TW200524942A - New compounds - Google Patents
New compounds Download PDFInfo
- Publication number
- TW200524942A TW200524942A TW093120518A TW93120518A TW200524942A TW 200524942 A TW200524942 A TW 200524942A TW 093120518 A TW093120518 A TW 093120518A TW 93120518 A TW93120518 A TW 93120518A TW 200524942 A TW200524942 A TW 200524942A
- Authority
- TW
- Taiwan
- Prior art keywords
- spiro
- azabicyclo
- oct
- pyridyl
- furan
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 244
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 44
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- 201000010099 disease Diseases 0.000 claims abstract description 25
- 239000003814 drug Substances 0.000 claims abstract description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 16
- 238000004519 manufacturing process Methods 0.000 claims abstract description 12
- 239000000126 substance Substances 0.000 claims abstract description 9
- 125000003003 spiro group Chemical group 0.000 claims description 333
- -1 3-pyranyl Chemical group 0.000 claims description 161
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 51
- 229910052739 hydrogen Inorganic materials 0.000 claims description 46
- 239000001257 hydrogen Substances 0.000 claims description 46
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 43
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 41
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 36
- 229960000649 oxyphenbutazone Drugs 0.000 claims description 32
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 31
- 150000002576 ketones Chemical class 0.000 claims description 28
- 125000002971 oxazolyl group Chemical group 0.000 claims description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 125000004122 cyclic group Chemical group 0.000 claims description 23
- 238000012360 testing method Methods 0.000 claims description 23
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 21
- 238000011282 treatment Methods 0.000 claims description 20
- 208000035475 disorder Diseases 0.000 claims description 19
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- 239000007789 gas Substances 0.000 claims description 18
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 18
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 17
- 125000001424 substituent group Chemical group 0.000 claims description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 16
- 150000002431 hydrogen Chemical class 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 125000004497 pyrazol-5-yl group Chemical group N1N=CC=C1* 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 13
- 125000004429 atom Chemical group 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 13
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 12
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 12
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 12
- 230000002265 prevention Effects 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- 241000282414 Homo sapiens Species 0.000 claims description 10
- 229960002715 nicotine Drugs 0.000 claims description 10
- 108010009685 Cholinergic Receptors Proteins 0.000 claims description 9
- 102000034337 acetylcholine receptors Human genes 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- 239000002689 soil Substances 0.000 claims description 9
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 8
- 206010026749 Mania Diseases 0.000 claims description 8
- 208000002193 Pain Diseases 0.000 claims description 8
- 125000002619 bicyclic group Chemical group 0.000 claims description 8
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 7
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 230000007246 mechanism Effects 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 7
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 7
- 230000036407 pain Effects 0.000 claims description 7
- 230000003389 potentiating effect Effects 0.000 claims description 7
- 208000020016 psychiatric disease Diseases 0.000 claims description 7
- 102000005962 receptors Human genes 0.000 claims description 7
- 108020003175 receptors Proteins 0.000 claims description 7
- 201000000980 schizophrenia Diseases 0.000 claims description 7
- 125000004434 sulfur atom Chemical group 0.000 claims description 7
- 208000011580 syndromic disease Diseases 0.000 claims description 7
- 208000019901 Anxiety disease Diseases 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- 206010023799 Large intestinal ulcer Diseases 0.000 claims description 6
- 208000012902 Nervous system disease Diseases 0.000 claims description 6
- 230000036506 anxiety Effects 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 210000000349 chromosome Anatomy 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 6
- 230000001771 impaired effect Effects 0.000 claims description 6
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims description 6
- 125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 claims description 6
- 125000003145 oxazol-4-yl group Chemical group O1C=NC(=C1)* 0.000 claims description 6
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 claims description 6
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 125000006017 1-propenyl group Chemical group 0.000 claims description 5
- 208000024827 Alzheimer disease Diseases 0.000 claims description 5
- 208000020925 Bipolar disease Diseases 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- 208000019888 Circadian rhythm sleep disease Diseases 0.000 claims description 5
- 208000001456 Jet Lag Syndrome Diseases 0.000 claims description 5
- 206010057852 Nicotine dependence Diseases 0.000 claims description 5
- 208000018737 Parkinson disease Diseases 0.000 claims description 5
- 208000025569 Tobacco Use disease Diseases 0.000 claims description 5
- 208000028683 bipolar I disease Diseases 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 208000033915 jet lag type circadian rhythm sleep disease Diseases 0.000 claims description 5
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 claims description 5
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 claims description 5
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 5
- 229920002554 vinyl polymer Polymers 0.000 claims description 5
- 241000282412 Homo Species 0.000 claims description 4
- 208000023105 Huntington disease Diseases 0.000 claims description 4
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 4
- 125000005605 benzo group Chemical group 0.000 claims description 4
- 230000027455 binding Effects 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 4
- RMBPEFMHABBEKP-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2C3=C[CH]C=CC3=CC2=C1 RMBPEFMHABBEKP-UHFFFAOYSA-N 0.000 claims description 4
- 125000006038 hexenyl group Chemical group 0.000 claims description 4
- 125000001041 indolyl group Chemical group 0.000 claims description 4
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N o-biphenylenemethane Natural products C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- 238000000926 separation method Methods 0.000 claims description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 3
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 3
- 208000025966 Neurological disease Diseases 0.000 claims description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 230000003042 antagnostic effect Effects 0.000 claims description 3
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 3
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 3
- 210000000941 bile Anatomy 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000006165 cyclic alkyl group Chemical group 0.000 claims description 3
- 230000003412 degenerative effect Effects 0.000 claims description 3
- 230000003340 mental effect Effects 0.000 claims description 3
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 3
- 230000004770 neurodegeneration Effects 0.000 claims description 3
- 230000002028 premature Effects 0.000 claims description 3
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 3
- 150000003254 radicals Chemical class 0.000 claims description 3
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 claims description 2
- 125000001541 3-thienyl group Chemical group S1C([H])=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
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 claims description 2
- MNOULQLXILYKNV-UHFFFAOYSA-N 5-[4-(trifluoromethyl)phenyl]-1h-pyrazole Chemical group C1=CC(C(F)(F)F)=CC=C1C1=CC=NN1 MNOULQLXILYKNV-UHFFFAOYSA-N 0.000 claims description 2
- AVRWEULSKHQETA-UHFFFAOYSA-N Thiophene-2 Chemical compound S1C=2CCCCCC=2C(C(=O)OC)=C1NC(=O)C1=C(F)C(F)=C(F)C(F)=C1F AVRWEULSKHQETA-UHFFFAOYSA-N 0.000 claims description 2
- 150000001345 alkine derivatives Chemical class 0.000 claims description 2
- 230000009286 beneficial effect Effects 0.000 claims description 2
- 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 2
- 230000004064 dysfunction Effects 0.000 claims description 2
- 150000007857 hydrazones Chemical class 0.000 claims description 2
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 230000036961 partial effect Effects 0.000 claims description 2
- DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 claims description 2
- 230000001737 promoting effect Effects 0.000 claims description 2
- 230000001105 regulatory effect Effects 0.000 claims description 2
- 239000000779 smoke Substances 0.000 claims description 2
- 125000004304 oxazol-5-yl group Chemical group O1C=NC=C1* 0.000 claims 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
- UDHZFLBMZZVHRA-UHFFFAOYSA-N 2-(furan-2-yl)furan Chemical compound C1=COC(C=2OC=CC=2)=C1 UDHZFLBMZZVHRA-UHFFFAOYSA-N 0.000 claims 1
- UXGVMFHEKMGWMA-UHFFFAOYSA-N 2-benzofuran Chemical compound C1=CC=CC2=COC=C21 UXGVMFHEKMGWMA-UHFFFAOYSA-N 0.000 claims 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 claims 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims 1
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 claims 1
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims 1
- 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims 1
- RECARWSUVKIFDV-UHFFFAOYSA-N C1=CC=CC2=C(C3=CC=CC=C3C(=C12)C=1C2=CC=CC=C2C=C2C=CC=CC=12)C1=CC=C2C=3C=CC(=CC=3C(C2=C1)(C)C)C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C34 Chemical compound C1=CC=CC2=C(C3=CC=CC=C3C(=C12)C=1C2=CC=CC=C2C=C2C=CC=CC=12)C1=CC=C2C=3C=CC(=CC=3C(C2=C1)(C)C)C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C34 RECARWSUVKIFDV-UHFFFAOYSA-N 0.000 claims 1
- 206010012289 Dementia Diseases 0.000 claims 1
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- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims 1
- 230000004913 activation Effects 0.000 claims 1
- 125000000129 anionic group Chemical group 0.000 claims 1
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 claims 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims 1
- 230000002759 chromosomal effect Effects 0.000 claims 1
- UBKHHFOBCZFFKL-UHFFFAOYSA-N cyclopenta[c]pyran Chemical compound C1=COC=C2C=CC=C21 UBKHHFOBCZFFKL-UHFFFAOYSA-N 0.000 claims 1
- 125000006001 difluoroethyl group Chemical group 0.000 claims 1
- 206010016256 fatigue Diseases 0.000 claims 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims 1
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- 239000010977 jade Substances 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 239000004005 microsphere Substances 0.000 claims 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 239000002547 new drug Substances 0.000 claims 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
- 125000005499 phosphonyl group Chemical group 0.000 claims 1
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- 238000000034 method Methods 0.000 abstract description 89
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- 239000007787 solid Substances 0.000 description 67
- 238000006243 chemical reaction Methods 0.000 description 58
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 34
- 239000002585 base Substances 0.000 description 29
- 239000002904 solvent Substances 0.000 description 28
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- 238000002360 preparation method Methods 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical group [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
- 239000003054 catalyst Substances 0.000 description 18
- 238000003818 flash chromatography Methods 0.000 description 18
- 239000003446 ligand Substances 0.000 description 18
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- 125000002524 organometallic group Chemical group 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 239000012442 inert solvent Substances 0.000 description 12
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 11
- 229910000027 potassium carbonate Inorganic materials 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 235000019441 ethanol Nutrition 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
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- WTFFOOAJSDVASL-UHFFFAOYSA-N tributyl(pyrimidin-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=NC=CC=N1 WTFFOOAJSDVASL-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- BPLUKJNHPBNVQL-UHFFFAOYSA-N triphenylarsine Chemical compound C1=CC=CC=C1[As](C=1C=CC=CC=1)C1=CC=CC=C1 BPLUKJNHPBNVQL-UHFFFAOYSA-N 0.000 description 1
- 125000005580 triphenylene group Chemical group 0.000 description 1
- 238000005533 tritiation Methods 0.000 description 1
- 150000003649 tritium Chemical class 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000001755 vocal effect Effects 0.000 description 1
- 210000004916 vomit Anatomy 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000004383 yellowing Methods 0.000 description 1
- NAWDYIZEMPQZHO-UHFFFAOYSA-N ytterbium Chemical compound [Yb] NAWDYIZEMPQZHO-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/20—Spiro-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P25/24—Antidepressants
-
- 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
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Pain & Pain Management (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Anesthesiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US48552303P | 2003-07-08 | 2003-07-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW200524942A true TW200524942A (en) | 2005-08-01 |
Family
ID=34062082
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW093120518A TW200524942A (en) | 2003-07-08 | 2004-07-08 | New compounds |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US7514567B2 (https=) |
| EP (1) | EP1654264A1 (https=) |
| JP (1) | JP2007516200A (https=) |
| KR (1) | KR20060057569A (https=) |
| CN (1) | CN1829721A (https=) |
| AR (1) | AR045040A1 (https=) |
| AU (1) | AU2004255920B2 (https=) |
| BR (1) | BRPI0412382A (https=) |
| CA (1) | CA2531510A1 (https=) |
| IL (1) | IL172762A0 (https=) |
| MX (1) | MXPA06000231A (https=) |
| NO (1) | NO20060612L (https=) |
| NZ (1) | NZ545132A (https=) |
| SA (1) | SA04250212B1 (https=) |
| TW (1) | TW200524942A (https=) |
| WO (1) | WO2005005435A1 (https=) |
| ZA (1) | ZA200600154B (https=) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20070090922A (ko) * | 2004-12-15 | 2007-09-06 | 아스트라제네카 아베 | 니코틴성 아세틸콜린 수용체 리간드 |
| US7649007B2 (en) | 2006-08-15 | 2010-01-19 | Wyeth Llc | Oxazolidine derivatives as PR modulators |
| TW200815428A (en) | 2006-08-15 | 2008-04-01 | Wyeth Corp | Oxazolidone derivatives as PR modulators |
| US7618989B2 (en) | 2006-08-15 | 2009-11-17 | Wyeth | Tricyclic oxazolidone derivatives useful as PR modulators |
| WO2008021309A1 (en) | 2006-08-15 | 2008-02-21 | Wyeth | Imidazolidin-2-one derivatives useful as pr modulators |
| WO2008021337A1 (en) * | 2006-08-15 | 2008-02-21 | Wyeth | Oxazinan-2-one derivatives useful as pr modulators |
| JP2010505844A (ja) * | 2006-10-03 | 2010-02-25 | ガレオン・フアーマシユーチカルズ・インコーポレーテツド | Ｓ−ニトロソチオール化合物および関連誘導体 |
| SA08290475B1 (ar) | 2007-08-02 | 2013-06-22 | Targacept Inc | (2s، 3r)-n-(2-((3-بيردينيل)ميثيل)-1-آزا بيسيكلو[2، 2، 2]أوكت-3-يل)بنزو فيوران-2-كربوكساميد، وصور أملاحه الجديدة وطرق استخدامه |
| US7863291B2 (en) * | 2008-04-23 | 2011-01-04 | Bristol-Myers Squibb Company | Quinuclidine compounds as alpha-7 nicotinic acetylcholine receptor ligands |
| US8309577B2 (en) | 2008-04-23 | 2012-11-13 | Bristol-Myers Squibb Company | Quinuclidine compounds as α-7 nicotinic acetylcholine receptor ligands |
| EP2586311B1 (de) * | 2008-07-17 | 2016-12-14 | Bayer CropScience AG | Heterocyclische Verbindungen als Schädlingsbekämpfungsmittel |
| TW201031664A (en) | 2009-01-26 | 2010-09-01 | Targacept Inc | Preparation and therapeutic applications of (2S,3R)-N-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)-3,5-difluorobenzamide |
| UA107791C2 (en) * | 2009-05-05 | 2015-02-25 | Dow Agrosciences Llc | Pesticidal compositions |
| US8759550B2 (en) | 2009-08-27 | 2014-06-24 | Yeda Research And Development Co. Ltd. | Oligo- and polyfurans, preparation and uses thereof |
| US8278320B2 (en) | 2009-10-28 | 2012-10-02 | Bristol-Myers Squibb Company | Azabicyclo[2.2.1]heptane compounds as alpha-7 nicotinic acetylcholine receptor ligands |
| US8507516B2 (en) | 2009-10-28 | 2013-08-13 | Bristol-Myers Squibb Company | Azabicyclic compounds as alpha-7 nicotinic acetylcholine receptor ligands |
| EP2558458B1 (de) | 2010-04-16 | 2017-09-06 | Bayer Intellectual Property GmbH | Neue heterocyclische verbindungen als schädlingsbekämpfungsmittel |
| CN103025744A (zh) | 2010-04-30 | 2013-04-03 | 百时美施贵宝公司 | 作为α-7烟碱乙酰胆碱受体配体前药的氮杂二环胺N-氧化物化合物 |
| EP2595983A1 (en) | 2010-07-22 | 2013-05-29 | Novartis AG | 2,3,5-trisubstituted thiophene compounds and uses thereof |
| WO2012052412A1 (de) | 2010-10-22 | 2012-04-26 | Bayer Cropscience Ag | Neue heterocylische verbindungen als schädlingsbekämpfungsmittel |
| KR20140138293A (ko) | 2012-03-16 | 2014-12-03 | 액시킨 파마수티컬스 인코포레이티드 | 3,5-다이아미노피라졸 키나아제 억제제 |
| CN104884449A (zh) | 2012-10-31 | 2015-09-02 | 拜尔农作物科学股份公司 | 作为害虫防治剂的新的杂环化合物 |
| NZ631142A (en) | 2013-09-18 | 2016-03-31 | Axikin Pharmaceuticals Inc | Pharmaceutically acceptable salts of 3,5-diaminopyrazole kinase inhibitors |
| US9546163B2 (en) | 2014-12-23 | 2017-01-17 | Axikin Pharmaceuticals, Inc. | 3,5-diaminopyrazole kinase inhibitors |
| EA202092441A1 (ru) | 2016-06-07 | 2021-05-21 | Джакобио Фармасьютикалс Ко., Лтд. | Новые гетероциклические производные, применимые в качестве ингибиторов shp2 |
| KR20240026521A (ko) | 2017-03-23 | 2024-02-28 | 자코바이오 파마슈티칼스 컴퍼니 리미티드 | Shp2 억제제로서 유용한 신규한 헤테로환형 유도체 |
| CN112839935A (zh) | 2018-09-26 | 2021-05-25 | 北京加科思新药研发有限公司 | 可用作shp2抑制剂的新型杂环衍生物 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4855290A (en) * | 1985-05-10 | 1989-08-08 | State Of Israel, Represented By Prime Minister's Office, Israel Institute For Biological Research | Derivatives of quinuclidine |
| JP3708962B2 (ja) * | 1994-08-24 | 2005-10-19 | アストラゼネカ・アクチエボラーグ | 治療に有用なスピロ−アザ二環式化合物 |
| WO2001066546A1 (en) * | 2000-03-09 | 2001-09-13 | Mitsubishi Pharma Corporation | Spiro compounds, process for preparing the same and use thereof as drugs |
-
2004
- 2004-07-06 CN CNA2004800218491A patent/CN1829721A/zh active Pending
- 2004-07-06 KR KR1020067000400A patent/KR20060057569A/ko not_active Ceased
- 2004-07-06 EP EP04743249A patent/EP1654264A1/en not_active Withdrawn
- 2004-07-06 AU AU2004255920A patent/AU2004255920B2/en not_active Ceased
- 2004-07-06 JP JP2006518343A patent/JP2007516200A/ja active Pending
- 2004-07-06 WO PCT/GB2004/002904 patent/WO2005005435A1/en not_active Ceased
- 2004-07-06 NZ NZ545132A patent/NZ545132A/en unknown
- 2004-07-06 BR BRPI0412382-4A patent/BRPI0412382A/pt not_active IP Right Cessation
- 2004-07-06 CA CA002531510A patent/CA2531510A1/en not_active Abandoned
- 2004-07-06 MX MXPA06000231A patent/MXPA06000231A/es active IP Right Grant
- 2004-07-06 US US10/563,271 patent/US7514567B2/en not_active Expired - Fee Related
- 2004-07-07 AR ARP040102394A patent/AR045040A1/es not_active Application Discontinuation
- 2004-07-08 TW TW093120518A patent/TW200524942A/zh unknown
- 2004-07-11 SA SA04250212A patent/SA04250212B1/ar unknown
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2005
- 2005-12-22 IL IL172762A patent/IL172762A0/en unknown
-
2006
- 2006-01-06 ZA ZA200600154A patent/ZA200600154B/en unknown
- 2006-02-08 NO NO20060612A patent/NO20060612L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| BRPI0412382A (pt) | 2006-09-19 |
| AU2004255920A1 (en) | 2005-01-20 |
| JP2007516200A (ja) | 2007-06-21 |
| CN1829721A (zh) | 2006-09-06 |
| KR20060057569A (ko) | 2006-05-26 |
| AU2004255920B2 (en) | 2008-05-15 |
| IL172762A0 (en) | 2006-04-10 |
| WO2005005435A1 (en) | 2005-01-20 |
| NO20060612L (no) | 2006-04-06 |
| AR045040A1 (es) | 2005-10-12 |
| ZA200600154B (en) | 2007-04-25 |
| MXPA06000231A (es) | 2006-04-11 |
| SA04250212B1 (ar) | 2009-08-11 |
| NZ545132A (en) | 2009-07-31 |
| CA2531510A1 (en) | 2005-01-20 |
| US20060154945A1 (en) | 2006-07-13 |
| US7514567B2 (en) | 2009-04-07 |
| EP1654264A1 (en) | 2006-05-10 |
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