RU2239642C1 - Селективные циклопептиды - Google Patents
Селективные циклопептиды Download PDFInfo
- Publication number
- RU2239642C1 RU2239642C1 RU2003107921/04A RU2003107921A RU2239642C1 RU 2239642 C1 RU2239642 C1 RU 2239642C1 RU 2003107921/04 A RU2003107921/04 A RU 2003107921/04A RU 2003107921 A RU2003107921 A RU 2003107921A RU 2239642 C1 RU2239642 C1 RU 2239642C1
- Authority
- RU
- Russia
- Prior art keywords
- lys
- asp
- hydrogen atom
- phe
- mmol
- Prior art date
Links
- 102000001189 Cyclic Peptides Human genes 0.000 title description 12
- 108010069514 Cyclic Peptides Proteins 0.000 title description 12
- 150000001875 compounds Chemical class 0.000 claims abstract description 221
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 134
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 127
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 89
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 88
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 71
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 56
- 238000000034 method Methods 0.000 claims abstract description 54
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 35
- 150000003839 salts Chemical class 0.000 claims abstract description 20
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 13
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 13
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 11
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims abstract description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
- OAMLVOVXNKILLQ-BQBZGAKWSA-N Asp-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC(O)=O OAMLVOVXNKILLQ-BQBZGAKWSA-N 0.000 claims description 36
- 108010092854 aspartyllysine Proteins 0.000 claims description 36
- 230000015572 biosynthetic process Effects 0.000 claims description 28
- 229910052760 oxygen Inorganic materials 0.000 claims description 27
- 108010021436 Type 4 Melanocortin Receptor Proteins 0.000 claims description 17
- 239000002243 precursor Substances 0.000 claims description 12
- 230000001270 agonistic effect Effects 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- OABOXRPGTFRBFZ-IMJSIDKUSA-N Cys-Cys Chemical compound SC[C@H](N)C(=O)N[C@@H](CS)C(O)=O OABOXRPGTFRBFZ-IMJSIDKUSA-N 0.000 claims description 6
- 108010004073 cysteinylcysteine Proteins 0.000 claims description 6
- BBBXWRGITSUJPB-YUMQZZPRSA-N Glu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CCC(O)=O BBBXWRGITSUJPB-YUMQZZPRSA-N 0.000 claims description 3
- 229910052727 yttrium Inorganic materials 0.000 claims description 3
- 125000001475 halogen functional group Chemical group 0.000 claims 11
- 102000001796 Melanocortin 4 receptors Human genes 0.000 claims 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
- NEHSHYOUIWBYSA-DCPHZVHLSA-N Phe-Ala-Trp Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CC3=CC=CC=C3)N NEHSHYOUIWBYSA-DCPHZVHLSA-N 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 abstract description 15
- 230000000694 effects Effects 0.000 abstract description 12
- 239000001257 hydrogen Substances 0.000 abstract description 8
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 8
- 239000000556 agonist Substances 0.000 abstract description 7
- 239000000126 substance Substances 0.000 abstract description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 4
- 125000005113 hydroxyalkoxy group Chemical group 0.000 abstract 1
- 230000007721 medicinal effect Effects 0.000 abstract 1
- 125000004430 oxygen atom Chemical group O* 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 290
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 243
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 194
- 239000000243 solution Substances 0.000 description 190
- 239000011541 reaction mixture Substances 0.000 description 178
- 238000006243 chemical reaction Methods 0.000 description 175
- 239000011347 resin Substances 0.000 description 174
- 229920005989 resin Polymers 0.000 description 174
- 239000000203 mixture Substances 0.000 description 166
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 165
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 160
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 150
- 235000019439 ethyl acetate Nutrition 0.000 description 136
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 112
- 239000007787 solid Substances 0.000 description 109
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 105
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 104
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 99
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 94
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 92
- 239000011734 sodium Substances 0.000 description 91
- 238000004128 high performance liquid chromatography Methods 0.000 description 90
- 239000000460 chlorine Substances 0.000 description 89
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 80
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 79
- 235000001014 amino acid Nutrition 0.000 description 77
- 239000000047 product Substances 0.000 description 76
- 150000001413 amino acids Chemical class 0.000 description 75
- 238000006482 condensation reaction Methods 0.000 description 74
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 72
- 239000003921 oil Substances 0.000 description 69
- 239000012267 brine Substances 0.000 description 68
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 68
- 239000010410 layer Substances 0.000 description 66
- 238000005160 1H NMR spectroscopy Methods 0.000 description 63
- 238000010894 electron beam technology Methods 0.000 description 61
- 239000000872 buffer Substances 0.000 description 58
- 239000012043 crude product Substances 0.000 description 58
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 54
- -1 alkoxy radical Chemical class 0.000 description 54
- 229940091173 hydantoin Drugs 0.000 description 54
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 53
- 238000002360 preparation method Methods 0.000 description 51
- 239000002904 solvent Substances 0.000 description 51
- 238000003818 flash chromatography Methods 0.000 description 49
- 239000002244 precipitate Substances 0.000 description 47
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 46
- 239000000725 suspension Substances 0.000 description 46
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 45
- 239000000284 extract Substances 0.000 description 45
- 238000000746 purification Methods 0.000 description 45
- 230000002829 reductive effect Effects 0.000 description 45
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 40
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 39
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 38
- 238000001914 filtration Methods 0.000 description 37
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 36
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 36
- 125000006239 protecting group Chemical group 0.000 description 35
- 239000012442 inert solvent Substances 0.000 description 34
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 33
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 32
- 238000007363 ring formation reaction Methods 0.000 description 31
- 238000009835 boiling Methods 0.000 description 30
- 239000000706 filtrate Substances 0.000 description 30
- HPPMDXOUISVKNA-UHFFFAOYSA-N ditert-butyl 2,5-dioxoimidazolidine-4,4-dicarboxylate Chemical compound CC(C)(C)OC(=O)C1(C(=O)OC(C)(C)C)NC(=O)NC1=O HPPMDXOUISVKNA-UHFFFAOYSA-N 0.000 description 28
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 27
- 239000001099 ammonium carbonate Substances 0.000 description 27
- 235000012501 ammonium carbonate Nutrition 0.000 description 27
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 27
- 239000002253 acid Substances 0.000 description 26
- 238000010532 solid phase synthesis reaction Methods 0.000 description 26
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 24
- 239000012044 organic layer Substances 0.000 description 24
- 239000003795 chemical substances by application Substances 0.000 description 23
- 238000003786 synthesis reaction Methods 0.000 description 23
- 239000003153 chemical reaction reagent Substances 0.000 description 22
- 238000004440 column chromatography Methods 0.000 description 22
- 239000005457 ice water Substances 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 238000002953 preparative HPLC Methods 0.000 description 21
- WMSUFWLPZLCIHP-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 9h-fluoren-9-ylmethyl carbonate Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1COC(=O)ON1C(=O)CCC1=O WMSUFWLPZLCIHP-UHFFFAOYSA-N 0.000 description 20
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 20
- 238000004458 analytical method Methods 0.000 description 20
- 239000000463 material Substances 0.000 description 20
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 20
- 125000003277 amino group Chemical group 0.000 description 19
- DHBXNPKRAUYBTH-UHFFFAOYSA-N 1,1-ethanedithiol Chemical compound CC(S)S DHBXNPKRAUYBTH-UHFFFAOYSA-N 0.000 description 18
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 18
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 18
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 18
- 125000004122 cyclic group Chemical group 0.000 description 17
- 239000007858 starting material Substances 0.000 description 17
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 16
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 16
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 16
- 235000019341 magnesium sulphate Nutrition 0.000 description 16
- 229920001184 polypeptide Polymers 0.000 description 16
- 238000005406 washing Methods 0.000 description 16
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
- 102000008316 Type 4 Melanocortin Receptor Human genes 0.000 description 15
- 150000008064 anhydrides Chemical class 0.000 description 15
- 239000011521 glass Substances 0.000 description 15
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 14
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 14
- 238000001514 detection method Methods 0.000 description 14
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 14
- 239000000843 powder Substances 0.000 description 14
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- 238000001816 cooling Methods 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- 238000004809 thin layer chromatography Methods 0.000 description 13
- 238000011282 treatment Methods 0.000 description 13
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 11
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 11
- 239000002585 base Substances 0.000 description 11
- 239000000839 emulsion Substances 0.000 description 11
- 238000005755 formation reaction Methods 0.000 description 11
- 238000006460 hydrolysis reaction Methods 0.000 description 11
- 229910052938 sodium sulfate Inorganic materials 0.000 description 11
- 235000011152 sodium sulphate Nutrition 0.000 description 11
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 10
- 208000008589 Obesity Diseases 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 239000000908 ammonium hydroxide Substances 0.000 description 10
- 230000007062 hydrolysis Effects 0.000 description 10
- 150000002576 ketones Chemical class 0.000 description 10
- 235000020824 obesity Nutrition 0.000 description 10
- 230000008569 process Effects 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- 238000004949 mass spectrometry Methods 0.000 description 9
- 150000007530 organic bases Chemical class 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- 229910052708 sodium Inorganic materials 0.000 description 9
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 9
- KPKNTUUIEVXMOH-UHFFFAOYSA-N 1,4-dioxa-8-azaspiro[4.5]decane Chemical compound O1CCOC11CCNCC1 KPKNTUUIEVXMOH-UHFFFAOYSA-N 0.000 description 8
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
- MGHPNCMVUAKAIE-UHFFFAOYSA-N diphenylmethanamine Chemical compound C=1C=CC=CC=1C(N)C1=CC=CC=C1 MGHPNCMVUAKAIE-UHFFFAOYSA-N 0.000 description 8
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 8
- 238000001035 drying Methods 0.000 description 7
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 7
- 229910017053 inorganic salt Inorganic materials 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 229910052744 lithium Inorganic materials 0.000 description 7
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 7
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 6
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 6
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 6
- FVAUUMOEPILPAD-UHFFFAOYSA-N 4-(2-bromophenyl)-1-diazoniobut-1-en-2-olate Chemical compound BrC1=CC=CC=C1CCC(=O)C=[N+]=[N-] FVAUUMOEPILPAD-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 102100034216 Melanocyte-stimulating hormone receptor Human genes 0.000 description 6
- 101710161100 Melanocyte-stimulating hormone receptor Proteins 0.000 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
- 230000002378 acidificating effect Effects 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 6
- 125000000539 amino acid group Chemical group 0.000 description 6
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 6
- 238000003776 cleavage reaction Methods 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 6
- LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 description 6
- 230000007017 scission Effects 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- QDMNNMIOWVJVLY-QMMMGPOBSA-N (4r)-4-phenyl-1,3-oxazolidin-2-one Chemical compound C1OC(=O)N[C@@H]1C1=CC=CC=C1 QDMNNMIOWVJVLY-QMMMGPOBSA-N 0.000 description 5
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 5
- VZUNGTLZRAYYDE-UHFFFAOYSA-N N-methyl-N'-nitro-N-nitrosoguanidine Chemical compound O=NN(C)C(=N)N[N+]([O-])=O VZUNGTLZRAYYDE-UHFFFAOYSA-N 0.000 description 5
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 5
- 230000003213 activating effect Effects 0.000 description 5
- 210000004900 c-terminal fragment Anatomy 0.000 description 5
- 238000010828 elution Methods 0.000 description 5
- 238000005984 hydrogenation reaction Methods 0.000 description 5
- 238000011065 in-situ storage Methods 0.000 description 5
- 150000003951 lactams Chemical class 0.000 description 5
- PMDKYLLIOLFQPO-UHFFFAOYSA-N monocyclohexyl phthalate Chemical compound OC(=O)C1=CC=CC=C1C(=O)OC1CCCCC1 PMDKYLLIOLFQPO-UHFFFAOYSA-N 0.000 description 5
- 238000006386 neutralization reaction Methods 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 230000002441 reversible effect Effects 0.000 description 5
- VUPQHSHTKBZVML-UHFFFAOYSA-J rhodium(3+);tetraacetate Chemical compound [Rh+3].[Rh+3].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O VUPQHSHTKBZVML-UHFFFAOYSA-J 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- SLJYPZJZQIHNGU-UHFFFAOYSA-N 4-(4-hydroxyphenyl)cyclohexan-1-one Chemical compound C1=CC(O)=CC=C1C1CCC(=O)CC1 SLJYPZJZQIHNGU-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
- 102000004378 Melanocortin Receptors Human genes 0.000 description 4
- 108090000950 Melanocortin Receptors Proteins 0.000 description 4
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 4
- 239000000370 acceptor Substances 0.000 description 4
- 230000008484 agonism Effects 0.000 description 4
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 4
- 150000008041 alkali metal carbonates Chemical class 0.000 description 4
- 150000001351 alkyl iodides Chemical class 0.000 description 4
- 235000008206 alpha-amino acids Nutrition 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 4
- 239000012876 carrier material Substances 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 4
- 238000010511 deprotection reaction Methods 0.000 description 4
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 150000007529 inorganic bases Chemical class 0.000 description 4
- 239000012948 isocyanate Substances 0.000 description 4
- 150000002513 isocyanates Chemical class 0.000 description 4
- 230000003472 neutralizing effect Effects 0.000 description 4
- 229910000510 noble metal Inorganic materials 0.000 description 4
- HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 description 4
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 238000004237 preparative chromatography Methods 0.000 description 4
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 239000011973 solid acid Substances 0.000 description 4
- 150000003512 tertiary amines Chemical class 0.000 description 4
- 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 4
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 4
- VKRKCBWIVLSRBJ-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]decan-8-one Chemical compound C1CC(=O)CCC21OCCO2 VKRKCBWIVLSRBJ-UHFFFAOYSA-N 0.000 description 3
- TWAYLYPZRSXEOS-UHFFFAOYSA-N 1-azaniumyl-4-phenylcyclohexane-1-carboxylate Chemical compound C1CC(N)(C(O)=O)CCC1C1=CC=CC=C1 TWAYLYPZRSXEOS-UHFFFAOYSA-N 0.000 description 3
- XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-tetralone Chemical compound C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- 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 3
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 3
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 150000001263 acyl chlorides Chemical class 0.000 description 3
- 150000001336 alkenes Chemical class 0.000 description 3
- 230000036528 appetite Effects 0.000 description 3
- 235000019789 appetite Nutrition 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 239000004202 carbamide Substances 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 239000013067 intermediate product Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- ZLDHYRXZZNDOKU-UHFFFAOYSA-N n,n-diethyl-3-trimethoxysilylpropan-1-amine Chemical compound CCN(CC)CCC[Si](OC)(OC)OC ZLDHYRXZZNDOKU-UHFFFAOYSA-N 0.000 description 3
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 239000012047 saturated solution Substances 0.000 description 3
- 150000003335 secondary amines Chemical class 0.000 description 3
- 150000003672 ureas Chemical class 0.000 description 3
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 3
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 2
- VYMPLPIFKRHAAC-UHFFFAOYSA-N 1,2-ethanedithiol Chemical compound SCCS VYMPLPIFKRHAAC-UHFFFAOYSA-N 0.000 description 2
- ZGXCBXRNNYACJW-UHFFFAOYSA-N 1,6-diethoxynaphthalene Chemical compound CCOC1=CC=CC2=CC(OCC)=CC=C21 ZGXCBXRNNYACJW-UHFFFAOYSA-N 0.000 description 2
- NQEWRICCONRTPO-UHFFFAOYSA-N 1-amino-4,4-diphenylcyclohexane-1-carboxylic acid Chemical compound C1CC(N)(C(O)=O)CCC1(C=1C=CC=CC=1)C1=CC=CC=C1 NQEWRICCONRTPO-UHFFFAOYSA-N 0.000 description 2
- NHESZUWTJISWMW-UHFFFAOYSA-N 1-amino-4-(4-hydroxyphenyl)cyclohexane-1-carboxylic acid Chemical compound C1CC(N)(C(O)=O)CCC1C1=CC=C(O)C=C1 NHESZUWTJISWMW-UHFFFAOYSA-N 0.000 description 2
- OUHFMUCLEQWCAV-UHFFFAOYSA-N 1-amino-4-cyclohexylcyclohexane-1-carboxylic acid Chemical compound C1CC(N)(C(O)=O)CCC1C1CCCCC1 OUHFMUCLEQWCAV-UHFFFAOYSA-N 0.000 description 2
- DTDJINWEWINFTH-UHFFFAOYSA-N 1-diazonio-4-(2-ethylphenyl)but-1-en-2-olate Chemical compound CCC1=CC=CC=C1CCC(=O)C=[N+]=[N-] DTDJINWEWINFTH-UHFFFAOYSA-N 0.000 description 2
- PNUHICIXXBYRSV-UHFFFAOYSA-N 1-diazonio-4-(2-methylphenyl)but-1-en-2-olate Chemical compound CC1=CC=CC=C1CCC(=O)C=[N+]=[N-] PNUHICIXXBYRSV-UHFFFAOYSA-N 0.000 description 2
- SORQIYFSJAWBNQ-UHFFFAOYSA-N 1-iodo-2-propan-2-ylbenzene Chemical compound CC(C)C1=CC=CC=C1I SORQIYFSJAWBNQ-UHFFFAOYSA-N 0.000 description 2
- RSHBAGGASAJQCH-UHFFFAOYSA-N 1-iodo-3-methoxybenzene Chemical compound COC1=CC=CC(I)=C1 RSHBAGGASAJQCH-UHFFFAOYSA-N 0.000 description 2
- UDHAWRUAECEBHC-UHFFFAOYSA-N 1-iodo-4-methylbenzene Chemical compound CC1=CC=C(I)C=C1 UDHAWRUAECEBHC-UHFFFAOYSA-N 0.000 description 2
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 2
- YECJUZIGFPJWGQ-UHFFFAOYSA-N 2,4,6-trimethylbenzenesulfonamide Chemical compound CC1=CC(C)=C(S(N)(=O)=O)C(C)=C1 YECJUZIGFPJWGQ-UHFFFAOYSA-N 0.000 description 2
- PVJZBZSCGJAWNG-UHFFFAOYSA-N 2,4,6-trimethylbenzenesulfonyl chloride Chemical compound CC1=CC(C)=C(S(Cl)(=O)=O)C(C)=C1 PVJZBZSCGJAWNG-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- VZKGHJWZNXLHGL-UHFFFAOYSA-N 2-amino-5-bromo-3,4-dihydro-1h-naphthalene-2-carboxylic acid Chemical compound C1=CC=C2CC(N)(C(O)=O)CCC2=C1Br VZKGHJWZNXLHGL-UHFFFAOYSA-N 0.000 description 2
- QJJJBCCHEJIXRN-UHFFFAOYSA-N 2-amino-5-chloro-3,4-dihydro-1h-naphthalene-2-carboxylic acid Chemical compound C1=CC=C2CC(N)(C(O)=O)CCC2=C1Cl QJJJBCCHEJIXRN-UHFFFAOYSA-N 0.000 description 2
- TZOUVKFDSMHCDO-UHFFFAOYSA-N 2-amino-5-ethoxy-3,4-dihydro-1h-naphthalene-2-carboxylic acid Chemical compound C1C(N)(C(O)=O)CCC2=C1C=CC=C2OCC TZOUVKFDSMHCDO-UHFFFAOYSA-N 0.000 description 2
- YWHHZSRATCCCFB-UHFFFAOYSA-N 2-amino-5-ethyl-3,4-dihydro-1h-naphthalene-2-carboxylic acid Chemical compound C1C(N)(C(O)=O)CCC2=C1C=CC=C2CC YWHHZSRATCCCFB-UHFFFAOYSA-N 0.000 description 2
- UGXYLCUDHNGECR-UHFFFAOYSA-N 2-amino-5-methyl-3,4-dihydro-1h-naphthalene-2-carboxylic acid Chemical compound C1C(N)(C(O)=O)CCC2=C1C=CC=C2C UGXYLCUDHNGECR-UHFFFAOYSA-N 0.000 description 2
- BJRDIGNYMJTPGG-UHFFFAOYSA-N 2-amino-5-propan-2-yl-3,4-dihydro-1h-naphthalene-2-carboxylic acid Chemical compound C1C(N)(C(O)=O)CCC2=C1C=CC=C2C(C)C BJRDIGNYMJTPGG-UHFFFAOYSA-N 0.000 description 2
- ACQBYUJUBTYSFF-UHFFFAOYSA-N 2-amino-5-propan-2-yloxy-3,4-dihydro-1h-naphthalene-2-carboxylic acid Chemical compound C1C(N)(C(O)=O)CCC2=C1C=CC=C2OC(C)C ACQBYUJUBTYSFF-UHFFFAOYSA-N 0.000 description 2
- QVIKUAVXSRNDPS-UHFFFAOYSA-N 2-methoxynaphthalen-1-ol Chemical compound C1=CC=CC2=C(O)C(OC)=CC=C21 QVIKUAVXSRNDPS-UHFFFAOYSA-N 0.000 description 2
- WPHUUIODWRNJLO-UHFFFAOYSA-N 2-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=CC=C1S(Cl)(=O)=O WPHUUIODWRNJLO-UHFFFAOYSA-N 0.000 description 2
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 2
- WJCNECQFLZSUEF-UHFFFAOYSA-N 3-(2-ethylphenyl)propanoyl chloride Chemical compound CCC1=CC=CC=C1CCC(Cl)=O WJCNECQFLZSUEF-UHFFFAOYSA-N 0.000 description 2
- RKVLCCNSCFCRQQ-UHFFFAOYSA-N 3-(2-propan-2-ylphenyl)propanoyl chloride Chemical compound CC(C)C1=CC=CC=C1CCC(Cl)=O RKVLCCNSCFCRQQ-UHFFFAOYSA-N 0.000 description 2
- PECYZEOJVXMISF-UHFFFAOYSA-N 3-aminoalanine Chemical compound [NH3+]CC(N)C([O-])=O PECYZEOJVXMISF-UHFFFAOYSA-N 0.000 description 2
- HJBLUNHMOKFZQX-UHFFFAOYSA-N 3-hydroxy-1,2,3-benzotriazin-4-one Chemical compound C1=CC=C2C(=O)N(O)N=NC2=C1 HJBLUNHMOKFZQX-UHFFFAOYSA-N 0.000 description 2
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 2
- QJPHZZUBQAASNR-UHFFFAOYSA-N 4,4-diphenylcyclohexan-1-one Chemical compound C1CC(=O)CCC1(C=1C=CC=CC=1)C1=CC=CC=C1 QJPHZZUBQAASNR-UHFFFAOYSA-N 0.000 description 2
- DWBASXJXOOJROY-UHFFFAOYSA-N 4-(3-methoxyphenyl)cyclohexan-1-one Chemical compound COC1=CC=CC(C2CCC(=O)CC2)=C1 DWBASXJXOOJROY-UHFFFAOYSA-N 0.000 description 2
- JNBOVWFOTNYTES-UHFFFAOYSA-N 4-(4-chlorophenyl)cyclohexan-1-one Chemical compound C1=CC(Cl)=CC=C1C1CCC(=O)CC1 JNBOVWFOTNYTES-UHFFFAOYSA-N 0.000 description 2
- VBGMDGDDOADTCY-UHFFFAOYSA-N 4-(4-ethoxyphenyl)cyclohexan-1-one Chemical compound C1=CC(OCC)=CC=C1C1CCC(=O)CC1 VBGMDGDDOADTCY-UHFFFAOYSA-N 0.000 description 2
- ZMMQLFXRGHSTSW-UHFFFAOYSA-N 4-(4-methoxyphenyl)cyclohexan-1-one Chemical compound C1=CC(OC)=CC=C1C1CCC(=O)CC1 ZMMQLFXRGHSTSW-UHFFFAOYSA-N 0.000 description 2
- XDHMORMQXOUOHT-UHFFFAOYSA-N 4-(4-methylphenyl)cyclohexan-1-one Chemical compound C1=CC(C)=CC=C1C1CCC(=O)CC1 XDHMORMQXOUOHT-UHFFFAOYSA-N 0.000 description 2
- SUFQPKJYDDUXQC-UHFFFAOYSA-N 4-(4-propan-2-yloxyphenyl)cyclohexan-1-one Chemical compound C1=CC(OC(C)C)=CC=C1C1CCC(=O)CC1 SUFQPKJYDDUXQC-UHFFFAOYSA-N 0.000 description 2
- OEBIVOHKFYSBPE-UHFFFAOYSA-N 4-Benzyloxybenzyl alcohol Chemical compound C1=CC(CO)=CC=C1OCC1=CC=CC=C1 OEBIVOHKFYSBPE-UHFFFAOYSA-N 0.000 description 2
- BJZMFQQWGQAXHI-UHFFFAOYSA-N 4-amino-1-(4-chlorophenyl)piperidine-4-carboxylic acid Chemical compound C1CC(N)(C(O)=O)CCN1C1=CC=C(Cl)C=C1 BJZMFQQWGQAXHI-UHFFFAOYSA-N 0.000 description 2
- DJNWXMMFBXAOLF-UHFFFAOYSA-N 4-amino-1-(4-methylphenyl)piperidine-4-carboxylic acid Chemical compound C1=CC(C)=CC=C1N1CCC(N)(C(O)=O)CC1 DJNWXMMFBXAOLF-UHFFFAOYSA-N 0.000 description 2
- SFTGJHTVCZFZTF-UHFFFAOYSA-N 4-amino-1-(4-phenoxyphenyl)piperidine-4-carboxylic acid Chemical compound C1CC(N)(C(O)=O)CCN1C(C=C1)=CC=C1OC1=CC=CC=C1 SFTGJHTVCZFZTF-UHFFFAOYSA-N 0.000 description 2
- FPGAOFXYANTSRQ-UHFFFAOYSA-N 4-amino-1-phenylpiperidine-4-carboxylic acid Chemical compound C1CC(N)(C(O)=O)CCN1C1=CC=CC=C1 FPGAOFXYANTSRQ-UHFFFAOYSA-N 0.000 description 2
- YKAYMASDSHFOGI-UHFFFAOYSA-N 4-phenylcyclohexan-1-one Chemical class C1CC(=O)CCC1C1=CC=CC=C1 YKAYMASDSHFOGI-UHFFFAOYSA-N 0.000 description 2
- RFVGWKGXIDITMO-UHFFFAOYSA-N 6-methoxy-1-propan-2-yloxynaphthalene Chemical compound CC(C)OC1=CC=CC2=CC(OC)=CC=C21 RFVGWKGXIDITMO-UHFFFAOYSA-N 0.000 description 2
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 239000000275 Adrenocorticotropic Hormone Substances 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 102400000739 Corticotropin Human genes 0.000 description 2
- 101800000414 Corticotropin Proteins 0.000 description 2
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 2
- 241000400611 Eucalyptus deanei Species 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 229910004373 HOAc Inorganic materials 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 239000000637 Melanocyte-Stimulating Hormone Substances 0.000 description 2
- 108010007013 Melanocyte-Stimulating Hormones Proteins 0.000 description 2
- 102400000740 Melanocyte-stimulating hormone alpha Human genes 0.000 description 2
- 101710200814 Melanotropin alpha Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 238000006957 Michael reaction Methods 0.000 description 2
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 238000010934 O-alkylation reaction Methods 0.000 description 2
- 206010033307 Overweight Diseases 0.000 description 2
- 102000007079 Peptide Fragments Human genes 0.000 description 2
- 108010033276 Peptide Fragments Proteins 0.000 description 2
- OZILORBBPKKGRI-RYUDHWBXSA-N Phe-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 OZILORBBPKKGRI-RYUDHWBXSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 2
- 108010069820 Pro-Opiomelanocortin Proteins 0.000 description 2
- 239000000683 Pro-Opiomelanocortin Substances 0.000 description 2
- 102100027467 Pro-opiomelanocortin Human genes 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 125000005076 adamantyloxycarbonyl group Chemical group C12(CC3CC(CC(C1)C3)C2)OC(=O)* 0.000 description 2
- 238000007605 air drying Methods 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 125000003275 alpha amino acid group Chemical group 0.000 description 2
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 2
- 125000003368 amide group Chemical group 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 150000001540 azides Chemical class 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- UWCHSDIUMBNDLT-UHFFFAOYSA-L copper;methylsulfanylmethane;dibromide Chemical compound CSC.Br[Cu]Br UWCHSDIUMBNDLT-UHFFFAOYSA-L 0.000 description 2
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 2
- 229960000258 corticotropin Drugs 0.000 description 2
- XXTZHYXQVWRADW-UHFFFAOYSA-N diazomethanone Chemical compound [N]N=C=O XXTZHYXQVWRADW-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 230000006806 disease prevention Effects 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- BJXYHBKEQFQVES-NWDGAFQWSA-N enpatoran Chemical compound N[C@H]1CN(C[C@H](C1)C(F)(F)F)C1=C2C=CC=NC2=C(C=C1)C#N BJXYHBKEQFQVES-NWDGAFQWSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000012259 ether extract Substances 0.000 description 2
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 2
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 2
- 239000002360 explosive Substances 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N guanidine group Chemical group NC(=N)N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- 150000008282 halocarbons Chemical class 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- 150000001469 hydantoins Chemical class 0.000 description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 2
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 2
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 2
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 238000010647 peptide synthesis reaction Methods 0.000 description 2
- 108010018625 phenylalanylarginine Proteins 0.000 description 2
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 150000005376 secondary alkyl halides Chemical class 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000011343 solid material Substances 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 230000000707 stereoselective effect Effects 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 229940124530 sulfonamide Drugs 0.000 description 2
- 150000003456 sulfonamides Chemical class 0.000 description 2
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- GMRIOAVKKGNMMV-UHFFFAOYSA-N tetrabutylazanium;azide Chemical compound [N-]=[N+]=[N-].CCCC[N+](CCCC)(CCCC)CCCC GMRIOAVKKGNMMV-UHFFFAOYSA-N 0.000 description 2
- 150000003573 thiols Chemical group 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- WHNFPRLDDSXQCL-UAZQEYIDSA-N α-msh Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(N)=O)NC(=O)[C@H](CO)NC(C)=O)C1=CC=C(O)C=C1 WHNFPRLDDSXQCL-UAZQEYIDSA-N 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- JDKLPDJLXHXHNV-MFVUMRCOSA-N (3s,6s,9r,12s,15s,23s)-15-[[(2s)-2-acetamidohexanoyl]amino]-9-benzyl-6-[3-(diaminomethylideneamino)propyl]-12-(1h-imidazol-5-ylmethyl)-3-(1h-indol-3-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide Chemical compound C([C@@H]1C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCNC(=O)C[C@@H](C(N[C@@H](CC=2NC=NC=2)C(=O)N1)=O)NC(=O)[C@@H](NC(C)=O)CCCC)C(N)=O)C1=CC=CC=C1 JDKLPDJLXHXHNV-MFVUMRCOSA-N 0.000 description 1
- STPKWKPURVSAJF-LJEWAXOPSA-N (4r,5r)-5-[4-[[4-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylmethyl)phenyl]methoxy]phenyl]-3,3-dibutyl-7-(dimethylamino)-1,1-dioxo-4,5-dihydro-2h-1$l^{6}-benzothiepin-4-ol Chemical compound O[C@H]1C(CCCC)(CCCC)CS(=O)(=O)C2=CC=C(N(C)C)C=C2[C@H]1C(C=C1)=CC=C1OCC(C=C1)=CC=C1C[N+]1(CC2)CCN2CC1 STPKWKPURVSAJF-LJEWAXOPSA-N 0.000 description 1
- PLVPPLCLBIEYEA-AATRIKPKSA-N (E)-3-(indol-3-yl)acrylic acid Chemical compound C1=CC=C2C(/C=C/C(=O)O)=CNC2=C1 PLVPPLCLBIEYEA-AATRIKPKSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- IBXMKLPFLZYRQZ-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 IBXMKLPFLZYRQZ-UHFFFAOYSA-N 0.000 description 1
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
- XHBDUHFCJSMXIU-UHFFFAOYSA-N 1-amino-4-(3-methoxyphenyl)cyclohexane-1-carboxylic acid Chemical compound COC1=CC=CC(C2CCC(N)(CC2)C(O)=O)=C1 XHBDUHFCJSMXIU-UHFFFAOYSA-N 0.000 description 1
- JYFVOJODHSMLNN-UHFFFAOYSA-N 1-amino-4-(4-ethoxyphenyl)cyclohexane-1-carboxylic acid Chemical compound C1=CC(OCC)=CC=C1C1CCC(N)(C(O)=O)CC1 JYFVOJODHSMLNN-UHFFFAOYSA-N 0.000 description 1
- MTBXEODIGPQIDZ-UHFFFAOYSA-N 1-amino-4-(4-methoxyphenyl)cyclohexane-1-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C1CCC(N)(C(O)=O)CC1 MTBXEODIGPQIDZ-UHFFFAOYSA-N 0.000 description 1
- ZIZOGQRCTIPNGS-UHFFFAOYSA-N 1-amino-4-(4-methylphenyl)cyclohexane-1-carboxylic acid Chemical compound C1=CC(C)=CC=C1C1CCC(N)(C(O)=O)CC1 ZIZOGQRCTIPNGS-UHFFFAOYSA-N 0.000 description 1
- IHLDNVAQWDLAOY-UHFFFAOYSA-N 1-amino-4-(4-propan-2-yloxyphenyl)cyclohexane-1-carboxylic acid Chemical compound C1=CC(OC(C)C)=CC=C1C1CCC(N)(C(O)=O)CC1 IHLDNVAQWDLAOY-UHFFFAOYSA-N 0.000 description 1
- XOKJVJPRWMSSRV-UHFFFAOYSA-N 1-azaniumyl-4-(4-chlorophenyl)cyclohexane-1-carboxylate Chemical compound C1CC(N)(C(O)=O)CCC1C1=CC=C(Cl)C=C1 XOKJVJPRWMSSRV-UHFFFAOYSA-N 0.000 description 1
- LZSYGJNFCREHMD-UHFFFAOYSA-N 1-bromo-2-(bromomethyl)benzene Chemical compound BrCC1=CC=CC=C1Br LZSYGJNFCREHMD-UHFFFAOYSA-N 0.000 description 1
- NHDODQWIKUYWMW-UHFFFAOYSA-N 1-bromo-4-chlorobenzene Chemical compound ClC1=CC=C(Br)C=C1 NHDODQWIKUYWMW-UHFFFAOYSA-N 0.000 description 1
- GWQSENYKCGJTRI-UHFFFAOYSA-N 1-chloro-4-iodobenzene Chemical compound ClC1=CC=C(I)C=C1 GWQSENYKCGJTRI-UHFFFAOYSA-N 0.000 description 1
- GMUGZOXMLMELEQ-UHFFFAOYSA-N 1-diazonio-4-(2-propan-2-ylphenyl)but-1-en-2-olate Chemical compound CC(C)C1=CC=CC=C1CCC(=O)C=[N+]=[N-] GMUGZOXMLMELEQ-UHFFFAOYSA-N 0.000 description 1
- ZEJZDNMOGNUIHL-UHFFFAOYSA-N 1-ethyl-2-iodobenzene Chemical compound CCC1=CC=CC=C1I ZEJZDNMOGNUIHL-UHFFFAOYSA-N 0.000 description 1
- RINOYHWVBUKAQE-UHFFFAOYSA-N 1-iodo-2-methylbenzene Chemical compound CC1=CC=CC=C1I RINOYHWVBUKAQE-UHFFFAOYSA-N 0.000 description 1
- VLCPISYURGTGLP-UHFFFAOYSA-N 1-iodo-3-methylbenzene Chemical compound CC1=CC=CC(I)=C1 VLCPISYURGTGLP-UHFFFAOYSA-N 0.000 description 1
- BDKOUDYNKRCDEC-UHFFFAOYSA-N 1-iodo-4-phenoxybenzene Chemical compound C1=CC(I)=CC=C1OC1=CC=CC=C1 BDKOUDYNKRCDEC-UHFFFAOYSA-N 0.000 description 1
- KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical group C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 description 1
- OZGSEIVTQLXWRO-UHFFFAOYSA-N 2,4,6-trichlorobenzoyl chloride Chemical compound ClC(=O)C1=C(Cl)C=C(Cl)C=C1Cl OZGSEIVTQLXWRO-UHFFFAOYSA-N 0.000 description 1
- LXFQSRIDYRFTJW-UHFFFAOYSA-N 2,4,6-trimethylbenzenesulfonic acid Chemical compound CC1=CC(C)=C(S(O)(=O)=O)C(C)=C1 LXFQSRIDYRFTJW-UHFFFAOYSA-N 0.000 description 1
- QEBYEVQKHRUYPE-UHFFFAOYSA-N 2-(2-chlorophenyl)-5-[(1-methylpyrazol-3-yl)methyl]-4-[[methyl(pyridin-3-ylmethyl)amino]methyl]-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C1=CN(C)N=C1CN1C(=O)C=C2NN(C=3C(=CC=CC=3)Cl)C(=O)C2=C1CN(C)CC1=CC=CN=C1 QEBYEVQKHRUYPE-UHFFFAOYSA-N 0.000 description 1
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 1
- BBLVLRHQGNQNEH-UHFFFAOYSA-N 2-amino-5-methoxy-3,4-dihydro-1h-naphthalene-2-carboxylic acid Chemical compound C1C(N)(C(O)=O)CCC2=C1C=CC=C2OC BBLVLRHQGNQNEH-UHFFFAOYSA-N 0.000 description 1
- NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
- KCKZIWSINLBROE-UHFFFAOYSA-N 3,4-dihydro-1h-naphthalen-2-one Chemical group C1=CC=C2CC(=O)CCC2=C1 KCKZIWSINLBROE-UHFFFAOYSA-N 0.000 description 1
- AOACQJFIGWNQBC-UHFFFAOYSA-N 3-(2-bromophenyl)propanoic acid Chemical compound OC(=O)CCC1=CC=CC=C1Br AOACQJFIGWNQBC-UHFFFAOYSA-N 0.000 description 1
- GGFPFUUJHMSPJS-UHFFFAOYSA-N 3-(2-bromophenyl)propanoyl chloride Chemical compound ClC(=O)CCC1=CC=CC=C1Br GGFPFUUJHMSPJS-UHFFFAOYSA-N 0.000 description 1
- KZMDFTFGWIVSNQ-UHFFFAOYSA-N 3-(2-chlorophenyl)propanoic acid Chemical compound OC(=O)CCC1=CC=CC=C1Cl KZMDFTFGWIVSNQ-UHFFFAOYSA-N 0.000 description 1
- QOQYBKQKBZOSAK-UHFFFAOYSA-N 3-(2-chlorophenyl)propanoyl chloride Chemical compound ClC(=O)CCC1=CC=CC=C1Cl QOQYBKQKBZOSAK-UHFFFAOYSA-N 0.000 description 1
- URITYXSLGYPLMS-UHFFFAOYSA-N 3-(2-ethylphenyl)propanoic acid Chemical compound CCC1=CC=CC=C1CCC(O)=O URITYXSLGYPLMS-UHFFFAOYSA-N 0.000 description 1
- JIRKNEAMPYVPTD-UHFFFAOYSA-N 3-(2-methylphenyl)propanoic acid Chemical compound CC1=CC=CC=C1CCC(O)=O JIRKNEAMPYVPTD-UHFFFAOYSA-N 0.000 description 1
- HLIIURRHLIYNGV-UHFFFAOYSA-N 3-(2-methylphenyl)propanoyl chloride Chemical compound CC1=CC=CC=C1CCC(Cl)=O HLIIURRHLIYNGV-UHFFFAOYSA-N 0.000 description 1
- VAKITVVRJHONDZ-UHFFFAOYSA-N 3-(2-propan-2-ylphenyl)propanoic acid Chemical compound CC(C)C1=CC=CC=C1CCC(O)=O VAKITVVRJHONDZ-UHFFFAOYSA-N 0.000 description 1
- PECYZEOJVXMISF-REOHCLBHSA-N 3-amino-L-alanine Chemical compound [NH3+]C[C@H](N)C([O-])=O PECYZEOJVXMISF-REOHCLBHSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- DLJIJDIDJDCWHF-UHFFFAOYSA-N 4-(2-chlorophenyl)-1-diazoniobut-1-en-2-olate Chemical compound ClC1=CC=CC=C1CCC(=O)C=[N+]=[N-] DLJIJDIDJDCWHF-UHFFFAOYSA-N 0.000 description 1
- OQSHSLCHNWPCHO-UHFFFAOYSA-N 4-amino-1-(2-methylphenyl)piperidine-4-carboxylic acid Chemical compound CC1=CC=CC=C1N1CCC(N)(C(O)=O)CC1 OQSHSLCHNWPCHO-UHFFFAOYSA-N 0.000 description 1
- NERBJUDMBDWQNT-UHFFFAOYSA-N 4-amino-1-(2-propan-2-ylphenyl)piperidine-4-carboxylic acid Chemical compound CC(C)C1=CC=CC=C1N1CCC(N)(C(O)=O)CC1 NERBJUDMBDWQNT-UHFFFAOYSA-N 0.000 description 1
- LPBXKPRVUOLGGX-UHFFFAOYSA-N 4-amino-1-(3-methoxyphenyl)piperidine-4-carboxylic acid Chemical compound COC1=CC=CC(N2CCC(N)(CC2)C(O)=O)=C1 LPBXKPRVUOLGGX-UHFFFAOYSA-N 0.000 description 1
- OPZDTJADUMAIOP-UHFFFAOYSA-N 4-amino-1-(3-methylphenyl)piperidine-4-carboxylic acid Chemical compound CC1=CC=CC(N2CCC(N)(CC2)C(O)=O)=C1 OPZDTJADUMAIOP-UHFFFAOYSA-N 0.000 description 1
- JLYNSPSTPQAEAX-UHFFFAOYSA-N 4-cyclohexylcyclohexan-1-one Chemical compound C1CC(=O)CCC1C1CCCCC1 JLYNSPSTPQAEAX-UHFFFAOYSA-N 0.000 description 1
- MNALUTYMBUBKNX-UHFFFAOYSA-N 6-methoxy-3,4-dihydro-2h-naphthalen-1-one Chemical compound O=C1CCCC2=CC(OC)=CC=C21 MNALUTYMBUBKNX-UHFFFAOYSA-N 0.000 description 1
- NSXJEEMTGWMJPY-UHFFFAOYSA-N 9-[3-(3-carbazol-9-ylphenyl)phenyl]carbazole Chemical compound C12=CC=CC=C2C2=CC=CC=C2N1C1=CC(C=2C=CC=C(C=2)N2C3=CC=CC=C3C3=CC=CC=C32)=CC=C1 NSXJEEMTGWMJPY-UHFFFAOYSA-N 0.000 description 1
- 102100022455 Adrenocorticotropic hormone receptor Human genes 0.000 description 1
- 101710115814 Adrenocorticotropic hormone receptor Proteins 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- IVRMZWNICZWHMI-UHFFFAOYSA-N Azide Chemical compound [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- KCGKYAORRXGWMN-UHFFFAOYSA-N CNS(=O)=O Chemical compound CNS(=O)=O KCGKYAORRXGWMN-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 102000009025 Endorphins Human genes 0.000 description 1
- 108010049140 Endorphins Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 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
- 239000002841 Lewis acid Substances 0.000 description 1
- 229940126661 MC4 antagonist Drugs 0.000 description 1
- 102100023726 Melanocortin receptor 3 Human genes 0.000 description 1
- 101710085774 Melanocortin receptor 3 Proteins 0.000 description 1
- 102100023723 Melanocortin receptor 5 Human genes 0.000 description 1
- 101710085771 Melanocortin receptor 5 Proteins 0.000 description 1
- 108010008364 Melanocortins Proteins 0.000 description 1
- 101710201349 Metallothionein B Proteins 0.000 description 1
- 101710094505 Metallothionein-2 Proteins 0.000 description 1
- 102100031347 Metallothionein-2 Human genes 0.000 description 1
- 238000006751 Mitsunobu reaction Methods 0.000 description 1
- 230000006181 N-acylation Effects 0.000 description 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 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
- YQNBKXUTWBRQCS-BVSLBCMMSA-N Phe-Arg-Trp Chemical compound C([C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)C1=CC=CC=C1 YQNBKXUTWBRQCS-BVSLBCMMSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 241000270942 Rana pipiens Species 0.000 description 1
- 208000000453 Skin Neoplasms 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
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 102000008314 Type 1 Melanocortin Receptor Human genes 0.000 description 1
- 108010021428 Type 1 Melanocortin Receptor Proteins 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 229960004308 acetylcysteine Drugs 0.000 description 1
- 238000007171 acid catalysis Methods 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 150000001347 alkyl bromides Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000010640 amide synthesis reaction Methods 0.000 description 1
- 229960003375 aminomethylbenzoic acid Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 150000001499 aryl bromides Chemical class 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 150000001503 aryl iodides Chemical class 0.000 description 1
- YCOXTKKNXUZSKD-UHFFFAOYSA-N as-o-xylenol Natural products CC1=CC=C(O)C=C1C YCOXTKKNXUZSKD-UHFFFAOYSA-N 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
- 229910001863 barium hydroxide Inorganic materials 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 108010042362 beta-Lipotropin Proteins 0.000 description 1
- 229940000635 beta-alanine Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000006243 carbonyl protecting group Chemical group 0.000 description 1
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 229940125810 compound 20 Drugs 0.000 description 1
- 150000003997 cyclic ketones Chemical class 0.000 description 1
- DCZFGQYXRKMVFG-UHFFFAOYSA-N cyclohexane-1,4-dione Chemical compound O=C1CCC(=O)CC1 DCZFGQYXRKMVFG-UHFFFAOYSA-N 0.000 description 1
- JHIVVAPYMSGYDF-PTQBSOBMSA-N cyclohexanone Chemical class O=[13C]1CCCCC1 JHIVVAPYMSGYDF-PTQBSOBMSA-N 0.000 description 1
- YKFKEYKJGVSEIX-UHFFFAOYSA-N cyclohexanone, 4-(1,1-dimethylethyl)- Chemical compound CC(C)(C)C1CCC(=O)CC1 YKFKEYKJGVSEIX-UHFFFAOYSA-N 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- KPUNOVLMCQQCSK-UHFFFAOYSA-N diazomethane;ethoxyethane Chemical compound C=[N+]=[N-].CCOCC KPUNOVLMCQQCSK-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002084 enol ethers Chemical class 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- IRXSLJNXXZKURP-UHFFFAOYSA-N fluorenylmethyloxycarbonyl chloride Chemical compound C1=CC=C2C(COC(=O)Cl)C3=CC=CC=C3C2=C1 IRXSLJNXXZKURP-UHFFFAOYSA-N 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 1
- 239000002865 melanocortin Substances 0.000 description 1
- 210000002752 melanocyte Anatomy 0.000 description 1
- 230000001802 melanotrophic effect Effects 0.000 description 1
- AFCCDDWKHLHPDF-UHFFFAOYSA-M metam-sodium Chemical compound [Na+].CNC([S-])=S AFCCDDWKHLHPDF-UHFFFAOYSA-M 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- 210000004898 n-terminal fragment Anatomy 0.000 description 1
- NXPPAOGUKPJVDI-UHFFFAOYSA-N naphthalene-1,2-diol Chemical compound C1=CC=CC2=C(O)C(O)=CC=C21 NXPPAOGUKPJVDI-UHFFFAOYSA-N 0.000 description 1
- FZZQNEVOYIYFPF-UHFFFAOYSA-N naphthalene-1,6-diol Chemical compound OC1=CC=CC2=CC(O)=CC=C21 FZZQNEVOYIYFPF-UHFFFAOYSA-N 0.000 description 1
- 230000003880 negative regulation of appetite Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- RWZYAGGXGHYGMB-UHFFFAOYSA-N o-aminobenzenecarboxylic acid Natural products NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000813 peptide hormone Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 230000019612 pigmentation Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 150000005375 primary alkyl halides Chemical class 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006894 reductive elimination reaction Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- SVOOVMQUISJERI-UHFFFAOYSA-K rhodium(3+);triacetate Chemical compound [Rh+3].CC([O-])=O.CC([O-])=O.CC([O-])=O SVOOVMQUISJERI-UHFFFAOYSA-K 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
- 125000000565 sulfonamide group Chemical group 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- UJJDEOLXODWCGK-UHFFFAOYSA-N tert-butyl carbonochloridate Chemical compound CC(C)(C)OC(Cl)=O UJJDEOLXODWCGK-UHFFFAOYSA-N 0.000 description 1
- MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000000211 third ventricle Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000006478 transmetalation reaction Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/64—Cyclic peptides containing only normal peptide links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/50—Cyclic peptides containing at least one abnormal peptide link
- C07K7/54—Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring
- C07K7/56—Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring the cyclisation not occurring through 2,4-diamino-butanoic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/665—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin
- C07K14/68—Melanocyte-stimulating hormone [MSH]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Child & Adolescent Psychology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US22918400P | 2000-08-30 | 2000-08-30 | |
| US60/229,184 | 2000-08-30 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2003107921A RU2003107921A (ru) | 2004-10-10 |
| RU2239642C1 true RU2239642C1 (ru) | 2004-11-10 |
Family
ID=22860145
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2003107921/04A RU2239642C1 (ru) | 2000-08-30 | 2001-08-21 | Селективные циклопептиды |
Country Status (35)
| Country | Link |
|---|---|
| US (1) | US7045591B2 (https=) |
| EP (1) | EP1315750B1 (https=) |
| JP (1) | JP4217069B2 (https=) |
| KR (1) | KR100483300B1 (https=) |
| CN (1) | CN100491396C (https=) |
| AR (2) | AR030504A1 (https=) |
| AT (1) | ATE353918T1 (https=) |
| AU (2) | AU2001284026B2 (https=) |
| BR (1) | BR0113637A (https=) |
| CA (1) | CA2420058C (https=) |
| CY (1) | CY1106562T1 (https=) |
| CZ (1) | CZ2003584A3 (https=) |
| DE (1) | DE60126624T2 (https=) |
| DK (1) | DK1315750T3 (https=) |
| EC (1) | ECSP034503A (https=) |
| ES (1) | ES2280393T3 (https=) |
| HR (1) | HRP20030126B1 (https=) |
| HU (1) | HUP0303078A3 (https=) |
| IL (2) | IL154575A0 (https=) |
| JO (1) | JO2454B1 (https=) |
| MA (1) | MA27681A1 (https=) |
| MX (1) | MXPA03001721A (https=) |
| MY (1) | MY137457A (https=) |
| NO (1) | NO20030916L (https=) |
| NZ (1) | NZ523989A (https=) |
| PA (1) | PA8527201A1 (https=) |
| PE (1) | PE20020483A1 (https=) |
| PL (1) | PL366630A1 (https=) |
| PT (1) | PT1315750E (https=) |
| RU (1) | RU2239642C1 (https=) |
| SI (1) | SI1315750T1 (https=) |
| TW (1) | TWI248941B (https=) |
| WO (1) | WO2002018437A2 (https=) |
| YU (1) | YU15603A (https=) |
| ZA (1) | ZA200301015B (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2450017C2 (ru) * | 2007-05-25 | 2012-05-10 | Ипсен Фарма С.А.С. | Лиганды меланокортиновых рецепторов, модифицированные гидантоином |
Families Citing this family (59)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1409521A2 (en) * | 2001-07-12 | 2004-04-21 | Merck & Co., Inc. | Cyclic peptides as potent and selective melanocortin-4 receptor agonists |
| CA2462200A1 (en) | 2001-08-10 | 2003-02-20 | Palatin Technologies, Inc. | Peptidomimetics of biologically active metallopeptides |
| US7456184B2 (en) | 2003-05-01 | 2008-11-25 | Palatin Technologies Inc. | Melanocortin receptor-specific compounds |
| US7732451B2 (en) | 2001-08-10 | 2010-06-08 | Palatin Technologies, Inc. | Naphthalene-containing melanocortin receptor-specific small molecule |
| US7655658B2 (en) | 2001-08-10 | 2010-02-02 | Palatin Technologies, Inc. | Thieno [2,3-D]pyrimidine-2,4-dione melanocortin-specific compounds |
| US7354923B2 (en) | 2001-08-10 | 2008-04-08 | Palatin Technologies, Inc. | Piperazine melanocortin-specific compounds |
| US7718802B2 (en) | 2001-08-10 | 2010-05-18 | Palatin Technologies, Inc. | Substituted melanocortin receptor-specific piperazine compounds |
| WO2004005324A2 (en) | 2002-07-09 | 2004-01-15 | Palatin Technologies, Inc. | Peptide composition for treatment of sexual dysfunction |
| US7727990B2 (en) | 2003-05-01 | 2010-06-01 | Palatin Technologies, Inc. | Melanocortin receptor-specific piperazine and keto-piperazine compounds |
| US7968548B2 (en) | 2003-05-01 | 2011-06-28 | Palatin Technologies, Inc. | Melanocortin receptor-specific piperazine compounds with diamine groups |
| US7727991B2 (en) | 2003-05-01 | 2010-06-01 | Palatin Technologies, Inc. | Substituted melanocortin receptor-specific single acyl piperazine compounds |
| KR20060026011A (ko) | 2003-05-09 | 2006-03-22 | 노보 노르디스크 에이/에스 | 비만 치료용 펩티드 |
| BRPI0409976A (pt) * | 2003-05-09 | 2006-05-09 | Novo Nordisk As | composto, métodos para retardar a progressão de igt diabetes do tipo 2, para retardar a progressão de diabetes do tipo 2 para diabetes que requer insulina, para tratar obesidade ou prevenir excesso de peso para regular o apetite para induzir saciedade, para prevenir ganho de peso após se ter tido sucesso em perder peso, para aumentar dispêndio de energia, para tratar uma doença ou estado e para tratar bulimia, composição farmacêutica, e, uso de um composto |
| CA2530024A1 (en) * | 2003-06-19 | 2005-01-06 | Eli Lilly And Company | Melanocortin receptor 4(mc4) agonists and their uses |
| WO2005000338A1 (en) * | 2003-06-19 | 2005-01-06 | Eli Lilly And Company | Uses of melanocortin-3 receptor (mc3r) agonist peptides |
| US7084111B2 (en) | 2003-06-23 | 2006-08-01 | University Of Florida Research Foundation, Inc. | Melanocortin receptor templates, peptides, and use thereof |
| EP1670815A2 (en) * | 2003-09-30 | 2006-06-21 | Novo Nordisk A/S | Melanocortin receptor agonists |
| US7550602B1 (en) | 2004-01-14 | 2009-06-23 | Palatin Technologies, Inc. | Small molecule compositions for sexual dysfunction |
| US6974187B2 (en) * | 2004-01-28 | 2005-12-13 | Tachi-S Co., Ltd. | Vehicle seat structure |
| US20070123453A1 (en) * | 2004-03-29 | 2007-05-31 | Heiman Mark L | Uses of melanocortin-4 receptor (mc4r) agonist peptides administered by continuous infusion |
| KR101176758B1 (ko) * | 2004-04-08 | 2012-08-23 | 아스테라스 세이야쿠 가부시키가이샤 | 화합물 ｗｓ727713 |
| US7709484B1 (en) | 2004-04-19 | 2010-05-04 | Palatin Technologies, Inc. | Substituted melanocortin receptor-specific piperazine compounds |
| EP1809665A2 (en) * | 2004-11-04 | 2007-07-25 | Novo Nordisk A/S | Mc4r selective peptides and their use in the treatment of obesity |
| JP2008519008A (ja) * | 2004-11-04 | 2008-06-05 | ノボ ノルディスク アクティーゼルスカブ | 肥満症の治療に使用するためのペプチド |
| EP1809666A2 (en) * | 2004-11-04 | 2007-07-25 | Novo Nordisk A/S | Peptides for use in the treating obesity |
| JP2008519009A (ja) * | 2004-11-04 | 2008-06-05 | ノボ ノルディスク アクティーゼルスカブ | 肥満症の治療に使用するためのペプチド |
| CN101203527A (zh) * | 2005-05-31 | 2008-06-18 | 耶路撒冷希伯来大学伊森姆研究发展公司 | 主链环化的促黑皮质素激素（αMSH）类似物 |
| US20090042790A1 (en) * | 2005-06-13 | 2009-02-12 | Nastech Pharmaceutical Company Inc. | Transmucosal delivery of peptide derivatives |
| US20080015304A1 (en) | 2006-07-13 | 2008-01-17 | Klaus Hintzer | Aqueous emulsion polymerization process for producing fluoropolymers |
| US7671112B2 (en) * | 2005-07-15 | 2010-03-02 | 3M Innovative Properties Company | Method of making fluoropolymer dispersion |
| GB2430437A (en) * | 2005-09-27 | 2007-03-28 | 3M Innovative Properties Co | Method of making a fluoropolymer |
| US7834017B2 (en) | 2006-08-11 | 2010-11-16 | Palatin Technologies, Inc. | Diamine-containing, tetra-substituted piperazine compounds having identical 1- and 4-substituents |
| EP2125862A1 (en) * | 2006-12-29 | 2009-12-02 | F. Hoffmann-Roche AG | Methods for the synthesis of cyclic peptides |
| CN101605728B (zh) * | 2007-02-16 | 2013-07-24 | 3M创新有限公司 | 用于从水中去除含氟化合物的系统和方法 |
| US20080264864A1 (en) * | 2007-04-27 | 2008-10-30 | 3M Innovative Properties Company | PROCESS FOR REMOVING FLUORINATED EMULSIFIER FROM FLUOROPOLMER DISPERSIONS USING AN ANION-EXCHANGE RESIN AND A pH-DEPENDENT SURFACTANT AND FLUOROPOLYMER DISPERSIONS CONTAINING A pH-DEPENDENT SURFACTANT |
| US8258313B2 (en) | 2007-07-19 | 2012-09-04 | Tokuyama Corporation | Compound having hydantoin ring and method of producing the same |
| ES2464102T3 (es) | 2008-03-27 | 2014-05-30 | Grünenthal GmbH | Derivados de 4-aminociclohexano sustituidos |
| EP2280941B1 (de) * | 2008-03-27 | 2015-05-06 | Grünenthal GmbH | (hetero-)aryl-cyclohexan-derivate |
| KR101687037B1 (ko) | 2008-06-09 | 2016-12-15 | 팔라틴 테크놀로지스 인코포레이티드 | 성기능 장애 치료용 멜라노코르틴 수용체-특이적 펩티드 |
| TW201002340A (en) * | 2008-06-09 | 2010-01-16 | Palatin Technologies Inc | Melanocortin receptor-specific peptides for treatment of obesity |
| KR101726893B1 (ko) | 2009-06-08 | 2017-04-13 | 팔라틴 테크놀로지스 인코포레이티드 | 멜라노코르틴 수용체-특이적 펩티드 |
| WO2010144341A2 (en) | 2009-06-08 | 2010-12-16 | Palatin Technologies, Inc. | Lactam-bridged melanocortin receptor-specific peptides |
| UY32690A (es) | 2009-06-08 | 2011-01-31 | Astrazeneca Ab | Péptidos específicos para receptores de melanocortina |
| WO2011063366A1 (en) | 2009-11-23 | 2011-05-26 | Palatin Technologies, Inc. | Melanocortin-1 receptor-specific cyclic peptides |
| JP2013511554A (ja) | 2009-11-23 | 2013-04-04 | パラティン テクノロジーズ，インコーポレイテッド | メラノコルチン−１受容体特異的線状ペプチド |
| RU2020120797A (ru) | 2013-03-15 | 2020-07-02 | Ритм Фармасьютикалз, Инк. | Пептидные композиции |
| GB201416351D0 (en) * | 2014-09-16 | 2014-10-29 | Shire Internat Gmbh | Heterocyclic derivatives |
| GB201416352D0 (en) | 2014-09-16 | 2014-10-29 | Shire Internat Gmbh | Spirocyclic derivatives |
| US20180022780A1 (en) * | 2014-09-26 | 2018-01-25 | Bayer Pharma Aktiengesellschaft | Stabilization adrenomedullin derivatives and use thereof |
| US11542302B2 (en) | 2015-10-15 | 2023-01-03 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Modulators of melanocortin receptors for the treatment of depression and anxiety |
| WO2017066754A1 (en) | 2015-10-15 | 2017-04-20 | The Arizona Board Of Regents On Behalf Of The University Of Arizona | Compositions and methods for the treatment of depression and anxiety |
| US10899793B2 (en) | 2016-05-27 | 2021-01-26 | Regents Of The University Of Minnesota | Melanocortin ligands and methods of use thereof |
| US20190255142A1 (en) * | 2016-10-17 | 2019-08-22 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Novel modulators of melanocortin receptors for the treatment of depression and anxiety |
| US11124541B2 (en) | 2016-10-18 | 2021-09-21 | Regents Of The University Of Minnesota | Chimeric melanocortin ligands and methods of use thereof |
| CN106496008A (zh) * | 2016-10-20 | 2017-03-15 | 上海毕得医药科技有限公司 | 一种合成4‑(4‑氯苯基)环己酮的方法 |
| CN106496005B (zh) * | 2016-10-20 | 2019-04-09 | 上海毕得医药科技有限公司 | 一种4-(4-氯苯基)环己酮的合成方法 |
| US10745444B2 (en) * | 2017-04-17 | 2020-08-18 | National Tsing Hua University | Cyclopeptide, pharmaceutical or cosmetic composition comprising the same and method for preparing the same |
| US11332499B2 (en) | 2018-08-16 | 2022-05-17 | Regents Of The University Of Minnesota | Cyclic peptides and methods of use thereof |
| CN118530294B (zh) * | 2024-05-10 | 2025-02-14 | 浙江大学 | 一种芳基二胺固载连接子、其前体以及制备方法和应用 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2129563C1 (ru) * | 1992-11-06 | 1999-04-27 | Мерк Патент Гмбх | Циклопептиды или их соли, способ их получения, фармацевтические композиции и способ их получения, способ лечения |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5811391A (en) | 1994-08-25 | 1998-09-22 | Cytel Corporation | Cyclic CS-1 peptidomimetics, compositions and methods of using same |
| US5731408A (en) * | 1995-04-10 | 1998-03-24 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Peptides having potent antagonist and agonist bioactivities at melanocortin receptors |
| US5858972A (en) | 1996-01-11 | 1999-01-12 | La Jolla Cancer Research Foundation | Antithrombotic agents and methods of use |
| SE9700620D0 (sv) * | 1997-02-21 | 1997-02-21 | Wapharm Ab | Cykliska peptider med selektivitet för MSH-receptor subtyper |
| DK1165613T3 (da) | 1999-03-29 | 2008-08-25 | Procter & Gamble | Melanocortinreceptorligander |
-
2001
- 2001-08-21 CZ CZ2003584A patent/CZ2003584A3/cs unknown
- 2001-08-21 SI SI200130703T patent/SI1315750T1/sl unknown
- 2001-08-21 BR BR0113637-2A patent/BR0113637A/pt not_active IP Right Cessation
- 2001-08-21 IL IL15457501A patent/IL154575A0/xx unknown
- 2001-08-21 CN CNB018150284A patent/CN100491396C/zh not_active Expired - Fee Related
- 2001-08-21 YU YU15603A patent/YU15603A/sh unknown
- 2001-08-21 HU HU0303078A patent/HUP0303078A3/hu unknown
- 2001-08-21 HR HR20030126A patent/HRP20030126B1/xx not_active IP Right Cessation
- 2001-08-21 AU AU2001284026A patent/AU2001284026B2/en not_active Ceased
- 2001-08-21 CA CA002420058A patent/CA2420058C/en not_active Expired - Fee Related
- 2001-08-21 PL PL01366630A patent/PL366630A1/xx not_active Application Discontinuation
- 2001-08-21 EP EP01962958A patent/EP1315750B1/en not_active Expired - Lifetime
- 2001-08-21 RU RU2003107921/04A patent/RU2239642C1/ru not_active IP Right Cessation
- 2001-08-21 NZ NZ523989A patent/NZ523989A/en unknown
- 2001-08-21 AU AU8402601A patent/AU8402601A/xx active Pending
- 2001-08-21 WO PCT/EP2001/009630 patent/WO2002018437A2/en not_active Ceased
- 2001-08-21 DK DK01962958T patent/DK1315750T3/da active
- 2001-08-21 AT AT01962958T patent/ATE353918T1/de active
- 2001-08-21 JP JP2002523951A patent/JP4217069B2/ja not_active Expired - Fee Related
- 2001-08-21 PT PT01962958T patent/PT1315750E/pt unknown
- 2001-08-21 ES ES01962958T patent/ES2280393T3/es not_active Expired - Lifetime
- 2001-08-21 MX MXPA03001721A patent/MXPA03001721A/es active IP Right Grant
- 2001-08-21 DE DE60126624T patent/DE60126624T2/de not_active Expired - Lifetime
- 2001-08-21 KR KR10-2003-7002931A patent/KR100483300B1/ko not_active Expired - Fee Related
- 2001-08-23 JO JO2001138A patent/JO2454B1/en active
- 2001-08-27 US US09/939,966 patent/US7045591B2/en not_active Expired - Fee Related
- 2001-08-28 AR ARP010104096A patent/AR030504A1/es active IP Right Grant
- 2001-08-28 PE PE2001000859A patent/PE20020483A1/es not_active Application Discontinuation
- 2001-08-28 PA PA20018527201A patent/PA8527201A1/es unknown
- 2001-08-28 MY MYPI20014025A patent/MY137457A/en unknown
- 2001-08-30 TW TW090121400A patent/TWI248941B/zh not_active IP Right Cessation
-
2003
- 2003-02-05 ZA ZA200301015A patent/ZA200301015B/en unknown
- 2003-02-20 IL IL154575A patent/IL154575A/en not_active IP Right Cessation
- 2003-02-27 NO NO20030916A patent/NO20030916L/no not_active Application Discontinuation
- 2003-02-27 MA MA27059A patent/MA27681A1/fr unknown
- 2003-03-06 EC EC2003004503A patent/ECSP034503A/es unknown
-
2007
- 2007-05-07 CY CY20071100594T patent/CY1106562T1/el unknown
- 2007-05-30 AR ARP070102336A patent/AR061422A2/es unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2129563C1 (ru) * | 1992-11-06 | 1999-04-27 | Мерк Патент Гмбх | Циклопептиды или их соли, способ их получения, фармацевтические композиции и способ их получения, способ лечения |
Non-Patent Citations (1)
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2450017C2 (ru) * | 2007-05-25 | 2012-05-10 | Ипсен Фарма С.А.С. | Лиганды меланокортиновых рецепторов, модифицированные гидантоином |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2239642C1 (ru) | Селективные циклопептиды | |
| JP3938690B2 (ja) | メラノコルチン−４受容体（ｍｃ４−ｒ）アゴニスト活性を持つ選択性線状ペプチド | |
| AU2001284026A1 (en) | Cyclic peptides having melanocortin-4 receptor agonist activity | |
| CA2368431C (en) | Melanocortin receptor ligands | |
| US5550110A (en) | Endothelin Antagonists II | |
| CN102202681A (zh) | 神经肽-2受体(y-2r)激动剂及其用途 | |
| BRPI0619399A2 (pt) | derivado de metastina ou um sal do mesmo, composto ou um sal do mesmo, prà-droga, medicamento, e, uso de uma dose eficaz do derivado de metastina | |
| EP3647319A1 (en) | Peptide compound, application thereof and composition containing same | |
| US5733881A (en) | Opioid peptide antagonists | |
| US7598342B2 (en) | Alpha-fetoprotein peptides and uses thereof | |
| US7964701B2 (en) | Alpha-fetoprotein peptides | |
| US9249189B2 (en) | Alpha-fetoprotein “ring and tail” peptides | |
| WO2026080412A1 (en) | Formulation for oral administration of non-naturally occurring melanocortin analogs for modulating kidney function and/or glucose uptake | |
| KR20070119614A (ko) | 노시셉틴/오파닌 에프큐 수용체의 고강력 완전 및 부분작동물질 및 길항물질 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | The patent is invalid due to non-payment of fees |
Effective date: 20090822 |