CA2532925C - Azolo triazines et pyrimidines - Google Patents
Azolo triazines et pyrimidines Download PDFInfo
- Publication number
- CA2532925C CA2532925C CA002532925A CA2532925A CA2532925C CA 2532925 C CA2532925 C CA 2532925C CA 002532925 A CA002532925 A CA 002532925A CA 2532925 A CA2532925 A CA 2532925A CA 2532925 C CA2532925 C CA 2532925C
- Authority
- CA
- Canada
- Prior art keywords
- compound
- formula
- nhch
- alkyl
- ch2ome
- Prior art date
- 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.)
- Expired - Lifetime
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- 150000003230 pyrimidines Chemical class 0.000 title description 2
- SHCRKMNTWSCEBT-UHFFFAOYSA-N N1N=NC=C2N=CC=C21 Chemical class N1N=NC=C2N=CC=C21 SHCRKMNTWSCEBT-UHFFFAOYSA-N 0.000 title 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 22
- 208000019901 Anxiety disease Diseases 0.000 claims abstract description 12
- 230000036506 anxiety Effects 0.000 claims abstract description 12
- 150000001875 compounds Chemical class 0.000 claims description 494
- -1 2,3-dihydrobenzofuranyl Chemical group 0.000 claims description 150
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 92
- 125000001072 heteroaryl group Chemical group 0.000 claims description 89
- 239000000203 mixture Substances 0.000 claims description 88
- 150000003839 salts Chemical group 0.000 claims description 76
- 239000000651 prodrug Chemical group 0.000 claims description 73
- 229940002612 prodrug Drugs 0.000 claims description 73
- 125000003118 aryl group Chemical group 0.000 claims description 72
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 71
- 125000000623 heterocyclic group Chemical group 0.000 claims description 71
- 125000001424 substituent group Chemical group 0.000 claims description 66
- 125000000217 alkyl group Chemical group 0.000 claims description 64
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 60
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 58
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 46
- 229910052736 halogen Inorganic materials 0.000 claims description 46
- 150000002367 halogens Chemical class 0.000 claims description 46
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 39
- 125000004076 pyridyl group Chemical group 0.000 claims description 33
- 101100440695 Dictyostelium discoideum corB gene Proteins 0.000 claims description 21
- 125000001188 haloalkyl group Chemical group 0.000 claims description 21
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 18
- 125000003342 alkenyl group Chemical group 0.000 claims description 17
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 17
- 125000000304 alkynyl group Chemical group 0.000 claims description 17
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 16
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 15
- 208000035475 disorder Diseases 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 15
- 125000001624 naphthyl group Chemical group 0.000 claims description 15
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 14
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 14
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 13
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 12
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 12
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 12
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 12
- 125000001544 thienyl group Chemical group 0.000 claims description 11
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 10
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 10
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 10
- 125000002541 furyl group Chemical group 0.000 claims description 10
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 9
- 125000005865 C2-C10alkynyl group Chemical group 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- 125000004306 triazinyl group Chemical group 0.000 claims description 8
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 7
- 208000019022 Mood disease Diseases 0.000 claims description 7
- 208000024891 symptom Diseases 0.000 claims description 7
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 6
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 6
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 6
- 208000028173 post-traumatic stress disease Diseases 0.000 claims description 6
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 6
- 208000017194 Affective disease Diseases 0.000 claims description 5
- 208000024827 Alzheimer disease Diseases 0.000 claims description 5
- 206010048327 Supranuclear palsy Diseases 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 5
- 125000001041 indolyl group Chemical group 0.000 claims description 5
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 5
- 208000000103 Anorexia Nervosa Diseases 0.000 claims description 4
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 4
- 241000725303 Human immunodeficiency virus Species 0.000 claims description 4
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 4
- 208000029650 alcohol withdrawal Diseases 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 4
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 4
- 230000035558 fertility Effects 0.000 claims description 4
- 208000027866 inflammatory disease Diseases 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 3
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 3
- 125000000081 (C5-C8) cycloalkenyl group Chemical group 0.000 claims description 3
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 3
- 208000018460 Feeding disease Diseases 0.000 claims description 3
- 206010019233 Headaches Diseases 0.000 claims description 3
- 208000013016 Hypoglycemia Diseases 0.000 claims description 3
- 208000008589 Obesity Diseases 0.000 claims description 3
- 208000006011 Stroke Diseases 0.000 claims description 3
- 208000025865 Ulcer Diseases 0.000 claims description 3
- 230000003042 antagnostic effect Effects 0.000 claims description 3
- 206010013663 drug dependence Diseases 0.000 claims description 3
- 206010015037 epilepsy Diseases 0.000 claims description 3
- 231100000869 headache Toxicity 0.000 claims description 3
- 230000002008 hemorrhagic effect Effects 0.000 claims description 3
- 230000002218 hypoglycaemic effect Effects 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 230000008629 immune suppression Effects 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
- 208000014674 injury Diseases 0.000 claims description 3
- 235000020824 obesity Nutrition 0.000 claims description 3
- 125000002971 oxazolyl group Chemical group 0.000 claims description 3
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
- 210000000278 spinal cord Anatomy 0.000 claims description 3
- 208000011117 substance-related disease Diseases 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 230000008733 trauma Effects 0.000 claims description 3
- 231100000397 ulcer Toxicity 0.000 claims description 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 2
- 230000009385 viral infection Effects 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 13
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 2
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000002098 pyridazinyl group Chemical group 0.000 claims 1
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 abstract description 39
- 201000010099 disease Diseases 0.000 abstract description 7
- 108010022152 Corticotropin-Releasing Hormone Proteins 0.000 abstract description 6
- 208000012902 Nervous system disease Diseases 0.000 abstract description 6
- 208000025966 Neurological disease Diseases 0.000 abstract description 6
- 206010020751 Hypersensitivity Diseases 0.000 abstract description 5
- 230000002526 effect on cardiovascular system Effects 0.000 abstract description 5
- 208000026935 allergic disease Diseases 0.000 abstract description 4
- 239000005557 antagonist Substances 0.000 abstract description 4
- 230000000112 colonic effect Effects 0.000 abstract description 4
- 230000009610 hypersensitivity Effects 0.000 abstract description 4
- 230000001900 immune effect Effects 0.000 abstract description 4
- 102000012289 Corticotropin-Releasing Hormone Human genes 0.000 abstract 2
- AUHZEENZYGFFBQ-UHFFFAOYSA-N 1,3,5-Me3C6H3 Natural products CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 169
- 239000000460 chlorine Substances 0.000 description 107
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 85
- 239000003921 oil Substances 0.000 description 83
- 235000019198 oils Nutrition 0.000 description 83
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 81
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 75
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 72
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 71
- 101150041968 CDC13 gene Proteins 0.000 description 70
- 239000012442 inert solvent Substances 0.000 description 66
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 64
- 239000002585 base Substances 0.000 description 63
- 238000006243 chemical reaction Methods 0.000 description 63
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 61
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 60
- 238000004458 analytical method Methods 0.000 description 60
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 58
- 239000002904 solvent Substances 0.000 description 54
- 229910052783 alkali metal Inorganic materials 0.000 description 50
- 150000008064 anhydrides Chemical class 0.000 description 50
- 125000005843 halogen group Chemical group 0.000 description 50
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 47
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 239000002253 acid Substances 0.000 description 45
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 41
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 39
- 239000003795 chemical substances by application Substances 0.000 description 36
- 102100021752 Corticoliberin Human genes 0.000 description 34
- 150000001340 alkali metals Chemical class 0.000 description 33
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 33
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 30
- 238000000034 method Methods 0.000 description 29
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 28
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 27
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
- 150000007513 acids Chemical class 0.000 description 25
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 25
- 229940076134 benzene Drugs 0.000 description 25
- 150000004292 cyclic ethers Chemical class 0.000 description 25
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 24
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 22
- 150000003950 cyclic amides Chemical class 0.000 description 22
- 150000001983 dialkylethers Chemical class 0.000 description 22
- 235000019439 ethyl acetate Nutrition 0.000 description 22
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- 150000004820 halides Chemical class 0.000 description 21
- 239000000543 intermediate Substances 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 125000005233 alkylalcohol group Chemical group 0.000 description 18
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 17
- 239000000243 solution Substances 0.000 description 17
- 125000005270 trialkylamine group Chemical group 0.000 description 17
- 239000007787 solid Substances 0.000 description 16
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 15
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 15
- 150000008046 alkali metal hydrides Chemical class 0.000 description 15
- 150000001408 amides Chemical class 0.000 description 15
- 150000004982 aromatic amines Chemical class 0.000 description 15
- 239000003153 chemical reaction reagent Substances 0.000 description 15
- 229910000104 sodium hydride Inorganic materials 0.000 description 15
- 239000012312 sodium hydride Substances 0.000 description 15
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 14
- 150000001342 alkaline earth metals Chemical class 0.000 description 14
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 14
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 14
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 13
- 150000008041 alkali metal carbonates Chemical class 0.000 description 13
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
- 235000019341 magnesium sulphate Nutrition 0.000 description 13
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 13
- 239000012044 organic layer Substances 0.000 description 13
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 13
- QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical group C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 description 12
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 12
- 230000002140 halogenating effect Effects 0.000 description 11
- 238000003786 synthesis reaction Methods 0.000 description 11
- 229910014033 C-OH Inorganic materials 0.000 description 10
- 229910014570 C—OH Inorganic materials 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 10
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- 239000004480 active ingredient Substances 0.000 description 10
- 238000000262 chemical ionisation mass spectrometry Methods 0.000 description 10
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 10
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 10
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 9
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 9
- 150000001350 alkyl halides Chemical class 0.000 description 9
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 9
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- 229940086542 triethylamine Drugs 0.000 description 9
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 8
- 229960000583 acetic acid Drugs 0.000 description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- 229910052739 hydrogen Inorganic materials 0.000 description 8
- 238000001819 mass spectrum Methods 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 229910052708 sodium Inorganic materials 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 125000003545 alkoxy group Chemical group 0.000 description 7
- 239000002168 alkylating agent Substances 0.000 description 7
- 229940100198 alkylating agent Drugs 0.000 description 7
- 239000003054 catalyst Substances 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 229910052801 chlorine Inorganic materials 0.000 description 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- 229910052717 sulfur Inorganic materials 0.000 description 7
- 239000003638 chemical reducing agent Substances 0.000 description 6
- 239000002769 corticotropin releasing factor antagonist Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical class [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 239000007800 oxidant agent Substances 0.000 description 6
- 239000008188 pellet Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 5
- PEYVWBGHBCDXRT-UHFFFAOYSA-N N1=NNC2=CN=NC2=C1 Chemical class N1=NNC2=CN=NC2=C1 PEYVWBGHBCDXRT-UHFFFAOYSA-N 0.000 description 5
- 125000004414 alkyl thio group Chemical group 0.000 description 5
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 5
- 230000000949 anxiolytic effect Effects 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 230000003542 behavioural effect Effects 0.000 description 5
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 5
- 229940092714 benzenesulfonic acid Drugs 0.000 description 5
- 229940049706 benzodiazepine Drugs 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 229940098779 methanesulfonic acid Drugs 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 208000020016 psychiatric disease Diseases 0.000 description 5
- 238000012552 review Methods 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 125000006519 CCH3 Chemical group 0.000 description 4
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2329096P | 1996-07-24 | 1996-07-24 | |
| US68604796A | 1996-07-24 | 1996-07-24 | |
| US60/023,290 | 1996-07-24 | ||
| US60/686,047 | 1996-07-24 | ||
| US08/899,242 | 1997-07-23 | ||
| US08/899,242 US6124289A (en) | 1996-07-24 | 1997-07-23 | Azolo triazines and pyrimidines |
| CA002259583A CA2259583C (fr) | 1996-07-24 | 1997-07-23 | Azolo triazines et pyrimidines |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002259583A Division CA2259583C (fr) | 1996-07-24 | 1997-07-23 | Azolo triazines et pyrimidines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2532925A1 CA2532925A1 (fr) | 1998-01-29 |
| CA2532925C true CA2532925C (fr) | 2009-10-20 |
Family
ID=36141771
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002532925A Expired - Lifetime CA2532925C (fr) | 1996-07-24 | 1997-07-23 | Azolo triazines et pyrimidines |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2532925C (fr) |
-
1997
- 1997-07-23 CA CA002532925A patent/CA2532925C/fr not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| CA2532925A1 (fr) | 1998-01-29 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKEX | Expiry |
Effective date: 20170724 |