KR20110098730A - 유기 화합물 - Google Patents

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Publication number

KR20110098730A

KR20110098730A KR1020117013107A KR20117013107A KR20110098730A KR 20110098730 A KR20110098730 A KR 20110098730A KR 1020117013107 A KR1020117013107 A KR 1020117013107A KR 20117013107 A KR20117013107 A KR 20117013107A KR 20110098730 A KR20110098730 A KR 20110098730A

Authority

KR

South Korea

Prior art keywords

alkyl

methyl

halo

formula

optionally substituted

Prior art date

2008-12-06

Legal status (The legal status 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 status listed.)

Withdrawn

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• 150000002894 organic compounds Chemical class 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 230
• 238000000034 method Methods 0.000 claims abstract description 101
• 239000003814 drug Substances 0.000 claims abstract description 22
• 229940079593 drug Drugs 0.000 claims abstract description 14
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
• QGKGASXQTBQINX-UHFFFAOYSA-N 3,4-dihydro-1h-pyrimidin-2-one Chemical compound O=C1NCC=CN1 QGKGASXQTBQINX-UHFFFAOYSA-N 0.000 claims abstract description 4
• -1 1-hydroxypropan-2-yl Chemical group 0.000 claims description 437
• 125000000217 alkyl group Chemical group 0.000 claims description 370
• 125000003118 aryl group Chemical group 0.000 claims description 141
• 125000005843 halogen group Chemical group 0.000 claims description 120
• 125000001072 heteroaryl group Chemical group 0.000 claims description 112
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 89
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 83
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 82
• 229910052799 carbon Inorganic materials 0.000 claims description 64
• 150000003839 salts Chemical group 0.000 claims description 62
• 125000001153 fluoro group Chemical group F* 0.000 claims description 58
• 229910052739 hydrogen Inorganic materials 0.000 claims description 58
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 58
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 53
• RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 claims description 50
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 49
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 45
• 229910052757 nitrogen Inorganic materials 0.000 claims description 45
• 125000004076 pyridyl group Chemical group 0.000 claims description 43
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 42
• 229910052736 halogen Inorganic materials 0.000 claims description 40
• 238000011282 treatment Methods 0.000 claims description 39
• 125000003545 alkoxy group Chemical group 0.000 claims description 38
• 150000002367 halogens Chemical class 0.000 claims description 38
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 36
• 201000010099 disease Diseases 0.000 claims description 36
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 36
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 34
• 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 33
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 33
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 32
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 32
• 229910052801 chlorine Inorganic materials 0.000 claims description 31
• 229910052731 fluorine Inorganic materials 0.000 claims description 31
• 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 claims description 31
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 30
• 125000001425 triazolyl group Chemical group 0.000 claims description 28
• 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 27
• 125000002947 alkylene group Chemical group 0.000 claims description 27
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 27
• 239000000203 mixture Substances 0.000 claims description 27
• 125000001113 thiadiazolyl group Chemical group 0.000 claims description 26
• 125000003386 piperidinyl group Chemical group 0.000 claims description 25
• 201000000980 schizophrenia Diseases 0.000 claims description 25
• 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 claims description 24
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 24
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 24
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 23
• 125000002720 diazolyl group Chemical group 0.000 claims description 23
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 23
• 239000000186 progesterone Substances 0.000 claims description 23
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 22
• 125000004512 1,2,3-thiadiazol-4-yl group Chemical group S1N=NC(=C1)* 0.000 claims description 22
• 229960003387 progesterone Drugs 0.000 claims description 22
• 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 22
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 22
• 125000004574 piperidin-2-yl group Chemical group N1C(CCCC1)* 0.000 claims description 21
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 20
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 20
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 19
• 125000005129 aryl carbonyl group Chemical group 0.000 claims description 19
• 125000000732 arylene group Chemical group 0.000 claims description 19
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 19
• 125000001188 haloalkyl group Chemical group 0.000 claims description 19
• 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 19
• 206010026749 Mania Diseases 0.000 claims description 18
• 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 claims description 17
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
• 125000005549 heteroarylene group Chemical group 0.000 claims description 17
• 125000005842 heteroatom Chemical group 0.000 claims description 17
• 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 17
• 125000001424 substituent group Chemical group 0.000 claims description 17
• 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 16
• RGTBLCLLSZPOKR-UHFFFAOYSA-N 5-methyl-1,2,4-oxadiazole Chemical compound CC1=NC=NO1 RGTBLCLLSZPOKR-UHFFFAOYSA-N 0.000 claims description 16
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 16
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 16
• 201000003631 narcolepsy Diseases 0.000 claims description 15
• 102000004076 Dopamine D1 Receptors Human genes 0.000 claims description 14
• 108090000511 Dopamine D1 Receptors Proteins 0.000 claims description 14
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 14
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 14
• 230000019491 signal transduction Effects 0.000 claims description 14
• 230000011664 signaling Effects 0.000 claims description 14
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 13
• 208000018737 Parkinson disease Diseases 0.000 claims description 13
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 13
• 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 claims description 13
• 239000001257 hydrogen Substances 0.000 claims description 13
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 13
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 13
• 230000002829 reductive effect Effects 0.000 claims description 13
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 12
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 12
• 208000010412 Glaucoma Diseases 0.000 claims description 12
• 208000030886 Traumatic Brain injury Diseases 0.000 claims description 12
• 229940011871 estrogen Drugs 0.000 claims description 12
• 239000000262 estrogen Substances 0.000 claims description 12
• 230000001965 increasing effect Effects 0.000 claims description 12
• 125000004289 pyrazol-3-yl group Chemical group [H]N1N=C(*)C([H])=C1[H] 0.000 claims description 12
• 230000009529 traumatic brain injury Effects 0.000 claims description 12
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 11
• 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 11
• 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 11
• 208000020925 Bipolar disease Diseases 0.000 claims description 11
• 206010057671 Female sexual dysfunction Diseases 0.000 claims description 11
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 11
• 125000001715 oxadiazolyl group Chemical group 0.000 claims description 11
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 10
• 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
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• 208000003532 hypothyroidism Diseases 0.000 claims description 10
• 230000002989 hypothyroidism Effects 0.000 claims description 10
• 238000004519 manufacturing process Methods 0.000 claims description 10
• 125000004274 oxetan-2-yl group Chemical group [H]C1([H])OC([H])(*)C1([H])[H] 0.000 claims description 10
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• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
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• 125000004429 atom Chemical group 0.000 claims description 9
• 239000003085 diluting agent Substances 0.000 claims description 9
• 125000002883 imidazolyl group Chemical group 0.000 claims description 9
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• 229910052794 bromium Inorganic materials 0.000 claims description 8
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• 230000004406 elevated intraocular pressure Effects 0.000 claims description 8
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• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 7
• 125000006591 (C2-C6) alkynylene group Chemical group 0.000 claims description 7
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• 235000010290 biphenyl Nutrition 0.000 claims description 7
• 125000002757 morpholinyl group Chemical group 0.000 claims description 7
• 208000002815 pulmonary hypertension Diseases 0.000 claims description 7
• 125000005551 pyridylene group Chemical group 0.000 claims description 7
• 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 7
• OXHNLMTVIGZXSG-UHFFFAOYSA-N 1-Methylpyrrole Chemical compound CN1C=CC=C1 OXHNLMTVIGZXSG-UHFFFAOYSA-N 0.000 claims description 6
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• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 6
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