SK3602000A3 - New npy antagonists - Google Patents

New npy antagonists Download PDF

Info

Publication number: SK3602000A3
Authority: SK; Slovakia
Prior art keywords: ethyl; diphenylacetyl; compound; mmol; amide
Prior art date: 1997-09-23

Application number

SK360-2000A

Other languages

English (en)

Slovak (sk)

Inventor

Nils-Ake Bergman

Ambra Thomas D

Garry Pilling

Original Assignee

Astrazeneca Ab

Priority date (The priority date 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 date listed.)

1997-09-23

Filing date

1998-09-21

Publication date

2001-01-18

1998-09-21 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

2001-01-18 Publication of SK3602000A3 publication Critical patent/SK3602000A3/sk

Links

239000005557 antagonist Substances 0.000 title abstract description 17
150000001875 compounds Chemical class 0.000 claims abstract description 335
101710151321 Melanostatin Proteins 0.000 claims abstract description 37
102400000064 Neuropeptide Y Human genes 0.000 claims abstract description 37
URPYMXQQVHTUDU-OFGSCBOVSA-N nucleopeptide y Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 URPYMXQQVHTUDU-OFGSCBOVSA-N 0.000 claims abstract description 36
208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 9
206010047139 Vasoconstriction Diseases 0.000 claims abstract description 7
230000025033 vasoconstriction Effects 0.000 claims abstract description 7
-1 phenoxy, benzyloxy Chemical group 0.000 claims description 442
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 199
238000000034 method Methods 0.000 claims description 155
ULEBESPCVWBNIF-BYPYZUCNSA-N L-arginine amide Chemical compound NC(=O)[C@@H](N)CCCNC(N)=N ULEBESPCVWBNIF-BYPYZUCNSA-N 0.000 claims description 141
125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 93
229910052739 hydrogen Inorganic materials 0.000 claims description 68
239000001257 hydrogen Substances 0.000 claims description 59
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 44
RRXSYZFVDIRTFB-UHFFFAOYSA-N C[CH]C1=CC=C(OC)C=C1 Chemical group C[CH]C1=CC=C(OC)C=C1 RRXSYZFVDIRTFB-UHFFFAOYSA-N 0.000 claims description 43
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 41
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 38
125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims description 26
150000001408 amides Chemical class 0.000 claims description 24
150000002431 hydrogen Chemical class 0.000 claims description 18
238000002360 preparation method Methods 0.000 claims description 17
125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 14
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 12
229910052736 halogen Inorganic materials 0.000 claims description 12
150000002367 halogens Chemical class 0.000 claims description 12
125000004129 indan-1-yl group Chemical group [H]C1=C([H])C([H])=C2C(=C1[H])C([H])([H])C([H])([H])C2([H])* 0.000 claims description 12
150000003839 salts Chemical class 0.000 claims description 11
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
239000003814 drug Substances 0.000 claims description 10
201000010099 disease Diseases 0.000 claims description 9
125000001424 substituent group Chemical group 0.000 claims description 9
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 claims description 9
125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 8
229910052799 carbon Inorganic materials 0.000 claims description 8
239000012634 fragment Substances 0.000 claims description 8
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 8
125000004432 carbon atom Chemical group C* 0.000 claims description 7
230000001404 mediated effect Effects 0.000 claims description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
UCQFSGCWHRTMGG-UHFFFAOYSA-N pyrazole-1-carboximidamide Chemical compound NC(=N)N1C=CC=N1 UCQFSGCWHRTMGG-UHFFFAOYSA-N 0.000 claims description 7
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 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
125000002947 alkylene group Chemical group 0.000 claims description 6
125000000217 alkyl group Chemical group 0.000 claims description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
230000008569 process Effects 0.000 claims description 4
239000004475 Arginine Substances 0.000 claims description 3
125000003545 alkoxy group Chemical group 0.000 claims description 3
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
229910052794 bromium Inorganic materials 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims 4
125000001272 (C1-C4)-alkylene-phenyl group Chemical group 0.000 claims 1
125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 426
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 414
235000019439 ethyl acetate Nutrition 0.000 description 202
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 187
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 146
239000000460 chlorine Substances 0.000 description 141
238000005481 NMR spectroscopy Methods 0.000 description 134
239000000243 solution Substances 0.000 description 133
239000007787 solid Substances 0.000 description 132
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 126
IWLOOJZAZACQFP-WXGMZPBLSA-N benzyl N-[(4R)-4-[(2,2-diphenylacetyl)amino]-5-[methyl-[(1R)-1-phenylethyl]amino]-5-oxopentyl]carbamate Chemical compound C([C@H](C(=O)N(C)[C@H](C)C=1C=CC=CC=1)NC(=O)C(C=1C=CC=CC=1)C=1C=CC=CC=1)CCNC(=O)OCC1=CC=CC=C1 IWLOOJZAZACQFP-WXGMZPBLSA-N 0.000 description 111
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 106
OERRZAJTKPMGBB-BYPYZUCNSA-N (2s)-2,5-diaminopentanamide Chemical compound NCCC[C@H](N)C(N)=O OERRZAJTKPMGBB-BYPYZUCNSA-N 0.000 description 92
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 88
230000035484 reaction time Effects 0.000 description 87
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 84
229910000041 hydrogen chloride Inorganic materials 0.000 description 84
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 78
BPQLYFCEVVKLLX-WCCKRBBISA-N [(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]azanium;chloride Chemical compound Cl.NC(=O)[C@@H](N)CCCN=C(N)N BPQLYFCEVVKLLX-WCCKRBBISA-N 0.000 description 61
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 58
239000000741 silica gel Substances 0.000 description 58
229910002027 silica gel Inorganic materials 0.000 description 58
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 56
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 55
239000011541 reaction mixture Substances 0.000 description 55
229910052763 palladium Inorganic materials 0.000 description 52
239000012043 crude product Substances 0.000 description 50
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 48
239000000203 mixture Substances 0.000 description 45
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
239000006260 foam Substances 0.000 description 41
238000004809 thin layer chromatography Methods 0.000 description 36
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
239000012267 brine Substances 0.000 description 33
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 33
229910004373 HOAc Inorganic materials 0.000 description 30
229960003244 ornithine hydrochloride Drugs 0.000 description 29
239000000047 product Substances 0.000 description 29
239000011734 sodium Substances 0.000 description 28
239000000377 silicon dioxide Substances 0.000 description 27
REIXPZBZEIRTQJ-TUYDZOLPSA-N benzyl 2-[[(4R)-4-[(2,2-diphenylacetyl)amino]-5-[[(1R)-1-(4-methoxyphenyl)ethyl]amino]-5-oxopentyl]-phenylmethoxycarbonylamino]-2-methylsulfanyliminoacetate Chemical compound C1=CC(OC)=CC=C1[C@@H](C)NC(=O)[C@H](NC(=O)C(C=1C=CC=CC=1)C=1C=CC=CC=1)CCCN(C(=NSC)C(=O)OCC=1C=CC=CC=1)C(=O)OCC1=CC=CC=C1 REIXPZBZEIRTQJ-TUYDZOLPSA-N 0.000 description 26
BVQBDZMBNFDAAF-WCCKRBBISA-N (2s)-2,5-diaminopentanamide;hydrochloride Chemical compound Cl.NCCC[C@H](N)C(N)=O BVQBDZMBNFDAAF-WCCKRBBISA-N 0.000 description 24
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 23
239000000908 ammonium hydroxide Substances 0.000 description 23
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 22
239000000706 filtrate Substances 0.000 description 22
238000002844 melting Methods 0.000 description 22
230000008018 melting Effects 0.000 description 22
230000002829 reductive effect Effects 0.000 description 22
229920006395 saturated elastomer Polymers 0.000 description 21
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 18
238000000746 purification Methods 0.000 description 18
YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 17
238000006243 chemical reaction Methods 0.000 description 17
239000003153 chemical reaction reagent Substances 0.000 description 17
238000010626 work up procedure Methods 0.000 description 17
CGAMNSKIHXUDMK-UHFFFAOYSA-N benzyl n-[methylsulfanyl(phenylmethoxycarbonylamino)methylidene]carbamate Chemical compound C=1C=CC=CC=1COC(=O)N=C(SC)NC(=O)OCC1=CC=CC=C1 CGAMNSKIHXUDMK-UHFFFAOYSA-N 0.000 description 16
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 16
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 14
239000012458 free base Substances 0.000 description 14
230000036571 hydration Effects 0.000 description 14
238000006703 hydration reaction Methods 0.000 description 14
SMOBIGANUYCTQO-UHFFFAOYSA-N 2-(2-nitrophenyl)-2,2-diphenylacetic acid Chemical compound C1=CC=C(C=C1)C(C2=CC=CC=C2)(C3=CC=CC=C3[N+](=O)[O-])C(=O)O SMOBIGANUYCTQO-UHFFFAOYSA-N 0.000 description 13
MSYLETHDEIJMAF-UHFFFAOYSA-N 2,2-diphenylacetyl chloride Chemical compound C=1C=CC=CC=1C(C(=O)Cl)C1=CC=CC=C1 MSYLETHDEIJMAF-UHFFFAOYSA-N 0.000 description 12
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
159000000021 acetate salts Chemical class 0.000 description 12
LIZKFOSWDPYJNO-DICHSLLOSA-N benzyl N-[(4S)-4-[(2,2-diphenylacetyl)amino]-5-[[(1R)-1-(4-methoxyphenyl)ethyl]amino]-5-oxopentyl]carbamate Chemical compound C1=CC(OC)=CC=C1[C@@H](C)NC(=O)[C@@H](NC(=O)C(C=1C=CC=CC=1)C=1C=CC=CC=1)CCCNC(=O)OCC1=CC=CC=C1 LIZKFOSWDPYJNO-DICHSLLOSA-N 0.000 description 12
238000010511 deprotection reaction Methods 0.000 description 12
102000005962 receptors Human genes 0.000 description 12
108020003175 receptors Proteins 0.000 description 12
238000012360 testing method Methods 0.000 description 12
RBZRMBCLZMEYEH-UHFFFAOYSA-N 1h-pyrazol-1-ium-1-carboximidamide;chloride Chemical compound Cl.NC(=N)N1C=CC=N1 RBZRMBCLZMEYEH-UHFFFAOYSA-N 0.000 description 11
238000002425 crystallisation Methods 0.000 description 11
230000008025 crystallization Effects 0.000 description 11
239000012044 organic layer Substances 0.000 description 11
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
239000000463 material Substances 0.000 description 10
239000003921 oil Substances 0.000 description 10
239000002904 solvent Substances 0.000 description 10
239000002585 base Substances 0.000 description 9
229910052757 nitrogen Inorganic materials 0.000 description 9
125000006239 protecting group Chemical group 0.000 description 9
238000003756 stirring Methods 0.000 description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 8
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
150000002148 esters Chemical class 0.000 description 8
239000003960 organic solvent Substances 0.000 description 8
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 8
AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 7
AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 7
UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 7
239000003054 catalyst Substances 0.000 description 7
238000004587 chromatography analysis Methods 0.000 description 7
229960003104 ornithine Drugs 0.000 description 7
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
230000000694 effects Effects 0.000 description 6
238000010898 silica gel chromatography Methods 0.000 description 6
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 5
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
238000004458 analytical method Methods 0.000 description 5
238000009739 binding Methods 0.000 description 5
239000013058 crude material Substances 0.000 description 5
239000013078 crystal Substances 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
238000010992 reflux Methods 0.000 description 5
239000000523 sample Substances 0.000 description 5
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
206010020772 Hypertension Diseases 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
241000700159 Rattus Species 0.000 description 4
UUWQVNOHLHVOEA-WCCKRBBISA-N acetic acid (2S)-2,5-diaminopentanamide Chemical compound C(C)(=O)O.N[C@@H](CCCN)C(=O)N UUWQVNOHLHVOEA-WCCKRBBISA-N 0.000 description 4
230000027455 binding Effects 0.000 description 4
239000003480 eluent Substances 0.000 description 4
238000000227 grinding Methods 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
239000010410 layer Substances 0.000 description 4
239000012528 membrane Substances 0.000 description 4
230000000144 pharmacologic effect Effects 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
238000005160 1H NMR spectroscopy Methods 0.000 description 3
WBJWXIQDBDZMAW-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carbonyl chloride Chemical compound C1=CC=CC2=C(C(Cl)=O)C(O)=CC=C21 WBJWXIQDBDZMAW-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
206010002383 Angina Pectoris Diseases 0.000 description 3
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
239000004698 Polyethylene Substances 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
PYHXGXCGESYPCW-UHFFFAOYSA-N alpha-phenylbenzeneacetic acid Natural products C=1C=CC=CC=1C(C(=O)O)C1=CC=CC=C1 PYHXGXCGESYPCW-UHFFFAOYSA-N 0.000 description 3
230000004872 arterial blood pressure Effects 0.000 description 3
210000001367 artery Anatomy 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
239000000872 buffer Substances 0.000 description 3
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 3
238000012512 characterization method Methods 0.000 description 3
238000007796 conventional method Methods 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
125000000524 functional group Chemical group 0.000 description 3
210000002216 heart Anatomy 0.000 description 3
238000001802 infusion Methods 0.000 description 3
230000003287 optical effect Effects 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
JOOKIPOTLNSDKT-SGXBNLSYSA-N (2R)-5-(diaminomethylideneamino)-2-[(2,2-diphenylacetyl)amino]-N-[(1R)-1-(4-phenylmethoxyphenyl)ethyl]pentanamide hydrochloride Chemical compound Cl.N([C@H](CCCNC(N)=N)C(=O)N[C@H](C)C=1C=CC(OCC=2C=CC=CC=2)=CC=1)C(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 JOOKIPOTLNSDKT-SGXBNLSYSA-N 0.000 description 2
GMQJUIZYRLBNHR-LNHWOQJCSA-N (2R)-5-(diaminomethylideneamino)-2-[(2,2-diphenylacetyl)amino]-N-[(1R)-1-naphthalen-1-ylethyl]pentanamide hydrochloride Chemical compound Cl.N([C@H](CCCNC(N)=N)C(=O)N[C@H](C)C=1C2=CC=CC=C2C=CC=1)C(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 GMQJUIZYRLBNHR-LNHWOQJCSA-N 0.000 description 2
VEKVTCHNDJWNIP-ITNPDYSASA-N (2R)-5-(diaminomethylideneamino)-2-[(2,2-diphenylacetyl)amino]-N-[(1R)-2-hydroxy-1-phenylethyl]pentanamide hydrochloride Chemical compound Cl.N([C@H](CCCNC(=N)N)C(=O)N[C@@H](CO)C=1C=CC=CC=1)C(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 VEKVTCHNDJWNIP-ITNPDYSASA-N 0.000 description 2
DLFVYDOTRNPUSP-CJFMBICVSA-N (2R)-5-amino-2-[(2,2-diphenylacetyl)amino]-N-[(1R)-1-(4-methoxyphenyl)ethyl]pentanamide Chemical compound C1=CC(OC)=CC=C1[C@@H](C)NC(=O)[C@@H](CCCN)NC(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 DLFVYDOTRNPUSP-CJFMBICVSA-N 0.000 description 2
CAWCFEVVTYJQMP-OOWIMERYSA-N (2R)-5-amino-2-[(2,2-diphenylacetyl)amino]-N-[(1R)-1-(4-phenylmethoxyphenyl)ethyl]pentanamide Chemical compound N([C@H](CCCN)C(=O)N[C@H](C)C=1C=CC(OCC=2C=CC=CC=2)=CC=1)C(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 CAWCFEVVTYJQMP-OOWIMERYSA-N 0.000 description 2
NQELYUQNPUWLNQ-SKCUWOTOSA-N (2R)-5-amino-2-[(2,2-diphenylacetyl)amino]-N-[(1R)-1-naphthalen-1-ylethyl]pentanamide Chemical compound N([C@H](CCCN)C(=O)N[C@H](C)C=1C2=CC=CC=C2C=CC=1)C(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 NQELYUQNPUWLNQ-SKCUWOTOSA-N 0.000 description 2
ZIEHUKUIDFRANI-PXDATVDWSA-N (2R)-5-amino-2-[(2,2-diphenylacetyl)amino]-N-methyl-N-[(1R)-1-phenylethyl]pentanamide Chemical compound N([C@H](CCCN)C(=O)N(C)[C@H](C)C=1C=CC=CC=1)C(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 ZIEHUKUIDFRANI-PXDATVDWSA-N 0.000 description 2
LFFUWCZWQAMTNS-NLEDUAFPSA-N (2S)-5-(diaminomethylideneamino)-2-[(2,2-diphenylacetyl)amino]-N-[(1R)-1-(4-methoxyphenyl)ethyl]pentanamide hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1[C@@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 LFFUWCZWQAMTNS-NLEDUAFPSA-N 0.000 description 2
VEKVTCHNDJWNIP-UKOKCHKQSA-N (2S)-5-(diaminomethylideneamino)-2-[(2,2-diphenylacetyl)amino]-N-[(1R)-2-hydroxy-1-phenylethyl]pentanamide hydrochloride Chemical compound Cl.N([C@@H](CCCNC(=N)N)C(=O)N[C@@H](CO)C=1C=CC=CC=1)C(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 VEKVTCHNDJWNIP-UKOKCHKQSA-N 0.000 description 2
ZIEHUKUIDFRANI-BWKNWUBXSA-N (2S)-5-amino-2-[(2,2-diphenylacetyl)amino]-N-methyl-N-[(1R)-1-phenylethyl]pentanamide Chemical compound N([C@@H](CCCN)C(=O)N(C)[C@H](C)C=1C=CC=CC=1)C(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 ZIEHUKUIDFRANI-BWKNWUBXSA-N 0.000 description 2
TUTGOCAHEZNUJM-RFVHGSKJSA-N (2r)-2-amino-5-(phenylmethoxycarbonylamino)pentanoic acid;hydrochloride Chemical compound Cl.OC(=O)[C@H](N)CCCNC(=O)OCC1=CC=CC=C1 TUTGOCAHEZNUJM-RFVHGSKJSA-N 0.000 description 2
MXUNEVMQOGSGJX-NTKDMRAZSA-N (2r)-5-amino-n-[(1r)-1-(4-bromophenyl)ethyl]-2-[(2,2-diphenylacetyl)amino]pentanamide Chemical compound N([C@H](CCCN)C(=O)N[C@H](C)C=1C=CC(Br)=CC=1)C(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 MXUNEVMQOGSGJX-NTKDMRAZSA-N 0.000 description 2
ARGJUYSHMHGUDP-VJTNNGHGSA-N (2r)-n-[(1r)-1-(4-bromophenyl)ethyl]-5-(diaminomethylideneamino)-2-[(2,2-diphenylacetyl)amino]pentanamide;hydrochloride Chemical compound Cl.N([C@H](CCCNC(N)=N)C(=O)N[C@H](C)C=1C=CC(Br)=CC=1)C(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 ARGJUYSHMHGUDP-VJTNNGHGSA-N 0.000 description 2
GGTYBZJRPHEQDG-WCCKRBBISA-N (2s)-2,5-diaminopentanoic acid hydrochloride Chemical compound Cl.NCCC[C@H](N)C(O)=O GGTYBZJRPHEQDG-WCCKRBBISA-N 0.000 description 2
ISNZAXUAQQZMNY-ZEQRLZLVSA-N (2s)-5-amino-2-[(2,2-diphenylacetyl)amino]-n-[(1r)-2-hydroxy-1-phenylethyl]pentanamide Chemical compound N([C@@H](CCCN)C(=O)N[C@@H](CO)C=1C=CC=CC=1)C(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 ISNZAXUAQQZMNY-ZEQRLZLVSA-N 0.000 description 2
MXUNEVMQOGSGJX-DVECYGJZSA-N (2s)-5-amino-n-[(1r)-1-(4-bromophenyl)ethyl]-2-[(2,2-diphenylacetyl)amino]pentanamide Chemical compound N([C@@H](CCCN)C(=O)N[C@H](C)C=1C=CC(Br)=CC=1)C(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 MXUNEVMQOGSGJX-DVECYGJZSA-N 0.000 description 2
SOZMSEPDYJGBEK-UHFFFAOYSA-N 1-(4-bromophenyl)ethanamine Chemical compound CC(N)C1=CC=C(Br)C=C1 SOZMSEPDYJGBEK-UHFFFAOYSA-N 0.000 description 2
FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
125000004924 2-naphthylethyl group Chemical group C1=C(C=CC2=CC=CC=C12)CC* 0.000 description 2
IQUPABOKLQSFBK-UHFFFAOYSA-N 2-nitrophenol Chemical compound OC1=CC=CC=C1[N+]([O-])=O IQUPABOKLQSFBK-UHFFFAOYSA-N 0.000 description 2
206010002091 Anaesthesia Diseases 0.000 description 2
102100030988 Angiotensin-converting enzyme Human genes 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
208000030814 Eating disease Diseases 0.000 description 2
208000019454 Feeding and Eating disease Diseases 0.000 description 2
206010019280 Heart failures Diseases 0.000 description 2
208000019695 Migraine disease Diseases 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
125000002015 acyclic group Chemical group 0.000 description 2
UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
125000004682 aminothiocarbonyl group Chemical group NC(=S)* 0.000 description 2
230000037005 anaesthesia Effects 0.000 description 2
229960003121 arginine Drugs 0.000 description 2
229960003589 arginine hydrochloride Drugs 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
230000008901 benefit Effects 0.000 description 2
QKDXVEQIDHFQQR-GUZYMRFCSA-N benzyl N-[(4R)-4-[(2,2-diphenylacetyl)amino]-5-[[(1R)-1-naphthalen-1-ylethyl]amino]-5-oxopentyl]carbamate Chemical compound C([C@H](C(=O)N[C@H](C)C=1C2=CC=CC=C2C=CC=1)NC(=O)C(C=1C=CC=CC=1)C=1C=CC=CC=1)CCNC(=O)OCC1=CC=CC=C1 QKDXVEQIDHFQQR-GUZYMRFCSA-N 0.000 description 2
SQCOVVLFNIVHMG-JSOSNVBQSA-N benzyl N-[(4R)-4-[(2,2-diphenylacetyl)amino]-5-[[(1R)-2-hydroxy-1-phenylethyl]amino]-5-oxopentyl]carbamate Chemical compound C([C@H](C(=O)N[C@@H](CO)C=1C=CC=CC=1)NC(=O)C(C=1C=CC=CC=1)C=1C=CC=CC=1)CCNC(=O)OCC1=CC=CC=C1 SQCOVVLFNIVHMG-JSOSNVBQSA-N 0.000 description 2
MYEYIBDPDJPGDY-WJOKGBTCSA-N benzyl N-[(4R)-4-[(2,2-diphenylacetyl)amino]-5-oxo-5-(2-phenylpropan-2-ylamino)pentyl]carbamate Chemical compound C([C@H](C(=O)NC(C)(C)C=1C=CC=CC=1)NC(=O)C(C=1C=CC=CC=1)C=1C=CC=CC=1)CCNC(=O)OCC1=CC=CC=C1 MYEYIBDPDJPGDY-WJOKGBTCSA-N 0.000 description 2
GBUYOGQOARSOHT-XWDCEDKXSA-N benzyl N-[(4R)-4-[(2,2-diphenylacetyl)amino]-5-oxo-5-[[(1R)-1-(4-phenylmethoxyphenyl)ethyl]amino]pentyl]carbamate Chemical compound C([C@H](C(=O)N[C@H](C)C=1C=CC(OCC=2C=CC=CC=2)=CC=1)NC(=O)C(C=1C=CC=CC=1)C=1C=CC=CC=1)CCNC(=O)OCC1=CC=CC=C1 GBUYOGQOARSOHT-XWDCEDKXSA-N 0.000 description 2
MLGMOGGRUHQXDV-MXBOTTGLSA-N benzyl N-[(4R)-4-[(2,2-diphenylacetyl)amino]-5-oxo-5-[[(1R)-1-phenylethyl]amino]pentyl]carbamate Chemical compound C([C@H](C(=O)N[C@H](C)C=1C=CC=CC=1)NC(=O)C(C=1C=CC=CC=1)C=1C=CC=CC=1)CCNC(=O)OCC1=CC=CC=C1 MLGMOGGRUHQXDV-MXBOTTGLSA-N 0.000 description 2
LJWQBGYEQILQPP-JOCHJYFZSA-N benzyl N-[(4R)-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxo-5-(2-phenylpropan-2-ylamino)pentyl]carbamate Chemical compound C([C@@H](NC(=O)OC(C)(C)C)C(=O)NC(C)(C)C=1C=CC=CC=1)CCNC(=O)OCC1=CC=CC=C1 LJWQBGYEQILQPP-JOCHJYFZSA-N 0.000 description 2
HVCSVGYYRGVGFN-FUFSCUOVSA-N benzyl N-[(4R)-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxo-5-[[(1R)-1-(4-phenylmethoxyphenyl)ethyl]amino]pentyl]carbamate Chemical compound C([C@H](C(=O)N[C@H](C)C=1C=CC(OCC=2C=CC=CC=2)=CC=1)NC(=O)OC(C)(C)C)CCNC(=O)OCC1=CC=CC=C1 HVCSVGYYRGVGFN-FUFSCUOVSA-N 0.000 description 2
XFQKWAWHARJSCQ-DENIHFKCSA-N benzyl N-[(4R)-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxo-5-[[(1R)-1-phenylethyl]amino]pentyl]carbamate Chemical compound C([C@H](C(=O)N[C@H](C)C=1C=CC=CC=1)NC(=O)OC(C)(C)C)CCNC(=O)OCC1=CC=CC=C1 XFQKWAWHARJSCQ-DENIHFKCSA-N 0.000 description 2
INIGWAQAQROTDA-KYSFMIDTSA-N benzyl N-[(4R)-4-amino-5-[[(1R)-1-(4-methoxyphenyl)ethyl]amino]-5-oxopentyl]carbamate hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1[C@@H](C)NC(=O)[C@H](N)CCCNC(=O)OCC1=CC=CC=C1 INIGWAQAQROTDA-KYSFMIDTSA-N 0.000 description 2
PQCBNUIAJRLXHU-XMSQKQJNSA-N benzyl N-[(4R)-5-[[(1R)-1-(4-hydroxyphenyl)ethyl]amino]-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentyl]carbamate Chemical compound C([C@H](C(=O)N[C@H](C)C=1C=CC(O)=CC=1)NC(=O)OC(C)(C)C)CCNC(=O)OCC1=CC=CC=C1 PQCBNUIAJRLXHU-XMSQKQJNSA-N 0.000 description 2
IMLZDOVPHGLEME-AUSIDOKSSA-N benzyl N-[(4R)-5-[[(1R)-1-(4-methoxyphenyl)ethyl]amino]-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentyl]carbamate Chemical compound C1=CC(OC)=CC=C1[C@@H](C)NC(=O)[C@H](NC(=O)OC(C)(C)C)CCCNC(=O)OCC1=CC=CC=C1 IMLZDOVPHGLEME-AUSIDOKSSA-N 0.000 description 2
IWLOOJZAZACQFP-ZUKKLESISA-N benzyl N-[(4S)-4-[(2,2-diphenylacetyl)amino]-5-[methyl-[(1R)-1-phenylethyl]amino]-5-oxopentyl]carbamate Chemical compound C([C@@H](C(=O)N(C)[C@H](C)C=1C=CC=CC=1)NC(=O)C(C=1C=CC=CC=1)C=1C=CC=CC=1)CCNC(=O)OCC1=CC=CC=C1 IWLOOJZAZACQFP-ZUKKLESISA-N 0.000 description 2
MLGMOGGRUHQXDV-NEEKEDPPSA-N benzyl N-[(4S)-4-[(2,2-diphenylacetyl)amino]-5-oxo-5-[[(1R)-1-phenylethyl]amino]pentyl]carbamate Chemical compound C([C@@H](C(=O)N[C@H](C)C=1C=CC=CC=1)NC(=O)C(C=1C=CC=CC=1)C=1C=CC=CC=1)CCNC(=O)OCC1=CC=CC=C1 MLGMOGGRUHQXDV-NEEKEDPPSA-N 0.000 description 2
BTONRFRRAWZMAB-VXKWHMMOSA-N benzyl N-[(4S)-5-[[(1R)-2-hydroxy-1-phenylethyl]amino]-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentyl]carbamate Chemical compound C([C@H](NC(=O)OC(C)(C)C)C(=O)N[C@@H](CO)C=1C=CC=CC=1)CCNC(=O)OCC1=CC=CC=C1 BTONRFRRAWZMAB-VXKWHMMOSA-N 0.000 description 2
FAEXLKAWIYRNQW-UHFFFAOYSA-N benzyl n-(c-methylsulfanylcarbonimidoyl)-n-phenylmethoxycarbonylcarbamate Chemical compound C=1C=CC=CC=1COC(=O)N(C(=N)SC)C(=O)OCC1=CC=CC=C1 FAEXLKAWIYRNQW-UHFFFAOYSA-N 0.000 description 2
VJOVVUDDGXNJAZ-XMSQKQJNSA-N benzyl n-[(4r)-5-[[(1r)-1-(4-bromophenyl)ethyl]amino]-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentyl]carbamate Chemical compound C([C@H](C(=O)N[C@H](C)C=1C=CC(Br)=CC=1)NC(=O)OC(C)(C)C)CCNC(=O)OCC1=CC=CC=C1 VJOVVUDDGXNJAZ-XMSQKQJNSA-N 0.000 description 2
SQCOVVLFNIVHMG-CONSDPRKSA-N benzyl n-[(4s)-4-[(2,2-diphenylacetyl)amino]-5-[[(1r)-2-hydroxy-1-phenylethyl]amino]-5-oxopentyl]carbamate Chemical compound C([C@@H](C(=O)N[C@@H](CO)C=1C=CC=CC=1)NC(=O)C(C=1C=CC=CC=1)C=1C=CC=CC=1)CCNC(=O)OCC1=CC=CC=C1 SQCOVVLFNIVHMG-CONSDPRKSA-N 0.000 description 2
SCMLDRDMHIJSTG-NJHZRGNWSA-N benzyl n-[(4s)-5-[[(1r)-1-(4-bromophenyl)ethyl]amino]-4-[(2,2-diphenylacetyl)amino]-5-oxopentyl]carbamate Chemical compound C([C@@H](C(=O)N[C@H](C)C=1C=CC(Br)=CC=1)NC(=O)C(C=1C=CC=CC=1)C=1C=CC=CC=1)CCNC(=O)OCC1=CC=CC=C1 SCMLDRDMHIJSTG-NJHZRGNWSA-N 0.000 description 2
VJOVVUDDGXNJAZ-GCJKJVERSA-N benzyl n-[(4s)-5-[[(1r)-1-(4-bromophenyl)ethyl]amino]-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentyl]carbamate Chemical compound C([C@@H](C(=O)N[C@H](C)C=1C=CC(Br)=CC=1)NC(=O)OC(C)(C)C)CCNC(=O)OCC1=CC=CC=C1 VJOVVUDDGXNJAZ-GCJKJVERSA-N 0.000 description 2
PQCBNUIAJRLXHU-GCJKJVERSA-N benzyl n-[(4s)-5-[[(1r)-1-(4-hydroxyphenyl)ethyl]amino]-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentyl]carbamate Chemical compound C([C@@H](C(=O)N[C@H](C)C=1C=CC(O)=CC=1)NC(=O)OC(C)(C)C)CCNC(=O)OCC1=CC=CC=C1 PQCBNUIAJRLXHU-GCJKJVERSA-N 0.000 description 2
KOUGMUCWVTXWDU-UHFFFAOYSA-N benzyl n-methyl-n-(phenylmethoxycarbonylcarbamothioyl)carbamate Chemical compound C=1C=CC=CC=1COC(=O)N=C(S)N(C)C(=O)OCC1=CC=CC=C1 KOUGMUCWVTXWDU-UHFFFAOYSA-N 0.000 description 2
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
230000002051 biphasic effect Effects 0.000 description 2
230000036772 blood pressure Effects 0.000 description 2
230000037396 body weight Effects 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
238000001816 cooling Methods 0.000 description 2
230000008878 coupling Effects 0.000 description 2
238000010168 coupling process Methods 0.000 description 2
238000005859 coupling reaction Methods 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
235000014632 disordered eating Nutrition 0.000 description 2
238000006345 epimerization reaction Methods 0.000 description 2
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
239000000284 extract Substances 0.000 description 2
238000001640 fractional crystallisation Methods 0.000 description 2
239000008187 granular material Substances 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 2
239000003446 ligand Substances 0.000 description 2
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 2
206010027599 migraine Diseases 0.000 description 2
208000010125 myocardial infarction Diseases 0.000 description 2
230000009871 nonspecific binding Effects 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
230000036961 partial effect Effects 0.000 description 2
230000001717 pathogenic effect Effects 0.000 description 2
238000005897 peptide coupling reaction Methods 0.000 description 2
230000002093 peripheral effect Effects 0.000 description 2
239000000825 pharmaceutical preparation Substances 0.000 description 2
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 2
229910000343 potassium bisulfate Inorganic materials 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
230000003389 potentiating effect Effects 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
238000012746 preparative thin layer chromatography Methods 0.000 description 2
230000006340 racemization Effects 0.000 description 2
230000008327 renal blood flow Effects 0.000 description 2
238000000926 separation method Methods 0.000 description 2
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
238000013222 sprague-dawley male rat Methods 0.000 description 2
239000007858 starting material Substances 0.000 description 2
239000000126 substance Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
230000002889 sympathetic effect Effects 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
RQEUFEKYXDPUSK-ZETCQYMHSA-N (1S)-1-phenylethanamine Chemical compound C[C@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-ZETCQYMHSA-N 0.000 description 1
ZTNKTVBJMXQOBQ-SBSPUUFOSA-N (1r)-1-naphthalen-1-ylethanamine;hydrochloride Chemical compound Cl.C1=CC=C2C([C@H](N)C)=CC=CC2=C1 ZTNKTVBJMXQOBQ-SBSPUUFOSA-N 0.000 description 1
RCSSHZGQHHEHPZ-MRVPVSSYSA-N (1r)-n-methyl-1-phenylethanamine Chemical compound CN[C@H](C)C1=CC=CC=C1 RCSSHZGQHHEHPZ-MRVPVSSYSA-N 0.000 description 1
RCSSHZGQHHEHPZ-QMMMGPOBSA-N (1s)-n-methyl-1-phenylethanamine Chemical compound CN[C@@H](C)C1=CC=CC=C1 RCSSHZGQHHEHPZ-QMMMGPOBSA-N 0.000 description 1
LFFUWCZWQAMTNS-RGFBGPCLSA-N (2R)-5-(diaminomethylideneamino)-2-[(2,2-diphenylacetyl)amino]-N-[(1R)-1-(4-methoxyphenyl)ethyl]pentanamide hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1[C@@H](C)NC(=O)[C@@H](CCCNC(N)=N)NC(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 LFFUWCZWQAMTNS-RGFBGPCLSA-N 0.000 description 1
USFSQRUBANGMNX-OSMGBBKRSA-N (2R)-5-(diaminomethylideneamino)-2-[(2,2-diphenylacetyl)amino]-N-[(1R)-1-phenylethyl]pentanamide hydrochloride Chemical compound Cl.N([C@H](CCCNC(N)=N)C(=O)N[C@H](C)C=1C=CC=CC=1)C(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 USFSQRUBANGMNX-OSMGBBKRSA-N 0.000 description 1
CGLVIOCHCASQHU-GJFSDDNBSA-N (2R)-5-amino-2-[(2,2-diphenylacetyl)amino]-N-(2-phenylpropan-2-yl)pentanamide hydrochloride Chemical compound Cl.N([C@H](CCCN)C(=O)NC(C)(C)C=1C=CC=CC=1)C(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 CGLVIOCHCASQHU-GJFSDDNBSA-N 0.000 description 1
GCGJWMVWDYDCQX-NTKDMRAZSA-N (2R)-5-amino-2-[(2,2-diphenylacetyl)amino]-N-[(1R)-1-(4-hydroxyphenyl)ethyl]pentanamide Chemical compound N([C@H](CCCN)C(=O)N[C@H](C)C=1C=CC(O)=CC=1)C(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 GCGJWMVWDYDCQX-NTKDMRAZSA-N 0.000 description 1
OWFSNEXMQIEXAI-OSMGBBKRSA-N (2R)-5-amino-2-[(2,2-diphenylacetyl)amino]-N-[(1R)-1-phenylethyl]pentanamide hydrochloride Chemical compound Cl.N([C@H](CCCN)C(=O)N[C@H](C)C=1C=CC=CC=1)C(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 OWFSNEXMQIEXAI-OSMGBBKRSA-N 0.000 description 1
KYANTXXKTNWWQY-KGQXAQPSSA-N (2R)-5-amino-2-[(2,2-diphenylacetyl)amino]-N-[(1R)-2-hydroxy-1-(4-methoxyphenyl)ethyl]pentanamide hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1[C@H](CO)NC(=O)[C@@H](CCCN)NC(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 KYANTXXKTNWWQY-KGQXAQPSSA-N 0.000 description 1
KQBXGRPLFJPQGW-ITNPDYSASA-N (2R)-5-amino-2-[(2,2-diphenylacetyl)amino]-N-[(1R)-2-hydroxy-1-phenylethyl]pentanamide hydrochloride Chemical compound Cl.N([C@H](CCCN)C(=O)N[C@@H](CO)C=1C=CC=CC=1)C(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 KQBXGRPLFJPQGW-ITNPDYSASA-N 0.000 description 1
OWFSNEXMQIEXAI-UFZJIDKFSA-N (2S)-5-amino-2-[(2,2-diphenylacetyl)amino]-N-[(1R)-1-phenylethyl]pentanamide hydrochloride Chemical compound Cl.N([C@@H](CCCN)C(=O)N[C@H](C)C=1C=CC=CC=1)C(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 OWFSNEXMQIEXAI-UFZJIDKFSA-N 0.000 description 1
BIIBYWQGRFWQKM-JVVROLKMSA-N (2S)-N-[4-(cyclopropylamino)-3,4-dioxo-1-[(3S)-2-oxopyrrolidin-3-yl]butan-2-yl]-2-[[(E)-3-(2,4-dichlorophenyl)prop-2-enoyl]amino]-4,4-dimethylpentanamide Chemical compound CC(C)(C)C[C@@H](C(NC(C[C@H](CCN1)C1=O)C(C(NC1CC1)=O)=O)=O)NC(/C=C/C(C=CC(Cl)=C1)=C1Cl)=O BIIBYWQGRFWQKM-JVVROLKMSA-N 0.000 description 1
ZPTCDGSPWWBTPA-HSZRJFAPSA-N (2r)-2-[(2,2-diphenylacetyl)amino]-5-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C([C@H](C(=O)O)NC(=O)C(C=1C=CC=CC=1)C=1C=CC=CC=1)CCNC(=O)OCC1=CC=CC=C1 ZPTCDGSPWWBTPA-HSZRJFAPSA-N 0.000 description 1
MAXXCANBKVBAQQ-FVGYRXGTSA-N (2r)-2-amino-2-(4-methoxyphenyl)ethanol;hydrochloride Chemical compound Cl.COC1=CC=C([C@@H](N)CO)C=C1 MAXXCANBKVBAQQ-FVGYRXGTSA-N 0.000 description 1
HNEILONISONLCI-WCCKRBBISA-N (2s)-2,5-diaminopentanamide;hydroiodide Chemical compound I.NCCC[C@H](N)C(N)=O HNEILONISONLCI-WCCKRBBISA-N 0.000 description 1
MAXXCANBKVBAQQ-SBSPUUFOSA-N (2s)-2-amino-2-(4-methoxyphenyl)ethanol;hydrochloride Chemical compound Cl.COC1=CC=C([C@H](N)CO)C=C1 MAXXCANBKVBAQQ-SBSPUUFOSA-N 0.000 description 1
IJXJGQCXFSSHNL-MRVPVSSYSA-N (2s)-2-amino-2-phenylethanol Chemical compound OC[C@@H](N)C1=CC=CC=C1 IJXJGQCXFSSHNL-MRVPVSSYSA-N 0.000 description 1
IJXJGQCXFSSHNL-QMMMGPOBSA-N (R)-(-)-2-Phenylglycinol Chemical compound OC[C@H](N)C1=CC=CC=C1 IJXJGQCXFSSHNL-QMMMGPOBSA-N 0.000 description 1
MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical class C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
CJWGCBRQAHCVHW-UHFFFAOYSA-N 1-(3-methoxyphenyl)ethanamine Chemical compound COC1=CC=CC(C(C)N)=C1 CJWGCBRQAHCVHW-UHFFFAOYSA-N 0.000 description 1
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical group C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical group C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 1
RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
XJEVHMGJSYVQBQ-UHFFFAOYSA-N 2,3-dihydro-1h-inden-1-amine Chemical compound C1=CC=C2C(N)CCC2=C1 XJEVHMGJSYVQBQ-UHFFFAOYSA-N 0.000 description 1
TZADAWVLFGIAKY-UHFFFAOYSA-N 2-amino-2-(4-methoxyphenyl)acetamide Chemical compound COC1=CC=C(C(N)C(N)=O)C=C1 TZADAWVLFGIAKY-UHFFFAOYSA-N 0.000 description 1
KIYRSYYOVDHSPG-UHFFFAOYSA-N 2-amino-2-phenylacetamide Chemical compound NC(=O)C(N)C1=CC=CC=C1 KIYRSYYOVDHSPG-UHFFFAOYSA-N 0.000 description 1
VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 1
KDFDOINBXBEOLZ-UHFFFAOYSA-N 2-phenylpropan-2-amine Chemical compound CC(C)(N)C1=CC=CC=C1 KDFDOINBXBEOLZ-UHFFFAOYSA-N 0.000 description 1
CDQPLIAKRDYOCB-ZCFIWIBFSA-N 4-[(1r)-1-aminoethyl]phenol Chemical compound C[C@@H](N)C1=CC=C(O)C=C1 CDQPLIAKRDYOCB-ZCFIWIBFSA-N 0.000 description 1
CDQPLIAKRDYOCB-LURJTMIESA-N 4-[(1s)-1-aminoethyl]phenol Chemical compound C[C@H](N)C1=CC=C(O)C=C1 CDQPLIAKRDYOCB-LURJTMIESA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
239000005541 ACE inhibitor Substances 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
229940127291 Calcium channel antagonist Drugs 0.000 description 1
244000025254 Cannabis sativa Species 0.000 description 1
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
208000006561 Cluster Headache Diseases 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
206010015719 Exsanguination Diseases 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
206010020850 Hyperthyroidism Diseases 0.000 description 1
206010061216 Infarction Diseases 0.000 description 1
OBSIQMZKFXFYLV-QMMMGPOBSA-N L-phenylalanine amide Chemical class NC(=O)[C@@H](N)CC1=CC=CC=C1 OBSIQMZKFXFYLV-QMMMGPOBSA-N 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
208000008589 Obesity Diseases 0.000 description 1
QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 1
108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 1
208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
206010049418 Sudden Cardiac Death Diseases 0.000 description 1
206010047163 Vasospasm Diseases 0.000 description 1
XYPKYROZUALECQ-VJTNNGHGSA-N acetic acid (2R)-5-amino-2-[(2,2-diphenylacetyl)amino]-N-[(1R)-1-(4-hydroxyphenyl)ethyl]pentanamide Chemical compound CC(O)=O.N([C@H](CCCN)C(=O)N[C@H](C)C=1C=CC(O)=CC=1)C(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 XYPKYROZUALECQ-VJTNNGHGSA-N 0.000 description 1
PHEDTXJYYFZENX-WCCKRBBISA-N acetic acid;(2s)-2,5-diaminopentanoic acid Chemical compound CC(O)=O.NCCC[C@H](N)C(O)=O PHEDTXJYYFZENX-WCCKRBBISA-N 0.000 description 1
OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
229960004373 acetylcholine Drugs 0.000 description 1
239000002253 acid Substances 0.000 description 1
230000009471 action Effects 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
150000001409 amidines Chemical class 0.000 description 1
229940024606 amino acid Drugs 0.000 description 1
150000003862 amino acid derivatives Chemical class 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
239000000538 analytical sample Substances 0.000 description 1
229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
ZRALSGWEFCBTJO-UHFFFAOYSA-N anhydrous guanidine Natural products NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 1
229940054051 antipsychotic indole derivative Drugs 0.000 description 1
229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 description 1
238000010936 aqueous wash Methods 0.000 description 1
206010003119 arrhythmia Diseases 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
239000012131 assay buffer Substances 0.000 description 1
210000000467 autonomic pathway Anatomy 0.000 description 1
238000010533 azeotropic distillation Methods 0.000 description 1
125000003236 benzoyl group Chemical class [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
CPEKAXYCDKETEN-UHFFFAOYSA-N benzoyl isothiocyanate Chemical compound S=C=NC(=O)C1=CC=CC=C1 CPEKAXYCDKETEN-UHFFFAOYSA-N 0.000 description 1
NQAUDQZDGPDEQF-OIZGGULRSA-N benzyl 2-(benzylhydrazinylidene)-2-[[(4R)-4-[(2,2-diphenylacetyl)amino]-5-[[(1R)-1-(4-methoxyphenyl)ethyl]amino]-5-oxopentyl]-phenylmethoxycarbonylamino]acetate Chemical compound C1=CC(OC)=CC=C1[C@@H](C)NC(=O)[C@H](NC(=O)C(C=1C=CC=CC=1)C=1C=CC=CC=1)CCCN(C(=NNCC=1C=CC=CC=1)C(=O)OCC=1C=CC=CC=1)C(=O)OCC1=CC=CC=C1 NQAUDQZDGPDEQF-OIZGGULRSA-N 0.000 description 1
AKOYJBYBRLTUEV-QFQXNSOFSA-N benzyl N-[(4R)-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-[[(1R)-1-naphthalen-1-ylethyl]amino]-5-oxopentyl]carbamate Chemical compound C([C@H](C(=O)N[C@H](C)C=1C2=CC=CC=C2C=CC=1)NC(=O)OC(C)(C)C)CCNC(=O)OCC1=CC=CC=C1 AKOYJBYBRLTUEV-QFQXNSOFSA-N 0.000 description 1
QXWMEACMLZCHPA-DOTFVSGYSA-N benzyl N-[(4R)-4-amino-5-[[(1R)-1-naphthalen-1-ylethyl]amino]-5-oxopentyl]carbamate hydrochloride Chemical compound Cl.C([C@@H](N)C(=O)N[C@H](C)C=1C2=CC=CC=C2C=CC=1)CCNC(=O)OCC1=CC=CC=C1 QXWMEACMLZCHPA-DOTFVSGYSA-N 0.000 description 1
MTEGDVLVDFAPCR-VOMIJIAVSA-N benzyl N-[(4R)-4-amino-5-[[(1R)-2-hydroxy-1-phenylethyl]amino]-5-oxopentyl]carbamate hydrochloride Chemical compound Cl.C([C@@H](N)C(=O)N[C@@H](CO)C=1C=CC=CC=1)CCNC(=O)OCC1=CC=CC=C1 MTEGDVLVDFAPCR-VOMIJIAVSA-N 0.000 description 1
NMFZGUPCSSLXOB-JEHHVLJISA-N benzyl N-[(4R)-4-amino-5-oxo-5-[[(1R)-1-(4-phenylmethoxyphenyl)ethyl]amino]pentyl]carbamate hydrochloride Chemical compound Cl.C([C@@H](N)C(=O)N[C@H](C)C=1C=CC(OCC=2C=CC=CC=2)=CC=1)CCNC(=O)OCC1=CC=CC=C1 NMFZGUPCSSLXOB-JEHHVLJISA-N 0.000 description 1
SCMLDRDMHIJSTG-OOWIMERYSA-N benzyl N-[(4R)-5-[[(1R)-1-(4-bromophenyl)ethyl]amino]-4-[(2,2-diphenylacetyl)amino]-5-oxopentyl]carbamate Chemical compound C([C@H](C(=O)N[C@H](C)C=1C=CC(Br)=CC=1)NC(=O)C(C=1C=CC=CC=1)C=1C=CC=CC=1)CCNC(=O)OCC1=CC=CC=C1 SCMLDRDMHIJSTG-OOWIMERYSA-N 0.000 description 1
BTONRFRRAWZMAB-YADHBBJMSA-N benzyl N-[(4R)-5-[[(1R)-2-hydroxy-1-phenylethyl]amino]-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentyl]carbamate Chemical compound C([C@@H](NC(=O)OC(C)(C)C)C(=O)N[C@@H](CO)C=1C=CC=CC=1)CCNC(=O)OCC1=CC=CC=C1 BTONRFRRAWZMAB-YADHBBJMSA-N 0.000 description 1
CLPLIDMSBZGYGR-NJHZRGNWSA-N benzyl N-[(4S)-4-[(2,2-diphenylacetyl)amino]-5-[[(1R)-1-(4-hydroxyphenyl)ethyl]amino]-5-oxopentyl]carbamate Chemical compound C([C@@H](C(=O)N[C@H](C)C=1C=CC(O)=CC=1)NC(=O)C(C=1C=CC=CC=1)C=1C=CC=CC=1)CCNC(=O)OCC1=CC=CC=C1 CLPLIDMSBZGYGR-NJHZRGNWSA-N 0.000 description 1
DYAMSPDDSBTIOG-ACHIHNKUSA-N benzyl N-[(4S)-4-[(2,2-diphenylacetyl)amino]-5-[[(1R)-2-hydroxy-1-(4-methoxyphenyl)ethyl]amino]-5-oxopentyl]carbamate Chemical compound C1=CC(OC)=CC=C1[C@H](CO)NC(=O)[C@@H](NC(=O)C(C=1C=CC=CC=1)C=1C=CC=CC=1)CCCNC(=O)OCC1=CC=CC=C1 DYAMSPDDSBTIOG-ACHIHNKUSA-N 0.000 description 1
XFQKWAWHARJSCQ-KNQAVFIVSA-N benzyl N-[(4S)-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxo-5-[[(1R)-1-phenylethyl]amino]pentyl]carbamate Chemical compound C([C@@H](C(=O)N[C@H](C)C=1C=CC=CC=1)NC(=O)OC(C)(C)C)CCNC(=O)OCC1=CC=CC=C1 XFQKWAWHARJSCQ-KNQAVFIVSA-N 0.000 description 1
LUOUQWSCMKEINJ-FKLPMGAJSA-N benzyl N-[(4S)-4-amino-5-[[(1R)-2-hydroxy-1-(4-methoxyphenyl)ethyl]amino]-5-oxopentyl]carbamate hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1[C@H](CO)NC(=O)[C@@H](N)CCCNC(=O)OCC1=CC=CC=C1 LUOUQWSCMKEINJ-FKLPMGAJSA-N 0.000 description 1
MTEGDVLVDFAPCR-HLRBRJAUSA-N benzyl N-[(4S)-4-amino-5-[[(1R)-2-hydroxy-1-phenylethyl]amino]-5-oxopentyl]carbamate hydrochloride Chemical compound Cl.C([C@H](N)C(=O)N[C@@H](CO)C=1C=CC=CC=1)CCNC(=O)OCC1=CC=CC=C1 MTEGDVLVDFAPCR-HLRBRJAUSA-N 0.000 description 1
CWUVHFBSCPNYQM-OFNKIYASSA-N benzyl N-[(4S)-5-[methyl-[(1R)-1-phenylethyl]amino]-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentyl]carbamate Chemical compound C([C@@H](C(=O)N(C)[C@H](C)C=1C=CC=CC=1)NC(=O)OC(C)(C)C)CCNC(=O)OCC1=CC=CC=C1 CWUVHFBSCPNYQM-OFNKIYASSA-N 0.000 description 1
HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
DLZGHXBFBPZIQE-AEFICSSHSA-N benzyl n-[(4r)-4-amino-5-[[(1r)-1-(4-bromophenyl)ethyl]amino]-5-oxopentyl]carbamate;hydrochloride Chemical compound Cl.C([C@@H](N)C(=O)N[C@H](C)C=1C=CC(Br)=CC=1)CCNC(=O)OCC1=CC=CC=C1 DLZGHXBFBPZIQE-AEFICSSHSA-N 0.000 description 1
NLTOJMMWVFWMSB-AEFICSSHSA-N benzyl n-[(4r)-4-amino-5-[[(1r)-1-(4-hydroxyphenyl)ethyl]amino]-5-oxopentyl]carbamate;hydrochloride Chemical compound Cl.C([C@@H](N)C(=O)N[C@H](C)C=1C=CC(O)=CC=1)CCNC(=O)OCC1=CC=CC=C1 NLTOJMMWVFWMSB-AEFICSSHSA-N 0.000 description 1
DLZGHXBFBPZIQE-WSCVZUBPSA-N benzyl n-[(4s)-4-amino-5-[[(1r)-1-(4-bromophenyl)ethyl]amino]-5-oxopentyl]carbamate;hydrochloride Chemical compound Cl.C([C@H](N)C(=O)N[C@H](C)C=1C=CC(Br)=CC=1)CCNC(=O)OCC1=CC=CC=C1 DLZGHXBFBPZIQE-WSCVZUBPSA-N 0.000 description 1
NLTOJMMWVFWMSB-WSCVZUBPSA-N benzyl n-[(4s)-4-amino-5-[[(1r)-1-(4-hydroxyphenyl)ethyl]amino]-5-oxopentyl]carbamate;hydrochloride Chemical compound Cl.C([C@H](N)C(=O)N[C@H](C)C=1C=CC(O)=CC=1)CCNC(=O)OCC1=CC=CC=C1 NLTOJMMWVFWMSB-WSCVZUBPSA-N 0.000 description 1
150000003939 benzylamines Chemical class 0.000 description 1
125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
210000004204 blood vessel Anatomy 0.000 description 1
230000036760 body temperature Effects 0.000 description 1
229940098773 bovine serum albumin Drugs 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
235000011089 carbon dioxide Nutrition 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
210000003710 cerebral cortex Anatomy 0.000 description 1
239000003610 charcoal Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
208000020832 chronic kidney disease Diseases 0.000 description 1
208000022831 chronic renal failure syndrome Diseases 0.000 description 1
230000004087 circulation Effects 0.000 description 1
208000018912 cluster headache syndrome Diseases 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
238000004590 computer program Methods 0.000 description 1
208000029078 coronary artery disease Diseases 0.000 description 1
210000004351 coronary vessel Anatomy 0.000 description 1
239000006184 cosolvent Substances 0.000 description 1
239000002178 crystalline material Substances 0.000 description 1
125000004093 cyano group Chemical group *C#N 0.000 description 1
238000001212 derivatisation Methods 0.000 description 1
206010012601 diabetes mellitus Diseases 0.000 description 1
229940085304 dihydropyridine derivative selective calcium channel blockers with mainly vascular effects Drugs 0.000 description 1
125000004925 dihydropyridyl group Chemical class N1(CC=CC=C1)* 0.000 description 1
229940043279 diisopropylamine Drugs 0.000 description 1
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
239000002934 diuretic Substances 0.000 description 1
229940030606 diuretics Drugs 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
229940079593 drug Drugs 0.000 description 1
238000001647 drug administration Methods 0.000 description 1
235000005686 eating Nutrition 0.000 description 1
230000002526 effect on cardiovascular system Effects 0.000 description 1
230000002996 emotional effect Effects 0.000 description 1
239000002024 ethyl acetate extract Substances 0.000 description 1
OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
239000012065 filter cake Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
230000010006 flight Effects 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 1
239000011521 glass Substances 0.000 description 1
239000003365 glass fiber Substances 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
150000002475 indoles Chemical class 0.000 description 1
230000007574 infarction Effects 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000001282 iso-butane Substances 0.000 description 1
238000002955 isolation Methods 0.000 description 1
150000002540 isothiocyanates Chemical class 0.000 description 1
210000004731 jugular vein Anatomy 0.000 description 1
231100001231 less toxic Toxicity 0.000 description 1
238000005567 liquid scintillation counting Methods 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
AGJSNMGHAVDLRQ-HUUJSLGLSA-N methyl (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-HUUJSLGLSA-N 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
230000002107 myocardial effect Effects 0.000 description 1
208000031225 myocardial ischemia Diseases 0.000 description 1
210000004165 myocardium Anatomy 0.000 description 1
RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
210000005036 nerve Anatomy 0.000 description 1
210000001640 nerve ending Anatomy 0.000 description 1
230000001537 neural effect Effects 0.000 description 1
BPGXUIVWLQTVLZ-OFGSCBOVSA-N neuropeptide y(npy) Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 BPGXUIVWLQTVLZ-OFGSCBOVSA-N 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
235000020824 obesity Nutrition 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
208000028591 pheochromocytoma Diseases 0.000 description 1
230000036470 plasma concentration Effects 0.000 description 1
229920000573 polyethylene Polymers 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
230000010349 pulsation Effects 0.000 description 1
125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
239000002464 receptor antagonist Substances 0.000 description 1
229940044551 receptor antagonist Drugs 0.000 description 1
238000001525 receptor binding assay Methods 0.000 description 1
238000006268 reductive amination reaction Methods 0.000 description 1
210000002254 renal artery Anatomy 0.000 description 1
230000029058 respiratory gaseous exchange Effects 0.000 description 1
230000004044 response Effects 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
238000012552 review Methods 0.000 description 1
238000005070 sampling Methods 0.000 description 1
230000035939 shock Effects 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
239000012453 solvate Substances 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
210000000952 spleen Anatomy 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
238000013223 sprague-dawley female rat Methods 0.000 description 1
230000006641 stabilisation Effects 0.000 description 1
238000011105 stabilization Methods 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
210000002820 sympathetic nervous system Anatomy 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
UGGLLJXYVCTVRU-IUODEOHRSA-N tert-butyl N-[(2R)-5-amino-1-[[(1R)-1-(4-hydroxyphenyl)ethyl]amino]-1-oxopentan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H](CCCN)C(=O)N[C@H](C)C1=CC=C(O)C=C1 UGGLLJXYVCTVRU-IUODEOHRSA-N 0.000 description 1
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
125000004665 trialkylsilyl group Chemical group 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000003828 vacuum filtration Methods 0.000 description 1
230000001515 vagal effect Effects 0.000 description 1
230000003639 vasoconstrictive effect Effects 0.000 description 1
208000003663 ventricular fibrillation Diseases 0.000 description 1
238000005303 weighing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/04—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton
- C07C279/14—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton being further substituted by carboxyl groups
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Diabetes (AREA)
Urology & Nephrology (AREA)
Endocrinology (AREA)
Hematology (AREA)
Obesity (AREA)
Pain & Pain Management (AREA)
Neurology (AREA)
Vascular Medicine (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Emergency Medicine (AREA)
Biomedical Technology (AREA)
Hospice & Palliative Care (AREA)
Neurosurgery (AREA)
Child & Adolescent Psychology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Peptides Or Proteins (AREA)

SK360-2000A 1997-09-23 1998-09-21 New npy antagonists SK3602000A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
SE9703414A SE9703414D0 (sv)	1997-09-23	1997-09-23	New compounds
PCT/SE1998/001686 WO1999015498A1 (en)	1997-09-23	1998-09-21	New npy antagonists

Publications (1)

Publication Number	Publication Date
SK3602000A3 true SK3602000A3 (en)	2001-01-18

Family

ID=20408331

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK360-2000A SK3602000A3 (en)	1997-09-23	1998-09-21	New npy antagonists

Country Status (21)

Country	Link
US (1)	US6127414A (de)
EP (1)	EP1017672B1 (de)
JP (1)	JP2001517651A (de)
KR (1)	KR20010024220A (de)
CN (1)	CN1279666A (de)
AR (1)	AR017138A1 (de)
AT (1)	ATE228500T1 (de)
AU (1)	AU9288998A (de)
BR (1)	BR9812492A (de)
CA (1)	CA2303528A1 (de)
DE (1)	DE69809782T2 (de)
EE (1)	EE200000171A (de)
IL (1)	IL134993A0 (de)
IS (1)	IS5410A (de)
NO (1)	NO20001483L (de)
PL (1)	PL339617A1 (de)
SE (1)	SE9703414D0 (de)
SK (1)	SK3602000A3 (de)
TR (1)	TR200000785T2 (de)
WO (1)	WO1999015498A1 (de)
ZA (1)	ZA988353B (de)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
SE9802075D0 (sv) *	1998-06-11	1998-06-11	Astra Ab	New use
US6312898B1 (en) *	1999-04-15	2001-11-06	Hormos Medical Oy, Ltd.	Diagnosis of a person's risk of developing atherosclerosis or diabetic retinopathy based on leucine 7 to proline 7 polymorphism in the prepro-neuropeptide Y gene
SE9902596D0 (sv) *	1999-07-06	1999-07-06	Astra Ab	Pharmaceutically active compounds
EP1095933A1 (de)	1999-10-30	2001-05-02	Aventis Pharma Deutschland GmbH	N-Guanidinoalkylamide, Verfahren zu ihrer Herstellung, ihre Verwendung und pharmazeutische Zusammensetzungen, die sie enthalten
SE0101328D0 (sv) *	2001-04-12	2001-04-12	Astrazeneca Ab	Therapeutic treatment
JP4010951B2 (ja) *	2001-05-15	2007-11-21	大正製薬株式会社	アルギニン誘導体
ATE462432T1 (de)	2003-05-05	2010-04-15	Probiodrug Ag	Glutaminylcyclase-hemmer
JP2007509898A (ja)	2003-11-03	2007-04-19	プロビオドルグエージー	神経障害治療に有用な組合せ
FR2864830B1 (fr) *	2004-01-06	2006-03-10	Centre Nat Rech Scient	Procede de synthese sur support solide de composes peptidiques, notamment de composes peptidiques comportant un residu arginine
KR101099206B1 (ko)	2004-02-05	2011-12-27	프로비오드룩 아게	신규한 글루타미닐 시클라제 저해제
FR2884516B1 (fr) *	2005-04-15	2007-06-22	Cerep Sa	Antagonistes npy, preparation et utilisations
KR100689499B1 (ko) *	2005-10-26	2007-03-02	삼성전자주식회사	휴대단말기에서 키 설정 정보 디스플레이 방법
WO2007064272A1 (en) *	2005-11-29	2007-06-07	Astrazeneca Ab	Benzhydryl amide derivatives as cannabinoid receptor antagonists or inverse agonists
JP5379692B2 (ja)	2006-11-09	2013-12-25	プロビオドルグエージー	潰瘍、癌及び他の疾患の治療のためのグルタミニルシクラーゼの阻害薬としての３−ヒドロキシ−１，５−ジヒドロ−ピロール−２−オン誘導体
EP2091948B1 (de)	2006-11-30	2012-04-18	Probiodrug AG	Neue inhibitoren von glutaminylcyclase
CA2679446C (en)	2007-03-01	2016-05-17	Probiodrug Ag	New use of glutaminyl cyclase inhibitors
US9656991B2 (en)	2007-04-18	2017-05-23	Probiodrug Ag	Inhibitors of glutaminyl cyclase
BR112012008346B1 (pt)	2009-09-11	2021-12-21	Vivoryon Therapeutics N.V.	Derivados heterocíclicos, seu processo de preparação, e composição farmacêutica
WO2011107530A2 (en)	2010-03-03	2011-09-09	Probiodrug Ag	Novel inhibitors
DK2545047T3 (da)	2010-03-10	2014-07-28	Probiodrug Ag	Heterocycliske inhibitorer af glutaminylcyclase (QC, EC 2.3.2.5)
EP2560953B1 (de)	2010-04-21	2016-01-06	Probiodrug AG	Hemmer der glutaminylzyklase
WO2012123563A1 (en)	2011-03-16	2012-09-20	Probiodrug Ag	Benz imidazole derivatives as inhibitors of glutaminyl cyclase
PL3461819T3 (pl)	2017-09-29	2020-11-30	Probiodrug Ag	Inhibitory cyklazy glutaminylowej
JP2025540658A (ja) *	2022-11-23	2025-12-16	ラディオネティクスオンコロジー，インク．	神経ペプチドｙ１受容体（ｎｐｙ１ｒ）を標的とした治療薬およびその使用
TW202535356A (zh) *	2023-12-28	2025-09-16	美商萊迪奧尼提斯腫瘤醫學公司	神經肽y1受體(npy1r)靶向治療劑及其用途

Family Cites Families (20)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5873821A (en) *	1992-05-18	1999-02-23	Non-Invasive Technology, Inc.	Lateralization spectrophotometer
DE4326465A1 (de) *	1993-01-20	1995-02-09	Thomae Gmbh Dr K	Aminosäurederivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung
DE19544687A1 (de) *	1995-11-30	1997-06-05	Thomae Gmbh Dr K	Aminosäurederivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung
DE19544686A1 (de) *	1995-11-30	1997-06-05	Thomae Gmbh Dr K	Aminosäurederivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung
CA2242579A1 (en) *	1996-01-09	1997-07-17	Eli Lilly And Company	Benzimidzolyl neuropeptide y receptor antagonists
US6011039A (en) *	1996-03-21	2000-01-04	Banyu Pharmaceutical Co., Ltd.	Aminopyridine derivatives
EP1007073A4 (de) *	1996-06-04	2002-03-27	Synaptic Pharma Corp	Verfahren zur änderung der essgewohnheiten, für diese verfahren geeignete verbindungen, sowie eine für einen hypothalamisches atypisches neuropeptid y/ peptide yy rezeptor kodierende dna
ATE230403T1 (de) *	1996-07-23	2003-01-15	Neurogen Corp	Einige amido- und ammo- substituierte benzylaminderivate: eine neue klasse von neuropeptid y1 spezifische ligande
CA2260982A1 (en) *	1996-07-23	1998-01-29	Neurogen Corporation	Certain substituted benzylamine derivatives; a new class of neuropeptide-y1 specific ligands
DE69721541T2 (de) *	1996-07-23	2004-03-18	Neurogen Corp., Branford	Einige amido-und amino-substituierte benzylaminderivate: eine neue klasse von neuropeptid y1 spezifischen liganden
EP0984778B1 (de) *	1996-08-23	2002-06-12	Agouron Pharmaceuticals, Inc.	Liganden des neuropeptids y
AU5135998A (en) *	1996-12-03	1998-06-29	Banyu Pharmaceutical Co., Ltd.	Novel urea derivatives
WO1998025907A1 (en) *	1996-12-12	1998-06-18	Banyu Pharmaceutical Co., Ltd.	Pyrazole derivatives
CA2274593A1 (en) *	1996-12-13	1998-06-18	Banyu Pharmaceutical Co., Ltd.	Novel aminopyrazole derivatives
CA2274594C (en) *	1996-12-16	2006-10-10	Banyu Pharmaceutical Co., Ltd.	Aminopyrazole derivatives
JP2002514199A (ja) *	1997-02-04	2002-05-14	ブリストル−マイヤーズスクイブカンパニー	Ｎｐｙ拮抗剤としてのジヒドロピリミドン誘導体
CA2251580A1 (en) *	1997-02-14	1998-08-20	Bayer Corporation	Amides as npy5 receptor antagonists
JP2002241368A (ja) *	1997-02-18	2002-08-28	Shionogi & Co Ltd	新規ベンゾラクタム誘導体およびそれを含有する医薬組成物
AU6309698A (en) *	1997-03-12	1998-09-29	Banyu Pharmaceutical Co., Ltd.	Drugs containing aminopyridine derivatives as the active ingredient
US5889016A (en) *	1997-06-26	1999-03-30	Bristol-Myers Squibb Company	Dihydropyrimidone derivatives as NPY antagonists

1997
- 1997-09-23 SE SE9703414A patent/SE9703414D0/xx unknown
1998
- 1998-09-11 ZA ZA988353A patent/ZA988353B/xx unknown
- 1998-09-21 PL PL98339617A patent/PL339617A1/xx unknown
- 1998-09-21 US US09/171,779 patent/US6127414A/en not_active Expired - Fee Related
- 1998-09-21 WO PCT/SE1998/001686 patent/WO1999015498A1/en not_active Ceased
- 1998-09-21 CN CN98811336A patent/CN1279666A/zh active Pending
- 1998-09-21 AT AT98945708T patent/ATE228500T1/de not_active IP Right Cessation
- 1998-09-21 JP JP2000512808A patent/JP2001517651A/ja active Pending
- 1998-09-21 SK SK360-2000A patent/SK3602000A3/sk unknown
- 1998-09-21 EP EP98945708A patent/EP1017672B1/de not_active Expired - Lifetime
- 1998-09-21 CA CA002303528A patent/CA2303528A1/en not_active Abandoned
- 1998-09-21 KR KR1020007003029A patent/KR20010024220A/ko not_active Withdrawn
- 1998-09-21 AU AU92889/98A patent/AU9288998A/en not_active Abandoned
- 1998-09-21 IL IL13499398A patent/IL134993A0/xx unknown
- 1998-09-21 EE EEP200000171A patent/EE200000171A/xx unknown
- 1998-09-21 BR BR9812492-7A patent/BR9812492A/pt not_active IP Right Cessation
- 1998-09-21 TR TR2000/00785T patent/TR200000785T2/xx unknown
- 1998-09-21 DE DE69809782T patent/DE69809782T2/de not_active Expired - Fee Related
- 1998-09-22 AR ARP980104740A patent/AR017138A1/es unknown
2000
- 2000-03-20 IS IS5410A patent/IS5410A/is unknown
- 2000-03-22 NO NO20001483A patent/NO20001483L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
CN1279666A (zh)	2001-01-10
IL134993A0 (en)	2001-05-20
CA2303528A1 (en)	1999-04-01
ATE228500T1 (de)	2002-12-15
BR9812492A (pt)	2000-09-26
EP1017672A1 (de)	2000-07-12
NO20001483D0 (no)	2000-03-22
EP1017672B1 (de)	2002-11-27
AR017138A1 (es)	2001-08-22
DE69809782T2 (de)	2003-07-17
SE9703414D0 (sv)	1997-09-23
IS5410A (is)	2000-03-20
US6127414A (en)	2000-10-03
KR20010024220A (ko)	2001-03-26
ZA988353B (en)	1999-03-23
NO20001483L (no)	2000-05-23
JP2001517651A (ja)	2001-10-09
WO1999015498A1 (en)	1999-04-01
EE200000171A (et)	2001-04-16
TR200000785T2 (tr)	2000-09-21
PL339617A1 (en)	2001-01-02
DE69809782D1 (de)	2003-01-09
AU9288998A (en)	1999-04-12

Publication	Publication Date	Title
SK3602000A3 (en)	2001-01-18	New npy antagonists
US7893279B2 (en)	2011-02-22	Cyclohexanecarboxylic acid compound
RU2186763C2 (ru)	2002-08-10	Амидные производные или их соли
EP0072286B1 (de)	1986-10-29	Organische Amidverbindungen aus stickstoffhaltigen Lipiden abgeleitet
EP0082088B1 (de)	1986-04-02	Aminosäurederivate und ihre therapeutischen Verwendungen
DE60014588T2 (de)	2006-02-23	Thioamidderivate
EP0372486A2 (de)	1990-06-13	Neue Benzoesäure- und Phenylessigsäurederivate, ihre Herstellung und Verwendung als Heilmittel
CZ23299A3 (cs)	1999-06-16	Inhibitory adheze buněk a farmaceutický prostředek, který je obsahuje
JPH09512010A (ja)	1997-12-02	タキキニン拮抗薬
BG65755B1 (bg)	2009-10-30	Инхибитори на клетъчна адхезия
JP2003513002A (ja)	2003-04-08	カルニチンパルミトイル−トランスフェラーゼの可逆的阻害活性を有する化合物
KR20140014081A (ko)	2014-02-05	아밀로이드 피브릴 형성과 관련된 증상 치료용 디펩티드 유사체
CZ283508B6 (cs)	1998-04-15	Deriváty N-acyl-alfa-aminokyselin, způsob jejich výroby a farmaceutické přípravky na jejich bázi
KR102790657B1 (ko)	2025-04-02	뇌 손상을 치료하기 위한 조성물 및 방법
JPS6112911B2 (de)	1986-04-10
EP1431290A1 (de)	2004-06-23	Neue stickstoffhaltige verbindung und deren verwendung
KR102552795B1 (ko)	2023-07-06	결정질 형태
US8193218B2 (en)	2012-06-05	Aroyl-piperidine derivatives and method of treating disorders induced by substance P
EP0403828A1 (de)	1990-12-27	Renininhibitorische Peptide, Verfahren zur ihrer Herstellung und ihre Verwendung in Arzneimitteln
US6066672A (en)	2000-05-23	Amino compounds and angiotensin IV receptor agonists
US6518458B1 (en)	2003-02-11	(Aminoiminomethyl) amino) alkane-carboxamides and their applications in therapy
FR2594831A1 (fr)	1987-08-28	Derives de proline, leur procede de preparation, composition pharmaceutique en comportant et procede d'inhibition de l'enzyme transformant l'angiotensine
TW202100146A (zh)	2021-01-01	用於治療高血壓或心衰竭的化合物及包含其之組成物
JP4842254B2 (ja)	2011-12-21	Ｐａｒ−２アゴニスト
KR100245980B1 (ko)	2000-04-01	호모바닐릭아미드 유도체 및 이의 제조방법