SK77498A3 - Nonpeptide derivatives, pharmaceutical composition containing them and their use - Google Patents
Nonpeptide derivatives, pharmaceutical composition containing them and their use Download PDFInfo
- Publication number
- SK77498A3 SK77498A3 SK774-98A SK77498A SK77498A3 SK 77498 A3 SK77498 A3 SK 77498A3 SK 77498 A SK77498 A SK 77498A SK 77498 A3 SK77498 A3 SK 77498A3
- Authority
- SK
- Slovakia
- Prior art keywords
- substituted
- alkyl
- aryl
- piperazine
- ethyl
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 177
- 150000003839 salts Chemical class 0.000 claims abstract description 24
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 claims abstract description 13
- 239000003163 gonadal steroid hormone Substances 0.000 claims abstract description 12
- -1 C (O) OR 11 Chemical group 0.000 claims description 134
- 239000000203 mixture Substances 0.000 claims description 117
- 229910052739 hydrogen Inorganic materials 0.000 claims description 47
- 239000001257 hydrogen Substances 0.000 claims description 45
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 40
- 125000003118 aryl group Chemical group 0.000 claims description 39
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 36
- 125000003107 substituted aryl group Chemical group 0.000 claims description 33
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 28
- 125000000623 heterocyclic group Chemical group 0.000 claims description 26
- 125000005842 heteroatom Chemical group 0.000 claims description 21
- 125000004429 atom Chemical group 0.000 claims description 19
- 229910052760 oxygen Inorganic materials 0.000 claims description 17
- 229910052717 sulfur Inorganic materials 0.000 claims description 17
- 125000002837 carbocyclic group Chemical group 0.000 claims description 16
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 claims description 14
- 102000018997 Growth Hormone Human genes 0.000 claims description 14
- 108010051696 Growth Hormone Proteins 0.000 claims description 14
- 239000000122 growth hormone Substances 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 230000003287 optical effect Effects 0.000 claims description 13
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 13
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 12
- 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 claims description 12
- 229940035638 gonadotropin-releasing hormone Drugs 0.000 claims description 12
- 239000000126 substance Substances 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 10
- 206010046798 Uterine leiomyoma Diseases 0.000 claims description 9
- 201000010260 leiomyoma Diseases 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 230000001419 dependent effect Effects 0.000 claims description 8
- 150000004677 hydrates Chemical class 0.000 claims description 8
- 230000001817 pituitary effect Effects 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 229920001774 Perfluoroether Polymers 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 6
- 210000002307 prostate Anatomy 0.000 claims description 6
- 201000009273 Endometriosis Diseases 0.000 claims description 5
- 208000035475 disorder Diseases 0.000 claims description 5
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 4
- 125000002619 bicyclic group Chemical group 0.000 claims description 4
- 230000001456 gonadotroph Effects 0.000 claims description 4
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 201000010065 polycystic ovary syndrome Diseases 0.000 claims description 4
- 230000002028 premature Effects 0.000 claims description 4
- 206010020880 Hypertrophy Diseases 0.000 claims description 3
- 206010036618 Premenstrual syndrome Diseases 0.000 claims description 3
- 206010038669 Respiratory arrest Diseases 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 3
- 206010025135 lupus erythematosus Diseases 0.000 claims description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- 208000003200 Adenoma Diseases 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- 230000035935 pregnancy Effects 0.000 claims description 2
- 208000019116 sleep disease Diseases 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 206010001233 Adenoma benign Diseases 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 1
- 208000010579 uterine corpus leiomyoma Diseases 0.000 claims 1
- 201000007954 uterine fibroid Diseases 0.000 claims 1
- 239000005557 antagonist Substances 0.000 abstract description 5
- NMJREATYWWNIKX-UHFFFAOYSA-N GnRH Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CC(C)C)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 NMJREATYWWNIKX-UHFFFAOYSA-N 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 342
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 258
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 225
- 239000000243 solution Substances 0.000 description 202
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 110
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 86
- 239000011541 reaction mixture Substances 0.000 description 73
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 72
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 70
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 69
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 63
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 56
- 238000006243 chemical reaction Methods 0.000 description 54
- 229910052757 nitrogen Inorganic materials 0.000 description 54
- 239000000741 silica gel Substances 0.000 description 52
- 229910002027 silica gel Inorganic materials 0.000 description 52
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 51
- 238000000034 method Methods 0.000 description 50
- 238000003818 flash chromatography Methods 0.000 description 45
- 238000001819 mass spectrum Methods 0.000 description 41
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 38
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 38
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 36
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
- 238000004809 thin layer chromatography Methods 0.000 description 35
- 239000000047 product Substances 0.000 description 34
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 33
- 229920006395 saturated elastomer Polymers 0.000 description 31
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 30
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 29
- 239000003921 oil Substances 0.000 description 28
- 235000019198 oils Nutrition 0.000 description 28
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 25
- PMZURENOXWZQFD-UHFFFAOYSA-L sodium sulphate Substances [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
- 229910052938 sodium sulfate Inorganic materials 0.000 description 23
- 235000011152 sodium sulphate Nutrition 0.000 description 23
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 21
- 239000000460 chlorine Substances 0.000 description 21
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 20
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 19
- 239000000908 ammonium hydroxide Substances 0.000 description 19
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
- 239000007787 solid Substances 0.000 description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 17
- 239000002253 acid Substances 0.000 description 17
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 17
- 235000019341 magnesium sulphate Nutrition 0.000 description 17
- 239000003960 organic solvent Substances 0.000 description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 17
- 239000000725 suspension Substances 0.000 description 16
- 239000000706 filtrate Substances 0.000 description 15
- 238000010992 reflux Methods 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- 239000004480 active ingredient Substances 0.000 description 14
- 239000011780 sodium chloride Substances 0.000 description 14
- 239000000463 material Substances 0.000 description 13
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 13
- 239000002585 base Substances 0.000 description 12
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 12
- 238000001914 filtration Methods 0.000 description 12
- 229940121381 gonadotrophin releasing hormone (gnrh) antagonists Drugs 0.000 description 12
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 12
- XAVHSCJGBMICAM-UHFFFAOYSA-N n-[4-(4-oxobutyl)phenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=C(CCCC=O)C=C1 XAVHSCJGBMICAM-UHFFFAOYSA-N 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
- 238000010521 absorption reaction Methods 0.000 description 11
- 150000001412 amines Chemical class 0.000 description 11
- 239000003054 catalyst Substances 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 11
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 102000009151 Luteinizing Hormone Human genes 0.000 description 9
- 108010073521 Luteinizing Hormone Proteins 0.000 description 9
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 229960000583 acetic acid Drugs 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- 239000003112 inhibitor Substances 0.000 description 9
- 229940040129 luteinizing hormone Drugs 0.000 description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 8
- 108010066551 Cholestenone 5 alpha-Reductase Proteins 0.000 description 8
- 206010056438 Growth hormone deficiency Diseases 0.000 description 8
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 8
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 238000012746 preparative thin layer chromatography Methods 0.000 description 8
- 239000008259 solid foam Substances 0.000 description 8
- 229940122361 Bisphosphonate Drugs 0.000 description 7
- 235000019270 ammonium chloride Nutrition 0.000 description 7
- 150000004663 bisphosphonates Chemical class 0.000 description 7
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
- JHFAEUICJHBVHB-UHFFFAOYSA-N 1h-indol-2-ol Chemical compound C1=CC=C2NC(O)=CC2=C1 JHFAEUICJHBVHB-UHFFFAOYSA-N 0.000 description 6
- YHYICNMHQHRSAN-UHFFFAOYSA-N 2-[2-(1h-indol-3-yl)ethylamino]isoindole-1,3-dione Chemical class O=C1C2=CC=CC=C2C(=O)N1NCCC1=CNC2=CC=CC=C12 YHYICNMHQHRSAN-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 206010065687 Bone loss Diseases 0.000 description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 229910000085 borane Inorganic materials 0.000 description 6
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 239000000796 flavoring agent Substances 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 6
- 239000012442 inert solvent Substances 0.000 description 6
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 239000003765 sweetening agent Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 6
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- WZEAFDRGKYFRED-UHFFFAOYSA-N 4-chloro-1-(3,5-dimethylphenyl)butan-1-one Chemical compound CC1=CC(C)=CC(C(=O)CCCCl)=C1 WZEAFDRGKYFRED-UHFFFAOYSA-N 0.000 description 5
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 5
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
- 206010062767 Hypophysitis Diseases 0.000 description 5
- 239000005909 Kieselgur Substances 0.000 description 5
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 5
- 239000003098 androgen Substances 0.000 description 5
- 229940030486 androgens Drugs 0.000 description 5
- 239000011575 calcium Substances 0.000 description 5
- 229910052791 calcium Inorganic materials 0.000 description 5
- 235000003599 food sweetener Nutrition 0.000 description 5
- 229910052763 palladium Inorganic materials 0.000 description 5
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 210000003635 pituitary gland Anatomy 0.000 description 5
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-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
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 4
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 4
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 4
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
- 239000007900 aqueous suspension Substances 0.000 description 4
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 4
- 239000003086 colorant Substances 0.000 description 4
- 239000007859 condensation product Substances 0.000 description 4
- 229940124558 contraceptive agent Drugs 0.000 description 4
- 239000003433 contraceptive agent Substances 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 125000004494 ethyl ester group Chemical group 0.000 description 4
- 239000012065 filter cake Substances 0.000 description 4
- 229940028334 follicle stimulating hormone Drugs 0.000 description 4
- 235000013355 food flavoring agent Nutrition 0.000 description 4
- 239000003324 growth hormone secretagogue Substances 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 239000002480 mineral oil Substances 0.000 description 4
- 235000010446 mineral oil Nutrition 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 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
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 4
- 239000001119 stannous chloride Substances 0.000 description 4
- 235000011150 stannous chloride Nutrition 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 239000000375 suspending agent Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 150000003512 tertiary amines Chemical class 0.000 description 4
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 4
- 239000000080 wetting agent Substances 0.000 description 4
- NSPYRFXQDUFQOM-UHFFFAOYSA-N 1-ethylimidazolidin-2-one Chemical compound CCN1CCNC1=O NSPYRFXQDUFQOM-UHFFFAOYSA-N 0.000 description 3
- IHWDSEPNZDYMNF-UHFFFAOYSA-N 1H-indol-2-amine Chemical class C1=CC=C2NC(N)=CC2=C1 IHWDSEPNZDYMNF-UHFFFAOYSA-N 0.000 description 3
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 3
- HAVZBHRYAVZGCM-UHFFFAOYSA-N 2-[2-(3,5-dimethylphenyl)-3-[2-[4-[4-(methanesulfonamido)phenyl]butyl-phenylmethoxycarbonylamino]ethyl]-1h-indol-5-yl]-2-methylpropanoic acid Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(=CC=C3N2)C(C)(C)C(O)=O)CCN(CCCCC=2C=CC(NS(C)(=O)=O)=CC=2)C(=O)OCC=2C=CC=CC=2)=C1 HAVZBHRYAVZGCM-UHFFFAOYSA-N 0.000 description 3
- DUGMCDWNXXFHDE-VZYDHVRKSA-N 2-amino-2-methyl-n-[(2r)-1-(1-methylsulfonylspiro[2h-indole-3,4'-piperidine]-1'-yl)-1-oxo-3-phenylmethoxypropan-2-yl]propanamide;methanesulfonic acid Chemical compound CS(O)(=O)=O.C([C@@H](NC(=O)C(C)(N)C)C(=O)N1CCC2(C3=CC=CC=C3N(C2)S(C)(=O)=O)CC1)OCC1=CC=CC=C1 DUGMCDWNXXFHDE-VZYDHVRKSA-N 0.000 description 3
- JTNCEQNHURODLX-UHFFFAOYSA-N 2-phenylethanimidamide Chemical compound NC(=N)CC1=CC=CC=C1 JTNCEQNHURODLX-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102000008238 LHRH Receptors Human genes 0.000 description 3
- 108010021290 LHRH Receptors Proteins 0.000 description 3
- LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- DRHKJLXJIQTDTD-OAHLLOKOSA-N Tamsulosine Chemical compound CCOC1=CC=CC=C1OCCN[C@H](C)CC1=CC=C(OC)C(S(N)(=O)=O)=C1 DRHKJLXJIQTDTD-OAHLLOKOSA-N 0.000 description 3
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 229960004343 alendronic acid Drugs 0.000 description 3
- WNMJYKCGWZFFKR-UHFFFAOYSA-N alfuzosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(C)CCCNC(=O)C1CCCO1 WNMJYKCGWZFFKR-UHFFFAOYSA-N 0.000 description 3
- 229960004607 alfuzosin Drugs 0.000 description 3
- 230000002280 anti-androgenic effect Effects 0.000 description 3
- 239000000051 antiandrogen Substances 0.000 description 3
- 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 229940097647 casodex Drugs 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 229960000978 cyproterone acetate Drugs 0.000 description 3
- UWFYSQMTEOIJJG-FDTZYFLXSA-N cyproterone acetate Chemical compound C1=C(Cl)C2=CC(=O)[C@@H]3C[C@@H]3[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 UWFYSQMTEOIJJG-FDTZYFLXSA-N 0.000 description 3
- 229960002887 deanol Drugs 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
- AFABGHUZZDYHJO-UHFFFAOYSA-N dimethyl butane Natural products CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 3
- 239000012972 dimethylethanolamine Substances 0.000 description 3
- 239000002270 dispersing agent Substances 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- RUZYUOTYCVRMRZ-UHFFFAOYSA-N doxazosin Chemical compound C1OC2=CC=CC=C2OC1C(=O)N(CC1)CCN1C1=NC(N)=C(C=C(C(OC)=C2)OC)C2=N1 RUZYUOTYCVRMRZ-UHFFFAOYSA-N 0.000 description 3
- 229960001389 doxazosin Drugs 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 229940011871 estrogen Drugs 0.000 description 3
- 239000000262 estrogen Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 description 3
- 229960004039 finasteride Drugs 0.000 description 3
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 3
- 229960002074 flutamide Drugs 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 150000002475 indoles Chemical class 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229940057995 liquid paraffin Drugs 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 3
- SCNLVTKLRJMOPM-UHFFFAOYSA-N n-[4-[4-[2-[5-amino-2-(3,5-dimethylphenyl)-1h-indol-3-yl]ethyl-benzylamino]butyl]phenyl]methanesulfonamide Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(N)=CC=C3N2)CCN(CCCCC=2C=CC(NS(C)(=O)=O)=CC=2)CC=2C=CC=CC=2)=C1 SCNLVTKLRJMOPM-UHFFFAOYSA-N 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 239000004006 olive oil Substances 0.000 description 3
- 235000008390 olive oil Nutrition 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 3
- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 3
- 229960001289 prazosin Drugs 0.000 description 3
- 239000000186 progesterone Substances 0.000 description 3
- 150000003146 progesterones Chemical class 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 150000003335 secondary amines Chemical class 0.000 description 3
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000001476 sodium potassium tartrate Substances 0.000 description 3
- 239000012453 solvate Substances 0.000 description 3
- 125000000547 substituted alkyl group Chemical group 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 229960002613 tamsulosin Drugs 0.000 description 3
- VCKUSRYTPJJLNI-UHFFFAOYSA-N terazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1CCCO1 VCKUSRYTPJJLNI-UHFFFAOYSA-N 0.000 description 3
- 229960001693 terazosin Drugs 0.000 description 3
- WHLCBXPNLXLAGQ-UHFFFAOYSA-N tert-butyl n-[2-[2-(3,5-dimethylphenyl)-5-nitro-1h-indol-3-yl]ethyl]-n-[4-[4-(methanesulfonamido)phenyl]butyl]carbamate Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(=CC=C3N2)[N+]([O-])=O)CCN(CCCCC=2C=CC(NS(C)(=O)=O)=CC=2)C(=O)OC(C)(C)C)=C1 WHLCBXPNLXLAGQ-UHFFFAOYSA-N 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- DJGHSJBYKIQHIK-UHFFFAOYSA-N (3,5-dimethylphenyl)boronic acid Chemical compound CC1=CC(C)=CC(B(O)O)=C1 DJGHSJBYKIQHIK-UHFFFAOYSA-N 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 2
- LMFRTSBQRLSJHC-UHFFFAOYSA-N 1-bromo-3,5-dimethylbenzene Chemical group CC1=CC(C)=CC(Br)=C1 LMFRTSBQRLSJHC-UHFFFAOYSA-N 0.000 description 2
- UNOODTRRFVGKFK-UHFFFAOYSA-N 1-ethyl-3-methyl-3-(4-nitrophenyl)pyrrolidin-2-one Chemical compound O=C1N(CC)CCC1(C)C1=CC=C([N+]([O-])=O)C=C1 UNOODTRRFVGKFK-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- FFRBMBIXVSCUFS-UHFFFAOYSA-N 2,4-dinitro-1-naphthol Chemical compound C1=CC=C2C(O)=C([N+]([O-])=O)C=C([N+]([O-])=O)C2=C1 FFRBMBIXVSCUFS-UHFFFAOYSA-N 0.000 description 2
- CRSWRWMNNQWAGO-UHFFFAOYSA-N 2-(3,5-dimethylphenyl)-1h-indol-5-amine Chemical compound CC1=CC(C)=CC(C=2NC3=CC=C(N)C=C3C=2)=C1 CRSWRWMNNQWAGO-UHFFFAOYSA-N 0.000 description 2
- XVEDHFFEMGIIDZ-UHFFFAOYSA-N 2-(3,5-dimethylphenyl)-3-[2-[4-(4-phenylmethoxyphenyl)butylamino]ethyl]-1h-indol-5-ol Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(O)=CC=C3N2)CCNCCCCC=2C=CC(OCC=3C=CC=CC=3)=CC=2)=C1 XVEDHFFEMGIIDZ-UHFFFAOYSA-N 0.000 description 2
- NZAYKRAHEJPLIX-UHFFFAOYSA-N 2-(3,5-dimethylphenyl)-5-nitro-1h-indole Chemical compound CC1=CC(C)=CC(C=2NC3=CC=C(C=C3C=2)[N+]([O-])=O)=C1 NZAYKRAHEJPLIX-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- GFKNAKPOOOYZIL-UHFFFAOYSA-N 2-[2-(2-bromo-5-phenylmethoxy-1h-indol-3-yl)ethyl]isoindole-1,3-dione Chemical compound C1=C2C(CCN3C(C4=CC=CC=C4C3=O)=O)=C(Br)NC2=CC=C1OCC1=CC=CC=C1 GFKNAKPOOOYZIL-UHFFFAOYSA-N 0.000 description 2
- QFRRHAQULKWQCQ-UHFFFAOYSA-N 2-[2-(3,5-dimethylphenyl)-5-(1,3-thiazol-2-yl)-1h-indol-3-yl]ethanamine Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(=CC=C3N2)C=2SC=CN=2)CCN)=C1 QFRRHAQULKWQCQ-UHFFFAOYSA-N 0.000 description 2
- DWNQRWHWCUVEOV-UHFFFAOYSA-N 2-[2-(5-phenylmethoxy-1h-indol-3-yl)ethyl]isoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1CCC(C1=C2)=CNC1=CC=C2OCC1=CC=CC=C1 DWNQRWHWCUVEOV-UHFFFAOYSA-N 0.000 description 2
- UZIPPKGKKNOXEC-UHFFFAOYSA-N 2-[2-[2-(3,5-dimethylphenyl)-5-hydroxy-1h-indol-3-yl]ethyl]isoindole-1,3-dione Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(O)=CC=C3N2)CCN2C(C3=CC=CC=C3C2=O)=O)=C1 UZIPPKGKKNOXEC-UHFFFAOYSA-N 0.000 description 2
- GVOMLDDLSHERCW-UHFFFAOYSA-N 2-[2-[2-(3,5-dimethylphenyl)-5-phenylmethoxy-1h-indol-3-yl]ethyl]isoindole-1,3-dione Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(OCC=4C=CC=CC=4)=CC=C3N2)CCN2C(C3=CC=CC=C3C2=O)=O)=C1 GVOMLDDLSHERCW-UHFFFAOYSA-N 0.000 description 2
- KEEINFONYVTGJN-UHFFFAOYSA-N 2-[5-[(1-butylimidazol-2-yl)methyl]-2-(3,5-dimethylphenyl)-1h-indol-3-yl]ethanamine Chemical compound CCCCN1C=CN=C1CC1=CC=C(NC(=C2CCN)C=3C=C(C)C=C(C)C=3)C2=C1 KEEINFONYVTGJN-UHFFFAOYSA-N 0.000 description 2
- BUZSHGOBJWGNIN-UHFFFAOYSA-N 2-acetamido-n-[3-[2-[benzyl-[4-(4-nitrophenyl)butyl]amino]ethyl]-2-(3,5-dimethylphenyl)-1h-indol-5-yl]acetamide Chemical compound C12=CC(NC(=O)CNC(=O)C)=CC=C2NC(C=2C=C(C)C=C(C)C=2)=C1CCN(CC=1C=CC=CC=1)CCCCC1=CC=C([N+]([O-])=O)C=C1 BUZSHGOBJWGNIN-UHFFFAOYSA-N 0.000 description 2
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 2
- YIBJJHXHBWSKCJ-UHFFFAOYSA-N 2-ethyl-4,4-dimethyl-5-(4-nitrophenyl)pyrazol-3-one Chemical compound CC1(C)C(=O)N(CC)N=C1C1=CC=C([N+]([O-])=O)C=C1 YIBJJHXHBWSKCJ-UHFFFAOYSA-N 0.000 description 2
- ARIAKJUPEOGARI-UHFFFAOYSA-N 2-ethyl-5-(4-hydrazinylphenyl)-4,4-dimethylpyrazol-3-one Chemical compound CC1(C)C(=O)N(CC)N=C1C1=CC=C(NN)C=C1 ARIAKJUPEOGARI-UHFFFAOYSA-N 0.000 description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
- XKSFNBWCJGQKCP-UHFFFAOYSA-N 3-(2-aminoethyl)-2-(3,5-dimethylphenyl)-1h-indol-5-ol Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(O)=CC=C3N2)CCN)=C1 XKSFNBWCJGQKCP-UHFFFAOYSA-N 0.000 description 2
- HDTKGEYSQJUDJP-UHFFFAOYSA-N 3-(4-aminophenyl)-1-ethyl-3-methylpyrrolidin-2-one Chemical compound O=C1N(CC)CCC1(C)C1=CC=C(N)C=C1 HDTKGEYSQJUDJP-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- ITBFNSWDQWRRBH-UHFFFAOYSA-N 3-[2-[benzyl-[4-(4-nitrophenyl)butyl]amino]ethyl]-2-(3,5-dimethylphenyl)-1h-indol-5-amine Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(N)=CC=C3N2)CCN(CCCCC=2C=CC(=CC=2)[N+]([O-])=O)CC=2C=CC=CC=2)=C1 ITBFNSWDQWRRBH-UHFFFAOYSA-N 0.000 description 2
- XLOLCNHTSMUPRD-UHFFFAOYSA-N 4-(4-aminophenyl)-n-methoxy-n-methylbutanamide Chemical compound CON(C)C(=O)CCCC1=CC=C(N)C=C1 XLOLCNHTSMUPRD-UHFFFAOYSA-N 0.000 description 2
- RKDXPVYOANKPNA-UHFFFAOYSA-N 4-(4-phenylmethoxyphenyl)butanoic acid Chemical compound C1=CC(CCCC(=O)O)=CC=C1OCC1=CC=CC=C1 RKDXPVYOANKPNA-UHFFFAOYSA-N 0.000 description 2
- LLYNXSNROKQOCU-UHFFFAOYSA-N 4-[(1-butylimidazol-2-yl)methyl]aniline Chemical compound CCCCN1C=CN=C1CC1=CC=C(N)C=C1 LLYNXSNROKQOCU-UHFFFAOYSA-N 0.000 description 2
- DUFGMUIKKFKWMC-UHFFFAOYSA-N 4-[4-[2-[2-(3,5-dimethylphenyl)-5-(1,3-thiazol-2-yl)-1h-indol-3-yl]ethylamino]butyl]phenol Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(=CC=C3N2)C=2SC=CN=2)CCNCCCCC=2C=CC(O)=CC=2)=C1 DUFGMUIKKFKWMC-UHFFFAOYSA-N 0.000 description 2
- OTYOBNBVRQAUCH-UHFFFAOYSA-N 4-chloro-n-methoxy-n-methylbutanamide Chemical compound CON(C)C(=O)CCCCl OTYOBNBVRQAUCH-UHFFFAOYSA-N 0.000 description 2
- BNLCOJDDGYNPSK-UHFFFAOYSA-N 5-(4-aminophenyl)-2-ethyl-4,4-dimethylpyrazol-3-one Chemical compound CC1(C)C(=O)N(CC)N=C1C1=CC=C(N)C=C1 BNLCOJDDGYNPSK-UHFFFAOYSA-N 0.000 description 2
- 239000005541 ACE inhibitor Substances 0.000 description 2
- 101710129690 Angiotensin-converting enzyme inhibitor Proteins 0.000 description 2
- 235000003911 Arachis Nutrition 0.000 description 2
- 244000105624 Arachis hypogaea Species 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
- 208000006386 Bone Resorption Diseases 0.000 description 2
- 208000018083 Bone metabolism disease Diseases 0.000 description 2
- 101710086378 Bradykinin-potentiating and C-type natriuretic peptides Proteins 0.000 description 2
- 239000002083 C09CA01 - Losartan Substances 0.000 description 2
- PUHXMBLXNLNNGD-UHFFFAOYSA-N CS(=O)(=O)NC1=CC=C(C=C1)CCCC(CC1=CC=CC=C1)NCCC1=C(NC2=CC=C(C=C12)[N+](=O)[O-])C1=CC(=CC(=C1)C)C Chemical compound CS(=O)(=O)NC1=CC=C(C=C1)CCCC(CC1=CC=CC=C1)NCCC1=C(NC2=CC=C(C=C12)[N+](=O)[O-])C1=CC(=CC(=C1)C)C PUHXMBLXNLNNGD-UHFFFAOYSA-N 0.000 description 2
- 102000029816 Collagenase Human genes 0.000 description 2
- 108060005980 Collagenase Proteins 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 108010061435 Enalapril Proteins 0.000 description 2
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 2
- 108700012941 GNRH1 Proteins 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 239000000095 Growth Hormone-Releasing Hormone Substances 0.000 description 2
- 102000038461 Growth Hormone-Releasing Hormone Human genes 0.000 description 2
- 206010060800 Hot flush Diseases 0.000 description 2
- 108010003272 Hyaluronate lyase Proteins 0.000 description 2
- 102000001974 Hyaluronidases Human genes 0.000 description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
- 240000007472 Leucaena leucocephala Species 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- OKJIRPAQVSHGFK-UHFFFAOYSA-N N-acetylglycine Chemical compound CC(=O)NCC(O)=O OKJIRPAQVSHGFK-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 101710142969 Somatoliberin Proteins 0.000 description 2
- 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 2
- 229930006000 Sucrose Natural products 0.000 description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- HQIQSQWYWJFBGZ-UHFFFAOYSA-N [2-(3,5-dimethylphenyl)-3-[2-[4-(4-hydroxyphenyl)butylamino]ethyl]-1h-indol-5-yl] morpholine-4-carboxylate Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(OC(=O)N4CCOCC4)=CC=C3N2)CCNCCCCC=2C=CC(O)=CC=2)=C1 HQIQSQWYWJFBGZ-UHFFFAOYSA-N 0.000 description 2
- VNWDHMOFIKPIDP-UHFFFAOYSA-N [4-(1,3-thiazol-2-yl)phenyl]hydrazine Chemical compound C1=CC(NN)=CC=C1C1=NC=CS1 VNWDHMOFIKPIDP-UHFFFAOYSA-N 0.000 description 2
- VZOLMKVFKFDVQL-UHFFFAOYSA-N [4-[(1-butylimidazol-2-yl)methyl]phenyl]hydrazine Chemical compound CCCCN1C=CN=C1CC1=CC=C(NN)C=C1 VZOLMKVFKFDVQL-UHFFFAOYSA-N 0.000 description 2
- DCSBSVSZJRSITC-UHFFFAOYSA-M alendronate sodium trihydrate Chemical group O.O.O.[Na+].NCCCC(O)(P(O)(O)=O)P(O)([O-])=O DCSBSVSZJRSITC-UHFFFAOYSA-M 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 2
- 229940126317 angiotensin II receptor antagonist Drugs 0.000 description 2
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 2
- 229940046836 anti-estrogen Drugs 0.000 description 2
- 230000001833 anti-estrogenic effect Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- HIJIBMRIDBXADC-UHFFFAOYSA-N benzyl 4-(4-phenylmethoxyphenyl)butanoate Chemical compound C=1C=CC=CC=1COC(=O)CCCC(C=C1)=CC=C1OCC1=CC=CC=C1 HIJIBMRIDBXADC-UHFFFAOYSA-N 0.000 description 2
- PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical compound NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 description 2
- PBODDXJUWRJZJK-UHFFFAOYSA-N benzyl n-[2-(3,5-dimethylphenyl)-1h-indol-5-yl]carbamate Chemical compound CC1=CC(C)=CC(C=2NC3=CC=C(NC(=O)OCC=4C=CC=CC=4)C=C3C=2)=C1 PBODDXJUWRJZJK-UHFFFAOYSA-N 0.000 description 2
- 230000024279 bone resorption Effects 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 2
- 229960000830 captopril Drugs 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 229940110456 cocoa butter Drugs 0.000 description 2
- 235000019868 cocoa butter Nutrition 0.000 description 2
- 229960002424 collagenase Drugs 0.000 description 2
- 239000007822 coupling agent Substances 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000006193 diazotization reaction Methods 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 2
- 229960000873 enalapril Drugs 0.000 description 2
- 239000003797 essential amino acid Substances 0.000 description 2
- 235000020776 essential amino acid Nutrition 0.000 description 2
- 239000000328 estrogen antagonist Substances 0.000 description 2
- PZUCPNVPSYYDQJ-UHFFFAOYSA-N ethyl 2-(3,5-dimethylphenyl)-3-[2-[4-[4-(methanesulfonamido)phenyl]butylamino]ethyl]-1h-indole-5-carboxylate Chemical compound C12=CC(C(=O)OCC)=CC=C2NC(C=2C=C(C)C=C(C)C=2)=C1CCNCCCCC1=CC=C(NS(C)(=O)=O)C=C1 PZUCPNVPSYYDQJ-UHFFFAOYSA-N 0.000 description 2
- QLWOMLYAERSUKT-UHFFFAOYSA-N ethyl 2-(4-aminophenyl)-2-methylpropanoate Chemical compound CCOC(=O)C(C)(C)C1=CC=C(N)C=C1 QLWOMLYAERSUKT-UHFFFAOYSA-N 0.000 description 2
- YZHOQTLDPBAQPZ-UHFFFAOYSA-N ethyl 2-(4-hydrazinylphenyl)-2-methylpropanoate Chemical compound CCOC(=O)C(C)(C)C1=CC=C(NN)C=C1 YZHOQTLDPBAQPZ-UHFFFAOYSA-N 0.000 description 2
- SEQTUSZKRDHNDC-UHFFFAOYSA-N ethyl 2-methyl-2-(4-nitrophenyl)propanoate Chemical compound CCOC(=O)C(C)(C)C1=CC=C([N+]([O-])=O)C=C1 SEQTUSZKRDHNDC-UHFFFAOYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 230000004720 fertilization Effects 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 238000005187 foaming Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 239000002474 gonadorelin antagonist Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 229960002773 hyaluronidase Drugs 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 description 2
- 229960004773 losartan Drugs 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- IUBHHOLKTCAPNQ-UHFFFAOYSA-N n-[2-(3,5-dimethylphenyl)-3-[2-[4-[4-(methanesulfonamido)phenyl]butylamino]ethyl]-1h-indol-5-yl]pyridine-3-carboxamide Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(NC(=O)C=4C=NC=CC=4)=CC=C3N2)CCNCCCCC=2C=CC(NS(C)(=O)=O)=CC=2)=C1 IUBHHOLKTCAPNQ-UHFFFAOYSA-N 0.000 description 2
- YPPGSTGLZNPNGW-UHFFFAOYSA-N n-[2-[2-(3,5-dimethylphenyl)-5-hydroxy-1h-indol-3-yl]ethyl]-4-(4-phenylmethoxyphenyl)butanamide Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(O)=CC=C3N2)CCNC(=O)CCCC=2C=CC(OCC=3C=CC=CC=3)=CC=2)=C1 YPPGSTGLZNPNGW-UHFFFAOYSA-N 0.000 description 2
- SFESSUGSXILDGJ-UHFFFAOYSA-N n-[3-[2-[benzyl-[4-[4-(methanesulfonamido)phenyl]butyl]amino]ethyl]-2-(3,5-dimethylphenyl)-1h-indol-5-yl]pyridine-3-carboxamide Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(NC(=O)C=4C=NC=CC=4)=CC=C3N2)CCN(CCCCC=2C=CC(NS(C)(=O)=O)=CC=2)CC=2C=CC=CC=2)=C1 SFESSUGSXILDGJ-UHFFFAOYSA-N 0.000 description 2
- RRLFSIAYEBCALH-UHFFFAOYSA-N n-[4-[4-[2-[2-(3,5-dimethylphenyl)-1h-indol-3-yl]ethylamino]butyl]phenyl]methanesulfonamide Chemical compound CC1=CC(C)=CC(C2=C(C3=CC=CC=C3N2)CCNCCCCC=2C=CC(NS(C)(=O)=O)=CC=2)=C1 RRLFSIAYEBCALH-UHFFFAOYSA-N 0.000 description 2
- JENIJHXCQYIIPI-UHFFFAOYSA-N n-[4-[4-[2-[2-(3,5-dimethylphenyl)-5-(1-ethyl-3-methyl-2-oxopyrrolidin-3-yl)-1h-indol-3-yl]ethylamino]butyl]phenyl]methanesulfonamide Chemical compound O=C1N(CC)CCC1(C)C1=CC=C(NC(=C2CCNCCCCC=3C=CC(NS(C)(=O)=O)=CC=3)C=3C=C(C)C=C(C)C=3)C2=C1 JENIJHXCQYIIPI-UHFFFAOYSA-N 0.000 description 2
- AILVMVTWHQIORO-UHFFFAOYSA-N n-[4-[4-[2-[2-(3,5-dimethylphenyl)-5-(4-methyl-5-oxotetrazol-1-yl)-1h-indol-3-yl]ethylamino]butyl]phenyl]methanesulfonamide Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(=CC=C3N2)N2C(N(C)N=N2)=O)CCNCCCCC=2C=CC(NS(C)(=O)=O)=CC=2)=C1 AILVMVTWHQIORO-UHFFFAOYSA-N 0.000 description 2
- WXTVHGAUYIDOSI-UHFFFAOYSA-N n-[4-[4-[2-[2-(3,5-dimethylphenyl)-5-[(5-phenyl-1,3-oxazol-2-yl)amino]-1h-indol-3-yl]ethylamino]butyl]phenyl]methanesulfonamide Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(NC=4OC(=CN=4)C=4C=CC=CC=4)=CC=C3N2)CCNCCCCC=2C=CC(NS(C)(=O)=O)=CC=2)=C1 WXTVHGAUYIDOSI-UHFFFAOYSA-N 0.000 description 2
- CHCXYBRJCYEMJR-UHFFFAOYSA-N n-[4-[4-[2-[5-[(1-butylimidazol-2-yl)methyl]-2-(3,5-dimethylphenyl)-1h-indol-3-yl]ethylamino]butyl]phenyl]methanesulfonamide Chemical compound CCCCN1C=CN=C1CC1=CC=C(NC(=C2CCNCCCCC=3C=CC(NS(C)(=O)=O)=CC=3)C=3C=C(C)C=C(C)C=3)C2=C1 CHCXYBRJCYEMJR-UHFFFAOYSA-N 0.000 description 2
- UTDOQEHNJTXCKK-UHFFFAOYSA-N n-[4-[4-[benzyl-[2-[2-(3,5-dimethylphenyl)-5-nitro-1h-indol-3-yl]ethyl]amino]butyl]phenyl]methanesulfonamide Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(=CC=C3N2)[N+]([O-])=O)CCN(CCCCC=2C=CC(NS(C)(=O)=O)=CC=2)CC=2C=CC=CC=2)=C1 UTDOQEHNJTXCKK-UHFFFAOYSA-N 0.000 description 2
- ITJVUJUGDLYYEN-UHFFFAOYSA-N n-benzyl-2-[2-(3,5-dimethylphenyl)-5-nitro-1h-indol-3-yl]-n-[4-[4-(methanesulfonamido)phenyl]butyl]-2-oxoacetamide Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(=CC=C3N2)[N+]([O-])=O)C(=O)C(=O)N(CCCCC=2C=CC(NS(C)(=O)=O)=CC=2)CC=2C=CC=CC=2)=C1 ITJVUJUGDLYYEN-UHFFFAOYSA-N 0.000 description 2
- ABQPQRKYTJPENM-UHFFFAOYSA-N n-methoxy-n-methyl-4-(4-nitrophenyl)butanamide Chemical compound CON(C)C(=O)CCCC1=CC=C([N+]([O-])=O)C=C1 ABQPQRKYTJPENM-UHFFFAOYSA-N 0.000 description 2
- KHNDGDMDYRDYBR-UHFFFAOYSA-N n-methoxy-n-methylbutanamide Chemical compound CCCC(=O)N(C)OC KHNDGDMDYRDYBR-UHFFFAOYSA-N 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- LCDCPQHFCOBUEF-UHFFFAOYSA-N pyrrolidine-1-carboxamide Chemical compound NC(=O)N1CCCC1 LCDCPQHFCOBUEF-UHFFFAOYSA-N 0.000 description 2
- 239000002287 radioligand Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000001525 receptor binding assay Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 239000002461 renin inhibitor Substances 0.000 description 2
- 229940086526 renin-inhibitors Drugs 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 2
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- 238000000638 solvent extraction Methods 0.000 description 2
- 239000001593 sorbitan monooleate Substances 0.000 description 2
- 235000011069 sorbitan monooleate Nutrition 0.000 description 2
- 229940035049 sorbitan monooleate Drugs 0.000 description 2
- 239000003270 steroid hormone Substances 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- KKJOBGQNEJFICZ-UHFFFAOYSA-N tert-butyl n-[2-[5-(carbamothioylamino)-2-(3,5-dimethylphenyl)-1h-indol-3-yl]ethyl]-n-[4-[4-(methanesulfonamido)phenyl]butyl]carbamate Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(NC(N)=S)=CC=C3N2)CCN(CCCCC=2C=CC(NS(C)(=O)=O)=CC=2)C(=O)OC(C)(C)C)=C1 KKJOBGQNEJFICZ-UHFFFAOYSA-N 0.000 description 2
- WGTYBPLFGIVFAS-UHFFFAOYSA-M tetramethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C WGTYBPLFGIVFAS-UHFFFAOYSA-M 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- QFDUTPNKBRXHTC-UHFFFAOYSA-N zinc diazide Chemical compound [Zn++].[N-]=[N+]=[N-].[N-]=[N+]=[N-] QFDUTPNKBRXHTC-UHFFFAOYSA-N 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- NWQWNCILOXTTHF-HLCSKTDOSA-N (2s)-6-amino-2-[[(2r)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2s)-2-[[(2s)-2-aminopropanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]propanoyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]-3-phenylpropanoyl]amino]hexanamide Chemical compound C([C@H](NC(=O)[C@@H](N)C)C(=O)N[C@H](CC=1C=C2C=CC=CC2=CC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CNC=N1 NWQWNCILOXTTHF-HLCSKTDOSA-N 0.000 description 1
- WZHKXNSOCOQYQX-FUAFALNISA-N (2s)-6-amino-2-[[(2r)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2s)-2-amino-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]propanoyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]-3-phenylpropanoyl]amino]hexanamide Chemical compound C([C@H](N)C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CN=CN1 WZHKXNSOCOQYQX-FUAFALNISA-N 0.000 description 1
- RVWNMGKSNGWLOL-GIIHNPQRSA-N (2s)-6-amino-2-[[(2r)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2s)-2-amino-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(2-methyl-1h-indol-3-yl)propanoyl]amino]propanoyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]-3-phenylpropanoyl]amino]hexanamide Chemical compound C([C@H](N)C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CN=CN1 RVWNMGKSNGWLOL-GIIHNPQRSA-N 0.000 description 1
- HRNLPPBUBKMZMT-SSSXJSFTSA-N (2s)-6-amino-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2r)-2-aminopropanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]propanoyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]-3-phenylpropanoyl]amino]hexanamide Chemical compound C([C@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](C)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(=O)[C@H](N)C)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CC=CC=C1 HRNLPPBUBKMZMT-SSSXJSFTSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- OTPDWCMLUKMQNO-UHFFFAOYSA-N 1,2,3,4-tetrahydropyrimidine Chemical compound C1NCC=CN1 OTPDWCMLUKMQNO-UHFFFAOYSA-N 0.000 description 1
- TUPNSSNDXLGGBQ-UHFFFAOYSA-N 1,3-dioxoisoindole-2-carboxylic acid Chemical compound C1=CC=C2C(=O)N(C(=O)O)C(=O)C2=C1 TUPNSSNDXLGGBQ-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- MKZHJJQCUIZEDE-UHFFFAOYSA-N 1-[(2-hydroxy-3-naphthalen-1-yloxypropyl)-propan-2-ylamino]-3-naphthalen-1-yloxypropan-2-ol Chemical compound C1=CC=C2C(OCC(O)CN(CC(O)COC=3C4=CC=CC=C4C=CC=3)C(C)C)=CC=CC2=C1 MKZHJJQCUIZEDE-UHFFFAOYSA-N 0.000 description 1
- UJUATHKLZAKHML-UHFFFAOYSA-N 1-[3-[2-[benzyl-[4-(4-nitrophenyl)butyl]amino]ethyl]-2-(3,5-dimethylphenyl)-1h-indol-5-yl]-3-ethylimidazolidin-2-one Chemical compound O=C1N(CC)CCN1C1=CC=C(NC(=C2CCN(CCCCC=3C=CC(=CC=3)[N+]([O-])=O)CC=3C=CC=CC=3)C=3C=C(C)C=C(C)C=3)C2=C1 UJUATHKLZAKHML-UHFFFAOYSA-N 0.000 description 1
- IKHODJWZXDNNII-UHFFFAOYSA-N 1-ethyl-3-(4-hydrazinylphenyl)-3-methylpyrrolidin-2-one Chemical compound O=C1N(CC)CCC1(C)C1=CC=C(NN)C=C1 IKHODJWZXDNNII-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- HESJZXOBRLYTEX-UHFFFAOYSA-N 2-(2-bromo-1h-indol-3-yl)ethanamine Chemical compound C1=CC=C2C(CCN)=C(Br)NC2=C1 HESJZXOBRLYTEX-UHFFFAOYSA-N 0.000 description 1
- JECYNCQXXKQDJN-UHFFFAOYSA-N 2-(2-methylhexan-2-yloxymethyl)oxirane Chemical compound CCCCC(C)(C)OCC1CO1 JECYNCQXXKQDJN-UHFFFAOYSA-N 0.000 description 1
- VSZMQMZZNQDLEA-UHFFFAOYSA-N 2-(3,5-dimethylphenyl)-1h-indole-5-carboxylic acid Chemical compound CC1=CC(C)=CC(C=2NC3=CC=C(C=C3C=2)C(O)=O)=C1 VSZMQMZZNQDLEA-UHFFFAOYSA-N 0.000 description 1
- SNNOGTYHXPPIFE-UHFFFAOYSA-N 2-(3,5-dimethylphenyl)-3-[2-[4-[4-(methanesulfonamido)phenyl]butyl-phenylmethoxycarbonylamino]ethyl]-1h-indole-5-carboxylic acid Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(=CC=C3N2)C(O)=O)CCN(CCCCC=2C=CC(NS(C)(=O)=O)=CC=2)C(=O)OCC=2C=CC=CC=2)=C1 SNNOGTYHXPPIFE-UHFFFAOYSA-N 0.000 description 1
- QBSIFZWYKGBSFI-UHFFFAOYSA-N 2-(4-hydrazinylphenyl)acetic acid;hydrochloride Chemical compound Cl.NNC1=CC=C(CC(O)=O)C=C1 QBSIFZWYKGBSFI-UHFFFAOYSA-N 0.000 description 1
- GEQWCUVIQMRCAZ-UHFFFAOYSA-N 2-(4-hydroxyphenyl)butanoic acid Chemical compound CCC(C(O)=O)C1=CC=C(O)C=C1 GEQWCUVIQMRCAZ-UHFFFAOYSA-N 0.000 description 1
- LGDOGDJADXLHLA-UHFFFAOYSA-N 2-(4-nitrophenyl)-1,3-thiazole Chemical compound C1=CC([N+](=O)[O-])=CC=C1C1=NC=CS1 LGDOGDJADXLHLA-UHFFFAOYSA-N 0.000 description 1
- MNSDWKQEXPQMMM-UHFFFAOYSA-N 2-(4-phenylmethoxyphenyl)butanoic acid Chemical compound C1=CC(C(C(O)=O)CC)=CC=C1OCC1=CC=CC=C1 MNSDWKQEXPQMMM-UHFFFAOYSA-N 0.000 description 1
- MIJDSYMOBYNHOT-UHFFFAOYSA-N 2-(ethylamino)ethanol Chemical compound CCNCCO MIJDSYMOBYNHOT-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- HZHZGPFRBYYBPM-OAQYLSRUSA-N 2-amino-n-[(2r)-1-(1,1-dioxospiro[2h-1-benzothiophene-3,4'-piperidine]-1'-yl)-1-oxo-3-phenylmethoxypropan-2-yl]-2-methylpropanamide Chemical compound C([C@@H](NC(=O)C(C)(N)C)C(=O)N1CCC2(C3=CC=CC=C3S(=O)(=O)C2)CC1)OCC1=CC=CC=C1 HZHZGPFRBYYBPM-OAQYLSRUSA-N 0.000 description 1
- MHTRBQIBYZSLHD-JOCHJYFZSA-N 2-amino-n-[(2r)-1-(5-fluoro-1-methylsulfonylspiro[2h-indole-3,4'-piperidine]-1'-yl)-1-oxo-3-phenylmethoxypropan-2-yl]-2-methylpropanamide Chemical compound C([C@@H](NC(=O)C(C)(N)C)C(=O)N1CCC2(C3=CC(F)=CC=C3N(C2)S(C)(=O)=O)CC1)OCC1=CC=CC=C1 MHTRBQIBYZSLHD-JOCHJYFZSA-N 0.000 description 1
- KMJYYKLCENIDIT-MUUNZHRXSA-N 2-amino-n-[(2r)-1-[1-(benzenesulfonyl)spiro[2h-indole-3,4'-piperidine]-1'-yl]-3-(1h-indol-3-yl)-1-oxopropan-2-yl]-2-methylpropanamide Chemical compound O=C([C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)C(C)(N)C)N(CC1)CCC1(C1=CC=CC=C11)CN1S(=O)(=O)C1=CC=CC=C1 KMJYYKLCENIDIT-MUUNZHRXSA-N 0.000 description 1
- MQYFBDDPLDAEQH-HSZRJFAPSA-N 2-amino-n-[(2r)-3-(1h-indol-3-yl)-1-(1-methylsulfonylspiro[2h-indole-3,4'-piperidine]-1'-yl)-1-oxopropan-2-yl]-2-methylpropanamide Chemical compound C1N(S(C)(=O)=O)C2=CC=CC=C2C1(CC1)CCN1C(=O)[C@H](NC(=O)C(C)(N)C)CC1=CNC2=CC=CC=C12 MQYFBDDPLDAEQH-HSZRJFAPSA-N 0.000 description 1
- IDMDHHMWNLCWAO-JOCHJYFZSA-N 2-amino-n-[(2r)-4-cyclohexyl-1-(1-methylsulfonylspiro[2h-indole-3,4'-piperidine]-1'-yl)-1-oxobutan-2-yl]-2-methylpropanamide Chemical compound C([C@@H](NC(=O)C(C)(N)C)C(=O)N1CCC2(C3=CC=CC=C3N(C2)S(C)(=O)=O)CC1)CC1CCCCC1 IDMDHHMWNLCWAO-JOCHJYFZSA-N 0.000 description 1
- KPBAGSRKBBQBEU-JOCHJYFZSA-N 2-amino-n-[(2s)-3-benzylsulfanyl-1-(1-methylsulfonylspiro[2h-indole-3,4'-piperidine]-1'-yl)-1-oxopropan-2-yl]-2-methylpropanamide Chemical compound C([C@@H](NC(=O)C(C)(N)C)C(=O)N1CCC2(C3=CC=CC=C3N(C2)S(C)(=O)=O)CC1)SCC1=CC=CC=C1 KPBAGSRKBBQBEU-JOCHJYFZSA-N 0.000 description 1
- AIZGBPJAKQNCSD-UHFFFAOYSA-N 2-azaniumyl-2-(1h-indol-3-yl)acetate Chemical class C1=CC=C2C(C(C(O)=O)N)=CNC2=C1 AIZGBPJAKQNCSD-UHFFFAOYSA-N 0.000 description 1
- HCGYMSSYSAKGPK-UHFFFAOYSA-N 2-nitro-1h-indole Chemical compound C1=CC=C2NC([N+](=O)[O-])=CC2=C1 HCGYMSSYSAKGPK-UHFFFAOYSA-N 0.000 description 1
- VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical compound C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 description 1
- NEAHTABRXFKZGG-UHFFFAOYSA-N 2-pyridin-4-yl-3h-imidazo[4,5-c]pyridine Chemical compound C1=NC=CC(C=2NC3=CN=CC=C3N=2)=C1 NEAHTABRXFKZGG-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- BINFIDXPHBXCNU-UHFFFAOYSA-N 3-[3-(2-aminoethyl)-2-(3,5-dimethylphenyl)-1h-indol-5-yl]-1-ethyl-3-methylpyrrolidin-2-one Chemical compound O=C1N(CC)CCC1(C)C1=CC=C(NC(=C2CCN)C=3C=C(C)C=C(C)C=3)C2=C1 BINFIDXPHBXCNU-UHFFFAOYSA-N 0.000 description 1
- ZGOFHPZQYOXFCP-UHFFFAOYSA-N 4-(1,3-thiazol-2-yl)aniline Chemical compound C1=CC(N)=CC=C1C1=NC=CS1 ZGOFHPZQYOXFCP-UHFFFAOYSA-N 0.000 description 1
- WTDBNDAYNLGKGW-UHFFFAOYSA-N 4-(4-hydroxyphenyl)butanoic acid Chemical compound OC(=O)CCCC1=CC=C(O)C=C1 WTDBNDAYNLGKGW-UHFFFAOYSA-N 0.000 description 1
- WQMLUHZFRFCQDB-UHFFFAOYSA-N 4-(4-nitrophenyl)butyric acid Chemical compound OC(=O)CCCC1=CC=C([N+]([O-])=O)C=C1 WQMLUHZFRFCQDB-UHFFFAOYSA-N 0.000 description 1
- CDIIZULDSLKBKV-UHFFFAOYSA-N 4-chlorobutanoyl chloride Chemical compound ClCCCC(Cl)=O CDIIZULDSLKBKV-UHFFFAOYSA-N 0.000 description 1
- PCNFLKVWBDNNOW-UHFFFAOYSA-N 4-hydrazinylbenzoic acid Chemical compound NNC1=CC=C(C(O)=O)C=C1 PCNFLKVWBDNNOW-UHFFFAOYSA-N 0.000 description 1
- FXRJLBJOSBDHCO-UHFFFAOYSA-N 5-[3-(2-aminoethyl)-2-(3,5-dimethylphenyl)-1h-indol-5-yl]-2-ethyl-4,4-dimethylpyrazol-3-one Chemical compound CC1(C)C(=O)N(CC)N=C1C1=CC=C(NC(=C2CCN)C=3C=C(C)C=C(C)C=3)C2=C1 FXRJLBJOSBDHCO-UHFFFAOYSA-N 0.000 description 1
- WKPDXBXNJWWWGQ-UHFFFAOYSA-N 5-benzyloxytryptamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1OCC1=CC=CC=C1 WKPDXBXNJWWWGQ-UHFFFAOYSA-N 0.000 description 1
- NWKAOBOBUWRISU-UHFFFAOYSA-N 5-fluoro-1-methylsulfonylspiro[2h-indole-3,4'-piperidine] Chemical compound C12=CC(F)=CC=C2N(S(=O)(=O)C)CC21CCNCC2 NWKAOBOBUWRISU-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 102100033367 Appetite-regulating hormone Human genes 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 240000001851 Artemisia dracunculus Species 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- 229940078581 Bone resorption inhibitor Drugs 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- YWSZLIOGPYYFKU-UHFFFAOYSA-N CC1=CC(=C(C(=C1)C(=O)C2=CC(=CC(=C2CCCCl)C)C)CCCCl)C Chemical compound CC1=CC(=C(C(=C1)C(=O)C2=CC(=CC(=C2CCCCl)C)C)CCCCl)C YWSZLIOGPYYFKU-UHFFFAOYSA-N 0.000 description 1
- CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical compound NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 101710119601 Growth hormone-releasing peptides Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000033830 Hot Flashes Diseases 0.000 description 1
- 208000001953 Hypotension 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
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229910010082 LiAlH Inorganic materials 0.000 description 1
- 208000015924 Lithiasis Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
- 102000003797 Neuropeptides Human genes 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
- MBJMCOJMDMARNB-UHFFFAOYSA-N O.O.O.O.[Na].[Na].OP(O)(=O)C(Cl)(Cl)P(O)(O)=O Chemical compound O.O.O.O.[Na].[Na].OP(O)(=O)C(Cl)(Cl)P(O)(O)=O MBJMCOJMDMARNB-UHFFFAOYSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 208000007913 Pituitary Neoplasms Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 208000003782 Raynaud disease Diseases 0.000 description 1
- 208000012322 Raynaud phenomenon Diseases 0.000 description 1
- IIDJRNMFWXDHID-UHFFFAOYSA-N Risedronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=CN=C1 IIDJRNMFWXDHID-UHFFFAOYSA-N 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 description 1
- DKJJVAGXPKPDRL-UHFFFAOYSA-N Tiludronic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)SC1=CC=C(Cl)C=C1 DKJJVAGXPKPDRL-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- IFFUUIRWVNTCTO-UHFFFAOYSA-N [2-(3,5-dimethylphenyl)-3-[2-[4-(4-hydroxyphenyl)butylamino]ethyl]-1h-indol-5-yl]-morpholin-4-ylmethanone Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(=CC=C3N2)C(=O)N2CCOCC2)CCNCCCCC=2C=CC(O)=CC=2)=C1 IFFUUIRWVNTCTO-UHFFFAOYSA-N 0.000 description 1
- NPJNLOPBFGLRGV-UHFFFAOYSA-N [2-(3,5-dimethylphenyl)-3-[2-[phenylmethoxycarbonyl-[4-(4-phenylmethoxyphenyl)butyl]amino]ethyl]-1h-indol-5-yl] morpholine-4-carboxylate Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(OC(=O)N4CCOCC4)=CC=C3N2)CCN(CCCCC=2C=CC(OCC=3C=CC=CC=3)=CC=2)C(=O)OCC=2C=CC=CC=2)=C1 NPJNLOPBFGLRGV-UHFFFAOYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002908 adrenolytic effect Effects 0.000 description 1
- 108010083553 alanyl-histidyl-(2-naphthyl)alanyl-tryptophyl-phenylalanyl-lysinamide Proteins 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229940062527 alendronate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- YDPLDMLRERBXAV-UHFFFAOYSA-N aluminum;triazide Chemical compound [Al+3].[N-]=[N+]=[N-].[N-]=[N+]=[N-].[N-]=[N+]=[N-] YDPLDMLRERBXAV-UHFFFAOYSA-N 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000000708 anti-progestin effect Effects 0.000 description 1
- 230000000794 anti-serotonin Effects 0.000 description 1
- 229940053202 antiepileptics carboxamide derivative Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000003418 antiprogestin Substances 0.000 description 1
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 1
- 239000003420 antiserotonin agent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 150000001543 aryl boronic acids Chemical class 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 125000005604 azodicarboxylate group Chemical group 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical compound C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- IOTOAQSOJXPQPG-UHFFFAOYSA-N benzyl n-[2-[2-(3,5-dimethylphenyl)-5-hydroxy-1h-indol-3-yl]ethyl]-n-[4-(4-phenylmethoxyphenyl)butyl]carbamate Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(O)=CC=C3N2)CCN(CCCCC=2C=CC(OCC=3C=CC=CC=3)=CC=2)C(=O)OCC=2C=CC=CC=2)=C1 IOTOAQSOJXPQPG-UHFFFAOYSA-N 0.000 description 1
- VIHHAWXIADYLHY-UHFFFAOYSA-N benzyl n-[3-[2-[benzyl-[4-(4-nitrophenyl)butyl]amino]ethyl]-2-(3,5-dimethylphenyl)-1h-indol-5-yl]carbamate Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(NC(=O)OCC=4C=CC=CC=4)=CC=C3N2)CCN(CCCCC=2C=CC(=CC=2)[N+]([O-])=O)CC=2C=CC=CC=2)=C1 VIHHAWXIADYLHY-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000002617 bone density conservation agent Substances 0.000 description 1
- 230000004097 bone metabolism Effects 0.000 description 1
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 1
- 229940045348 brown mixture Drugs 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000006309 butyl amino group Chemical group 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000002327 cardiovascular agent Substances 0.000 description 1
- 229940125692 cardiovascular agent Drugs 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 229960002023 chloroprocaine Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229960002286 clodronic acid Drugs 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000002704 decyl 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])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 150000001989 diazonium salts Chemical class 0.000 description 1
- UFMVNSFONAZFOT-UHFFFAOYSA-N dichloromethane;n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound ClCCl.CCN(C(C)C)C(C)C UFMVNSFONAZFOT-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 125000003438 dodecyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 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
- 238000010828 elution Methods 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- DAXYXMPJYKIZAI-UHFFFAOYSA-N ethanamine Chemical compound CCN.CCN DAXYXMPJYKIZAI-UHFFFAOYSA-N 0.000 description 1
- 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 1
- VRHAQNTWKSVEEC-UHFFFAOYSA-N ethyl 1,3-dioxoisoindole-2-carboxylate Chemical compound C1=CC=C2C(=O)N(C(=O)OCC)C(=O)C2=C1 VRHAQNTWKSVEEC-UHFFFAOYSA-N 0.000 description 1
- SVDSAMKKFQPFDS-UHFFFAOYSA-N ethyl 2-(3,5-dimethylphenyl)-3-[2-[4-[4-(methanesulfonamido)phenyl]butyl-phenylmethoxycarbonylamino]ethyl]-1h-indole-5-carboxylate Chemical compound C12=CC(C(=O)OCC)=CC=C2NC(C=2C=C(C)C=C(C)C=2)=C1CCN(C(=O)OCC=1C=CC=CC=1)CCCCC1=CC=C(NS(C)(=O)=O)C=C1 SVDSAMKKFQPFDS-UHFFFAOYSA-N 0.000 description 1
- CFNDVXUTYPXOPG-UHFFFAOYSA-N ethyl 2-(4-aminophenyl)acetate Chemical compound CCOC(=O)CC1=CC=C(N)C=C1 CFNDVXUTYPXOPG-UHFFFAOYSA-N 0.000 description 1
- BLPVZFJCXFBMJC-UHFFFAOYSA-N ethyl 2-(4-nitrophenyl)ethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)CC1=CC=C([N+]([O-])=O)C=C1 BLPVZFJCXFBMJC-UHFFFAOYSA-N 0.000 description 1
- GMOOHUQPPFJAQB-UHFFFAOYSA-N ethyl 2-(4-nitrophenyl)propanoate Chemical compound CCOC(=O)C(C)C1=CC=C([N+]([O-])=O)C=C1 GMOOHUQPPFJAQB-UHFFFAOYSA-N 0.000 description 1
- BCIRPBHKMMHSSH-UHFFFAOYSA-N ethyl 2-[2-(3,5-dimethylphenyl)-3-[2-[4-[4-(methanesulfonamido)phenyl]butylamino]ethyl]-1h-indol-5-yl]-2-methylpropanoate Chemical compound C12=CC(C(C)(C)C(=O)OCC)=CC=C2NC(C=2C=C(C)C=C(C)C=2)=C1CCNCCCCC1=CC=C(NS(C)(=O)=O)C=C1 BCIRPBHKMMHSSH-UHFFFAOYSA-N 0.000 description 1
- WEUFORLWFCPAGZ-UHFFFAOYSA-N ethyl 2-[3-(2-aminoethyl)-2-(3,5-dimethylphenyl)-1h-indol-5-yl]-2-methylpropanoate Chemical compound NCCC=1C2=CC(C(C)(C)C(=O)OCC)=CC=C2NC=1C1=CC(C)=CC(C)=C1 WEUFORLWFCPAGZ-UHFFFAOYSA-N 0.000 description 1
- GUFQWKNZGWGHFD-UHFFFAOYSA-N ethyl 3-(2-aminoethyl)-2-(3,5-dimethylphenyl)-1h-indole-5-carboxylate Chemical compound NCCC=1C2=CC(C(=O)OCC)=CC=C2NC=1C1=CC(C)=CC(C)=C1 GUFQWKNZGWGHFD-UHFFFAOYSA-N 0.000 description 1
- 239000002038 ethyl acetate fraction Substances 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 230000008217 follicular development Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 229940001490 fosamax Drugs 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- UHUSDOQQWJGJQS-UHFFFAOYSA-N glycerol 1,2-dioctadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(CO)OC(=O)CCCCCCCCCCCCCCCCC UHUSDOQQWJGJQS-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 210000002149 gonad Anatomy 0.000 description 1
- 108010015153 growth hormone releasing hexapeptide Proteins 0.000 description 1
- 108010085742 growth hormone-releasing peptide-2 Proteins 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 108010070965 hexarelin Proteins 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 1
- 229940091173 hydantoin Drugs 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 208000021822 hypotensive Diseases 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 230000009027 insemination Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910012375 magnesium hydride Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- DOPNTMPPGFVLDO-UHFFFAOYSA-N methyl 2,2-dimethyl-3-(4-nitrophenyl)-3-oxopropanoate Chemical compound COC(=O)C(C)(C)C(=O)C1=CC=C([N+]([O-])=O)C=C1 DOPNTMPPGFVLDO-UHFFFAOYSA-N 0.000 description 1
- GSYSFVSGPABNNL-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-(phenylmethoxycarbonylamino)acetate Chemical group COC(=O)C(P(=O)(OC)OC)NC(=O)OCC1=CC=CC=C1 GSYSFVSGPABNNL-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- VDCLSGXZVUDARN-UHFFFAOYSA-N molecular bromine;pyridine;hydrobromide Chemical compound Br.BrBr.C1=CC=NC=C1 VDCLSGXZVUDARN-UHFFFAOYSA-N 0.000 description 1
- NSBNSZAXNUGWDJ-UHFFFAOYSA-O monopyridin-1-ium tribromide Chemical compound Br[Br-]Br.C1=CC=[NH+]C=C1 NSBNSZAXNUGWDJ-UHFFFAOYSA-O 0.000 description 1
- STUHQDIOZQUPGP-UHFFFAOYSA-N morpholin-4-ium-4-carboxylate Chemical compound OC(=O)N1CCOCC1 STUHQDIOZQUPGP-UHFFFAOYSA-N 0.000 description 1
- XXGPJVZDKNCYDC-UHFFFAOYSA-N n,n'-dicyclohexylmethanediimine;hydrochloride Chemical compound Cl.C1CCCCC1N=C=NC1CCCCC1 XXGPJVZDKNCYDC-UHFFFAOYSA-N 0.000 description 1
- GXJOGIZULUFHMK-UHFFFAOYSA-N n-[2-[2-(3,5-dimethylphenyl)-5-(1,3-thiazol-2-yl)-1h-indol-3-yl]ethyl]-4-(4-hydroxyphenyl)butanamide Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(=CC=C3N2)C=2SC=CN=2)CCNC(=O)CCCC=2C=CC(O)=CC=2)=C1 GXJOGIZULUFHMK-UHFFFAOYSA-N 0.000 description 1
- DBHZQAGMOINZHB-UHFFFAOYSA-N n-[4-[4-(benzylamino)butyl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1CCCCNCC1=CC=CC=C1 DBHZQAGMOINZHB-UHFFFAOYSA-N 0.000 description 1
- VYKQSRLLIVRENL-UHFFFAOYSA-N n-[4-[4-[2-[2-(3,5-dimethylphenyl)-5-(2-methyl-1-oxo-1-pyrrolidin-1-ylpropan-2-yl)-1h-indol-3-yl]ethylamino]butyl]phenyl]methanesulfonamide Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(=CC=C3N2)C(C)(C)C(=O)N2CCCC2)CCNCCCCC=2C=CC(NS(C)(=O)=O)=CC=2)=C1 VYKQSRLLIVRENL-UHFFFAOYSA-N 0.000 description 1
- BKPIVMYVSGXJCB-UHFFFAOYSA-N n-[4-[4-[2-[2-(3,5-dimethylphenyl)-5-(3-ethyl-2-oxoimidazolidin-1-yl)-1h-indol-3-yl]ethylamino]butyl]phenyl]methanesulfonamide Chemical compound O=C1N(CC)CCN1C1=CC=C(NC(=C2CCNCCCCC=3C=CC(NS(C)(=O)=O)=CC=3)C=3C=C(C)C=C(C)C=3)C2=C1 BKPIVMYVSGXJCB-UHFFFAOYSA-N 0.000 description 1
- DEELIPXTZMJFRL-UHFFFAOYSA-N n-[4-[4-[2-[2-(3,5-dimethylphenyl)-5-(5-methyltetrazol-1-yl)-1h-indol-3-yl]ethylamino]butyl]phenyl]methanesulfonamide Chemical compound CC1=NN=NN1C1=CC=C(NC(=C2CCNCCCCC=3C=CC(NS(C)(=O)=O)=CC=3)C=3C=C(C)C=C(C)C=3)C2=C1 DEELIPXTZMJFRL-UHFFFAOYSA-N 0.000 description 1
- FUNSVWNYPBWHOX-UHFFFAOYSA-N n-[4-[4-[2-[2-(3,5-dimethylphenyl)-5-(morpholine-4-carbonyl)-1h-indol-3-yl]ethylamino]butyl]phenyl]methanesulfonamide Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(=CC=C3N2)C(=O)N2CCOCC2)CCNCCCCC=2C=CC(NS(C)(=O)=O)=CC=2)=C1 FUNSVWNYPBWHOX-UHFFFAOYSA-N 0.000 description 1
- IPQCYXWQCNGRPN-UHFFFAOYSA-N n-[4-[4-[2-[2-(3,5-dimethylphenyl)-5-[(4-methyl-1,3-thiazol-2-yl)amino]-1h-indol-3-yl]ethylamino]butyl]phenyl]methanesulfonamide Chemical compound CC1=CSC(NC=2C=C3C(CCNCCCCC=4C=CC(NS(C)(=O)=O)=CC=4)=C(NC3=CC=2)C=2C=C(C)C=C(C)C=2)=N1 IPQCYXWQCNGRPN-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- PUUSSSIBPPTKTP-UHFFFAOYSA-N neridronic acid Chemical compound NCCCCCC(O)(P(O)(O)=O)P(O)(O)=O PUUSSSIBPPTKTP-UHFFFAOYSA-N 0.000 description 1
- 239000003176 neuroleptic agent Substances 0.000 description 1
- 230000000701 neuroleptic effect Effects 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 150000002924 oxiranes Chemical class 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 description 1
- 229960003978 pamidronic acid Drugs 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 125000005543 phthalimide group Chemical group 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
- 229940074439 potassium sodium tartrate Drugs 0.000 description 1
- 239000001120 potassium sulphate Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229960000208 pralmorelin Drugs 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- WWKUMKJLPJGKHU-UHFFFAOYSA-N pyrrolidin-2-one;trihydrobromide Chemical compound Br.Br.Br.O=C1CCCN1 WWKUMKJLPJGKHU-UHFFFAOYSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000003488 releasing hormone Substances 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 229960000759 risedronic acid Drugs 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 208000022925 sleep disturbance Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 1
- QAHVHSLSRLSVGS-UHFFFAOYSA-N sulfamoyl chloride Chemical compound NS(Cl)(=O)=O QAHVHSLSRLSVGS-UHFFFAOYSA-N 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 description 1
- AIOAWQJLDMSASE-UHFFFAOYSA-N tert-butyl n-[2-[5-amino-2-(3,5-dimethylphenyl)-1h-indol-3-yl]ethyl]-n-[4-[4-(methanesulfonamido)phenyl]butyl]carbamate Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(N)=CC=C3N2)CCN(CCCCC=2C=CC(NS(C)(=O)=O)=CC=2)C(=O)OC(C)(C)C)=C1 AIOAWQJLDMSASE-UHFFFAOYSA-N 0.000 description 1
- VOVZHHIXKHCPLM-UHFFFAOYSA-N tert-butyl n-[4-[4-amino-2,3-bis(methylsulfonyl)phenyl]butyl]-n-[2-[2-(3,5-dimethylphenyl)-5-(5-methyltetrazol-1-yl)-1h-indol-3-yl]ethyl]carbamate Chemical compound CC1=NN=NN1C1=CC=C(NC(=C2CCN(CCCCC=3C(=C(C(N)=CC=3)S(C)(=O)=O)S(C)(=O)=O)C(=O)OC(C)(C)C)C=3C=C(C)C=C(C)C=3)C2=C1 VOVZHHIXKHCPLM-UHFFFAOYSA-N 0.000 description 1
- KQRALTHTWHBNOY-UHFFFAOYSA-N tert-butyl n-[4-[4-amino-2,3-bis(methylsulfonyl)phenyl]butyl]-n-[2-[5-amino-2-(3,5-dimethylphenyl)-1h-indol-3-yl]ethyl]carbamate Chemical compound CC1=CC(C)=CC(C2=C(C3=CC(N)=CC=C3N2)CCN(CCCCC=2C(=C(C(N)=CC=2)S(C)(=O)=O)S(C)(=O)=O)C(=O)OC(C)(C)C)=C1 KQRALTHTWHBNOY-UHFFFAOYSA-N 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229960005324 tiludronic acid Drugs 0.000 description 1
- 238000006257 total synthesis reaction Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 229940100640 transdermal system Drugs 0.000 description 1
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000009736 wetting Methods 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
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/02—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 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
- C07D405/02—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
- 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
- C07D413/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US863195P | 1995-12-14 | 1995-12-14 | |
| GBGB9603344.4A GB9603344D0 (en) | 1996-02-16 | 1996-02-16 | Antagonists of gonadotropin releasing hormone |
| PCT/US1996/019767 WO1997021707A1 (en) | 1995-12-14 | 1996-12-10 | Antagonists of gonadotropin releasing hormone |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK77498A3 true SK77498A3 (en) | 1999-01-11 |
Family
ID=26308739
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK774-98A SK77498A3 (en) | 1995-12-14 | 1996-12-10 | Nonpeptide derivatives, pharmaceutical composition containing them and their use |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US6197975B1 (cs) |
| EP (1) | EP0882040A4 (cs) |
| JP (2) | JP3092946B2 (cs) |
| KR (1) | KR19990072123A (cs) |
| CN (1) | CN1209129A (cs) |
| AU (1) | AU707277B2 (cs) |
| CA (1) | CA2240111A1 (cs) |
| CZ (1) | CZ183198A3 (cs) |
| EA (1) | EA000828B1 (cs) |
| EE (1) | EE9800180A (cs) |
| IL (1) | IL124554A0 (cs) |
| NO (1) | NO982730L (cs) |
| NZ (1) | NZ325060A (cs) |
| PL (1) | PL327397A1 (cs) |
| SK (1) | SK77498A3 (cs) |
| WO (1) | WO1997021707A1 (cs) |
Families Citing this family (59)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997021435A1 (en) * | 1995-12-14 | 1997-06-19 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
| US5981550A (en) * | 1997-06-05 | 1999-11-09 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
| EP0986385A4 (en) * | 1997-06-05 | 2001-05-16 | Merck & Co Inc | GONADORELIN ANTAGONISTS |
| US6156767A (en) * | 1997-06-05 | 2000-12-05 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
| US6004984A (en) * | 1997-06-05 | 1999-12-21 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
| US6156772A (en) * | 1997-06-05 | 2000-12-05 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
| US5985901A (en) * | 1997-06-05 | 1999-11-16 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
| DK1027047T3 (da) * | 1997-08-06 | 2007-01-29 | Smithkline Beecham Corp | Eprosartan-arginyl-ladningsneutraliseringskompleks og fremgangsmåde til dets fremstilling og formulering |
| US6211224B1 (en) | 1997-10-28 | 2001-04-03 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
| US6159975A (en) * | 1998-02-11 | 2000-12-12 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
| US6110931A (en) * | 1998-04-02 | 2000-08-29 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
| US6077847A (en) * | 1998-04-02 | 2000-06-20 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
| US6025366A (en) * | 1998-04-02 | 2000-02-15 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
| US5998432A (en) * | 1998-04-02 | 1999-12-07 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
| US6228867B1 (en) | 1998-04-02 | 2001-05-08 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
| US5985892A (en) * | 1998-04-02 | 1999-11-16 | Merck & Co., Ltd. | Antagonists of gonadotropin releasing hormone |
| US7101878B1 (en) | 1998-08-20 | 2006-09-05 | Agouron Pharmaceuticals, Inc. | Non-peptide GNRH agents, methods and intermediates for their preparation |
| HUP0103622A3 (en) * | 1998-08-20 | 2003-01-28 | Agouron Pharmaceuticals Inc La | Non-peptide gnrh agents, methods and intermediates for their preparation and medicaments containing them |
| US6346534B1 (en) | 1998-09-23 | 2002-02-12 | Neurocrine Biosciences, Inc. | Gonadotropin-releasing hormone receptor antagonists and methods relating thereto |
| EP1171125A1 (en) | 1999-03-10 | 2002-01-16 | Merck & Co., Inc. | 6-azaindole compounds as antagonists of gonadotropin releasing hormone |
| AU3514200A (en) | 1999-03-10 | 2000-09-28 | Merck & Co., Inc. | 6-azaindole compounds as antagonists of gonadotropin releasing hormone |
| CA2367121A1 (en) * | 1999-03-10 | 2000-09-14 | Merck & Co., Inc. | 6-azaindole compounds as antagonists of gonadotropin releasing hormone |
| EP1161431A4 (en) * | 1999-03-10 | 2002-04-24 | Merck & Co Inc | 6-AZAINDOL COMPOUNDS AS AN ANTAGONISTS OF THE GONADOTROPIN RELEASE HORMONES |
| ATE278674T1 (de) * | 1999-03-12 | 2004-10-15 | Boehringer Ingelheim Pharma | Heterocyklischer harnstoff und verwandte verbindungen als entzündungshemmende mittel |
| US6537998B1 (en) | 1999-10-15 | 2003-03-25 | Neurocrine Biosciences, Inc. | Gonadotropin-releasing hormone receptor antagonists and methods relating thereto |
| WO2001055119A2 (en) | 2000-01-25 | 2001-08-02 | Neurocrine Biosciences, Inc. | Gonadotropin-releasing hormone receptor antagonists and methods relating thereto |
| US20020037912A1 (en) * | 2000-08-11 | 2002-03-28 | Leahy Ellen M. | Factor viia inhibitors |
| US6645990B2 (en) | 2000-08-15 | 2003-11-11 | Amgen Inc. | Thiazolyl urea compounds and methods of uses |
| GB0022670D0 (en) | 2000-09-15 | 2000-11-01 | Astrazeneca Ab | Molecules |
| US6583153B2 (en) | 2000-12-12 | 2003-06-24 | Ortho-Mcneil Pharmaceutical, Inc. | 7-heterocyclyl quinoline and thieno[2,3-b]yridine derivatives useful as antagonists of gonadotropin releasing hormone |
| SE0100566D0 (sv) | 2001-02-20 | 2001-02-20 | Astrazeneca Ab | Compounds |
| SE0101692D0 (sv) | 2001-05-14 | 2001-05-14 | Astrazeneca Ab | Compounds |
| EP1411941A2 (en) | 2001-08-02 | 2004-04-28 | Neurocrine Biosciences, Inc. | Pyridinone and pyridazinone derivatives as gonadotropin-releasing hormone receptor antagonists |
| AU2002324586B2 (en) | 2001-08-02 | 2008-04-24 | Neurocrine Biosciences, Inc. | 1,3,5-triazine-2,4,6-triones, preparation and use as gonadotropin-releasing hormone receptor antagonists |
| WO2003011870A1 (en) | 2001-08-02 | 2003-02-13 | Neurocrine Biosciences, Inc. | Gonadotropin-releasing hormone receptor antagonists |
| JP2005500352A (ja) | 2001-08-02 | 2005-01-06 | ニューロクライン バイオサイエンシーズ, インコーポレイテッド | ゴナドトロピン放出ホルモンレセプター(GnRH)アンタゴニストとしての1,2,4−トリアジン−3,5−ジオン |
| US6939883B2 (en) | 2001-08-02 | 2005-09-06 | Neurocrine Biosciences, Inc. | Gonadotropin-releasing hormone receptor antagonists and methods relating thereto |
| DE10203086A1 (de) * | 2002-01-28 | 2003-07-31 | Bayer Ag | 5-Ring Heterozyklen |
| WO2003068769A1 (en) | 2002-02-12 | 2003-08-21 | Pfizer Inc. | Non-peptide compounds affecting the action of gonadotropin-releasing hormone (gnrh) |
| AU2003239508A1 (en) | 2002-05-21 | 2003-12-12 | Bristol-Myers Squibb Company | Indole compounds useful as impdh inhibitors |
| CA2489252A1 (en) | 2002-06-13 | 2003-12-24 | Pfizer Inc. | Non-peptide gnrh agents, pharmaceutical compositions and methods for their use |
| DE60314158T2 (de) | 2002-08-21 | 2008-01-31 | Astrazeneca Ab | Pyrazolderivate als gnrh-inhibitoren |
| GB0219472D0 (en) | 2002-08-21 | 2002-10-02 | Astrazeneca Ab | Chemical compounds |
| TW200413351A (en) | 2002-08-21 | 2004-08-01 | Astrazeneca Ab | Chemical compounds |
| JP2006508050A (ja) | 2002-08-21 | 2006-03-09 | アストラゼネカ アクチボラグ | ゴナドトロピン放出ホルモンのアンタゴニストとしてのチエノピロール化合物 |
| TW200407127A (en) | 2002-08-21 | 2004-05-16 | Astrazeneca Ab | Chemical compounds |
| US7189712B2 (en) * | 2002-10-10 | 2007-03-13 | Smithkline Beecham Corporation | 1,3-Oxazole compounds for the treatment of cancer |
| DE602004020638D1 (de) | 2003-07-07 | 2009-05-28 | Neurocrine Biosciences Inc | Pyrimidin-2,4-dion-derivate als gonadotropin freisetzende hormon-rezeptor-antagonisten |
| ES2387495T3 (es) | 2003-07-07 | 2012-09-25 | Neurocrine Biosciences, Inc. | Arilpirimidinas útiles en el tratamiento de trastornos relacionados con las hormonas sexuales, tales como endometriosis, cáncer de próstata y similares |
| AU2004257639B2 (en) | 2003-07-07 | 2011-01-06 | Neurocrine Biosciences, Inc. | Pyrimidine-2, 4-dione derivatives as gonadotropin-releasing hormone receptor antagonists |
| US20070142437A1 (en) * | 2005-04-08 | 2007-06-21 | Brown Matthew L | Chemical compounds |
| EP2204368B1 (en) * | 2007-09-21 | 2014-05-21 | Msd K.K. | 4-sulfonylpiperidine derivatives |
| JP2011511800A (ja) | 2008-02-07 | 2011-04-14 | アボット・ラボラトリーズ | 正のアロステリックな修飾物質としてのアミド誘導体およびこれらの使用方法 |
| JP5468289B2 (ja) * | 2008-04-18 | 2014-04-09 | 石原産業株式会社 | ピリミジン系化合物の製造方法 |
| TW201130854A (en) | 2009-12-22 | 2011-09-16 | Bayer Schering Pharma Ag | Pyridinone derivatives and pharmaceutical compositions thereof |
| WO2012175514A1 (en) | 2011-06-21 | 2012-12-27 | Bayer Intellectual Property Gmbh | Pyridinone derivatives and pharmaceutical compositions thereof |
| WO2018002673A1 (en) | 2016-07-01 | 2018-01-04 | N4 Pharma Uk Limited | Novel formulations of angiotensin ii receptor antagonists |
| CN113527254B (zh) * | 2021-07-07 | 2022-05-03 | 北京华氏信华科生物科技有限公司 | 7-甲氧基-1h-吲哚类化合物、制备方法、药物组合物及应用 |
| CN113387867B (zh) * | 2021-07-15 | 2023-03-14 | 南华大学 | 一种氨基甲酸酯类邻氨基苯甲酸色胺衍生物及其制备与应用 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2825734A (en) | 1955-04-11 | 1958-03-04 | Upjohn Co | Reduction of carbonylic radicals in indolyl-3 compounds |
| FR2181559A1 (en) * | 1972-04-28 | 1973-12-07 | Aec Chimie Organique Bio | N-Phenylalkyl-N-3-indolylalkyl-alkylamines - with sedative, neuroleptic, analgesic, hypotensive, antiserotonin, adrenolytic activity |
| FR2354766A1 (fr) | 1976-06-17 | 1978-01-13 | Labaz | Derives n-aminoalkyles d'indole et procedes pour les preparer |
| ZA795239B (en) | 1978-10-12 | 1980-11-26 | Glaxo Group Ltd | Heterocyclic compounds |
| US4678784A (en) * | 1984-04-11 | 1987-07-07 | Mcneilab, Inc. | Method for the treatment of LHRH diseases and conditions |
| US4544663A (en) | 1984-05-07 | 1985-10-01 | Sandoz, Inc. | Indolamine derivatives as anti-fertility agents |
| DE3821148A1 (de) | 1988-06-23 | 1989-12-28 | Erwin Von Dr Angerer | Aminoalkylindole, verfahren zu deren herstellung und diese enthaltende pharmazeutische praeparate |
| WO1990005721A1 (en) | 1988-11-14 | 1990-05-31 | The Upjohn Company | Alpha-amino-indole-3-acetic acids useful as anti-diabetic, anti-obesity and anti-atherosclerotic agents |
| US5030640A (en) | 1989-01-05 | 1991-07-09 | Merck & Co., Inc. | Novel β-adrenergic agonists and pharmaceutical compositions thereof |
| US6756388B1 (en) * | 1993-10-12 | 2004-06-29 | Pfizer Inc. | Benzothiophenes and related compounds as estrogen agonists |
| TW449600B (en) | 1994-04-19 | 2001-08-11 | Takeda Chemical Industries Ltd | Condensed-ring thiophene derivatives, their production and use |
| US5607939A (en) | 1994-04-28 | 1997-03-04 | Takeda Chemical Industries, Ltd. | Condensed heterocyclic compounds, their production and use |
| DE69528257T2 (de) | 1994-04-29 | 2003-05-15 | Takeda Chemical Industries, Ltd. | KONDENSIERTE HETEROCYCLISCHE VERBINDUNG, DEREN HERSTELLUNG UND VERWENDUNG ALS GnRH ANTAGONISTEN |
| WO1997021435A1 (en) * | 1995-12-14 | 1997-06-19 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
| US5780437A (en) | 1995-12-14 | 1998-07-14 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
| US5756507A (en) | 1995-12-14 | 1998-05-26 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
-
1996
- 1996-12-10 JP JP09522193A patent/JP3092946B2/ja not_active Expired - Fee Related
- 1996-12-10 EP EP96943711A patent/EP0882040A4/en not_active Withdrawn
- 1996-12-10 AU AU12876/97A patent/AU707277B2/en not_active Ceased
- 1996-12-10 EA EA199800559A patent/EA000828B1/ru not_active IP Right Cessation
- 1996-12-10 IL IL12455496A patent/IL124554A0/xx unknown
- 1996-12-10 EE EE9800180A patent/EE9800180A/xx unknown
- 1996-12-10 US US09/077,565 patent/US6197975B1/en not_active Expired - Fee Related
- 1996-12-10 CN CN96199923A patent/CN1209129A/zh active Pending
- 1996-12-10 PL PL96327397A patent/PL327397A1/xx unknown
- 1996-12-10 WO PCT/US1996/019767 patent/WO1997021707A1/en not_active Ceased
- 1996-12-10 CA CA002240111A patent/CA2240111A1/en not_active Abandoned
- 1996-12-10 NZ NZ325060A patent/NZ325060A/xx unknown
- 1996-12-10 SK SK774-98A patent/SK77498A3/sk unknown
- 1996-12-10 CZ CZ981831A patent/CZ183198A3/cs unknown
- 1996-12-10 KR KR1019980704441A patent/KR19990072123A/ko not_active Ceased
-
1998
- 1998-06-12 NO NO982730A patent/NO982730L/no not_active Application Discontinuation
-
2000
- 2000-02-15 JP JP2000036746A patent/JP2000212161A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US6197975B1 (en) | 2001-03-06 |
| JPH11502538A (ja) | 1999-03-02 |
| AU707277B2 (en) | 1999-07-08 |
| NZ325060A (en) | 2000-02-28 |
| JP2000212161A (ja) | 2000-08-02 |
| EE9800180A (et) | 1998-12-15 |
| MX9804819A (es) | 1998-10-31 |
| EP0882040A4 (en) | 1999-02-10 |
| NO982730L (no) | 1998-08-13 |
| NO982730D0 (no) | 1998-06-12 |
| CA2240111A1 (en) | 1997-06-19 |
| KR19990072123A (ko) | 1999-09-27 |
| EP0882040A1 (en) | 1998-12-09 |
| EA000828B1 (ru) | 2000-04-24 |
| EA199800559A1 (ru) | 1998-12-24 |
| JP3092946B2 (ja) | 2000-09-25 |
| CZ183198A3 (cs) | 1998-10-14 |
| AU1287697A (en) | 1997-07-03 |
| PL327397A1 (en) | 1998-12-07 |
| WO1997021707A1 (en) | 1997-06-19 |
| IL124554A0 (en) | 1998-12-06 |
| CN1209129A (zh) | 1999-02-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| SK77498A3 (en) | Nonpeptide derivatives, pharmaceutical composition containing them and their use | |
| AU707641B2 (en) | Antagonists of gonadotropin releasing hormone | |
| AU704937B2 (en) | Antagonists of gonadotropin releasing hormone | |
| SK77598A3 (en) | Nonpeptide derivatives, pharmaceutical composition containing them and their use | |
| AU729752B2 (en) | Antagonists of gonadotropin releasing hormone | |
| EP1095038B1 (en) | Antagonists of gonadotropin releasing hormone | |
| US6156772A (en) | Antagonists of gonadotropin releasing hormone | |
| JP2002503252A (ja) | ゴナドトロピン放出ホルモンの拮抗薬 | |
| US5981550A (en) | Antagonists of gonadotropin releasing hormone | |
| JP2001520996A (ja) | 性腺刺激ホルモン放出ホルモン拮抗薬 | |
| AU2597899A (en) | Antagonists of gonadotropin releasing hormone | |
| US5985901A (en) | Antagonists of gonadotropin releasing hormone |