JPH11501054A - 成長ホルモン放出特性を有する化合物 - Google Patents
成長ホルモン放出特性を有する化合物Info
- Publication number
- JPH11501054A JPH11501054A JP9523230A JP52323097A JPH11501054A JP H11501054 A JPH11501054 A JP H11501054A JP 9523230 A JP9523230 A JP 9523230A JP 52323097 A JP52323097 A JP 52323097A JP H11501054 A JPH11501054 A JP H11501054A
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- ethyl
- methylcarbamoyl
- amino
- naphthyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 141
- 108010051696 Growth Hormone Proteins 0.000 title claims description 42
- 239000000122 growth hormone Substances 0.000 title claims description 42
- 102000018997 Growth Hormone Human genes 0.000 title claims 8
- 230000003578 releasing effect Effects 0.000 title description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 59
- 125000003118 aryl group Chemical group 0.000 claims abstract description 36
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 16
- -1 C1-6A Lucoxy Chemical group 0.000 claims description 497
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 154
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 152
- 239000000203 mixture Substances 0.000 claims description 118
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 106
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 104
- BKMADDIPSQRZPU-ONEGZZNKSA-N (e)-5-amino-5-methylhex-2-enoic acid Chemical compound CC(C)(N)C\C=C\C(O)=O BKMADDIPSQRZPU-ONEGZZNKSA-N 0.000 claims description 102
- 150000001408 amides Chemical class 0.000 claims description 85
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 78
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 62
- 239000001257 hydrogen Substances 0.000 claims description 58
- 238000000034 method Methods 0.000 claims description 56
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 53
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 41
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 36
- 229940080818 propionamide Drugs 0.000 claims description 36
- LLAPDLPYIYKTGQ-UHFFFAOYSA-N 1-aminoethyl Chemical group C[CH]N LLAPDLPYIYKTGQ-UHFFFAOYSA-N 0.000 claims description 30
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 24
- 229910052736 halogen Inorganic materials 0.000 claims description 21
- 150000002367 halogens Chemical class 0.000 claims description 21
- 238000011282 treatment Methods 0.000 claims description 19
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 15
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 14
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- 229940090181 propyl acetate Drugs 0.000 claims description 14
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 14
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 13
- 241001465754 Metazoa Species 0.000 claims description 13
- 150000002431 hydrogen Chemical class 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 12
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 11
- 230000012010 growth Effects 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 10
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 9
- 150000002148 esters Chemical class 0.000 claims description 9
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims description 9
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- 206010053759 Growth retardation Diseases 0.000 claims description 8
- 206010062767 Hypophysitis Diseases 0.000 claims description 8
- 125000005605 benzo group Chemical group 0.000 claims description 8
- 231100000001 growth retardation Toxicity 0.000 claims description 8
- 210000003635 pituitary gland Anatomy 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 230000002829 reductive effect Effects 0.000 claims description 7
- 230000004936 stimulating effect Effects 0.000 claims description 7
- 230000000638 stimulation Effects 0.000 claims description 7
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 6
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 claims description 6
- 125000003368 amide group Chemical group 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- IZRYKPCDTFCCFL-HNQUOIGGSA-N (e)-4-(1-aminocyclobutyl)but-2-enoic acid Chemical compound OC(=O)/C=C/CC1(N)CCC1 IZRYKPCDTFCCFL-HNQUOIGGSA-N 0.000 claims description 5
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 5
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 claims description 5
- 230000009471 action Effects 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- DRNGLYHKYPNTEA-UHFFFAOYSA-N 4-azaniumylcyclohexane-1-carboxylate Chemical compound NC1CCC(C(O)=O)CC1 DRNGLYHKYPNTEA-UHFFFAOYSA-N 0.000 claims description 4
- 208000017667 Chronic Disease Diseases 0.000 claims description 4
- 208000008589 Obesity Diseases 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- 230000015556 catabolic process Effects 0.000 claims description 4
- 230000007812 deficiency Effects 0.000 claims description 4
- BZEUYEFVVDTLOD-UHFFFAOYSA-N hex-2-enamide Chemical compound CCCC=CC(N)=O BZEUYEFVVDTLOD-UHFFFAOYSA-N 0.000 claims description 4
- 230000013632 homeostatic process Effects 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 235000020824 obesity Nutrition 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 230000002685 pulmonary effect Effects 0.000 claims description 4
- NRVOYERVTLAKCL-KAYWLYCHSA-N (2r)-2-[[(2r)-2-[[2-(2-amino-2-methylpropoxy)acetyl]-methylamino]-3-naphthalen-1-ylpropanoyl]-methylamino]-n-methyl-3-phenylpropanamide Chemical compound C([C@H](C(=O)NC)N(C)C(=O)[C@@H](CC=1C2=CC=CC=C2C=CC=1)N(C)C(=O)COCC(C)(C)N)C1=CC=CC=C1 NRVOYERVTLAKCL-KAYWLYCHSA-N 0.000 claims description 3
- VSKYOHAAUJLQSE-PJQHKJQMSA-N (e)-5-amino-n,3,5-trimethyl-n-[(2r)-1-[methyl-[(2r)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]hex-2-enamide Chemical compound C([C@H](C(=O)NC)N(C)C(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)N(C)C(=O)\C=C(/C)CC(C)(C)N)C1=CC=CC=C1 VSKYOHAAUJLQSE-PJQHKJQMSA-N 0.000 claims description 3
- YKTXQGHXTSQFRH-UKYVYTSPSA-N (e)-5-amino-n,3,5-trimethyl-n-[(2r)-1-[methyl-[(2r)-1-oxo-1-(oxolan-2-ylmethylamino)-3-phenylpropan-2-yl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]hex-2-enamide Chemical compound C([C@@H](N(C)C(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)N(C)C(=O)\C=C(/C)CC(C)(C)N)C(=O)NCC1OCCC1)C1=CC=CC=C1 YKTXQGHXTSQFRH-UKYVYTSPSA-N 0.000 claims description 3
- NSRCJWRFTUMEEL-UHFFFAOYSA-N 3-(1-aminoethyl)benzoic acid Chemical compound CC(N)C1=CC=CC(C(O)=O)=C1 NSRCJWRFTUMEEL-UHFFFAOYSA-N 0.000 claims description 3
- IZRYKPCDTFCCFL-UHFFFAOYSA-N 4-(1-aminocyclobutyl)but-2-enoic acid Chemical compound OC(=O)C=CCC1(N)CCC1 IZRYKPCDTFCCFL-UHFFFAOYSA-N 0.000 claims description 3
- BKMADDIPSQRZPU-UHFFFAOYSA-N 5-amino-5-methylhex-2-enoic acid Chemical compound CC(C)(N)CC=CC(O)=O BKMADDIPSQRZPU-UHFFFAOYSA-N 0.000 claims description 3
- MOJGYBOHFQYDJR-XYOKQWHBSA-N CC(C)(N)C\C=C(C(O)=O)/Cc1ccccc1 Chemical compound CC(C)(N)C\C=C(C(O)=O)/Cc1ccccc1 MOJGYBOHFQYDJR-XYOKQWHBSA-N 0.000 claims description 3
- WTGCPYCMNTUELF-HZQJOESUSA-N C[C@@H](CNC([C@@H](CC1=CC=CS1)N(C)C([C@@H](CC1=CC2=CC=CC=C2C=C1)NC)=O)=O)O.CC(C)(CC=CC(O)=O)N Chemical compound C[C@@H](CNC([C@@H](CC1=CC=CS1)N(C)C([C@@H](CC1=CC2=CC=CC=C2C=C1)NC)=O)=O)O.CC(C)(CC=CC(O)=O)N WTGCPYCMNTUELF-HZQJOESUSA-N 0.000 claims description 3
- URCRDUDBMLPMEZ-OAOOJARCSA-N C[C@H](CNC([C@@H](CC1=CC=CC=C1)N(C)C([C@@H](CC1=CC=C(C=CC=C2)C2=C1)NC)=O)=O)O.CC(C)(CC=CC(O)=O)N Chemical compound C[C@H](CNC([C@@H](CC1=CC=CC=C1)N(C)C([C@@H](CC1=CC=C(C=CC=C2)C2=C1)NC)=O)=O)O.CC(C)(CC=CC(O)=O)N URCRDUDBMLPMEZ-OAOOJARCSA-N 0.000 claims description 3
- KJTYMGGWJQKNDZ-OHFFHBBESA-N [1-[[(2r)-2-[[(2r)-2-[[(e)-5-amino-5-methylhex-2-enoyl]-methylamino]-3-naphthalen-2-ylpropanoyl]-methylamino]-3-phenylpropanoyl]amino]-2-methylpropan-2-yl] acetate Chemical compound C([C@@H](N(C)C(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)N(C)C(=O)\C=C\CC(C)(C)N)C(=O)NCC(C)(C)OC(C)=O)C1=CC=CC=C1 KJTYMGGWJQKNDZ-OHFFHBBESA-N 0.000 claims description 3
- 230000037396 body weight Effects 0.000 claims description 3
- 230000002950 deficient Effects 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 210000000987 immune system Anatomy 0.000 claims description 3
- 230000002503 metabolic effect Effects 0.000 claims description 3
- 238000007911 parenteral administration Methods 0.000 claims description 3
- 102000004169 proteins and genes Human genes 0.000 claims description 3
- 108090000623 proteins and genes Proteins 0.000 claims description 3
- AGJAUFUNZWHLKE-UHFFFAOYSA-N (2E,4E)-N-isobutyl-2,4-tetradecadienamide Natural products CCCCCCCCCC=CC=CC(=O)NCC(C)C AGJAUFUNZWHLKE-UHFFFAOYSA-N 0.000 claims description 2
- XZKDFIVZWKRULX-NLZGHWOMSA-N (e)-5-amino-n,3,5-trimethyl-n-[(2r)-1-[methyl-[(2r)-1-(methylamino)-1-oxo-3-thiophen-2-ylpropan-2-yl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]hex-2-enamide Chemical compound C([C@H](C(=O)NC)N(C)C(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)N(C)C(=O)\C=C(/C)CC(C)(C)N)C1=CC=CS1 XZKDFIVZWKRULX-NLZGHWOMSA-N 0.000 claims description 2
- JRKHUXANSMUFHS-VWVBQYSISA-N (e)-5-amino-n-[(2r)-1-[[(2r)-1-(benzylamino)-1-oxo-3-phenylpropan-2-yl]-methylamino]-3-naphthalen-2-yl-1-oxopropan-2-yl]-n,5-dimethylhex-2-enamide Chemical compound C([C@@H](N(C)C(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)N(C)C(=O)\C=C\CC(C)(C)N)C(=O)NCC=1C=CC=CC=1)C1=CC=CC=C1 JRKHUXANSMUFHS-VWVBQYSISA-N 0.000 claims description 2
- FKMGDDQSZCZCNU-SNAWJCMRSA-N (e)-5-methyl-5-(methylamino)hex-2-enoic acid Chemical compound CNC(C)(C)C\C=C\C(O)=O FKMGDDQSZCZCNU-SNAWJCMRSA-N 0.000 claims description 2
- FKIJKEMQCOCIRQ-XGWWGWHESA-N (e)-n,5-dimethyl-5-(methylamino)-n-[(2r)-1-[methyl-[(2r)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]hex-2-enamide Chemical compound C([C@H](C(=O)NC)N(C)C(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)N(C)C(=O)\C=C\CC(C)(C)NC)C1=CC=CC=C1 FKIJKEMQCOCIRQ-XGWWGWHESA-N 0.000 claims description 2
- VSKYOHAAUJLQSE-XFXHVHLZSA-N (z)-5-amino-n,3,5-trimethyl-n-[(2r)-1-[methyl-[(2r)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]hex-2-enamide Chemical compound C([C@H](C(=O)NC)N(C)C(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)N(C)C(=O)\C=C(\C)CC(C)(C)N)C1=CC=CC=C1 VSKYOHAAUJLQSE-XFXHVHLZSA-N 0.000 claims description 2
- GHXGQRQJGZFRHS-UHFFFAOYSA-N 2-(2-amino-2-methylpropoxy)acetic acid Chemical compound CC(C)(N)COCC(O)=O GHXGQRQJGZFRHS-UHFFFAOYSA-N 0.000 claims description 2
- DYQVRDISZFVXHV-UHFFFAOYSA-N 4-(methylazaniumyl)cyclohexane-1-carboxylate Chemical compound CNC1CCC(C(O)=O)CC1 DYQVRDISZFVXHV-UHFFFAOYSA-N 0.000 claims description 2
- PLCINJNEFNITCT-UHFFFAOYSA-N 5-(methylamino)hex-2-enoic acid Chemical compound CNC(C)CC=CC(O)=O PLCINJNEFNITCT-UHFFFAOYSA-N 0.000 claims description 2
- AOGUDKCUEZSLHY-UHFFFAOYSA-N 5-amino-3,5-dimethylhex-2-enoic acid Chemical compound CC(N)(C)CC(C)=CC(O)=O AOGUDKCUEZSLHY-UHFFFAOYSA-N 0.000 claims description 2
- ITWDDDADSFZADI-UHFFFAOYSA-N 6-methylpiperidine-3-carboxylic acid Chemical compound CC1CCC(C(O)=O)CN1 ITWDDDADSFZADI-UHFFFAOYSA-N 0.000 claims description 2
- 208000030507 AIDS Diseases 0.000 claims description 2
- 208000024827 Alzheimer disease Diseases 0.000 claims description 2
- RQLHPGMBWUIKOT-OHIDFYLOSA-N CC(CC=CC(O)=O)NC.CN[C@H](CC1=CC2=CC=CC=C2C=C1)C(N(C)[C@H](CC(C=C1)=CC(F)=C1F)C(NC)=O)=O Chemical compound CC(CC=CC(O)=O)NC.CN[C@H](CC1=CC2=CC=CC=C2C=C1)C(N(C)[C@H](CC(C=C1)=CC(F)=C1F)C(NC)=O)=O RQLHPGMBWUIKOT-OHIDFYLOSA-N 0.000 claims description 2
- OIAXICOOJSZYSZ-YCFZMVJMSA-N C[C@@H](CNC([C@@H](CC(C=C1)=CC(F)=C1F)N(C)C([C@@H](CC1=CC2=CC=CC=C2C=C1)NC)=O)=O)O.CC(C)(CC=CC(O)=O)N Chemical compound C[C@@H](CNC([C@@H](CC(C=C1)=CC(F)=C1F)N(C)C([C@@H](CC1=CC2=CC=CC=C2C=C1)NC)=O)=O)O.CC(C)(CC=CC(O)=O)N OIAXICOOJSZYSZ-YCFZMVJMSA-N 0.000 claims description 2
- 208000014311 Cushing syndrome Diseases 0.000 claims description 2
- 206010060378 Hyperinsulinaemia Diseases 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- 206010029748 Noonan syndrome Diseases 0.000 claims description 2
- 208000004286 Osteochondrodysplasias Diseases 0.000 claims description 2
- 208000001132 Osteoporosis Diseases 0.000 claims description 2
- 241001494479 Pecora Species 0.000 claims description 2
- 206010072610 Skeletal dysplasia Diseases 0.000 claims description 2
- 208000026928 Turner syndrome Diseases 0.000 claims description 2
- 208000027418 Wounds and injury Diseases 0.000 claims description 2
- 230000010072 bone remodeling Effects 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 210000000845 cartilage Anatomy 0.000 claims description 2
- 230000001925 catabolic effect Effects 0.000 claims description 2
- 230000006378 damage Effects 0.000 claims description 2
- 230000003111 delayed effect Effects 0.000 claims description 2
- 230000004064 dysfunction Effects 0.000 claims description 2
- 230000003779 hair growth Effects 0.000 claims description 2
- 230000035876 healing Effects 0.000 claims description 2
- 230000003451 hyperinsulinaemic effect Effects 0.000 claims description 2
- 201000008980 hyperinsulinism Diseases 0.000 claims description 2
- 208000014674 injury Diseases 0.000 claims description 2
- 210000004153 islets of langerhan Anatomy 0.000 claims description 2
- 244000144972 livestock Species 0.000 claims description 2
- 238000012423 maintenance Methods 0.000 claims description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
- 210000003205 muscle Anatomy 0.000 claims description 2
- 210000000963 osteoblast Anatomy 0.000 claims description 2
- 230000017363 positive regulation of growth Effects 0.000 claims description 2
- 201000009395 primary hyperaldosteronism Diseases 0.000 claims description 2
- 230000000541 pulsatile effect Effects 0.000 claims description 2
- 238000011084 recovery Methods 0.000 claims description 2
- 230000008439 repair process Effects 0.000 claims description 2
- 230000000241 respiratory effect Effects 0.000 claims description 2
- 201000000980 schizophrenia Diseases 0.000 claims description 2
- 238000001356 surgical procedure Methods 0.000 claims description 2
- 230000029663 wound healing Effects 0.000 claims description 2
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims 3
- 229940079593 drug Drugs 0.000 claims 3
- QLWCMCRHYSQUND-FQLXRVMXSA-N (2r)-n-methyl-2-[methyl-[(2r)-2-[methyl-(2-piperidin-4-ylideneacetyl)amino]-3-naphthalen-2-ylpropanoyl]amino]-3-phenylpropanamide Chemical compound C([C@H](C(=O)NC)N(C)C(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)N(C)C(=O)C=C1CCNCC1)C1=CC=CC=C1 QLWCMCRHYSQUND-FQLXRVMXSA-N 0.000 claims 1
- TUYLAHAQKPGZDL-YGHOILDKSA-N (e)-4-(1-aminocyclobutyl)-n-methyl-n-[(2r)-1-[methyl-[(2r)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]but-2-enamide Chemical compound C([C@H](C(=O)NC)N(C)C(=O)[C@@H](CC=1C=CC(=CC=1)C=1C=CC=CC=1)N(C)C(=O)\C=C\CC1(N)CCC1)C1=CC=CC=C1 TUYLAHAQKPGZDL-YGHOILDKSA-N 0.000 claims 1
- PHRQDPHDWFYSEH-XGWWGWHESA-N (e)-5-amino-n-[(2r)-1-[ethyl-[(2r)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]-n,5-dimethylhex-2-enamide Chemical compound C([C@@H](N(CC)C(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)N(C)C(=O)\C=C\CC(C)(C)N)C(=O)NC)C1=CC=CC=C1 PHRQDPHDWFYSEH-XGWWGWHESA-N 0.000 claims 1
- KMZIQSXIZIDPBC-AREMUKBSSA-N 2-(2-amino-2-methylpropoxy)-n-[(2r)-1-[2-benzyl-2-(ethylcarbamoyl)hydrazinyl]-3-naphthalen-2-yl-1-oxopropan-2-yl]-n-methylacetamide Chemical compound O=C([C@@H](CC=1C=C2C=CC=CC2=CC=1)N(C)C(=O)COCC(C)(C)N)NN(C(=O)NCC)CC1=CC=CC=C1 KMZIQSXIZIDPBC-AREMUKBSSA-N 0.000 claims 1
- PGKFDTXLDPAZLJ-UHFFFAOYSA-N 2-methyl-n-[1-[methyl-[1-(3-methyl-1,2,4-oxadiazol-5-yl)-2-naphthalen-2-ylethyl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]piperidine-4-carboxamide Chemical compound C1CNC(C)CC1C(=O)NC(C(=O)N(C)C(CC=1C=C2C=CC=CC2=CC=1)C=1ON=C(C)N=1)CC1=CC=C(C=CC=C2)C2=C1 PGKFDTXLDPAZLJ-UHFFFAOYSA-N 0.000 claims 1
- LTPVSOCPYWDIFU-UHFFFAOYSA-N 4-methoxyphenylethylamine Chemical compound COC1=CC=C(CCN)C=C1 LTPVSOCPYWDIFU-UHFFFAOYSA-N 0.000 claims 1
- 206010006895 Cachexia Diseases 0.000 claims 1
- 208000020401 Depressive disease Diseases 0.000 claims 1
- 208000001362 Fetal Growth Retardation Diseases 0.000 claims 1
- 206010070531 Foetal growth restriction Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 208000001647 Renal Insufficiency Diseases 0.000 claims 1
- 238000009098 adjuvant therapy Methods 0.000 claims 1
- 230000032683 aging Effects 0.000 claims 1
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- POECFFCNUXZPJT-UHFFFAOYSA-M sodium;carbonic acid;hydrogen carbonate Chemical compound [Na+].OC(O)=O.OC([O-])=O POECFFCNUXZPJT-UHFFFAOYSA-M 0.000 description 1
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- NPSILQRSKNCBKB-NSHDSACASA-N tert-butyl (2s)-2-[(2-ethoxy-2-oxoethoxy)methyl]pyrrolidine-1-carboxylate Chemical compound CCOC(=O)COC[C@@H]1CCCN1C(=O)OC(C)(C)C NPSILQRSKNCBKB-NSHDSACASA-N 0.000 description 1
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- WBJWZGANDZSWGB-UHFFFAOYSA-N tert-butyl 3-(hydroxymethyl)azetidine-1-carboxylate 1-[(2-methylpropan-2-yl)oxycarbonyl]azetidine-3-carboxylic acid Chemical compound C(=O)(OC(C)(C)C)N1CC(C1)C(=O)O.C(=O)(OC(C)(C)C)N1CC(C1)CO WBJWZGANDZSWGB-UHFFFAOYSA-N 0.000 description 1
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- QUERMGFVJPRMJL-UHFFFAOYSA-N tert-butyl azetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC1 QUERMGFVJPRMJL-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
- RFEWTYBARDMNDQ-UHFFFAOYSA-N tert-butyl n-(2-naphthalen-2-ylethyl)carbamate Chemical compound C1=CC=CC2=CC(CCNC(=O)OC(C)(C)C)=CC=C21 RFEWTYBARDMNDQ-UHFFFAOYSA-N 0.000 description 1
- QHSUFODBDZQCHO-UHFFFAOYSA-N tert-butyl n-(4-hydroxy-2-methylbutan-2-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC(C)(C)CCO QHSUFODBDZQCHO-UHFFFAOYSA-N 0.000 description 1
- LVCBXYVQWHLNJD-OAHLLOKOSA-N tert-butyl n-[(2r)-1-(3-hydroxypropylamino)-1-oxo-3-phenylpropan-2-yl]-n-methylcarbamate Chemical compound OCCCNC(=O)[C@H](N(C)C(=O)OC(C)(C)C)CC1=CC=CC=C1 LVCBXYVQWHLNJD-OAHLLOKOSA-N 0.000 description 1
- NOLMOMCZGQELIB-HXUWFJFHSA-N tert-butyl n-[(2r)-1-(benzylamino)-3-phenylpropan-2-yl]-n-methylcarbamate Chemical compound C([C@H](N(C)C(=O)OC(C)(C)C)CC=1C=CC=CC=1)NCC1=CC=CC=C1 NOLMOMCZGQELIB-HXUWFJFHSA-N 0.000 description 1
- CYIYRRRYDJOHSV-CQSZACIVSA-N tert-butyl n-[(2r)-1-(dimethylamino)-1-oxo-3-phenylpropan-2-yl]-n-methylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)[C@@H](C(=O)N(C)C)CC1=CC=CC=C1 CYIYRRRYDJOHSV-CQSZACIVSA-N 0.000 description 1
- KRTYREVTUPWPFH-KAYWLYCHSA-N tert-butyl n-[(2r)-1-[[(2r)-1-(dimethylamino)-1-oxo-3-phenylpropan-2-yl]-methylamino]-3-naphthalen-2-yl-1-oxopropan-2-yl]-n-methylcarbamate Chemical compound C([C@H](C(=O)N(C)C)N(C)C(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)N(C)C(=O)OC(C)(C)C)C1=CC=CC=C1 KRTYREVTUPWPFH-KAYWLYCHSA-N 0.000 description 1
- FOKBEOZHWFJFRQ-CYBMUJFWSA-N tert-butyl n-[(2r)-1-amino-3-phenylpropan-2-yl]-n-methylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)[C@@H](CN)CC1=CC=CC=C1 FOKBEOZHWFJFRQ-CYBMUJFWSA-N 0.000 description 1
- MYWHFQAFNHICGY-CYBMUJFWSA-N tert-butyl n-[(2r)-1-hydroxy-3-phenylpropan-2-yl]-n-methylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)[C@@H](CO)CC1=CC=CC=C1 MYWHFQAFNHICGY-CYBMUJFWSA-N 0.000 description 1
- XDLGIXPSKMWYTK-WZBYNZJPSA-N tert-butyl n-[(e)-2,4-dimethyl-6-[methyl-[(2r)-1-[methyl-[(2r)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]amino]-6-oxohex-4-en-2-yl]carbamate Chemical compound C([C@H](C(=O)NC)N(C)C(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)N(C)C(=O)\C=C(/C)CC(C)(C)NC(=O)OC(C)(C)C)C1=CC=CC=C1 XDLGIXPSKMWYTK-WZBYNZJPSA-N 0.000 description 1
- AKEPLOSYBXUZHR-UPPMBFOJSA-N tert-butyl n-[(e)-2-methyl-6-[methyl-[(2r)-1-[methyl-[(2r)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]-6-oxohex-4-en-2-yl]carbamate Chemical compound C([C@H](C(=O)NC)N(C)C(=O)[C@@H](CC=1C=CC(=CC=1)C=1C=CC=CC=1)N(C)C(=O)\C=C\CC(C)(C)NC(=O)OC(C)(C)C)C1=CC=CC=C1 AKEPLOSYBXUZHR-UPPMBFOJSA-N 0.000 description 1
- WGHHLFITFHNYSA-NHOHKQBLSA-N tert-butyl n-[(e)-6-[[(2r)-1-[[(2r)-1-(methanesulfonamido)-3-phenylpropan-2-yl]-methylamino]-3-naphthalen-2-yl-1-oxopropan-2-yl]-methylamino]-2-methyl-6-oxohex-4-en-2-yl]carbamate Chemical compound C([C@H](CNS(C)(=O)=O)N(C)C(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)N(C)C(=O)\C=C\CC(C)(C)NC(=O)OC(C)(C)C)C1=CC=CC=C1 WGHHLFITFHNYSA-NHOHKQBLSA-N 0.000 description 1
- YWSXTMBDIBZHBB-UHFFFAOYSA-N tert-butyl n-but-3-enylcarbamate Chemical compound CC(C)(C)OC(=O)NCCC=C YWSXTMBDIBZHBB-UHFFFAOYSA-N 0.000 description 1
- JOLOYYRHPUVBJM-UHFFFAOYSA-N tert-butyl n-butan-2-ylcarbamate Chemical compound CCC(C)NC(=O)OC(C)(C)C JOLOYYRHPUVBJM-UHFFFAOYSA-N 0.000 description 1
- ISTGQSQWSKCNFJ-UHFFFAOYSA-N tert-butyl n-ethylcarbamate Chemical compound CCNC(=O)OC(C)(C)C ISTGQSQWSKCNFJ-UHFFFAOYSA-N 0.000 description 1
- VUMYDLDYDYPYAD-GOSISDBHSA-N tert-butyl n-methyl-n-[(1r)-1-(3-methyl-1,2,4-oxadiazol-5-yl)-2-naphthalen-2-ylethyl]carbamate Chemical compound C1([C@@H](CC=2C=C3C=CC=CC3=CC=2)N(C)C(=O)OC(C)(C)C)=NC(C)=NO1 VUMYDLDYDYPYAD-GOSISDBHSA-N 0.000 description 1
- KXOCMPRWGVYYLE-DHIUTWEWSA-N tert-butyl n-methyl-n-[(2r)-1-[methyl-[(2r)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]amino]-1-oxo-3-phenylmethoxypropan-2-yl]carbamate Chemical compound C([C@H](C(=O)NC)N(C)C(=O)[C@@H](COCC=1C=CC=CC=1)N(C)C(=O)OC(C)(C)C)C1=CC=CC=C1 KXOCMPRWGVYYLE-DHIUTWEWSA-N 0.000 description 1
- IQPYLTWSFHCBIZ-CLJLJLNGSA-N tert-butyl n-methyl-n-[(2r)-1-[methyl-[(2r)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]amino]-3-naphthalen-1-yl-1-oxopropan-2-yl]carbamate Chemical compound C([C@H](C(=O)NC)N(C)C(=O)[C@@H](CC=1C2=CC=CC=C2C=CC=1)N(C)C(=O)OC(C)(C)C)C1=CC=CC=C1 IQPYLTWSFHCBIZ-CLJLJLNGSA-N 0.000 description 1
- HAEUKIXVDAJECZ-FQLXRVMXSA-N tert-butyl n-methyl-n-[(2r)-1-[methyl-[(2r)-1-[(3-methyl-1,2,4-oxadiazol-5-yl)methoxy]-3-phenylpropan-2-yl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]carbamate Chemical compound C([C@H](N(C)C(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)N(C)C(=O)OC(C)(C)C)CC=1C=CC=CC=1)OCC1=NC(C)=NO1 HAEUKIXVDAJECZ-FQLXRVMXSA-N 0.000 description 1
- VPTLOBVYYCCPHH-GVKMRLRKSA-N tert-butyl n-methyl-n-[(2r)-1-[methyl-[(2r)-1-oxo-1-(oxolan-2-ylmethylamino)-3-phenylpropan-2-yl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]carbamate Chemical compound C([C@@H](N(C)C(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)N(C)C(=O)OC(C)(C)C)C(=O)NCC1OCCC1)C1=CC=CC=C1 VPTLOBVYYCCPHH-GVKMRLRKSA-N 0.000 description 1
- KYDJQJAIHCVQPO-UHFFFAOYSA-N tert-butyl n-tert-butylcarbamate Chemical compound CC(C)(C)NC(=O)OC(C)(C)C KYDJQJAIHCVQPO-UHFFFAOYSA-N 0.000 description 1
- XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical compound CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 0.000 description 1
- BFKJFAAPBSQJPD-UHFFFAOYSA-N tetrafluoroethene Chemical group FC(F)=C(F)F BFKJFAAPBSQJPD-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 230000002992 thymic effect Effects 0.000 description 1
- 230000005313 thymus development Effects 0.000 description 1
- 239000006208 topical dosage form Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 238000007738 vacuum evaporation Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
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- A61P15/14—Drugs for genital or sexual disorders; Contraceptives for lactation disorders, e.g. galactorrhoea
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- B41J—TYPEWRITERS; SELECTIVE PRINTING MECHANISMS, i.e. MECHANISMS PRINTING OTHERWISE THAN FROM A FORME; CORRECTION OF TYPOGRAPHICAL ERRORS
- B41J19/00—Character- or line-spacing mechanisms
- B41J19/18—Character-spacing or back-spacing mechanisms; Carriage return or release devices therefor
- B41J19/20—Positive-feed character-spacing mechanisms
- B41J19/202—Drive control means for carriage movement
- B41J19/205—Position or speed detectors therefor
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/22—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
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- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/0606—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing heteroatoms not provided for by C07K5/06086 - C07K5/06139, e.g. Ser, Met, Cys, Thr
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
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- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
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- A61K38/00—Medicinal preparations containing peptides
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.一般式I {上式中 R1およびR2は独立に水素であるか、またはアリールで置換されることがある C1-6アルキルであり; aおよびbは独立に1または2であり; Gは水素、−O−(CH2)k−R27、 であり; Jは水素、−O−(CH2)l−R32、 であり; ここで R27,R28,R29,R30,R31,R32,R33,R34,R35およびR36は独立に 水素、ハロゲン、アリール、C1-6アルキルまたはC1-6アルコキシであり; kおよびlは独立に0,1または2であり; Eが 〔ここで Xは−N(R15)−、−O−または−S−であり、 Vは−C(R16)=または−N=であり、 Yは−C(R17)=または−N=であり、 Zは−C(R18)=または−N=であり、 R15は水素であるか、またはアリールで置換されることがあるC1-6アルキルで あり、 R16,R17およびR18は独立に水素、−COOR19、−CONR20R21、−(C H2)wNR20R21、−(CH2)wOR19、−(CH2)wR19またはハロゲンであ り、 R12,R13,R19,R20およびR21は独立に水素であるか、またはハロゲン、− N(R22)R23、−CF3、ヒドロキシル、C1-6ア ルコキシ、C1-6アルコキシカルボニル、C1-6アルキルカルボニルオキシもしく はアリールにより置換されることがあるC1-6アルキルであり、 あるいはR13は であり、ここで Qは−CH<または−N<であり、 KおよびLは独立に−CH2−,−CO−,−O−,−S−,−NR26−または 原子価結合であり、ここでR26は水素またはC1-6アルキルであり、 tおよびuは独立に0,1,2,3または4であり、 R13aはアリールにより置換されたC1-6アルキルであり、 R14はC1-6アルキルであり R22およびR23は独立に水素またはC1-6アルキルであり、 vおよびwは独立に0,1,2または3である〕である時には、 Dは 〔ここで R3,R4,R5,R6,R7,R8およびR9は独立に水素であるか、またはハロゲ ンにより、アミノにより、ヒドロキシルにより もしくはアリールにより置換されることがあるC1-6アルキルであり; n,mおよびqは独立に0,1,2または3であり; pは0または1であり; Mは−CR11=CR11a−、アリール、−O−または−S−であり; R11およびR11aは独立に水素であるか、またはアリールにより置換されること があるC1-6アルキルであり; ただし、R3,R4,R5およびR6のうちの少なくとも1つが水素ではないことを 前提とする〕 であり;あるいは Eが 〔ここで R12およびR13は独立に水素であるか、またはハロゲン、−CONR22R23、− N(R22)R23、−CF3、ヒドロキシル、C1-6アルコキシ、C1-6アルコキシ カルボニル、C1-6アルキルカルボニルオキシもしくはアリールにより置換され ることがあるC1-6アルキルであり、 あるいはR13は であり、ここで Qは−CH<または−N<であり、 KおよびLは独立に−CH2−,−CO−,−O−,−S−, −NR26−または原子価結合であり、ここでR26は水素またはC1-6アルキルで あり、 tおよびuは独立に0,1,2,3または4であり、 R13aはアリールにより置換されたアルキルであり、 R14はC1-6アルキルであり、 R22およびR23は独立に水素またはC1-6アルキルであり、 vおよびwは独立に0,1,2または3である〕 である時には、 Dは 〔ここで R7,R8,R9およびR10は独立に水素であるかまたはハロゲンにより、アミノ により、ヒドロキシルによりもしくはアリールにより置換されることがあるC1- 6 アルキルであり、 あるいはR7とR8またはR7とR9またはR8とR9が場合により一緒になって−( CH2)i−U−(CH2)j−を形成し、ここでiおよびjは独立に1または2であり そしてUは−O−,−S−または原子価結合であり、 nおよびmは独立に0,1,2または3であり、 oおよびpは独立に0または1であり、 Mは−CR11=CR11a−、アリール、−O−または−S−であり、R11および R11aは独立に水素であるか、またはアリールにより置換されることがあるC1-6 アルキルである〕 である} により表される化合物;または医薬上許容されるその塩。 2.Eが 〔ここで Xは−N(R15)−、−O−または−S−であり、 Vは−C(R16)=または−N=であり、 Yは−C(R17)=または−N=であり、 Zは−C(R18)=または−N=であり、 R15は水素であるか、またはアリールで置換されることがあるC1-6アルキルで あり、 R16,R17およびR18は独立に水素、−COOR19、−CONR20R21、−(C H2)wNR20R21、−(CH2)wOR19、−(CH2)wR19またはハロゲンであ り、 R12,R13,R19,R20およびR21は独立に水素であるか、またはハロゲン、− N(R22)R23、−CF3、ヒドロキシル、C1-6アルコキシ、C1-6アルコキシ カルボニル、C1-6アルキルカルボニルオキシもしくはアリールにより置換され ることがあるC1-6アルキルであり、 あるいはR13は であり、ここで Qは−CH<または−N<であり、 KおよびLは独立に−CH2−,−CO−,−O−,−S−, −NR26−または原子価結合であり、ここでR26は水素またはC1-6アルキルで あり、 tおよびuは独立に0,1,2,3または4であり、 R13aはアリールにより置換されたC1-6アルキルであり、 R14はC1-6アルキルであり R22およびR23は独立に水素またはC1-6アルキルであり、そして vおよびwは独立に0,1,2または3である〕である時、 Dが 〔ここで R3,R4,R5,R6,R7,R8およびR9は独立に水素、またはメチルであり; n,mおよびqは独立に0,1または2であり; Mは−CR11=CR11a−、アリールまたは−O−であり; R11およびR11aは独立に水素であるか、またはアリールにより置換されること があるC1-6アルキルであり; ただし、R3,R4,R5およびR6のうちの少なくとも1つが水素ではないことを 前提とする〕 である、請求項1に記載の化合物。 3.Eが 〔ここで R12およびR13は独立に水素であるか、またはハロゲン、−CONR22R23、− N(R22)R23、−CF3、ヒドロキシル、C1-6アルコキシ、C1-6アルコキシ カルボニル、C1-6アルキルカルボニルオキシもしくはアリールにより置換され ることがあるC1-6アルキルであり、 あるいはR13は であり、ここで Qは−CH<または−N<であり、 KおよびLは独立に−CH2−,−CO−,−O−,−S−,−NR26−または 原子価結合であり、ここでR26は水素またはC1-6アルキルであり、 tおよびuは独立に0,1,2,3または4であり、 R13aはアリールにより置換されたC1-6アルキルであり、 R14はC1-6アルキルであり、 R22およびR23は独立に水素またはC1-6アルキルであり、 vおよびwは独立に0,1,2または3である〕 である時、 Dが 〔ここで R8およびR9は独立に水素またはメチルであり、 R7およびR10は独立に水素であるかまたはハロゲンにより、アミノにより、ヒ ドロキシルによりもしくはアリールにより置換される ことがあるC1-6アルキルであり、 あるいはR7とR8またはR8とR9が場合により一緒になって−(CH2)i−U−( CH2)j−を形成し、ここでiおよびjは独立に1または2でありそしてUは−O −,−S−または原子価結合であり、 nおよびmは独立に0,1または2であり、 Mは−CR11=CR11a−、アリールまたは−O−であり、 R11およびRN11aは独立に水素であるか、またはアリールにより置換されるこ とがあるC1-6アルキルである〕 である、請求項1に記載の化合物。 4.Dが3−(1−アミノエチル)フェニル、4−アミノ−4−エチルヘキサ −1−エニル、(1E)−2−(アゼチジン−3−イル)エテニル、ピペリジン −4−イリデニル、2−メチルピペリジン−4−イル、2−メチルピペリジン− 3−イル、2−メチルピペリジン−5−イル、(1,2,3,4−テトラヒドロ イソキノリン−1−イル)メチル、4−アミノシクロヘキシル、2−ピペリジル メトキシメチル、4−ピペリジルオキシメチル、2−(2−アミノ−2−メチル プロピル)シクロプロピル、(((2R)−ピロリジン−2−イル)メトキシ) メチル、(1E)−4−アミノ−1−ベンジル−4−メチルペンタ−1−エニル 、(1E)−4−アミノ−4−メチルペンタ−1−エニル、(2−アミノ−2− メチルプロポキシ)メチル、(2S)−(2−ピロリジニル)メトキシメチル、 (2R)−(2−ピロリジニル)メトキシメチル、(1E)−4−アミノ−2, 4−ジメチルペンタ−1−エニル、(1E)−4−メチル−4−(メチルアミノ )ペンタ−1−エニル、(1Z)−4−アミノ−4−メチルペンタ−1−エニル 、(1E)−4−((2R)−2−ヒドロキシプロピルアミノ)−4−メチルペ ンタ−1−エニ ル、(2−アミノブトキシ)メチル、3−(1−アミノエチル)フェニル、3− アミノメチルフェニル、3−(1−アミノ−1−メチルエチル)フェニル、2− (1−アミノシクロプロピル)エテニル、3−(1−アミノシクロブチル)−1 −プロペニル、3−(1−アミノシクロプロピル)−1−プロペニルまたは2− (1−アミノシクロブチル)エテニルである、請求項1,2または3に記載の化 合物。 5.Eがメチルカルバモイル、エチルカルバモイル、N,N−ジメチルカルバ モイル、2−メトキシエチルカルバモイル、(2S)−2−ヒドロキシプロピル カルバモイル、(2R)−2−ヒドロキシプロピルカルバモイル、(シクロプロ ピルメチル)カルバモイル、(2−(アセトキシ)−2−メチルプロピル)カル バモイル、フェニルエチルカルバモイル、4−ピリジルカルバモイル、(3−ア セトキシプロピル)カルバモイル、(3−ヒドロキシプロピル)カルバモイル、 メチルスルホニルアミノメチル、((テトラヒドロフラン−2−イル)メチル) カルバモイル、3−シクロプロピルチオウレイド、N−メチル−N−(メチルス ルホニルアミノ)メチル、(2,2,2−トリフルオロエチル)カルバモイル、 シクロプロピルカルバモイル、((3−メチル−1,2,4−オキサジアゾール −5−イル)メトキシ)メチル、3−メチル−1,2,4−オキサジアゾール− 5−イル、メチルスルホニルアミノメチル、2,2−ジメチル−3−ヒドロキシ プロピルカルバモイル、2−(1−メチルピロリジン−2−イル)エチルカルバ モイル、N−メチル−N−(3−(ジメチルアミノ)プロピル)カルバモイル、 N−(N,N−ジメチルカルバモイル)−N−メチルカルバモイル、N−(カル バモイルメチル)カルバモイルまたは3−シクロプロピルチオウレイドである、 請求項1,2または3に記載の化合物。 6.R1およびR2が独立に水素、メチルまたはエチルである、請求項1〜5の いずれか一項に記載の化合物。 7.aおよびbが独立に1である、請求項1〜6のいずれか一項に記載の化合 物。 8.Gが水素、−O−(CH2)k−R27、 であり; Jが水素、−O−(CH2)l−R32、 であり (ここでR27,R28,R29,R30,R31,R32,R33,R34,R35およびR36は 独立に水素、ハロゲン、アリール、C1-6アルキルまたはC1-6アルコキシである );そして kおよびlが1である、 請求項1〜7のいずれか一項に記載の化合物。 9.R27,R28,R29,R30,R31,R32,R33,R34,R35およびR36が水 素、ハロゲンまたはフェニルである、請求項1〜8のいずれか一項に記載の化合 物。 10.次の化合物: (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−(N−メチル−N−((1R)−1−(メ チルカルバモイル)−2−フェニルエチル)カルバモイル)−2−(2−ナフチ ル)エチル)アミド、もしくはその塩酸塩; (2E)−3−(3−アゼチジニル)アクリル酸N−メチル−N−((1R)− 1−(N−メチル−N−((1R)−1−(メチルカルバモイル)−2−フェニ ルエチル)カルバモイル)−2−(2−ナフチル)エチル)アミド; 2−(ピペリジン−4−イリデン)酢酸N−メチル−N−((1R)−1−(N −メチル−N−((1R)−1−(メチルカルバモイル)−2−フェニルエチル )カルバモイル)−2−(2−ナフチル)エチル)アミド; 2−(2−アミノ−2−メチルプロピル)シクロプロパンカルボン酸N−メチル −N−((1R)−1−(N−メチル−N−((1R)−1−(メチルカルバモ イル)−2−フェニルエチル)カルバモイル)−2−(2−ナフチル)エチル) アミド; 2−(2−アミノ−2−メチルプロポキシ)酢酸N−メチル−N−((1R)− 1−(N−メチル−N−((1R)−1−(メチルカルバモイル)−2−フェニ ルエチル)カルバモイル)−2−(2−ナフチル)エチル)アミド; 2−メチルピペリジン−4−カルボン酸N−メチル−N−((1R)−1−(N −メチル−N−((1R)−1−(メチルカルバモイル)−2−フェニルエチル )カルバモイル)−2−(2−ナフチル)エチル)アミド; 2−メチルピペリジン−3−カルボン酸N−メチル−N−((1R)−1−(N −メチル−N−((1R)−1−(メチルカルバモイル)−2−フェニルエチル )カルバモイル)−2−(2−ナフチル)エチル)アミド; 2−メチルピペリジン−5−カルボン酸N−メチル−N−((1R) −1−(N−メチル−N−((1R)−1−(メチルカルバモイル)−2−フェ ニルエチル)カルバモイル)−2−(2−ナフチル)エチル)アミド; 2−(1,2,3,4−テトラヒドロイソキノリン−1−イル)酢酸N−メチル −N−((1R)−1−(N−メチル−N−((1R)−1−(メチルカルバモ イル)−2−フェニルエチル)カルバモイル)−2−(2−ナフチル)エチル) アミド; 4−アミノシクロヘキサンカルボン酸N−メチル−N−((1R)−1−(N− メチル−N−((1R)−1−(メチルカルバモイル)−2−フェニルエチル) カルバモイル)−2−(2−ナフチル)エチル)アミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−((1R)−1−( N−((1R)−1−(ベンジルカルバモイル)−2−フェニルエチル)−N− メチルカルバモイル)−2−(2−ナフチル)エチル)−N−メチルアミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−(N−メチル−N−((1R)−1−(フェネチルカルバモイル)− 2−フェニルエチル)カルバモイル)−2−(2−ナフチル)エチル)アミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−((1R)−1−{ N−〔(1R)−1−(アセチルアミノメチル)−2−フェニルエチル〕−N− メチルカルバモイル}−2−(2−ナフチル)エチル)−N−メチルアミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−{N−メチル−N−〔(1R)−1−(メチルスルホニルアミノメチ ル)−2−フェニルエチル〕カルバモイル}−2−(2−ナフチル)エチル)ア ミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−((1R)−1−( N−((1R)−1−((シクロプロピルメチル)カルバモイル)−2−フェニ ルエチル)−N−メチルカルバモイル)−2−(2−ナフチル)エチル)−N− メチルアミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−((1R)−1−( N−((1R)−1−(N−(2−メトキシエチル)カルバモイル)−2−フェ ニルエチル)−N−メチルカルバモイル)−2−(2−ナフチル)エチル)−N −メチルアミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−(N−メチル−N−((1R)−2−フェニル−1−((N−テトラ ヒドロフラン−2−イル)メチル)カルバモイル)エチル)カルバモイル)−2 −(2−ナフチル)エチル)アミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−((1R)−1−( N−((1R)−1−(N−2−ヒドロキシプロピルカルバモイル)−2−フェ ニルエチル)−N−メチルカルバモイル)−2−(2−ナフチル)エチル)−N −メチルアミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−(N−メチル−N−((1R)−1−(N−(3−(2−オキソピロ リジン−1−イル)プロピル)カルバモイル)−2−フェニルエチル)カルバモ イル)−2−(2−ナフチル)エチル)アミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−((1R)−1−{ N−〔(1R)−1−((2,5−ジオキソピロリジン−1−イル)メチル)− 2−フェニルエチル〕−N−メチルカルバモイル}−2−(2−ナフチル)エチ ル)−N−メチルアミド; (2R)−2−(N−((2−アミノ−2−メチルプロポキシ)ア セチル)−N−メチルアミノ)−N−メチル−3−(2−ナフチル)−N−(( 1R)−2−フェニル−1−(((テトラヒドロフラン−2−イル)メチル)カ ルバモイル)エチル)プロピオンアミド; (2E)−5−アミノ−3,5−ジメチルヘキサ−2−エン酸N−メチル−N− ((1R)−1−(N−メチル−N−((1R)−2−フェニル−1−(((2 −テトラヒドロフラニル)メチル)カルバモイル)エチル)カルバモイル)−2 −(2−ナフチル)エチル)アミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−((1R)−2−ベ ンジルオキシ−1−(N−メチル−N−((1R)−1−メチルカルバモイル− 2−フェニルエチル)カルバモイル)エチル)−N−メチルアミド; (2R)−2−(N−((2−アミノ−2−メチルプロポキシ)アセチル)−N −メチルアミノ)−N−((1R)−1−(シクロプロピルメチル)カルバモイ ル)−2−フェニルエチル)−N−メチル−3−(2−ナフチル)プロピオンア ミド; (2R)−2−(N−((2−アミノ−2−メチルプロポキシ)アセチル)メチ ルアミノ)−N−((1R)−2−(2−フルオロフェニル)−1−(メチルカ ルバモイル)エチル)−N−メチル−3−(2−ナフチル)プロピオンアミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−((1R)−2−( 4−フルオロフェニル)−1−(メチルカルバモイル)エチル)−N−メチルカ ルバモイル)−2−(2−ナフチル)エチル)−N−メチルアミド; (2R)−2−(N−((2−アミノ−2−メチルプロポキシ)アセチル)−N −メチルアミノ)−N−((1R)−2−(4−フルオロフェニル)−1−(メ チルカルバモイル)エチル)−N−メチ ル−3−(2−ナフチル)プロピオンアミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−((1R)−2−( ビフェニル−4−イル)−1−(N−メチル−N−((1R)−1−(メチルカ ルバモイル)−2−フェニルエチル)カルバモイル)エチル)−N−メチルアミ ド; (2E)−5−アミノ−3,5−ジメチルヘキサ−2−エン酸N−メチル−N− ((1R)−1−(N−メチル−N−((1R)−1−(メチルカルバモイル) −2−フェニルエチル)カルバモイル)−2−(2−ナフチル)エチル)アミド ; 2−((2R)−2−(N−((2R)−2−(N−((2E)−5−アミノ− 5−メチルヘキサ−2−エノイル)−N−メチルアミノ)−3−(2−ナフチル )プロピオニル)−N−メチルアミノ)−3−フェニルプロピオニルアミノ)− 1,1−ジメチルエチルアセテート; (2E)−5−アミノ−2−ベンジル−5−メチルヘキサ−2−エン酸N−メチ ル−N−((1R)−1−(N−メチル−N−((1R)−1−(メチルカルバ モイル)−2−フェニルエチル)カルバモイル)−2−(2−ナフチル)エチル )アミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−(N−メチル−N−((1R)−1−(メチルカルバモイル)−2− フェニルエチル)カルバモイル)−2−(1−ナフチル)エチル)アミド; (2R)−2−(N−((2−アミノ−2−メチルプロポキシ)アセチル)−N −メチルアミノ)−N−メチル−N−((1R)−1−メチルカルバモイル−2 −フェニルエチル)−3−(1−ナフチル)プロピオンアミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−((1 R)−2−(ベンゾ〔b〕チオフェン−3−イル)−1−(N−メチル−N−( (1R)−1−(メチルカルバモイル)−2−フェニルエチル)カルバモイル) エチル)−N−メチルアミド; (2R)−2−(N−((2−アミノ−2−メチルプロポキシ)アセチル)−N −メチルアミノ)−3−(ベンゾ〔b〕チオフェン−3−イル)−N−メチル− N−((1R)−1−(メチルカルバモイル)−2−フェニルエチル)プロピオ ンアミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−(N−メチル−N−((1R)−2−フェニル−1−(((テトラヒ ドロフラン−2−イル)メチル)カルバモイル)エチル)カルバモイル)−2− (1−ナフチル)エチル)アミド; 3−((2R)−2−(N−((2R)−2−(N−((2E)−5−アミノ− 5−メチルヘキサ−2−エノイル)−N−メチルアミノ)−3−(2−ナフチル )プロピオニル)−N−メチルアミノ)−3−フェニルプロピオニルアミノ)プ ロピルアセテート、もしくはその塩酸塩; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−((1R)−1−( N−((1R)−1−(3−ヒドロキシプロピルカルバモイル)−2−フェニル エチル)−N−メチルカルバモイル)−2−(2−ナフチル)エチル)−N−メ チルアミド、もしくはその酢酸塩; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−(N−メチル−N−((1R)−1−(((3−メチル−1,2,4 −オキサジアゾール−5−イル)メトキシ)メチル)−2−フェニルエチル)カ ルバモイル)−2−(2−ナフチル)エチル)アミド、もしくはその塩酸塩; N−メチル−N−((1R)−1−(メチルカルバモイル)−2−フェニルエチ ル)−2−(N−メチル−N−{〔(2−ピペリジニル)メトキシ〕アセチル} アミノ)−3−(2−ナフチル)プロピオンアミド; 4−アミノシクロヘキサンカルボン酸N−メチル−N−((1R)−1−〔N− メチル−N−{(1R)−1−(メチルカルバモイル)−2−フェニルエチル} カルバモイル〕−2−(2−ナフチル)エチル)アミド、もしくはその酢酸塩; (2R)−N−メチル−N−((1R)−1−(メチルカルバモイル)−2−フ ェニルエチル)−2−(N−メチル−N−{〔ピペリジン−4−イルオキシ〕ア セチル}アミノ)−3−(2−ナフチル)プロピオンアミド; 2−メチルピペリジン−4−カルボン酸N−{1−〔N−メチル−N−(1−( 3−メチル−1,2,4−オキサジアゾール−5−イル)−2−(2−ナフチル )エチル)カルバモイル〕−2−(2−ナフチル)エチル}アミド、もしくはそ の酢酸塩; (2R)−2−(N−((2R)−2−(N−((2E)−5−((2R)−2 −ヒドロキシプロピルアミノ)−5−メチルヘキサ−2−エノイル)−N−メチ ルアミノ)−3−(2−ナフチル)プロピオニル)−N−メチルアミノ)−N− メチル−3−フェニルプロピオンアミド; (2E)−5−アミノ−N−((1R)−1−(N−((1R)−1−ベンジル −2−((メチルスルホニル)アミノ)エチル)−N−メチルカルバモイル)− 2−(2−ナフチル)エチル)−5−メチル−N−メチルヘキサ−2−エンアミ ド; 3−(1−アミノエチル)安息香酸N−メチル−N−((1R)−1−(N−メ チル−N−((1R)−1−(メチルカルバモイル) −2−フェニルエチル)カルバモイル)−2−(2−ナフチル)エチル)アミド ; 5−アミノ−5−メチルヘキサ−2−エン酸((1R)−1−(((1R)−1 −((2R)−2−ヒドロキシプロピルカルバモイル)−2−フェニルエチル) メチルカルバモイル)−2−(2−ナフチル)エチル)メチルアミド; (4−(1−アミノシクロブチル)ブタ−2−エン酸((1R)−1−(((1 R)−1−(1−メチルカルバモイル−2−フェニルエチル)メチルカルバモイ ル)−2−(2−ナフチル)エチル)メチルアミド; 5−アミノ−5−メチルヘキサ−2−エン酸((1R)−1−(((1R)−1 −((2S)−2−ヒドロキシプロピルカルバモイル)−2−(2−チエニル) エチル)メチルカルバモイル)−2−(2−ナフチル)エチル)メチルアミド; (2R)−2−(N−〔(2R)−2−(N−〔(2−アミノブトキシ)アセチ ル〕−N−メチルアミノ)−3−(2−ナフチル)プロピオニル〕−N−メチル アミノ)−N−メチル−3−フェニルプロピオンアミド; (2R)−N−メチル−2−(N−メチル−N−((2R)−2−(N−メチル −N−((((2S)−ピロリジン−2−イル)メトキシ)アセチル)アミノ) −3−(2−ナフチル)プロピオニル)アミノ)−3−フェニルプロピオンアミ ド; 3−((2R)−2−(N−((2R)−2−(N−((2−アミノ−2−メチ ルプロポキシ)アセチル)−N−メチルアミノ)−3−(2−ナフチル)プロピ オニル)−N−メチルアミノ)−3−フェニルプロピオニルアミノ)プロピルア セテート; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−((1 R)−1−(N−((1R)−1−(ジメチルカルバモイル)−2−フェニルエ チル)−N−メチルカルバモイル)−2−(2−ナフチル)エチル)−N−メチ ルアミド; (2R)−N−メチル−N−((1R)−1−(メチルカルバモイル)−2−フ ェニルエチル)−2−(N−メチル−N−{〔ピペリジン−4−イルオキシ〕ア セチル}アミノ)−3−(2−ナフチル)プロピオンアミド; N−メチル−N−((1R)−1−(メチルカルバモイル)−2−フェニルエチ ル)−2−(N−メチル−N−{〔(2−ピペリジニル)メトキシ〕アセチル} アミノ)−3−(2−ナフチル)プロピオンアミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−{N−〔(1R)−2−(1−ナフチル)−1−(メチルカルバモイ ル)エチル〕−N−メチルカルバモイル}−2−(2−ナフチル)エチル)アミ ド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−{N−〔(1R)−2−(1−ナフチル)−1−(メチルカルバモイ ル)エチル〕−N−メチルカルバモイル}−2−(4−メトキシフェニル)エチ ル)アミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−{N−〔(1R)−2−(1−ナフチル)−1−(メチルカルバモイ ル)エチル〕−N−メチルカルバモイル}−2−フェニルエチル)アミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−{N−〔(1R)−2−(2−ナフチル)−1−(メチルカルバモイ ル)エチル〕−N−メチルカルバモイル}−2−(1−ナフチル)エチル)アミ ド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−{N−〔(1R)−2−(2−ナフチル)−1−(メチルカルバモイ ル)エチル〕−N−メチルカルバモイル}−2−フェニルエチル)アミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−{N−〔(1R)−2−(4−メトキシフェニル)−1−(メチルカ ルバモイル)エチル〕−N−メチルカルバモイル}−2−(1−ナフチル)エチ ル)アミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−{N−〔(1R)−2−(4−メトキシフェニル)−1−(メチルカ ルバモイル)エチル〕−N−メチルカルバモイル}−2−(4−メトキシフェニ ル)エチル)アミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−{N−〔(1R)−2−(4−メトキシフェニル)−1−(メチルカ ルバモイル)エチル〕−N−メチルカルバモイル}−2−(2,3,4,5,6 −ペンタフルオロフェニル)エチル)アミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−{N−〔(1R)−2−(4−メトキシフェニル)−1−(メチルカ ルバモイル)エチル〕−N−メチルカルバモイル}−2−フェニルエチル)アミ ド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−{N−〔(1R)−2−(2,3,4,5,6−ペンタフルオロフェ ニル)−1−(メチルカルバモイル)エチル〕−N−メチルカルバモイル}−2 −(1−ナフチル)エチル)アミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル −N−((1R)−1−{N−〔(1R)−2−(2,3,4,5,6−ペンタ フルオロフェニル)−1−(メチルカルバモイル)エチル〕−N−メチルカルバ モイル}−2−(4−メトキシフェニル)エチル)アミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−{N−〔(1R)−2−(2,3,4,5,6−ペンタフルオロフェ ニル)−1−(メチルカルバモイル)エチル〕−N−メチルカルバモイル}−2 −フェニルエチル)アミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−{N−〔(1R)−2−フェニル−1−(メチルカルバモイル)エチ ル〕−N−メチルカルバモイル}−2−(4−メトキシフェニル)エチル)アミ ド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−{N−〔(1R)−2−フェニル−1−(メチルカルバモイル)エチ ル〕−N−メチルカルバモイル}−2−(2,3,4,5,6−ペンタフルオロ フェニル)エチル)アミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−{N−〔(1R)−2−フェニル−1−(メチルカルバモイル)エチ ル〕−N−メチルカルバモイル}−2−フェニルエチル)アミド; 1−((2R)−2−(N−((2E)−5−アミノ−5−メチルヘキサ−2− エノイル)−N−メチルアミノ)−3−(2−ナフチル)プロピオニル−2−ベ ンジル−4−エチルセミカルバジド; 1−((2S)−2−(N−(2−(((2R)−ピロリジン−2−イル)メト キシ)アセチル)−N−メチルアミノ)−3−(2−ナフチル)プロピオニル− 2−ベンジル−4−エチルセミカルバジ ド; 1−((2R)−2−(N−((2−アミノ−2−メチルプロポキシ)アセチル )−N−メチルアミノ)−3−(2−ナフチル)プロピオニル)−2−ベンジル −4−エチルセミカルバジド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−(N−メチル−N−((1R)−1−(メチルカルバモイル)−2− (チオフェン−2−イル)エチル)カルバモイル)−2−(2−ナフチル)エチ ル)アミド; (2E)−5−メチル−5−メチルアミノヘキサ−2−エン酸N−メチル−N− ((1R)−1−(N−メチル−N−((1R)−1−(メチルカルバモイル) −2−フェニルエチル)カルバモイル)−2−(2−ナフチル)エチル)アミド ; (2E)−5−アミノ−3,5−ジメチルヘキサ−2−エン酸N−メチル−N− ((1R)−1−(N−メチル−N−((1R)−1−(メチルカルバモイル) −2−(チオフェン−2−イル)エチル)カルバモイル)−2−(2−ナフチル )エチル)アミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−(N−メチル−N−(2−フェニル−1−(((テトラヒドロフラン −2−イル)メチル)カルバモイル)エチル)カルバモイル)−2−(1−ナフ チル)エチル)アミド; 5−アミノ−3,5−ジメチルヘキサ−2−エン酸N−((1R)−2−(ビフ ェニル−4−イル)−1−(N−メチル−N−((1R)−1−(メチルカルバ モイル)−2−フェニルエチル)カルバモイル)エチル)−N−メチルアミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−((1R)−1−( N−((1R)−2−(4−ヨードフェニル)−1−(メチルカルバモイル)エ チル)−N−メチルカルバモイル)−2 −(2−ナフチル)エチル)−N−メチルアミド; (2E)−5−メチル−5−メチルアミノヘキサ−2−エン酸N−((1R)− 1−(N−((1R)−2−(4−ヨードフェニル)−1−(メチルカルバモイ ル)エチル)−N−メチルカルバモイル)−2−(2−ナフチル)エチル)−N −メチルアミド; (2E)−5−メチル−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル −N−((1R)−1−(N−メチル−N−((1R)−1−(メチルカルバモ イル)−2−(チエン−2−イル)エチル)カルバモイル)−2−(2−ナフチ ル)エチル)アミド; 5−メチルアミノヘキサ−2−エン酸((1R)−1−(((1R)−2−(3 ,4−ジフルオロフェニル)−1−メチルカルバモイルエチル)メチルカルバモ イル)−2−(2−ナフチル)エチル)メチルアミド; 5−メチルアミノヘキサ−2−エン酸((1R)−1−(((1R)−2−フェ ニル−1−エチルカルバモイルエチル)メチルカルバモイル)−2−(2−ナフ チル)エチル)メチルアミド; 5−アミノ−5−メチルヘキサ−2−エン酸((1R)−1−(((1R)−1 −((2S)−2−ヒドロキシプロピルカルバモイル)−2−(3,4−ジフル オロフェニル)エチル)メチルカルバモイル)−2−(2−ナフチル)エチル) メチルアミド; 5−アミノ−5−メチルヘキサ−2−エン酸(1−{〔2−(2−フルオロフェ ニル)−1−メチルカルバモイルエチル〕メチルカルバモイル}−2−(2−ナ フチル)エチル)メチルアミド; (2Z)−5−アミノ−3,5−ジメチルヘキサ−2−エン酸N−メチル−N− ((1R)−1−(N−メチル−N−((1R)−1−メチルカルバモイル−2 −フェニルエチル)カルバモイル)−2−(2−ナフチル)エチル)アミド; (2R)−2−(N−((2E)−5−アミノ−5−メチルヘキサ−2−エノイ ル)−N−メチルアミノ)−N−((1R)−1−ベンジル−2−(3−シクロ プロピルチオウレイド)エチル)−N−メチル−3−(2−ナフチル)プロピオ ンアミド; (2R)−2−(N−〔{2−アミノ−2−メチルプロポキシ}アセチル〕−N −メチルアミノ)−N−((1R)−1−(ジメチルカルバモイル)−2−フェ ニルエチル)−N−メチル−3−(2−ナフチル)プロピオンアミド; (2E)−5−アミノ−5−メチル−N−メチル−N−((1R)−1−(N− メチル−N−((1R)−2−フェニル−1−((2,2,2−トリフルオロエ チル)カルバモイル)エチル)カルバモイル)−2−(2−ナフチル)エチル) ヘキサ−2−エンアミド、もしくはその酢酸塩; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−((1R)−1−( N−((1R)−1−(シクロプロピルカルバモイル)−2−フェニルエチル) −N−メチルカルバモイル)−2−(2−ナフチル)エチル)−N−メチルアミ ド; (2E)−4−(1−アミノシクロブチル)ブタ−2−エン酸N−((1R)− 1−(N−((1R)−2−(3,4−ジフルオロフェニル)−1−(メチルカ ルバモイル)エチル)−N−メチルカルバモイル)−2−(2−ナフチル)エチ ル)−N−メチルアミド; (2E)−4−(1−アミノシクロブチル)ブタ−2−エン酸N−((1R)− 1−(N−((1R)−1−(シクロプロピルカルバモイル)−2−フェニルエ チル)−N−メチルカルバモイル)−2−(2−ナフチル)エチル)−N−メチ ルアミド; (2E)−4−(1−アミノシクロブチル)ブタ−2−エン酸N−((1R)− 2−(ビフェニル−4−イル)−1−(N−メチル− N−((1R)−1−(メチルカルバモイル)−2−フェニルエチル)カルバモ イル)エチル)−N−メチルアミド; 3−(1−アミノエチル)−N−メチル−N−((1R)−1−(N−メチル− N−((1R)−1−(メチルカルバモイル)−2−(2−チエニル)エチル) カルバモイル)−2−(2−ナフチル)エチル)ベンズアミド; 3−アミノメチル−N−メチル−N−((1R)−1−(N−メチル−N−(( 1R)−1−(メチルカルバモイル)−2−(2−チエニル)エチル)カルバモ イル)−2−(2−ナフチル)エチル)ベンズアミド; (2R)−2−(N−((2−アミノブトキシ)アセチル)−N−メチルアミノ )−N−メチル−N−((1R)−1−(メチルカルバモイル)−2−(2−チ エニル)エチル)−3−(2−ナフチル)プロピオンアミド; (2R)−2−(N−((((2S)−2−ピロリジニル)メトキシ)アセチル )−N−メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモ イル)−2−(2−チエニル)エチル)−3−(2−ナフチル)プロピオンアミ ド; (2R)−2−(N−((2−アミノ−2−メチルプロポキシ)アセチル)−N −メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモイル) −2−(2−チエニル)エチル)−3−(2−ナフチル)プロピオンアミド; 3−(1−アミノエチル)−N−メチル−N−((1R)−1−(N−メチル− N−((1R)−1−(メチルカルバモイル)−2−(2−チエニル)エチル) カルバモイル)−2−(ベンゾ〔b〕チオフェン−3−イル)エチル)ベンズア ミド; 3−(1−アミノメチル)−N−メチル−N−((1R)−1− (N−メチル−N−((1R)−1−(メチルカルバモイル)−2−(2−チエ ニル)エチル)カルバモイル)−2−(ベンゾ〔b〕チオフェン−3−イル)エ チル)ベンズアミド; (2R)−2−(N−((2−アミノブトキシ)アセチル)−N−メチルアミノ )−N−メチル−N−((1R)−1−(メチルカルバモイル)−2−(2−チ エニル)エチル)−3−(ベンゾ〔b〕チオフェン−3−イル)プロピオンアミ ド; (2R)−2−(N−((((2S)−2−ピロリジニル)メトキシ)アセチル )−N−メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモ イル)−2−(2−チエニル)エチル)−3−(ベンゾ〔b〕チオフェン−3− イル)プロピオンアミド; (2R)−2−(N−((2−アミノ−2−メチルプロポキシ)アセチル)−N −メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモイル) −2−(2−チエニル)エチル)−3−(ベンゾ〔b〕チオフェン−3−イル) プロピオンアミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−(N−メチル−N−((1R)−1−(メチルカルバモイル)−2− (2−チエニル)エチル)カルバモイル)−2−(ベンゾ〔b〕チオフェン−3 −イル)エチル)アミド; 3−(1−アミノエチル)−N−メチル−N−((1R)−1−(N−メチル− N−((1R)−1−(メチルカルバモイル)−2−(2−チエニル)エチル) カルバモイル)−2−(ベンジルオキシ)エチル)ベンズアミド; 3−アミノメチル−N−メチル−N−((1R)−1−(N−メチル−N−(( 1R)−1−(メチルカルバモイル)−2−(2−チエニル)エチル)カルバモ イル)−2−(ベンジルオキシ)エチル)ベンズアミド; (2R)−2−(N−((2−アミノブトキシ)アセチル)−N−メチルアミノ )−N−メチル−N−((1R)−1−(メチルカルバモイル)−2−(2−チ エニル)エチル)−3−(ベンジルオキシ)プロピオンアミド; (2R)−2−(N−((((2S)−2−ピロリジニル)メトキシ)アセチル )−N−メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモ イル)−2−(2−チエニル)エチル)−3−(ベンジルオキシ)プロピオンア ミド; (2R)−2−(N−((2−アミノ−2−メチルプロポキシ)アセチル)−N −メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモイル) −2−(2−チエニル)エチル)−3−(ベンジルオキシ)プロピオンアミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−(N−メチル−N−((1R)−1−(メチルカルバモイル)−2− (2−チエニル)エチル)カルバモイル)−2−(ベンジルオキシ)エチル)ア ミド; 3−(1−アミノエチル)−N−メチル−N−((1R)−1−(N−メチル− N−((1R)−1−(メチルカルバモイル)−2−(2−チエニル)エチル) カルバモイル)−2−(ビフェニル−4−イル)エチル)ベンズアミド; 3−アミノメチル−N−メチル−N−((1R)−1−(N−メチル−N−(( 1R)−1−(メチルカルバモイル)−2−(2−チエニル)エチル)カルバモ イル)−2−(ビフェニル−4−イル)エチル)ベンズアミド; (2R)−2−(N−((2−アミノブトキシ)アセチル)−N−メチルアミノ )−N−メチル−N−((1R)−1−(メチルカルバモイル)−2−(2−チ エニル)エチル)−3−(ビフェニル− 4−イル)プロピオンアミド; (2R)−2−(N−((((2S)−2−ピロリジニル)メトキシ)アセチル )−N−メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモ イル)−2−(2−チエニル)エチル)−3−(ビフェニル−4−イル)プロピ オンアミド; (2R)−2−(N−((2−アミノ−2−メチルプロポキシ)アセチル)−N −メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモイル) −2−(2−チエニル)エチル)−3−(ビフェニル−4−イル)プロピオンア ミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−(N−メチル−N−((1R)−1−(メチルカルバモイル)−2− (2−チエニル)エチル)カルバモイル)−2−(ビフェニル−4−イル)エチ ル)アミド; 3−(1−アミノエチル)−N−メチル−N−((1R)−1−(N−メチル− N−((1R)−1−(メチルカルバモイル)−2−(2−フルオロフェニル) エチル)カルバモイル)−2−(2−ナフチル)エチル)ベンズアミド; 3−アミノメチル−N−メチル−N−((1R)−1−(N−メチル−N−(( 1R)−1−(メチルカルバモイル)−2−(2−フルオロフェニル)エチル) カルバモイル)−2−(2−ナフチル)エチル)ベンズアミド; (2R)−2−(N−((2−アミノブトキシ)アセチル)−N−メチルアミノ )−N−メチル−N−((1R)−1−(メチルカルバモイル)−2−(2−フ ルオロフェニル)エチル)−3−(2−ナフチル)プロピオンアミド; (2R)−2−(N−((((2S)−2−ピロリジニル)メトキシ)アセチル )−N−メチルアミノ)−N−メチル−N−((1R) −1−(メチルカルバモイル)−2−(2−フルオロフェニル)エチル)−3− (2−ナフチル)プロピオンアミド; (2R)−2−(N−((2−アミノ−2−メチルプロポキシ)アセチル)−N −メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモイル) −2−(2−フルオロフェニル)エチル)−3−(2−ナフチル)プロピオンア ミド; 3−(1−アミノエチル)−N−メチル−N−((1R)−1−(N−メチル− N−((1R)−1−(メチルカルバモイル)−2−(2−フルオロフェニル) エチル)カルバモイル)−2−(ベンゾ〔b〕チオフェン−3−イル)エチル) ベンズアミド; 3−アミノメチル−N−メチル−N−((1R)−1−(N−メチル−N−(( 1R)−1−(メチルカルバモイル)−2−(2−フルオロフェニル)エチル) カルバモイル)−2−(ベンゾ〔b〕チオフェン−3−イル)エチル)ベンズア ミド; (2R)−2−(N−((2−アミノブトキシ)アセチル)−N−メチルアミノ )−N−メチル−N−((1R)−1−(メチルカルバモイル)−2−(2−フ ルオロフェニル)エチル)−3−(ベンゾ〔b〕チオフェン−3−イル)プロピ オンアミド; (2R)−2−(N−((((2S)−2−ピロリジニル)メトキシ)アセチル )−N−メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモ イル)−2−(2−フルオロフェニル)エチル)−3−(ベンゾ〔b〕チオフェ ン−3−イル)プロピオンアミド; (2R)−2−(N−((2−アミノ−2−メチルプロポキシ)アセチル)−N −メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモイル) −2−(2−フルオロフェニル)エチル)−3−(ベンゾ〔b〕チオフェン−3 −イル)プロピオンアミド; 3−(1−アミノエチル)−N−メチル−N−((1R)−1−(N−メチル− N−((1R)−1−(メチルカルバモイル)−2−(2−フルオロフェニル) エチル)カルバモイル)−2−(ベンジルオキシ)エチル)ベンズアミド; 3−アミノメチル−N−メチル−N−((1R)−1−(N−メチル−N−(( 1R)−1−(メチルカルバモイル)−2−(2−フルオロフェニル)エチル) カルバモイル)−2−(ベンジルオキシ)エチル)ベンズアミド; (2R)−2−(N−((2−アミノブトキシ)アセチル)−N−メチルアミノ )−N−メチル−N−((1R)−1−(メチルカルバモイル)−2−(2−フ ルオロフェニル)エチル)−3−(ベンジルオキシ)プロピオンアミド; (2R)−2−(N−((((2S)−2−ピロリジニル)メトキシ)アセチル )−N−メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモ イル)−2−(2−フルオロフェニル)エチル)−3−(ベンジルオキシ)プロ ピオンアミド; (2R)−2−(N−((2−アミノ−2−メチルプロポキシ)アセチル)−N −メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモイル) −2−(2−フルオロフェニル)エチル)−3−(ベンジルオキシ)プロピオン アミド; 3−(1−アミノエチル)−N−メチル−N−((1R)−1−(N−メチル− N−((1R)−1−(メチルカルバモイル)−2−(2−フルオロフェニル) エチル)カルバモイル)−2−(ビフェニル−4−イル)エチル)ベンズアミド ; 3−アミノメチル−N−メチル−N−((1R)−1−(N−メチル−N−(( 1R)−1−(メチルカルバモイル)−2−(2−フルオロフェニル)エチル) カルバモイル)−2−(ビフェニル−4 −イル)エチル)ベンズアミド; (2R)−2−(N−((2−アミノブトキシ)アセチル)−N−メチルアミノ )−N−メチル−N−((1R)−1−(メチルカルバモイル)−2−(2−フ ルオロフェニル)エチル)−3−(ビフェニル−4−イル)プロピオンアミド; (2R)−2−(N−((((2S)−2−ピロリジニル)メトキシ)アセチル )−N−メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモ イル)−2−(2−フルオロフェニル)エチル)−3−(ビフェニル−4−イル )プロピオンアミド; (2R)−2−(N−((2−アミノ−2−メチルプロポキシ)アセチル)−N −メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモイル) −2−(2−フルオロフェニル)エチル)−3−(ビフェニル−4−イル)プロ ピオンアミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−(N−メチル−N−((1R)−1−(メチルカルバモイル)−2− (2−フルオロフェニル)エチル)カルバモイル)−2−(ビフェニル−4−イ ル)エチル)アミド; 3−(1−アミノエチル)−N−メチル−N−((1R)−1−(N−メチル− N−((1R)−1−(メチルカルバモイル)−2−フェニルエチル)カルバモ イル)−2−(ベンゾ〔b〕チオフェン−3−イル)エチル)ベンズアミド; 3−アミノメチル−N−メチル−N−((1R)−1−(N−メチル−N−(( 1R)−1−(メチルカルバモイル)−2−フェニルエチル)カルバモイル)− 2−(ベンゾ〔b〕チオフェン−3−イル)エチル)ベンズアミド; (2R)−2−(N−((2−アミノブトキシ)アセチル)−N−メチルアミノ )−N−メチル−N−((1R)−1−(メチルカル バモイル)−2−フェニルエチル)−3−(ベンゾ〔b〕チオフェン−3−イル )プロピオンアミド; (2R)−2−(N−((((2S)−2−ピロリジニル)メトキシ)アセチル )−N−メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモ イル)−2−フェニルエチル)−3−(ベンゾ〔b〕チオフェン−3−イル)プ ロピオンアミド; (2R)−2−(N−((2−アミノ−2−メチルプロポキシ)アセチル)−N −メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモイル) −2−フェニルエチル)−3−(ベンゾ〔b〕チオフェン−3−イル)プロピオ ンアミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−(N−メチル−N−((1R)−1−(メチルカルバモイル)−2− フェニルエチル)カルバモイル)−2−(ベンゾ〔b〕チオフェン−3−イル) エチル)アミド; 3−(1−アミノエチル)−N−メチル−N−((1R)−1−(N−メチル− N−((1R)−1−(メチルカルバモイル)−2−フェニルエチル)カルバモ イル)−2−(ベンジルオキシ)エチル)ベンズアミド; 3−アミノメチル−N−メチル−N−((1R)−1−(N−メチル−N−(( 1R)−1−(メチルカルバモイル)−2−フェニルエチル)カルバモイル)− 2−(ベンジルオキシ)エチル)ベンズアミド; (2R)−2−(N−((2−アミノブトキシ)アセチル)−N−メチルアミノ )−N−メチル−N−((1R)−1−(メチルカルバモイル)−2−フェニル エチル)−3−(ベンジルオキシ)プロピオンアミド; (2R)−2−(N−((((2S)−2−ピロリジニル)メトキ シ)アセチル)−N−メチルアミノ)−N−メチル−N−((1R)−1−(メ チルカルバモイル)−2−フェニルエチル)−3−(ベンジルオキシ)プロピオ ンアミド; (2R)−2−(N−((2−アミノ−2−メチルプロポキシ)アセチル)−N −メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモイル) −2−フェニルエチル)−3−(ベンジルオキシ)プロピオンアミド; 3−(1−アミノエチル)−N−メチル−N−((1R)−1−(N−メチル− N−((1R)−1−(メチルカルバモイル)−2−フェニルエチル)カルバモ イル)−2−(ビフェニル−4−イル)エチル)ベンズアミド; 3−アミノメチル−N−メチル−N−((1R)−1−(N−メチル−N−(( 1R)−1−(メチルカルバモイル)−2−フェニルエチル)カルバモイル)− 2−(ビフェニル−4−イル)エチル)ベンズアミド; (2R)−2−(N−((2−アミノブトキシ)アセチル)−N−メチルアミノ )−N−メチル−N−((1R)−1−(メチルカルバモイル)−2−フェニル エチル)−3−(ビフェニル−4−イル)プロピオンアミド; (2R)−2−(N−((((2S)−2−ピロリジニル)メトキシ)アセチル )−N−メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモ イル)−2−フェニルエチル)−3−(ビフェニル−4−イル)プロピオンアミ ド; (2R)−2−(N−((2−アミノ−2−メチルプロポキシ)アセチル)−N −メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモイル) −2−フェニルエチル)−3−(ビフェニル−4−イル)プロピオンアミド; 3−(1−アミノエチル)−N−メチル−N−((1R)−1−(N−メチル− N−((1R)−1−(メチルカルバモイル)−2−(4−メトキシフェニル) エチル)カルバモイル)−2−(2−ナフチル)エチル)ベンズアミド; 3−アミノメチル−N−メチル−N−((1R)−1−(N−メチル−N−(( 1R)−1−(メチルカルバモイル)−2−(4−メトキシフェニル)エチル) カルバモイル)−2−(2−ナフチル)エチル)ベンズアミド; (2R)−2−(N−((2−アミノブトキシ)アセチル)−N−メチルアミノ )−N−メチル−N−((1R)−1−(メチルカルバモイル)−2−(4−メ トキシフェニル)エチル)−3−(2−ナフチル)プロピオンアミド; (2R)−2−(N−((((2S)−2−ピロリジニル)メトキシ)アセチル )−N−メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモ イル)−2−(4−メトキシフェニル)エチル)−3−(2−ナフチル)プロピ オンアミド; (2R)−2−(N−((2−アミノ−2−メチルプロポキシ)アセチル)−N −メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモイル) −2−(4−メトキシフェニル)エチル)−3−(2−ナフチル)プロピオンア ミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−(N−メチル−N−((1R)−1−(メチルカルバモイル)−2− (4−メトキシフェニル)エチル)カルバモイル)−2−(2−ナフチル)エチ ル)アミド; 3−(1−アミノエチル)−N−メチル−N−((1R)−1−(N−メチル− N−((1R)−1−(メチルカルバモイル)−2−(4−メトキシフェニル) エチル)カルバモイル)−2−(ベン ゾ〔b〕チオフェン−3−イル)エチル)ベンズアミド; 3−アミノメチル−N−メチル−N−((1R)−1−(N−メチル−N−(( 1R)−1−(メチルカルバモイル)−2−(4−メトキシフェニル)エチル) カルバモイル)−2−(ベンゾ〔b〕チオフェン−3−イル)エチル)ベンズア ミド; (2R)−2−(N−((2−アミノブトキシ)アセチル)−N−メチルアミノ )−N−メチル−N−((1R)−1−(メチルカルバモイル)−2−(4−メ トキシフェニル)エチル)−3−(ベンゾ〔b〕チオフェン−3−イル)プロピ オンアミド; (2R)−2−(N−((((2S)−2−ピロリジニル)メトキシ)アセチル )−N−メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモ イル)−2−(4−メトキシフェニル)エチル)−3−(ベンゾ〔b〕チオフェ ン−3−イル)プロピオンアミド; (2R)−2−(N−((2−アミノ−2−メチルプロポキシ)アセチル)−N −メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモイル) −2−(4−メトキシフェニル)エチル)−3−(ベンゾ〔b〕チオフェン−3 −イル)プロピオンアミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−(N−メチル−N−((1R)−1−(メチルカルバモイル)−2− (4−メトキシフェニル)エチル)カルバモイル)−2−(ベンゾ〔b〕チオフ ェン−3−イル)エチル)アミド; 3−(1−アミノエチル)−N−メチル−N−((1R)−1−(N−メチル− N−((1R)−1−(メチルカルバモイル)−2−(4−メトキシフェニル) エチル)カルバモイル)−2−(ベンジルオキシ)エチル)ベンズアミド; 3−アミノメチル−N−メチル−N−((1R)−1−(N−メチル−N−(( 1R)−1−(メチルカルバモイル)−2−(4−メトキシフェニル)エチル) カルバモイル)−2−(ベンジルオキシ)エチル)ベンズアミド; (2R)−2−(N−((2−アミノブトキシ)アセチル)−N−メチルアミノ )−N−メチル−N−((1R)−1−(メチルカルバモイル)−2−(4−メ トキシフェニル)エチル)−3−(ベンジルオキシ)プロピオンアミド; (2R)−2−(N−((((2S)−2−ピロリジニル)メトキシ)アセチル )−N−メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモ イル)−2−(4−メトキシフェニル)エチル)−3−(ベンジルオキシ)プロ ピオンアミド; (2R)−2−(N−((2−アミノ−2−メチルプロポキシ)アセチル)−N −メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモイル) −2−(4−メトキシフェニル)エチル)−3−(ベンジルオキシ)プロピオン アミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−メチル−N−((1 R)−1−(N−メチル−N−((1R)−1−(メチルカルバモイル)−2− (4−メトキシフェニル)エチル)カルバモイル)−2−(ベンジルオキシ)エ チル)アミド; 3−(1−アミノエチル)−N−メチル−N−((1R)−1−(N−メチル− N−((1R)−1−(メチルカルバモイル)−2−(4−メトキシフェニル) エチル)カルバモイル)−2−(ビフェニル−4−イル)エチル)ベンズアミド ; 3−アミノメチル−N−メチル−N−((1R)−1−(N−メチル−N−(( 1R)−1−(メチルカルバモイル)−2−(4−メトキシフェニル)エチル) カルバモイル)−2−(ビフェニル−4 −イル)エチル)ベンズアミド; (2R)−2−(N−((2−アミノブトキシ)アセチル)−N−メチルアミノ )−N−メチル−N−((1R)−1−(メチルカルバモイル)−2−(4−メ トキシフェニル)エチル)−3−(ビフェニル−4−イル)プロピオンアミド; (2R)−2−(N−((((2S)−2−ピロリジニル)メトキシ)アセチル )−N−メチルアミノ)−N−メチル−N−((1R)−1−(メチルカルバモ イル)−2−(4−メトキシフェニル)エチル)−3−(ビフェニル−4−イル )プロピオンアミド; (2E)−5−アミノ−5−メチル−N−メチル−N−((1R)−1−(N− メチル−N−((1R)−1−((N−メチル−N−(メチルスルホニル)アミ ノ)メチル)−2−(2−チエニル)エチル)カルバモイル)−2−(2−ナフ チル)エチル)ヘキサ−2−エンアミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−((1R)−1−( N−((1R)−1−(N−メチル−N−(3−ジメチルアミノプロピル)カル バモイル)−2−フェニルエチル)−N−メチルカルバモイル)−2−(2−ナ フチル)エチル)−N−メチルアミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−((1R)−1−( N−((1R)−1−(N−メチルカルバモイル)−2−フェニルエチル)−N −エチルカルバモイル)−2−(2−ナフチル)エチル)−N−メチルアミド; (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−((1R)−1−( N−((1R)−1−(N−(N,N−ジメチルカルバモイルメチル)カルバモ イル)−2−フェニルエチル)−N−メチルカルバモイル)−2−(2−ナフチ ル)エチル)−N−メチル アミド;および (2E)−5−アミノ−5−メチルヘキサ−2−エン酸N−((1R)−1−( N−((1R)−1−(N−(カルバモイルメチル)カルバモイル)−2−フェ ニルエチル)−N−メチルカルバモイル)−2−(2−ナフチル)エチル)−N −メチルアミド から成る群より選ばれた化合物;または医薬上許容されるその塩。 11.下記の化合物から成る群より選ばれる、請求項1,2,3,4,5,6, 7,8または9に記載の化合物: 12.医薬上許容される担体または希釈剤と一緒に、活性成分として上記の化合 物請求項のいずれか一項に記載の化合物またはそれの医薬上許容される塩を含ん で成る医薬組成物。 13.1回量剤形において、上記の化合物請求項のいずれか一項に記載の化合物 またはそれの医薬上許容される塩を約10〜約200 mg含んで成る、請求項12に記載 の医薬組成物。 14.下垂体からの成長ホルモンの放出を刺激するための医薬組成物であって、 医薬上許容される担体または希釈剤と一緒に、活性成分として上記の化合物請求 項のいずれか一項に記載の化合物またはそれの医薬上許容される塩を含んで成る 医薬組成物。 15.経口、経鼻、経皮、肺または非経口投与用の請求項12〜14のいずれか一項 に記載の医薬組成物。 16.下垂体からの成長ホルモンの放出を刺激する方法であって、それを必要と する被検体に、上記の化合物請求項のいずれか一項に記載の化合物もしくはそれ の医薬上許容される塩のまたは上記の組成物請求項のいずれか一項に記載の組成 物の有効量を投与することを含んで成る方法。 17.動物の成長の速度および度合いを増加させるため、動物の乳生産もしくは 獣毛生産を増加させるため、または動物の治療のための方法であって、それを必 要とする被検体に、上記の化合物請求項のいずれか一項に記載の化合物もしくは それの医薬上許容される塩のまたは上記の組成物請求項のいずれか一項に記載の 組成物の有効量を投与することを含んで成る方法。 18.上記の化合物請求項のいずれか一項に記載の化合物またはそれの医薬上許 容される塩もしくはエステルの有効量が、約0.0001〜約100 mg/kg体重/日、好 ましくは約0.001 〜約50mg/kg体重/日の範囲内である、請求項16または17に記 載の方法。 19.前記投与が経口、経鼻、経皮、肺または非経口経路により行われる、請求 項16〜18のいずれか一項に記載の方法。 20.薬剤の調製のための、上記の化合物請求項のいずれか一項に記載の化合物 またはそれの医薬上許容される塩の使用。 21.下垂体からの成長ホルモンの放出を刺激するために用いる薬剤の調製のた めの、上記の化合物請求項のいずれか一項に記載の化合物またはそれの医薬上許 容される塩の使用。 22.動物の成長の速度および度合いを増加させるため、動物の乳生産もしくは 獣毛生産を増加させるため、または動物を治療するために用いる薬剤の調製のた めの、上記の化合物請求項いずれか一項に記載の化合物またはそれの医薬上許容 される塩の使用。 23.高齢者における成長ホルモン放出の刺激処置;糖質コルチコイドの異化副 作用の予防、オステオポローシスの予防と治療、免疫系の刺激、損傷治癒の促進 、骨折修復の促進、成長遅滞の治療、成長遅滞に起因する腎不全もしくは機能不 全の治療、成長ホルモン欠損児童を含む生理学的不足状態および慢性疾患に関連 した不足状態の治療、肥満および肥満に関連した成長遅滞の治療、プラーダー− ヴィリ症候群およびターナー症候群に関連した成長遅滞の治療;火傷患者の回復 の促進および入院の削減;子宮内発育遅滞、骨格形成異常、高コルチコイド症お よびクッシング症候群の治療;拍動性成長ホルモン放出の誘導;ストレス患者に おける成長ホルモンの代用、骨軟骨形成異常、ヌーナン症候群、精神分裂病、う つ病、アルツハイマー病、遅延損傷治癒および心理社会的剥奪の治療、肺機能不 全および呼吸器依存症の治療、大手術後のタンパク質異化反応の減衰、癌やエイ ズ(AIDS)のような慢性疾患によるタンパク損失および悪液質の減少;膵島細胞 症を含む高インスリン血症の治療、排卵誘発のためのアジュバント療法;胸腺の 発育を刺激するためおよび加齢 に伴う胸腺機能の衰退を防ぐため、免疫抑制患者の治療、筋肉強度、運動性の向 上、高齢者における皮膚の厚さ、代謝恒常性、腎恒常性の維持、骨芽細胞、骨再 造形および軟骨成長の刺激、伴生動物における免疫系の刺激、伴生動物における 高齢疾患の治療、家畜の成長促進並びにヒツジにおける増毛の刺激に用いる薬剤 の調製のための、上記の化合物請求項のいずれか一項に記載の化合物またはそれ の医薬上許容される塩の使用。
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DK1462/95 | 1995-12-22 | ||
DK146295 | 1995-12-22 | ||
DK69896 | 1996-06-25 | ||
DK0698/96 | 1996-06-25 | ||
US2206296P | 1996-07-22 | 1996-07-22 | |
DK0812/96 | 1996-07-24 | ||
DK81296 | 1996-07-24 | ||
DK124896 | 1996-11-06 | ||
DK1248/96 | 1996-11-06 | ||
PCT/DK1996/000529 WO1997023508A1 (en) | 1995-12-22 | 1996-12-16 | Compounds with growth hormone releasing properties |
US08/769,020 US5977178A (en) | 1995-12-22 | 1996-12-18 | Compounds with growth hormone releasing properties |
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1996
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- 1996-12-16 DE DE69637855T patent/DE69637855D1/de not_active Expired - Lifetime
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- 1996-12-16 EP EP96941591A patent/EP0869974B1/en not_active Expired - Lifetime
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- 1996-12-16 IL IL12470296A patent/IL124702A0/xx unknown
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- 1996-12-16 JP JP52323097A patent/JP3701686B2/ja not_active Expired - Fee Related
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006502162A (ja) * | 2002-09-04 | 2006-01-19 | ブリストル−マイヤーズ スクイブ カンパニー | 成長ホルモン分泌促進剤として有用なヘテロ環状芳香族化合物 |
JP4658600B2 (ja) * | 2002-09-04 | 2011-03-23 | ブリストル−マイヤーズ スクイブ カンパニー | 成長ホルモン分泌促進剤として有用なヘテロ環状芳香族化合物 |
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JP2000143613A (ja) | 2000-05-26 |
US6127391A (en) | 2000-10-03 |
ES2323159T3 (es) | 2009-07-07 |
JP3701686B2 (ja) | 2005-10-05 |
CZ195098A3 (cs) | 1998-10-14 |
JP4130519B2 (ja) | 2008-08-06 |
NO982872D0 (no) | 1998-06-19 |
WO1997023508A1 (en) | 1997-07-03 |
US6939880B2 (en) | 2005-09-06 |
HUP9802580A2 (hu) | 1999-02-01 |
AU1092997A (en) | 1997-07-17 |
HUP9802580A3 (en) | 1999-03-29 |
IL124702A0 (en) | 1998-12-06 |
TW480248B (en) | 2002-03-21 |
US5977178A (en) | 1999-11-02 |
CN1211991A (zh) | 1999-03-24 |
AU715856B2 (en) | 2000-02-10 |
EP0869974A1 (en) | 1998-10-14 |
MX9804830A (es) | 1998-09-30 |
US20030040483A1 (en) | 2003-02-27 |
US20030055261A1 (en) | 2003-03-20 |
JPH11209336A (ja) | 1999-08-03 |
EP0869974B1 (en) | 2009-03-04 |
NO982872L (no) | 1998-08-21 |
BR9612275A (pt) | 1999-07-13 |
US6555570B2 (en) | 2003-04-29 |
PL327227A1 (en) | 1998-12-07 |
DE69637855D1 (de) | 2009-04-16 |
ATE424412T1 (de) | 2009-03-15 |
CA2239711A1 (en) | 1997-07-03 |
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