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
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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
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IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
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QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 8
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125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 8
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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
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238000003786 synthesis reaction Methods 0.000 description 4
238000005160 1H NMR spectroscopy Methods 0.000 description 3
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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
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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
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238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
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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
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239000002243 precursor Substances 0.000 description 1
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102000004169 proteins and genes Human genes 0.000 description 1
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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
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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
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- 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
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- A—HUMAN NECESSITIES
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- 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
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- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
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- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A—HUMAN NECESSITIES
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- A61P9/06—Antiarrhythmics
- A—HUMAN NECESSITIES
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- 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
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- 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)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
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Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
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Pharmacology & Pharmacy (AREA)
General Health & Medical Sciences (AREA)
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Heart & Thoracic Surgery (AREA)
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Communicable Diseases (AREA)
Oncology (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 (is)
EP (1)	EP1017672B1 (is)
JP (1)	JP2001517651A (is)
KR (1)	KR20010024220A (is)
CN (1)	CN1279666A (is)
AR (1)	AR017138A1 (is)
AT (1)	ATE228500T1 (is)
AU (1)	AU9288998A (is)
BR (1)	BR9812492A (is)
CA (1)	CA2303528A1 (is)
DE (1)	DE69809782T2 (is)
EE (1)	EE200000171A (is)
IL (1)	IL134993A0 (is)
IS (1)	IS5410A (is)
NO (1)	NO20001483L (is)
PL (1)	PL339617A1 (is)
SE (1)	SE9703414D0 (is)
SK (1)	SK3602000A3 (is)
TR (1)	TR200000785T2 (is)
WO (1)	WO1999015498A1 (is)
ZA (1)	ZA988353B (is)

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SE9902596D0 (sv) *	1999-07-06	1999-07-06	Astra Ab	Pharmaceutically active compounds
EP1095933A1 (en) *	1999-10-30	2001-05-02	Aventis Pharma Deutschland GmbH	Novel N-guanidinoalkylamides, their preparation, their use, and pharmaceutical preparations comprising them
SE0101328D0 (sv) *	2001-04-12	2001-04-12	Astrazeneca Ab	Therapeutic treatment
WO2002092566A1 (en) *	2001-05-15	2002-11-21	Taisho Pharmaceutical Co.,Ltd.	Arginine derivatives
WO2004098591A2 (en)	2003-05-05	2004-11-18	Probiodrug Ag	Inhibitors of glutaminyl cyclase and their use in the treatment of neurological diseases
AU2004290499C1 (en)	2003-11-03	2011-02-24	Probiodrug Ag	Combinations useful for the treatment of neuronal disorders
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
CA2554809C (en)	2004-02-05	2014-04-29	Probiodrug Ag	Novel n-alkyl thiourea- and thioamide-substituted imidazolyl inhibitors of glutaminyl cyclase
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
US8278345B2 (en)	2006-11-09	2012-10-02	Probiodrug Ag	Inhibitors of glutaminyl cyclase
ATE554085T1 (de)	2006-11-30	2012-05-15	Probiodrug Ag	Neue inhibitoren von glutaminylcyclase
JP5930573B2 (ja)	2007-03-01	2016-06-15	プロビオドルグエージー	グルタミニルシクラーゼ阻害剤の新規使用
EP2142514B1 (en)	2007-04-18	2014-12-24	Probiodrug AG	Thiourea derivatives as glutaminyl cyclase inhibitors
JP5934645B2 (ja)	2009-09-11	2016-06-15	プロビオドルグエージー	グルタミニルシクラーゼ阻害剤としてのヘテロ環式誘導体
JP6026284B2 (ja)	2010-03-03	2016-11-16	プロビオドルグエージー	グルタミニルシクラーゼの阻害剤
NZ602312A (en)	2010-03-10	2014-02-28	Probiodrug Ag	Heterocyclic inhibitors of glutaminyl cyclase (qc, ec 2.3.2.5)
WO2011131748A2 (en)	2010-04-21	2011-10-27	Probiodrug Ag	Novel inhibitors
EP2686313B1 (en)	2011-03-16	2016-02-03	Probiodrug AG	Benzimidazole derivatives as inhibitors of glutaminyl cyclase
ES2812698T3 (es)	2017-09-29	2021-03-18	Probiodrug Ag	Inhibidores de glutaminil ciclasa
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US20250213735A1 (en) *	2023-12-28	2025-07-03	Radionetics Oncology, Inc.	Neuropeptide y1 receptor (npy1r) targeted therapeutics and uses thereof

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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
AU6267198A (en) *	1997-02-14	1998-09-08	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
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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 KR KR1020007003029A patent/KR20010024220A/ko not_active Withdrawn
- 1998-09-21 JP JP2000512808A patent/JP2001517651A/ja active Pending
- 1998-09-21 CA CA002303528A patent/CA2303528A1/en not_active Abandoned
- 1998-09-21 BR BR9812492-7A patent/BR9812492A/pt not_active IP Right Cessation
- 1998-09-21 AU AU92889/98A patent/AU9288998A/en not_active Abandoned
- 1998-09-21 DE DE69809782T patent/DE69809782T2/de not_active Expired - Fee Related
- 1998-09-21 EP EP98945708A patent/EP1017672B1/en not_active Expired - Lifetime
- 1998-09-21 TR TR2000/00785T patent/TR200000785T2/xx unknown
- 1998-09-21 SK SK360-2000A patent/SK3602000A3/sk unknown
- 1998-09-21 IL IL13499398A patent/IL134993A0/xx unknown
- 1998-09-21 CN CN98811336A patent/CN1279666A/zh active Pending
- 1998-09-21 WO PCT/SE1998/001686 patent/WO1999015498A1/en not_active Ceased
- 1998-09-21 EE EEP200000171A patent/EE200000171A/xx unknown
- 1998-09-21 US US09/171,779 patent/US6127414A/en not_active Expired - Fee Related
- 1998-09-21 PL PL98339617A patent/PL339617A1/xx unknown
- 1998-09-21 AT AT98945708T patent/ATE228500T1/de not_active IP Right Cessation
- 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
NO20001483L (no)	2000-05-23
AR017138A1 (es)	2001-08-22
JP2001517651A (ja)	2001-10-09
ZA988353B (en)	1999-03-23
US6127414A (en)	2000-10-03
AU9288998A (en)	1999-04-12
IS5410A (is)	2000-03-20
EE200000171A (et)	2001-04-16
WO1999015498A1 (en)	1999-04-01
ATE228500T1 (de)	2002-12-15
TR200000785T2 (tr)	2000-09-21
BR9812492A (pt)	2000-09-26
DE69809782D1 (de)	2003-01-09
SE9703414D0 (sv)	1997-09-23
EP1017672A1 (en)	2000-07-12
IL134993A0 (en)	2001-05-20
PL339617A1 (en)	2001-01-02
DE69809782T2 (de)	2003-07-17
EP1017672B1 (en)	2002-11-27
KR20010024220A (ko)	2001-03-26
NO20001483D0 (no)	2000-03-22
CA2303528A1 (en)	1999-04-01

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