに独立してOHに置換されてもよく;
Arは、6〜8個のC原子を有する芳香族単環式炭素環を表し、これは、A、Halまたは−(CY2)n−NY2に一もしくは二置換されてもよく;
Het3は、3〜6個のC原子ならびに1〜3個のN、Oおよび/またはS原子を有する飽和単環式複素環を表し、これは、=O、AまたはHalからなる群より選択される少なくとも1つの置換基により一もしくは二置換されてもよく;
Halは、F、ClまたはBrを表し;そして
nは、0、1、2または3を表す)
の化合物の中間体。 - 請求項1〜7のいずれか1項に記載の化合物および/またはそれらの生理学的に許容される塩の少なくとも1つを含む薬剤。
- 活性成分として請求項1〜7のいずれか1項に記載の化合物および/またはそれらの生理学的に許容される塩の少なくとも1つを、経口投与用の医薬的に許容される補助剤とともに、場合により少なくとも1つの別の活性医薬成分と組み合わせて含有する医薬組成物。
- 受精障害の予防的または治療的処置および/またはモニタリングに使用するための、請求項1〜7のいずれか1項に記載の化合物および/またはそれらの生理学的に許容される塩。
- 受精障害を治療する方法であって、請求項1〜7のいずれか1項に記載の化合物および/またはそれらの生理学的に許容される塩の少なくとも1つをかかる治療が必要な哺乳動物に投与する、受精障害を治療する方法。
- (a)請求項13に記載の方法に従って哺乳動物を治療する、
(b)前記哺乳動物から卵子を回収する、
(c)前記卵子を受精させる、および
(d)前記受精卵を宿主哺乳動物に移植する:工程を含む体外受精方法。 - FSH受容体を発現する系を、FSHの存在下で、請求項1〜7のいずれか1項に記載の化合物および/またはそれらの生理学的に許容される塩の少なくとも1つと、当該FSH受容体を調節するような条件で接触させる、FSH受容体を調節する方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201261585077P | 2012-01-10 | 2012-01-10 | |
US61/585,077 | 2012-01-10 | ||
PCT/US2013/020802 WO2013106409A1 (en) | 2012-01-10 | 2013-01-09 | Benzamide derivatives as modulators of the follicle stimulating hormone |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2015503615A true JP2015503615A (ja) | 2015-02-02 |
JP6219844B2 JP6219844B2 (ja) | 2017-10-25 |
Family
ID=47595088
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014552261A Expired - Fee Related JP6219844B2 (ja) | 2012-01-10 | 2013-01-09 | 卵胞刺激ホルモンの調節因子としてのベンズアミド誘導体 |
Country Status (10)
Country | Link |
---|---|
US (3) | US9409897B2 (ja) |
EP (2) | EP3327017B1 (ja) |
JP (1) | JP6219844B2 (ja) |
CN (1) | CN104080784B (ja) |
AU (1) | AU2013208082B2 (ja) |
CA (1) | CA2860808A1 (ja) |
ES (2) | ES2738600T3 (ja) |
HK (1) | HK1201826A1 (ja) |
IL (1) | IL233602A (ja) |
WO (1) | WO2013106409A1 (ja) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6162694B2 (ja) * | 2011-07-18 | 2017-07-12 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングMerck Patent Gesellschaft mit beschraenkter Haftung | ベンズアミド類 |
CN104080784B (zh) * | 2012-01-10 | 2017-07-18 | 默克专利有限公司 | 用作卵泡刺激素调节剂的苯甲酰胺衍生物 |
WO2015196335A1 (en) | 2014-06-23 | 2015-12-30 | Tocopherx, Inc. | Pyrazole compounds as modulators of fshr and uses thereof |
CN106177912B (zh) * | 2016-07-18 | 2019-06-18 | 暨南大学 | Ctrp3蛋白的应用 |
US11856264B2 (en) | 2016-11-15 | 2023-12-26 | Google Llc | Systems and methods for reducing download requirements |
US10513515B2 (en) | 2017-08-25 | 2019-12-24 | Biotheryx, Inc. | Ether compounds and uses thereof |
AU2019309894A1 (en) | 2018-07-27 | 2021-01-28 | Biotheryx, Inc. | Bifunctional compounds as CDK modulators |
US11034669B2 (en) | 2018-11-30 | 2021-06-15 | Nuvation Bio Inc. | Pyrrole and pyrazole compounds and methods of use thereof |
US11897930B2 (en) | 2020-04-28 | 2024-02-13 | Anwita Biosciences, Inc. | Interleukin-2 polypeptides and fusion proteins thereof, and their pharmaceutical compositions and therapeutic applications |
KR20240035820A (ko) | 2021-07-09 | 2024-03-18 | 플렉시움 인코포레이티드 | Ikzf2를 조절하는 아릴 화합물 및 약학 조성물 |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002522433A (ja) * | 1998-08-07 | 2002-07-23 | アプライド リサーチ システムズ エーアールエス ホールディング ナームロゼ フェンノートシャップ | 不妊症の治療のためのfsh模倣物 |
JP2003519676A (ja) * | 2000-01-13 | 2003-06-24 | トゥラリック インコーポレイテッド | 抗菌剤 |
WO2007037187A1 (ja) * | 2005-09-27 | 2007-04-05 | Shionogi & Co., Ltd. | Pgd2受容体アンタゴニスト活性を有するスルホンアミド誘導体 |
JP2010524848A (ja) * | 2007-03-23 | 2010-07-22 | アデックス ファーマ ソシエテ アノニム | 濾胞刺激ホルモンのモジュレーターとしての新規ベンズアミド誘導体 |
WO2011014681A1 (en) * | 2009-07-30 | 2011-02-03 | Takeda Pharmaceutical Company Limited | Poly (ADP-Ribose) Polymerase (PARP) INHIBITORS |
JP2011512412A (ja) * | 2008-02-19 | 2011-04-21 | サノフィ−アベンティス | ケモカイン受容体CxCR3の阻害剤 |
JP2014520886A (ja) * | 2011-07-18 | 2014-08-25 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | ベンズアミド類 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002009706A1 (en) * | 2000-07-27 | 2002-02-07 | Smithkline Beecham Corporation | Agonists of follicle stimulating hormone activity |
TWI461426B (zh) | 2009-05-27 | 2014-11-21 | Merck Sharp & Dohme | (二氫)咪唑並異〔5,1-a〕喹啉類 |
CN104080784B (zh) * | 2012-01-10 | 2017-07-18 | 默克专利有限公司 | 用作卵泡刺激素调节剂的苯甲酰胺衍生物 |
-
2013
- 2013-01-09 CN CN201380005089.4A patent/CN104080784B/zh not_active Expired - Fee Related
- 2013-01-09 JP JP2014552261A patent/JP6219844B2/ja not_active Expired - Fee Related
- 2013-01-09 US US14/364,193 patent/US9409897B2/en active Active
- 2013-01-09 ES ES17209280T patent/ES2738600T3/es active Active
- 2013-01-09 ES ES13700819.9T patent/ES2663972T3/es active Active
- 2013-01-09 EP EP17209280.1A patent/EP3327017B1/en active Active
- 2013-01-09 EP EP13700819.9A patent/EP2802575B1/en not_active Not-in-force
- 2013-01-09 AU AU2013208082A patent/AU2013208082B2/en not_active Ceased
- 2013-01-09 CA CA2860808A patent/CA2860808A1/en not_active Abandoned
- 2013-01-09 WO PCT/US2013/020802 patent/WO2013106409A1/en active Application Filing
-
2014
- 2014-07-10 IL IL233602A patent/IL233602A/en active IP Right Grant
-
2015
- 2015-03-04 HK HK15102218.5A patent/HK1201826A1/xx not_active IP Right Cessation
- 2015-11-18 US US14/944,324 patent/US20160137632A1/en not_active Abandoned
-
2017
- 2017-04-26 US US15/497,612 patent/US10183935B2/en not_active Expired - Fee Related
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002522433A (ja) * | 1998-08-07 | 2002-07-23 | アプライド リサーチ システムズ エーアールエス ホールディング ナームロゼ フェンノートシャップ | 不妊症の治療のためのfsh模倣物 |
JP2003519676A (ja) * | 2000-01-13 | 2003-06-24 | トゥラリック インコーポレイテッド | 抗菌剤 |
WO2007037187A1 (ja) * | 2005-09-27 | 2007-04-05 | Shionogi & Co., Ltd. | Pgd2受容体アンタゴニスト活性を有するスルホンアミド誘導体 |
JP2010524848A (ja) * | 2007-03-23 | 2010-07-22 | アデックス ファーマ ソシエテ アノニム | 濾胞刺激ホルモンのモジュレーターとしての新規ベンズアミド誘導体 |
JP2011512412A (ja) * | 2008-02-19 | 2011-04-21 | サノフィ−アベンティス | ケモカイン受容体CxCR3の阻害剤 |
WO2011014681A1 (en) * | 2009-07-30 | 2011-02-03 | Takeda Pharmaceutical Company Limited | Poly (ADP-Ribose) Polymerase (PARP) INHIBITORS |
JP2013500989A (ja) * | 2009-07-30 | 2013-01-10 | 武田薬品工業株式会社 | ポリ(adp−リボース)ポリメラーゼ(parp)阻害剤 |
JP2014520886A (ja) * | 2011-07-18 | 2014-08-25 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | ベンズアミド類 |
Non-Patent Citations (2)
Title |
---|
AFANTITIS A. ET AL., EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 44, no. 2, JPN6017000340, 2009, pages 877 - 84, ISSN: 0003626936 * |
REGISTRY(STN)[ONLINE], JPN6017000339, pages 1349020 - 13, ISSN: 0003626935 * |
Also Published As
Publication number | Publication date |
---|---|
WO2013106409A1 (en) | 2013-07-18 |
CA2860808A1 (en) | 2013-07-18 |
AU2013208082A1 (en) | 2014-07-03 |
CN104080784A (zh) | 2014-10-01 |
EP2802575A1 (en) | 2014-11-19 |
AU2013208082B2 (en) | 2017-07-20 |
EP3327017A1 (en) | 2018-05-30 |
US20150011562A1 (en) | 2015-01-08 |
ES2663972T3 (es) | 2018-04-17 |
EP3327017B1 (en) | 2019-04-24 |
CN104080784B (zh) | 2017-07-18 |
IL233602A (en) | 2016-04-21 |
US10183935B2 (en) | 2019-01-22 |
EP2802575B1 (en) | 2017-12-27 |
US9409897B2 (en) | 2016-08-09 |
IL233602A0 (en) | 2014-08-31 |
US20160137632A1 (en) | 2016-05-19 |
US20170226096A1 (en) | 2017-08-10 |
JP6219844B2 (ja) | 2017-10-25 |
ES2738600T3 (es) | 2020-01-24 |
HK1201826A1 (en) | 2015-09-11 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6219844B2 (ja) | 卵胞刺激ホルモンの調節因子としてのベンズアミド誘導体 | |
JP6254730B2 (ja) | ベンズアミド類 | |
EP3630748B1 (en) | Ire1 small molecule inhibitors | |
US10208055B2 (en) | Pyrazole compounds as modulators of FSHR and uses thereof | |
JP6438079B2 (ja) | ジヒドロピラゾール | |
AU2014302710B2 (en) | Imidazole compounds as modulators of FSHR and uses thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20151008 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20160502 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160510 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160809 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20170117 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170417 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20170627 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170720 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170814 |
|
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: 20170829 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20170928 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6219844 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
LAPS | Cancellation because of no payment of annual fees |