ZA200302970B - Pyrimidine derivatives and their use as neuropeptide Y receptor ligands. - Google Patents
Pyrimidine derivatives and their use as neuropeptide Y receptor ligands. Download PDFInfo
- Publication number
- ZA200302970B ZA200302970B ZA200302970A ZA200302970A ZA200302970B ZA 200302970 B ZA200302970 B ZA 200302970B ZA 200302970 A ZA200302970 A ZA 200302970A ZA 200302970 A ZA200302970 A ZA 200302970A ZA 200302970 B ZA200302970 B ZA 200302970B
- Authority
- ZA
- South Africa
- Prior art keywords
- methyl
- vinyl
- phenyl
- pyrimidine
- composition
- Prior art date
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- 239000003446 ligand Substances 0.000 title description 6
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 3
- 150000003230 pyrimidines Chemical class 0.000 title description 3
- 108050002826 Neuropeptide Y Receptor Proteins 0.000 title description 2
- 102000012301 Neuropeptide Y receptor Human genes 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 119
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 87
- -1 hydroxyalkoxyalkyl Chemical group 0.000 claims description 57
- 239000000203 mixture Substances 0.000 claims description 51
- 238000000034 method Methods 0.000 claims description 46
- 125000000217 alkyl group Chemical group 0.000 claims description 38
- 229920002554 vinyl polymer Polymers 0.000 claims description 35
- 238000002360 preparation method Methods 0.000 claims description 33
- 238000006243 chemical reaction Methods 0.000 claims description 30
- 238000011282 treatment Methods 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 26
- 239000000126 substance Substances 0.000 claims description 26
- 229940086609 Lipase inhibitor Drugs 0.000 claims description 23
- 125000003545 alkoxy group Chemical group 0.000 claims description 20
- 208000008589 Obesity Diseases 0.000 claims description 19
- 235000020824 obesity Nutrition 0.000 claims description 19
- 238000004519 manufacturing process Methods 0.000 claims description 17
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical group CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 claims description 15
- 229960001243 orlistat Drugs 0.000 claims description 15
- 238000011321 prophylaxis Methods 0.000 claims description 15
- 150000002148 esters Chemical class 0.000 claims description 13
- 208000030814 Eating disease Diseases 0.000 claims description 11
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 11
- 206010003246 arthritis Diseases 0.000 claims description 11
- 206010012601 diabetes mellitus Diseases 0.000 claims description 11
- 235000014632 disordered eating Nutrition 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- 101710151321 Melanostatin Proteins 0.000 claims description 8
- 102100028427 Pro-neuropeptide Y Human genes 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 125000001246 bromo group Chemical group Br* 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 230000009467 reduction Effects 0.000 claims description 7
- 238000002560 therapeutic procedure Methods 0.000 claims description 7
- TWQHYKCRVQJUKE-CMDGGOBGSA-N 2-[(e)-2-(3-methoxyphenyl)ethenyl]-4-methyl-6-pyrrolidin-1-ylpyrimidine Chemical compound COC1=CC=CC(\C=C\C=2N=C(C=C(C)N=2)N2CCCC2)=C1 TWQHYKCRVQJUKE-CMDGGOBGSA-N 0.000 claims description 6
- BFZWDYCUPULXDR-BQYQJAHWSA-N 3-[(e)-2-(4-methyl-6-pyrrolidin-1-ylpyrimidin-2-yl)ethenyl]benzonitrile Chemical compound N=1C(C)=CC(N2CCCC2)=NC=1\C=C\C1=CC=CC(C#N)=C1 BFZWDYCUPULXDR-BQYQJAHWSA-N 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 5
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 5
- 125000001072 heteroaryl group Chemical group 0.000 claims description 5
- YRLAKTSBTITNAC-FNORWQNLSA-N 2-[(e)-2-(3-chloro-4-fluorophenyl)ethenyl]-4-methyl-6-pyrrolidin-1-ylpyrimidine Chemical compound N=1C(C)=CC(N2CCCC2)=NC=1\C=C\C1=CC=C(F)C(Cl)=C1 YRLAKTSBTITNAC-FNORWQNLSA-N 0.000 claims description 4
- UQQDSRUWHUCSDM-BQYQJAHWSA-N 2-[(e)-2-(3-chlorophenyl)ethenyl]-4-methyl-6-pyrrolidin-1-ylpyrimidine Chemical compound N=1C(C)=CC(N2CCCC2)=NC=1\C=C\C1=CC=CC(Cl)=C1 UQQDSRUWHUCSDM-BQYQJAHWSA-N 0.000 claims description 4
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- FGGVKULRQBWAKD-FNORWQNLSA-N 2-[(e)-2-(3,4-difluorophenyl)ethenyl]-4-methyl-6-pyrrolidin-1-ylpyrimidine Chemical compound N=1C(C)=CC(N2CCCC2)=NC=1\C=C\C1=CC=C(F)C(F)=C1 FGGVKULRQBWAKD-FNORWQNLSA-N 0.000 claims description 3
- ZAXOKHLTHPETKE-VOTSOKGWSA-N 3-[(e)-2-[4-methyl-6-(3-methylazetidin-1-yl)pyrimidin-2-yl]ethenyl]benzonitrile Chemical compound C1C(C)CN1C1=CC(C)=NC(\C=C\C=2C=C(C=CC=2)C#N)=N1 ZAXOKHLTHPETKE-VOTSOKGWSA-N 0.000 claims description 3
- BILMBMKTDXSAQK-BQYQJAHWSA-N [3-[(e)-2-(4-methyl-6-pyrrolidin-1-ylpyrimidin-2-yl)ethenyl]phenyl]methanol Chemical compound N=1C(C)=CC(N2CCCC2)=NC=1\C=C\C1=CC=CC(CO)=C1 BILMBMKTDXSAQK-BQYQJAHWSA-N 0.000 claims description 3
- 239000013543 active substance Substances 0.000 claims description 3
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
- HLYUPLUTAUFOKU-SNAWJCMRSA-N n-methyl-2-[(e)-2-pyridin-4-ylethenyl]-6-pyrrolidin-1-ylpyrimidin-4-amine Chemical compound N=1C(NC)=CC(N2CCCC2)=NC=1\C=C\C1=CC=NC=C1 HLYUPLUTAUFOKU-SNAWJCMRSA-N 0.000 claims description 3
- YUYNAUBICMUPDF-FNORWQNLSA-N 2-[(e)-2-(2,4-dichlorophenyl)ethenyl]-4-methyl-6-pyrrolidin-1-ylpyrimidine Chemical compound N=1C(C)=CC(N2CCCC2)=NC=1\C=C\C1=CC=C(Cl)C=C1Cl YUYNAUBICMUPDF-FNORWQNLSA-N 0.000 claims description 2
- 125000002393 azetidinyl group Chemical group 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
- 239000007787 solid Substances 0.000 description 95
- 238000001819 mass spectrum Methods 0.000 description 94
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 66
- 239000007858 starting material Substances 0.000 description 26
- UQFHLJKWYIJISA-UHFFFAOYSA-N 2,6-dimethyl-1h-pyrimidin-4-one Chemical compound CC1=CC(O)=NC(C)=N1 UQFHLJKWYIJISA-UHFFFAOYSA-N 0.000 description 21
- PZASAAIJIFDWSB-CKPDSHCKSA-N 8-[(1S)-1-[8-(trifluoromethyl)-7-[4-(trifluoromethyl)cyclohexyl]oxynaphthalen-2-yl]ethyl]-8-azabicyclo[3.2.1]octane-3-carboxylic acid Chemical compound FC(F)(F)C=1C2=CC([C@@H](N3C4CCC3CC(C4)C(O)=O)C)=CC=C2C=CC=1OC1CCC(C(F)(F)F)CC1 PZASAAIJIFDWSB-CKPDSHCKSA-N 0.000 description 20
- 238000010438 heat treatment Methods 0.000 description 19
- 239000000460 chlorine Substances 0.000 description 17
- MWUBEFRDHNLYPF-AATRIKPKSA-N 3-[(e)-2-(4-chloro-6-methylpyrimidin-2-yl)ethenyl]benzonitrile Chemical compound CC1=CC(Cl)=NC(\C=C\C=2C=C(C=CC=2)C#N)=N1 MWUBEFRDHNLYPF-AATRIKPKSA-N 0.000 description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 13
- 239000000243 solution Substances 0.000 description 12
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
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- 125000000623 heterocyclic group Chemical group 0.000 description 7
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- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 6
- WSGRCEQBNLCXSZ-AATRIKPKSA-N 4-chloro-2-[(e)-2-(3-chlorophenyl)ethenyl]-6-methylpyrimidine Chemical compound CC1=CC(Cl)=NC(\C=C\C=2C=C(Cl)C=CC=2)=N1 WSGRCEQBNLCXSZ-AATRIKPKSA-N 0.000 description 6
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- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
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- 239000002671 adjuvant Substances 0.000 description 6
- 150000001299 aldehydes Chemical class 0.000 description 6
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 6
- 235000019439 ethyl acetate Nutrition 0.000 description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- MFYSUUPKMDJYPF-UHFFFAOYSA-N 2-[(4-methyl-2-nitrophenyl)diazenyl]-3-oxo-n-phenylbutanamide Chemical compound C=1C=CC=CC=1NC(=O)C(C(=O)C)N=NC1=CC=C(C)C=C1[N+]([O-])=O MFYSUUPKMDJYPF-UHFFFAOYSA-N 0.000 description 5
- IFLHSHGUNSEYTF-AATRIKPKSA-N 4-chloro-2-[(e)-2-(3-fluorophenyl)ethenyl]-6-methylpyrimidine Chemical compound CC1=CC(Cl)=NC(\C=C\C=2C=C(F)C=CC=2)=N1 IFLHSHGUNSEYTF-AATRIKPKSA-N 0.000 description 5
- RCIBPRJKTAOXCK-VMPITWQZSA-N 4-chloro-6-methyl-2-[(e)-2-(4-methylsulfanylphenyl)ethenyl]pyrimidine Chemical compound C1=CC(SC)=CC=C1\C=C\C1=NC(C)=CC(Cl)=N1 RCIBPRJKTAOXCK-VMPITWQZSA-N 0.000 description 5
- 101100460785 Mus musculus Npy5r gene Proteins 0.000 description 5
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- AEDLMXNXPIFFTO-UHFFFAOYSA-N 2-chloro-4-methyl-6-pyrrolidin-1-ylpyrimidine Chemical compound ClC1=NC(C)=CC(N2CCCC2)=N1 AEDLMXNXPIFFTO-UHFFFAOYSA-N 0.000 description 4
- NMTUHPSKJJYGML-UHFFFAOYSA-N 3-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=CC(C=O)=C1 NMTUHPSKJJYGML-UHFFFAOYSA-N 0.000 description 4
- GZWIPMXNMDBVPU-HWKANZROSA-N 4-chloro-2-[(e)-2-(3,4-difluorophenyl)ethenyl]-6-methylpyrimidine Chemical compound CC1=CC(Cl)=NC(\C=C\C=2C=C(F)C(F)=CC=2)=N1 GZWIPMXNMDBVPU-HWKANZROSA-N 0.000 description 4
- ZZDUDKNWIUKWPF-VOTSOKGWSA-N 4-chloro-2-[(e)-2-(3-methoxyphenyl)ethenyl]-6-methylpyrimidine Chemical compound COC1=CC=CC(\C=C\C=2N=C(Cl)C=C(C)N=2)=C1 ZZDUDKNWIUKWPF-VOTSOKGWSA-N 0.000 description 4
- BCPYEMNTAMPHEL-BQYQJAHWSA-N 4-methyl-2-[(e)-2-(3-nitrophenyl)ethenyl]-6-pyrrolidin-1-ylpyrimidine Chemical compound N=1C(C)=CC(N2CCCC2)=NC=1\C=C\C1=CC=CC([N+]([O-])=O)=C1 BCPYEMNTAMPHEL-BQYQJAHWSA-N 0.000 description 4
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- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
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- BEOOTMZSCBCOPI-CMDGGOBGSA-N methyl 3-[(e)-2-(4-methyl-6-pyrrolidin-1-ylpyrimidin-2-yl)ethenyl]benzoate Chemical compound COC(=O)C1=CC=CC(\C=C\C=2N=C(C=C(C)N=2)N2CCCC2)=C1 BEOOTMZSCBCOPI-CMDGGOBGSA-N 0.000 description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
- 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 description 4
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- SNAORKLLSUUVIU-HWKANZROSA-N 4-chloro-2-[(e)-2-(2,4-dichlorophenyl)ethenyl]-6-methylpyrimidine Chemical compound CC1=CC(Cl)=NC(\C=C\C=2C(=CC(Cl)=CC=2)Cl)=N1 SNAORKLLSUUVIU-HWKANZROSA-N 0.000 description 3
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- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 150000003003 phosphines Chemical class 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 229940081310 piperonal Drugs 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- JHHZLHWJQPUNKB-UHFFFAOYSA-N pyrrolidin-3-ol Chemical compound OC1CCNC1 JHHZLHWJQPUNKB-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000003153 stable transfection Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical group NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 230000035924 thermogenesis Effects 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/12—Antidiuretics, e.g. drugs for diabetes insipidus
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Diabetes (AREA)
- Animal Behavior & Ethology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Physical Education & Sports Medicine (AREA)
- Nutrition Science (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Child & Adolescent Psychology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00124610 | 2000-11-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200302970B true ZA200302970B (en) | 2004-07-15 |
Family
ID=8170342
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200302970A ZA200302970B (en) | 2000-11-10 | 2003-04-15 | Pyrimidine derivatives and their use as neuropeptide Y receptor ligands. |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US6657060B2 (enExample) |
| EP (1) | EP1335906B1 (enExample) |
| JP (1) | JP2004524279A (enExample) |
| KR (1) | KR100611853B1 (enExample) |
| CN (1) | CN1473156A (enExample) |
| AR (1) | AR034700A1 (enExample) |
| AT (1) | ATE340784T1 (enExample) |
| AU (2) | AU2790502A (enExample) |
| BR (1) | BR0115045A (enExample) |
| CA (1) | CA2427350A1 (enExample) |
| DE (1) | DE60123458T2 (enExample) |
| DK (1) | DK1335906T3 (enExample) |
| ES (1) | ES2271100T3 (enExample) |
| MX (1) | MXPA03004136A (enExample) |
| PA (1) | PA8531701A1 (enExample) |
| PE (1) | PE20020603A1 (enExample) |
| PT (1) | PT1335906E (enExample) |
| UY (1) | UY27018A1 (enExample) |
| WO (1) | WO2002038551A1 (enExample) |
| ZA (1) | ZA200302970B (enExample) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3813152B2 (ja) | 2002-03-12 | 2006-08-23 | メルク エンド カムパニー インコーポレーテッド | 置換アミド類 |
| EP1484971B1 (en) * | 2002-03-15 | 2007-07-04 | Ciba SC Holding AG | Use of 4-aminopyrimidines for the antimicrobial treatment of surfaces |
| GB0428328D0 (en) | 2004-12-24 | 2005-02-02 | Astrazeneca Uk Ltd | Chemical process |
| US7768604B2 (en) * | 2005-09-20 | 2010-08-03 | Au Optronics Corporation | Transflective liquid crystal display with partially shifted reflectivity curve |
| KR20080083188A (ko) * | 2006-01-11 | 2008-09-16 | 아스트라제네카 아베 | 모르폴리노 피리미딘 유도체 및 요법에서의 그 유도체의용도 |
| GB0616747D0 (en) * | 2006-08-24 | 2006-10-04 | Astrazeneca Ab | Novel compounds |
| EP2057129A1 (en) * | 2006-08-24 | 2009-05-13 | AstraZeneca AB | Morpholino pyrimidine derivatives useful in the treatment of proliferative disorders |
| AU2007287428B2 (en) * | 2006-08-24 | 2011-08-11 | Astrazeneca Ab | Morpholino pyrimidine derivatives useful in the treatment of proliferative disorders |
| CA2692720A1 (en) | 2007-07-09 | 2009-01-15 | Astrazeneca Ab | Morpholino pyrimidine derivatives used in diseases linked to mtor kinase and/or pi3k |
| EP2178866A2 (en) * | 2007-07-09 | 2010-04-28 | AstraZeneca AB | Trisubstituted pyrimidine derivatives for the treatment of proliferative diseases |
| EA201000092A1 (ru) * | 2007-07-09 | 2010-06-30 | Астразенека Аб | Тризамещенные пиримидиновые производные для лечения пролиферативных заболеваний |
| AU2008273892A1 (en) * | 2007-07-09 | 2009-01-15 | Astrazeneca Ab | Trisubstituted pyrimidine derivatives for the treatment of proliferative diseases |
| WO2010030027A1 (en) | 2008-09-10 | 2010-03-18 | Mitsubishi Tanabe Pharma Corporation | Aromatic nitrogen-containing 6-membered ring compounds and their use |
| US20110053923A1 (en) * | 2008-12-22 | 2011-03-03 | Astrazeneca | Chemical compounds 610 |
| JP2011201873A (ja) * | 2010-03-03 | 2011-10-13 | Mitsubishi Tanabe Pharma Corp | 三置換ピリミジン化合物及びそのｐｄｅ１０阻害薬としての使用 |
| EP2544690A4 (en) * | 2010-03-11 | 2013-07-10 | Targacept Inc | ARYLVINYLAZACYCLOALCANE COMPOUNDS FOR CONSTIPATION |
| SA111320519B1 (ar) | 2010-06-11 | 2014-07-02 | Astrazeneca Ab | مركبات بيريميدينيل للاستخدام كمثبطات atr |
| WO2015039292A1 (zh) * | 2013-09-18 | 2015-03-26 | 华安医学股份有限公司 | 一种活化ampk的化合物及其用途 |
| CN112375042A (zh) * | 2020-10-27 | 2021-02-19 | 安徽医科大学 | 三甲氧基苯乙烯基六元环类和吡唑并嘧啶类化合物、制剂及其制备与应用 |
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|---|---|---|---|---|
| JPH0720467B2 (ja) * | 1988-06-15 | 1995-03-08 | 松下電器産業株式会社 | 超音波診断装置 |
| JPH024345A (ja) * | 1988-06-15 | 1990-01-09 | Matsushita Electric Ind Co Ltd | 超音波変換装置 |
| JP2789134B2 (ja) | 1992-09-28 | 1998-08-20 | ファイザー・インク． | 糖尿病の合併症を制御する置換ピリミジン類 |
| US6011039A (en) | 1996-03-21 | 2000-01-04 | Banyu Pharmaceutical Co., Ltd. | Aminopyridine derivatives |
| WO1998040356A1 (en) * | 1997-03-12 | 1998-09-17 | Banyu Pharmaceutical Co., Ltd. | Drugs containing aminopyridine derivatives as the active ingredient |
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2001
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- 2001-11-06 EP EP01989438A patent/EP1335906B1/en not_active Expired - Lifetime
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2003
- 2003-04-15 ZA ZA200302970A patent/ZA200302970B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DE60123458T2 (de) | 2007-08-02 |
| DK1335906T3 (da) | 2007-02-05 |
| BR0115045A (pt) | 2004-02-03 |
| KR100611853B1 (ko) | 2006-08-11 |
| ATE340784T1 (de) | 2006-10-15 |
| WO2002038551A1 (en) | 2002-05-16 |
| DE60123458D1 (de) | 2006-11-09 |
| UY27018A1 (es) | 2002-06-20 |
| CA2427350A1 (en) | 2002-05-16 |
| PT1335906E (pt) | 2007-01-31 |
| US6657060B2 (en) | 2003-12-02 |
| PE20020603A1 (es) | 2002-07-20 |
| JP2004524279A (ja) | 2004-08-12 |
| MXPA03004136A (es) | 2003-08-19 |
| US20020086858A1 (en) | 2002-07-04 |
| AR034700A1 (es) | 2004-03-17 |
| AU2790502A (en) | 2002-05-21 |
| AU2002227905B2 (en) | 2006-10-05 |
| EP1335906A1 (en) | 2003-08-20 |
| KR20040004432A (ko) | 2004-01-13 |
| CN1473156A (zh) | 2004-02-04 |
| ES2271100T3 (es) | 2007-04-16 |
| EP1335906B1 (en) | 2006-09-27 |
| PA8531701A1 (es) | 2003-06-30 |
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