UA62972C2

UA62972C2 - Application of imidazopyrimidins and imidazopyridins for the treatment of neural disorders

Application of imidazopyrimidins and imidazopyridins for the treatment of neural disorders Download PDF

Info

Publication number: UA62972C2
Authority: UA; Ukraine
Prior art keywords: alkyl; cycloalkyl; substituted; case; haloalkyl
Prior art date: 1997-07-03

Application number

UA2000010041A

Other languages

English (en)

Ukrainian (uk)

Priority date

1997-07-03

Filing date

1998-02-07

Publication date

2004-01-15

1998-02-07 Application filed filed Critical

1998-07-02 Priority claimed from PCT/US1998/013913 external-priority patent/WO1999001454A1/en

2004-01-15 Publication of UA62972C2 publication Critical patent/UA62972C2/uk

Links

230000001537 neural effect Effects 0.000 title 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 28
208000035475 disorder Diseases 0.000 claims abstract description 25
208000019901 Anxiety disease Diseases 0.000 claims abstract description 9
230000002526 effect on cardiovascular system Effects 0.000 claims abstract description 8
206010048327 Supranuclear palsy Diseases 0.000 claims abstract description 6
208000028173 post-traumatic stress disease Diseases 0.000 claims abstract description 6
230000036506 anxiety Effects 0.000 claims abstract description 4
125000001424 substituent group Chemical group 0.000 claims description 368
125000000217 alkyl group Chemical group 0.000 claims description 315
-1 1-piperazinyl Chemical group 0.000 claims description 302
125000001072 heteroaryl group Chemical group 0.000 claims description 252
125000000753 cycloalkyl group Chemical group 0.000 claims description 250
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 196
150000001875 compounds Chemical class 0.000 claims description 194
229910052757 nitrogen Inorganic materials 0.000 claims description 179
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 179
125000003118 aryl group Chemical group 0.000 claims description 148
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 133
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 129
125000004432 carbon atom Chemical group C* 0.000 claims description 91
229910052739 hydrogen Inorganic materials 0.000 claims description 91
125000001188 haloalkyl group Chemical group 0.000 claims description 90
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 72
125000004433 nitrogen atom Chemical group N* 0.000 claims description 71
229910052740 iodine Inorganic materials 0.000 claims description 68
125000001544 thienyl group Chemical group 0.000 claims description 65
125000002541 furyl group Chemical group 0.000 claims description 63
125000000842 isoxazolyl group Chemical group 0.000 claims description 63
125000004076 pyridyl group Chemical group 0.000 claims description 60
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 57
125000000335 thiazolyl group Chemical group 0.000 claims description 57
125000003342 alkenyl group Chemical group 0.000 claims description 56
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 56
125000002971 oxazolyl group Chemical group 0.000 claims description 56
125000000304 alkynyl group Chemical group 0.000 claims description 55
125000002883 imidazolyl group Chemical group 0.000 claims description 49
125000003831 tetrazolyl group Chemical group 0.000 claims description 49
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 47
125000003226 pyrazolyl group Chemical group 0.000 claims description 42
125000001425 triazolyl group Chemical group 0.000 claims description 41
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 39
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 39
229910052796 boron Inorganic materials 0.000 claims description 36
229910052799 carbon Inorganic materials 0.000 claims description 34
238000000034 method Methods 0.000 claims description 34
125000001041 indolyl group Chemical group 0.000 claims description 33
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 32
125000000714 pyrimidinyl group Chemical group 0.000 claims description 32
125000000168 pyrrolyl group Chemical group 0.000 claims description 32
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 30
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 claims description 30
125000000623 heterocyclic group Chemical group 0.000 claims description 29
125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 29
125000003545 alkoxy group Chemical group 0.000 claims description 26
150000001721 carbon Chemical group 0.000 claims description 25
125000005322 morpholin-1-yl group Chemical group 0.000 claims description 25
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 24
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 24
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 24
229910052717 sulfur Inorganic materials 0.000 claims description 23
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 22
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 22
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 22
125000004306 triazinyl group Chemical group 0.000 claims description 22
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 21
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 21
LYKMMUBOEFYJQG-UHFFFAOYSA-N piperoxan Chemical compound C1OC2=CC=CC=C2OC1CN1CCCCC1 LYKMMUBOEFYJQG-UHFFFAOYSA-N 0.000 claims description 21
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 16
YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 15
125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 15
125000001624 naphthyl group Chemical group 0.000 claims description 15
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 14
150000003839 salts Chemical group 0.000 claims description 14
125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 13
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
229910052710 silicon Inorganic materials 0.000 claims description 13
125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 12
229920006395 saturated elastomer Polymers 0.000 claims description 12
210000005056 cell body Anatomy 0.000 claims description 11
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125000004434 sulfur atom Chemical group 0.000 claims description 9
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125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 7
208000024172 Cardiovascular disease Diseases 0.000 claims description 7
230000002829 reductive effect Effects 0.000 claims description 7
125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 6
XTFIVUDBNACUBN-UHFFFAOYSA-N 1,3,5-trinitro-1,3,5-triazinane Chemical compound [O-][N+](=O)N1CN([N+]([O-])=O)CN([N+]([O-])=O)C1 XTFIVUDBNACUBN-UHFFFAOYSA-N 0.000 claims description 6
GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 6
208000024827 Alzheimer disease Diseases 0.000 claims description 6
208000019022 Mood disease Diseases 0.000 claims description 6
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
125000004414 alkyl thio group Chemical group 0.000 claims description 6
229910052788 barium Inorganic materials 0.000 claims description 6
125000005843 halogen group Chemical group 0.000 claims description 6
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
208000017194 Affective disease Diseases 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 5
208000011580 syndromic disease Diseases 0.000 claims description 5
208000000103 Anorexia Nervosa Diseases 0.000 claims description 4
208000018522 Gastrointestinal disease Diseases 0.000 claims description 4
208000029650 alcohol withdrawal Diseases 0.000 claims description 4
206010013663 drug dependence Diseases 0.000 claims description 4
208000027866 inflammatory disease Diseases 0.000 claims description 4
208000002551 irritable bowel syndrome Diseases 0.000 claims description 4
208000011117 substance-related disease Diseases 0.000 claims description 4
208000031886 HIV Infections Diseases 0.000 claims description 3
206010019196 Head injury Diseases 0.000 claims description 3
206010019233 Headaches Diseases 0.000 claims description 3
241000725303 Human immunodeficiency virus Species 0.000 claims description 3
208000006011 Stroke Diseases 0.000 claims description 3
206010015037 epilepsy Diseases 0.000 claims description 3
230000035558 fertility Effects 0.000 claims description 3
125000004438 haloalkoxy group Chemical group 0.000 claims description 3
231100000869 headache Toxicity 0.000 claims description 3
230000002008 hemorrhagic effect Effects 0.000 claims description 3
125000004857 imidazopyridinyl group Chemical class N1C(=NC2=C1C=CC=N2)* 0.000 claims description 3
208000000509 infertility Diseases 0.000 claims description 3
230000036512 infertility Effects 0.000 claims description 3
231100000535 infertility Toxicity 0.000 claims description 3
208000020431 spinal cord injury Diseases 0.000 claims description 3
150000003852 triazoles Chemical class 0.000 claims description 3
208000008589 Obesity Diseases 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
150000005237 imidazopyrimidines Chemical class 0.000 claims description 2
235000020824 obesity Nutrition 0.000 claims description 2
125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 4
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 2
125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims 2
230000001079 digestive effect Effects 0.000 claims 1
230000036039 immunity Effects 0.000 claims 1
230000003533 narcotic effect Effects 0.000 claims 1
241000124008 Mammalia Species 0.000 abstract description 7
230000001900 immune effect Effects 0.000 abstract description 7
208000019454 Feeding and Eating disease Diseases 0.000 abstract description 6
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239000005557 antagonist Substances 0.000 abstract description 6
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208000026935 allergic disease Diseases 0.000 abstract description 2
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102000012289 Corticotropin-Releasing Hormone Human genes 0.000 abstract 2
108010022152 Corticotropin-Releasing Hormone Proteins 0.000 abstract 2
239000000055 Corticotropin-Releasing Hormone Substances 0.000 abstract 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 293
230000003595 spectral effect Effects 0.000 description 149
238000004949 mass spectrometry Methods 0.000 description 146
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 143
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 139
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125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 121
239000003921 oil Substances 0.000 description 113
235000019198 oils Nutrition 0.000 description 113
239000007858 starting material Substances 0.000 description 92
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239000000243 solution Substances 0.000 description 71
239000000203 mixture Substances 0.000 description 58
125000006526 (C1-C2) alkyl group Chemical group 0.000 description 55
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239000000047 product Substances 0.000 description 42
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239000003153 chemical reaction reagent Substances 0.000 description 36
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 35
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 34
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 33
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239000012267 brine Substances 0.000 description 32
230000015572 biosynthetic process Effects 0.000 description 29
239000007787 solid Substances 0.000 description 28
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238000004458 analytical method Methods 0.000 description 17
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238000002360 preparation method Methods 0.000 description 15
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QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
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235000011613 Pinus brutia Nutrition 0.000 description 13
241000018646 Pinus brutia Species 0.000 description 13
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WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
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235000019341 magnesium sulphate Nutrition 0.000 description 12
238000010992 reflux Methods 0.000 description 12
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