IL126895A - Antagonists to the D4 receptor of benzoxazinone dopamine derivatives - Google Patents

Antagonists to the D4 receptor of benzoxazinone dopamine derivatives

Info

Publication number: IL126895A
Authority: IL; Israel
Prior art keywords: ylmethyl; benzo; oxazin; piperazin; phenyl
Prior art date: 1996-05-29

Application number

IL12689597A

Other languages

English (en)

Hebrew (he)

Other versions

IL126895A0 (en

Original Assignee

Warner Lambert Co

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.)

1996-05-29

Filing date

1997-05-20

Publication date

2001-06-14

1997-05-20 Application filed by Warner Lambert Co filed Critical Warner Lambert Co

1999-09-22 Publication of IL126895A0 publication Critical patent/IL126895A0/xx

2001-06-14 Publication of IL126895A publication Critical patent/IL126895A/en

Links

HQQTZCPKNZVLFF-UHFFFAOYSA-N 4h-1,2-benzoxazin-3-one Chemical compound C1=CC=C2ONC(=O)CC2=C1 HQQTZCPKNZVLFF-UHFFFAOYSA-N 0.000 title claims description 7
229940124243 Dopamine D4 receptor antagonist Drugs 0.000 title description 4
150000001875 compounds Chemical class 0.000 claims abstract description 69
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 33
239000001257 hydrogen Substances 0.000 claims abstract description 16
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 15
150000003839 salts Chemical class 0.000 claims abstract description 14
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 13
229910052736 halogen Inorganic materials 0.000 claims abstract description 7
150000002367 halogens Chemical class 0.000 claims abstract description 7
125000001624 naphthyl group Chemical group 0.000 claims abstract description 7
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims abstract description 6
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 5
229930192474 thiophene Chemical group 0.000 claims abstract description 3
125000002883 imidazolyl group Chemical group 0.000 claims abstract 2
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims abstract 2
125000004076 pyridyl group Chemical group 0.000 claims abstract 2
125000000714 pyrimidinyl group Chemical group 0.000 claims abstract 2
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims abstract 2
125000000335 thiazolyl group Chemical group 0.000 claims abstract 2
-1 d-C6 alkyl Chemical group 0.000 claims description 39
239000000203 mixture Substances 0.000 claims description 24
238000000034 method Methods 0.000 claims description 23
QRCGFTXRXYMJOS-UHFFFAOYSA-N 4h-1,4-benzoxazin-3-one Chemical compound C1=CC=C2NC(=O)COC2=C1 QRCGFTXRXYMJOS-UHFFFAOYSA-N 0.000 claims description 12
125000000217 alkyl group Chemical group 0.000 claims description 12
208000028017 Psychotic disease Diseases 0.000 claims description 11
201000000980 schizophrenia Diseases 0.000 claims description 11
XEKAWZARUWARND-UHFFFAOYSA-N 6h-oxazin-3-one Chemical compound O=C1NOCC=C1 XEKAWZARUWARND-UHFFFAOYSA-N 0.000 claims description 8
241001465754 Metazoa Species 0.000 claims description 8
239000000546 pharmaceutical excipient Substances 0.000 claims description 8
239000003085 diluting agent Substances 0.000 claims description 5
125000003545 alkoxy group Chemical group 0.000 claims description 4
125000003944 tolyl group Chemical group 0.000 claims description 4
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
XISPDFMAOWZEQG-UHFFFAOYSA-N 4h-1,4-oxazin-3-one Chemical compound O=C1COC=CN1 XISPDFMAOWZEQG-UHFFFAOYSA-N 0.000 claims description 3
FBXGQDUVJBKEAJ-UHFFFAOYSA-N 4h-oxazin-3-one Chemical compound O=C1CC=CON1 FBXGQDUVJBKEAJ-UHFFFAOYSA-N 0.000 claims description 3
RKZVRIHTYWJVDD-UHFFFAOYSA-N 6-[[4-(4-methylphenyl)piperazin-1-yl]methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=CC(C)=CC=C1N1CCN(CC=2C=C3NC(=O)COC3=CC=2)CC1 RKZVRIHTYWJVDD-UHFFFAOYSA-N 0.000 claims description 3
LILUJJCOIBEHSU-UHFFFAOYSA-N 7-[[4-(4-methylphenyl)piperazin-1-yl]methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=CC(C)=CC=C1N1CCN(CC=2C=C3OCC(=O)NC3=CC=2)CC1 LILUJJCOIBEHSU-UHFFFAOYSA-N 0.000 claims description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
125000000565 sulfonamide group Chemical group 0.000 claims description 3
NRQPGKHEEBJOCT-UHFFFAOYSA-N 2-[4-[(3-oxo-4h-1,4-benzoxazin-6-yl)methyl]piperazin-1-yl]benzonitrile Chemical compound C1=C2NC(=O)COC2=CC=C1CN(CC1)CCN1C1=CC=CC=C1C#N NRQPGKHEEBJOCT-UHFFFAOYSA-N 0.000 claims description 2
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
NFRIERLNKMVOKN-UHFFFAOYSA-N 6-[(4-phenylpiperazin-1-yl)methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)COC2=CC=C1CN(CC1)CCN1C1=CC=CC=C1 NFRIERLNKMVOKN-UHFFFAOYSA-N 0.000 claims description 2
URZGAIFKYPHOKG-UHFFFAOYSA-N 6-[[4-(1,3-benzothiazol-2-yl)piperazin-1-yl]methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=CC=C2SC(N3CCN(CC3)CC3=CC=C4OCC(NC4=C3)=O)=NC2=C1 URZGAIFKYPHOKG-UHFFFAOYSA-N 0.000 claims description 2
VVOSVZFUEQAUTE-UHFFFAOYSA-N 6-[[4-(2-chloro-4-methylphenyl)piperazin-1-yl]methyl]-4h-1,4-benzoxazin-3-one Chemical compound ClC1=CC(C)=CC=C1N1CCN(CC=2C=C3NC(=O)COC3=CC=2)CC1 VVOSVZFUEQAUTE-UHFFFAOYSA-N 0.000 claims description 2
HYPGXKWWXBYXDB-UHFFFAOYSA-N 6-[[4-(4,5-dimethyl-1,3-thiazol-2-yl)piperazin-1-yl]methyl]-4h-1,4-benzoxazin-3-one Chemical compound S1C(C)=C(C)N=C1N1CCN(CC=2C=C3NC(=O)COC3=CC=2)CC1 HYPGXKWWXBYXDB-UHFFFAOYSA-N 0.000 claims description 2
MOWGNBXIJRPPMR-UHFFFAOYSA-N 6-[[4-(4-methoxyphenyl)piperazin-1-yl]methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=CC(OC)=CC=C1N1CCN(CC=2C=C3NC(=O)COC3=CC=2)CC1 MOWGNBXIJRPPMR-UHFFFAOYSA-N 0.000 claims description 2
AONOATOEMKXSHK-UHFFFAOYSA-N 6-[[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]methyl]-4h-1,4-benzoxazin-3-one Chemical compound FC(F)(F)C1=CC=CC(N2CCN(CC=3C=C4NC(=O)COC4=CC=3)CC2)=C1 AONOATOEMKXSHK-UHFFFAOYSA-N 0.000 claims description 2
DDNPFSNFHUDIIU-UHFFFAOYSA-N 6-[[4-[4-(trifluoromethyl)phenyl]piperazin-1-yl]methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=CC(C(F)(F)F)=CC=C1N1CCN(CC=2C=C3NC(=O)COC3=CC=2)CC1 DDNPFSNFHUDIIU-UHFFFAOYSA-N 0.000 claims description 2
PLLZRTCZPQQFEO-UHFFFAOYSA-N 7-[(4-phenylpiperidin-1-yl)methyl]-4h-1,4-benzoxazin-3-one Chemical compound C=1C=C2NC(=O)COC2=CC=1CN(CC1)CCC1C1=CC=CC=C1 PLLZRTCZPQQFEO-UHFFFAOYSA-N 0.000 claims description 2
VYJSEMNZGPEKAE-UHFFFAOYSA-N 7-[[4-(3,4-dimethylphenyl)piperazin-1-yl]methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=C(C)C(C)=CC=C1N1CCN(CC=2C=C3OCC(=O)NC3=CC=2)CC1 VYJSEMNZGPEKAE-UHFFFAOYSA-N 0.000 claims description 2
MEPWUVRGPZZAFY-UHFFFAOYSA-N 7-[[4-(3,4-dimethylphenyl)piperidin-1-yl]methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=C(C)C(C)=CC=C1C1CCN(CC=2C=C3OCC(=O)NC3=CC=2)CC1 MEPWUVRGPZZAFY-UHFFFAOYSA-N 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
241000282472 Canis lupus familiaris Species 0.000 claims 6
241000282326 Felis catus Species 0.000 claims 6
239000003937 drug carrier Substances 0.000 claims 3
XJCFFIUVQKFBHI-UHFFFAOYSA-N 6-[[4-(4-chlorophenyl)piperazin-1-yl]methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=CC(Cl)=CC=C1N1CCN(CC=2C=C3NC(=O)COC3=CC=2)CC1 XJCFFIUVQKFBHI-UHFFFAOYSA-N 0.000 claims 2
125000005059 halophenyl group Chemical group 0.000 claims 2
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims 1
GPGUDXIKRCJQNT-UHFFFAOYSA-N 4-[4-[(3-oxo-4h-1,4-benzoxazin-6-yl)methyl]piperazin-1-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1N1CCN(CC=2C=C3NC(=O)COC3=CC=2)CC1 GPGUDXIKRCJQNT-UHFFFAOYSA-N 0.000 claims 1
IUPDOAUDWJKQKD-UHFFFAOYSA-N 6-[(4-naphthalen-2-ylpiperazin-1-yl)methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=CC=CC2=CC(N3CCN(CC3)CC3=CC=C4OCC(NC4=C3)=O)=CC=C21 IUPDOAUDWJKQKD-UHFFFAOYSA-N 0.000 claims 1
RCWYEZYTOVCNOJ-UHFFFAOYSA-N 6-[[4-(3,4-dimethylphenyl)piperazin-1-yl]methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=C(C)C(C)=CC=C1N1CCN(CC=2C=C3NC(=O)COC3=CC=2)CC1 RCWYEZYTOVCNOJ-UHFFFAOYSA-N 0.000 claims 1
FDYRPFOMRUNDJD-UHFFFAOYSA-N 6-[[4-(3,5-dimethylphenyl)piperazin-1-yl]methyl]-4h-1,4-benzoxazin-3-one Chemical compound CC1=CC(C)=CC(N2CCN(CC=3C=C4NC(=O)COC4=CC=3)CC2)=C1 FDYRPFOMRUNDJD-UHFFFAOYSA-N 0.000 claims 1
CZSXHWSVDAMAMN-UHFFFAOYSA-N 6-[[4-(3-chlorophenyl)piperazin-1-yl]methyl]-4h-1,4-benzoxazin-3-one Chemical compound ClC1=CC=CC(N2CCN(CC=3C=C4NC(=O)COC4=CC=3)CC2)=C1 CZSXHWSVDAMAMN-UHFFFAOYSA-N 0.000 claims 1
PHOCTWVGFOPTKO-UHFFFAOYSA-N 7-[[4-(5-methylpyridin-2-yl)piperazin-1-yl]methyl]-4h-1,4-benzoxazin-3-one Chemical compound N1=CC(C)=CC=C1N1CCN(CC=2C=C3OCC(=O)NC3=CC=2)CC1 PHOCTWVGFOPTKO-UHFFFAOYSA-N 0.000 claims 1
125000001475 halogen functional group Chemical group 0.000 claims 1
125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
239000008194 pharmaceutical composition Substances 0.000 claims 1
125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract description 2
125000004093 cyano group Chemical group *C#N 0.000 abstract description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 3
229910052757 nitrogen Inorganic materials 0.000 description 19
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 12
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
150000001408 amides Chemical class 0.000 description 8
150000002148 esters Chemical class 0.000 description 8
102000005962 receptors Human genes 0.000 description 8
108020003175 receptors Proteins 0.000 description 8
239000002904 solvent Substances 0.000 description 8
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125000001072 heteroaryl group Chemical group 0.000 description 7
229940002612 prodrug Drugs 0.000 description 7
239000000651 prodrug Substances 0.000 description 7
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
238000004458 analytical method Methods 0.000 description 6
230000027455 binding Effects 0.000 description 6
229960003638 dopamine Drugs 0.000 description 6
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125000005842 heteroatom Chemical group 0.000 description 3
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125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
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239000000787 lecithin Substances 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
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238000012423 maintenance Methods 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
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238000002156 mixing Methods 0.000 description 1
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239000007922 nasal spray Substances 0.000 description 1
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210000001577 neostriatum Anatomy 0.000 description 1
210000005036 nerve Anatomy 0.000 description 1
239000002858 neurotransmitter agent Substances 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
231100000344 non-irritating Toxicity 0.000 description 1
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230000009871 nonspecific binding Effects 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
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150000007524 organic acids Chemical class 0.000 description 1
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239000012074 organic phase Substances 0.000 description 1
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239000000312 peanut oil Substances 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
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229910052698 phosphorus Inorganic materials 0.000 description 1
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239000013612 plasmid Substances 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
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238000000159 protein binding assay Methods 0.000 description 1
238000000746 purification Methods 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000001453 quaternary ammonium group Chemical group 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
238000001525 receptor binding assay Methods 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
210000000664 rectum Anatomy 0.000 description 1
230000000698 schizophrenic effect Effects 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
230000008054 signal transmission Effects 0.000 description 1
RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
229950001675 spiperone Drugs 0.000 description 1
108010092215 spiroperidol receptor Proteins 0.000 description 1
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235000019698 starch Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000011550 stock solution Substances 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
229940124530 sulfonamide Drugs 0.000 description 1
150000003456 sulfonamides Chemical class 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000012360 testing method Methods 0.000 description 1
CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
229940070710 valerate Drugs 0.000 description 1
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
238000009736 wetting Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
- C07D265/36—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings condensed with one six-membered ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Public Health (AREA)
Biomedical Technology (AREA)
Veterinary Medicine (AREA)
Neurology (AREA)
Neurosurgery (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Psychiatry (AREA)
Hospice & Palliative Care (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Plural Heterocyclic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

IL12689597A 1996-05-29 1997-05-20 Antagonists to the D4 receptor of benzoxazinone dopamine derivatives IL126895A (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US1838396P	1996-05-29	1996-05-29
US4020897P	1997-03-06	1997-03-06
PCT/US1997/008524 WO1997045419A1 (en)	1996-05-29	1997-05-20	Benzoxazinone dopamine d4 receptor antagonists

Publications (2)

Publication Number	Publication Date
IL126895A0 IL126895A0 (en)	1999-09-22
IL126895A true IL126895A (en)	2001-06-14

Family

ID=26691052

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL12689597A IL126895A (en)	1996-05-29	1997-05-20	Antagonists to the D4 receptor of benzoxazinone dopamine derivatives

Country Status (36)

Country	Link
EP (1)	EP0906294B1 (cs)
JP (1)	JP2000511534A (cs)
KR (1)	KR20000016151A (cs)
CN (1)	CN1074764C (cs)
AR (1)	AR008372A1 (cs)
AT (1)	ATE231846T1 (cs)
AU (1)	AU731104B2 (cs)
BG (1)	BG64049B1 (cs)
BR (1)	BR9709630A (cs)
CA (1)	CA2253406A1 (cs)
CO (1)	CO4940505A1 (cs)
CZ (1)	CZ384698A3 (cs)
DE (1)	DE69718786T2 (cs)
DK (1)	DK0906294T3 (cs)
EA (1)	EA001486B1 (cs)
EE (1)	EE03686B1 (cs)
ES (1)	ES2191180T3 (cs)
GE (1)	GEP20012389B (cs)
HN (1)	HN1997000075A (cs)
HR (1)	HRP970301B1 (cs)
HU (1)	HUP9903758A3 (cs)
ID (1)	ID17266A (cs)
IL (1)	IL126895A (cs)
NO (1)	NO312296B1 (cs)
NZ (1)	NZ332737A (cs)
PA (1)	PA8431101A1 (cs)
PE (1)	PE69398A1 (cs)
PL (1)	PL330195A1 (cs)
PT (1)	PT906294E (cs)
RO (1)	RO120845B1 (cs)
SI (1)	SI0906294T1 (cs)
SK (1)	SK282703B6 (cs)
SV (1)	SV1997000047A (cs)
TW (1)	TW542833B (cs)
UY (1)	UY24569A1 (cs)
WO (1)	WO1997045419A1 (cs)

Families Citing this family (19)

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Publication number	Priority date	Publication date	Assignee	Title
US6177422B1 (en)	1996-05-29	2001-01-23	Warner-Lambert Company	Benzoxazinone dopamine D4 receptor antagonists
GB9801392D0 (en) *	1998-01-22	1998-03-18	Smithkline Beecham Plc	Novel compounds
US6177566B1 (en)	1998-06-30	2001-01-23	Neurogen Corporation	6-(4-arylalkylpiperazin-1-yl) benzodioxane and 6-(4-arylalkylpiperazin-1-yl) chromane derivatives: dopamine receptor subtype specific ligands
CA2336089A1 (en) *	1998-06-30	2000-01-06	Neurogen Corporation	6-(4-arylalkylpiperazin-1-yl)benzodioxane and 6-(4-arylalkylpiperazin-1-yl)chromane derivatives: dopamine receptor subtype specific ligands
US6291463B1 (en)	1998-06-30	2001-09-18	Neurogen Corporation	1-(Benzothiazol-2-yl)-4-(1-phenylmethyl) piperazines: dopamine receptor subtype specific ligands
WO2000000482A1 (en) *	1998-06-30	2000-01-06	Neurogen Corporation	1-(benzothiazol-2-yl)-4-(1-phenylmethyl)piperazines: dopamine receptor subtype specific ligands
DE19844291A1 (de)	1998-09-18	2000-03-23	Schering Ag	Benzoxazin- und Benzothiazin-Derivate und deren Verwendung in Arzneimitteln
GB9912411D0 (en) *	1999-05-28	1999-07-28	Pfizer Ltd	Compounds useful in therapy
US6939871B2 (en) *	2000-10-26	2005-09-06	Smithkline Beecham P.L.C.	Benzoxazinone derivatives, their preparation and use
GB0203804D0 (en)	2002-02-18	2002-04-03	Glaxo Group Ltd	Compounds
GB0209244D0 (en) *	2002-04-23	2002-06-05	Glaxo Group Ltd	Compounds
GB0227240D0 (en) *	2002-11-21	2002-12-31	Glaxo Group Ltd	Compounds
ES2232292B1 (es) *	2003-07-30	2006-11-01	Laboratorios Del Dr. Esteve, S.A.	Compuestos sulfonamidicos derivados de benzoxazinona, su preparacion y uso como medicamentos.
CN100455573C (zh) *	2005-11-11	2009-01-28	华东理工大学	一种制备1,4-苯并噁唑嗪-3-酮化合物的微波合成方法
KR200482995Y1 (ko)	2015-08-19	2017-03-23	이현진	물 공급부를 구비하는 얼음 트레이
CN116601148A (zh) *	2021-04-23	2023-08-15	上海翰森生物医药科技有限公司	杂环类衍生物抑制剂、其制备方法和应用
US20250214980A1 (en)	2022-03-14	2025-07-03	Slap Pharmaceuticals Llc	Multicyclic compounds
EP4514795A4 (en) *	2022-04-28	2025-12-31	Ningbo Newbay Tech Development Co Ltd	COMPOUNDS USED AS PARP1 INHIBITORS
CN117903159A (zh) *	2022-12-30	2024-04-19	成都硕德药业有限公司	一种内酰胺类衍生物、其制备方法及用途

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US4613598A (en) *	1984-03-13	1986-09-23	Mitsubishi Chemical Industries Limited	Piperazine derivatives and their acid addition salts
EP0233728A1 (en) *	1986-02-11	1987-08-26	Takeda Chemical Industries, Ltd.	1,4-Benzoxazine derivatives their production and use
ATE171162T1 (de) *	1992-08-06	1998-10-15	Smithkline Beecham Plc	5-(2-oxyphenyl)-pyrrol-derivate als dopamin-d3- rezeptor-antagonisten

1997
- 1997-05-20 SI SI9730482T patent/SI0906294T1/xx unknown
- 1997-05-20 CZ CZ983846A patent/CZ384698A3/cs unknown
- 1997-05-20 SK SK1627-98A patent/SK282703B6/sk unknown
- 1997-05-20 ES ES97925651T patent/ES2191180T3/es not_active Expired - Lifetime
- 1997-05-20 EE EE9800417A patent/EE03686B1/xx not_active IP Right Cessation
- 1997-05-20 BR BR9709630A patent/BR9709630A/pt not_active Application Discontinuation
- 1997-05-20 DE DE69718786T patent/DE69718786T2/de not_active Expired - Fee Related
- 1997-05-20 AT AT97925651T patent/ATE231846T1/de not_active IP Right Cessation
- 1997-05-20 JP JP09542647A patent/JP2000511534A/ja not_active Ceased
- 1997-05-20 GE GEAP19974623A patent/GEP20012389B/en unknown
- 1997-05-20 NZ NZ332737A patent/NZ332737A/en unknown
- 1997-05-20 EP EP97925651A patent/EP0906294B1/en not_active Expired - Lifetime
- 1997-05-20 KR KR1019980709719A patent/KR20000016151A/ko not_active Ceased
- 1997-05-20 HU HU9903758A patent/HUP9903758A3/hu unknown
- 1997-05-20 PL PL97330195A patent/PL330195A1/xx unknown
- 1997-05-20 IL IL12689597A patent/IL126895A/en not_active IP Right Cessation
- 1997-05-20 EA EA199800987A patent/EA001486B1/ru not_active IP Right Cessation
- 1997-05-20 WO PCT/US1997/008524 patent/WO1997045419A1/en not_active Ceased
- 1997-05-20 PT PT97925651T patent/PT906294E/pt unknown
- 1997-05-20 DK DK97925651T patent/DK0906294T3/da active
- 1997-05-20 CA CA002253406A patent/CA2253406A1/en not_active Abandoned
- 1997-05-20 RO RO98-01622A patent/RO120845B1/ro unknown
- 1997-05-20 CN CN97195015A patent/CN1074764C/zh not_active Expired - Fee Related
- 1997-05-20 AU AU30727/97A patent/AU731104B2/en not_active Ceased
- 1997-05-22 HN HN1997000075A patent/HN1997000075A/es unknown
- 1997-05-27 AR ARP970102249A patent/AR008372A1/es unknown
- 1997-05-28 PE PE1997000432A patent/PE69398A1/es not_active Application Discontinuation
- 1997-05-28 SV SV1997000047A patent/SV1997000047A/es not_active Application Discontinuation
- 1997-05-28 ID IDP971778A patent/ID17266A/id unknown
- 1997-05-28 PA PA19978431101A patent/PA8431101A1/es unknown
- 1997-05-28 CO CO97029474A patent/CO4940505A1/es unknown
- 1997-05-28 TW TW086107221A patent/TW542833B/zh active
- 1997-05-28 UY UY24569A patent/UY24569A1/es not_active Application Discontinuation
- 1997-05-29 HR HR970301A patent/HRP970301B1/xx not_active IP Right Cessation
1998
- 1998-11-26 BG BG102959A patent/BG64049B1/bg unknown
- 1998-11-27 NO NO19985531A patent/NO312296B1/no not_active IP Right Cessation

Also Published As

Publication number	Publication date
KR20000016151A (ko)	2000-03-25
PA8431101A1 (es)	2001-12-14
PE69398A1 (es)	1998-12-02
SK162798A3 (en)	1999-06-11
DE69718786T2 (de)	2003-10-23
IL126895A0 (en)	1999-09-22
HK1019737A1 (en)	2000-02-25
DK0906294T3 (da)	2003-05-05
ID17266A (id)	1997-12-18
SV1997000047A (es)	1998-08-13
HRP970301A2 (en)	1998-04-30
TW542833B (en)	2003-07-21
BR9709630A (pt)	1999-08-10
JP2000511534A (ja)	2000-09-05
HN1997000075A (es)	1997-07-30
DE69718786D1 (de)	2003-03-06
AU3072797A (en)	1998-01-05
HRP970301B1 (en)	2002-08-31
GEP20012389B (en)	2001-03-25
EA199800987A1 (ru)	1999-06-24
CO4940505A1 (es)	2000-07-24
ATE231846T1 (de)	2003-02-15
NO312296B1 (no)	2002-04-22
WO1997045419A1 (en)	1997-12-04
NZ332737A (en)	2000-06-23
NO985531D0 (no)	1998-11-27
NO985531L (no)	1998-11-27
CA2253406A1 (en)	1997-12-04
AU731104B2 (en)	2001-03-22
SI0906294T1 (en)	2003-04-30
PT906294E (pt)	2003-06-30
AR008372A1 (es)	2000-01-19
EP0906294A1 (en)	1999-04-07
PL330195A1 (en)	1999-04-26
BG64049B1 (bg)	2003-11-28
EP0906294B1 (en)	2003-01-29
HUP9903758A3 (en)	2000-07-28
HUP9903758A2 (hu)	2000-06-28
UY24569A1 (es)	2001-08-27
BG102959A (en)	1999-08-31
EE03686B1 (et)	2002-04-15
EA001486B1 (ru)	2001-04-23
CN1074764C (zh)	2001-11-14
CZ384698A3 (cs)	1999-03-17
ES2191180T3 (es)	2003-09-01
EE9800417A (et)	1999-06-15
RO120845B1 (ro)	2006-08-30
SK282703B6 (sk)	2002-11-06
CN1219930A (zh)	1999-06-16

Legal Events

Date	Code	Title
2002-02-10	KB	Patent renewed
2003-07-06	KB	Patent renewed
2008-01-22	MM9K	Patent not in force due to non-payment of renewal fees

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