HRP970413A2 - Azolo triazines and pyrimidines - Google Patents
Azolo triazines and pyrimidinesInfo
- Publication number
- HRP970413A2 HRP970413A2 HRP970413A HRP970413A2 HR P970413 A2 HRP970413 A2 HR P970413A2 HR P970413 A HRP970413 A HR P970413A HR P970413 A2 HRP970413 A2 HR P970413A2
- Authority
- HR
- Croatia
- Prior art keywords
- compound
- formula
- stereoisomeric forms
- alkyl
- cycloalkyl
- Prior art date
Links
- SHCRKMNTWSCEBT-UHFFFAOYSA-N N1N=NC=C2N=CC=C21 Chemical class N1N=NC=C2N=CC=C21 SHCRKMNTWSCEBT-UHFFFAOYSA-N 0.000 title 1
- 150000003230 pyrimidines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 634
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 146
- 125000001072 heteroaryl group Chemical group 0.000 claims description 144
- -1 2,3-dihydrobenzofuranyl Chemical group 0.000 claims description 132
- 239000000203 mixture Substances 0.000 claims description 129
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 126
- 125000000623 heterocyclic group Chemical group 0.000 claims description 121
- 125000003118 aryl group Chemical group 0.000 claims description 113
- 150000003839 salts Chemical group 0.000 claims description 112
- 239000000651 prodrug Chemical group 0.000 claims description 108
- 229940002612 prodrug Drugs 0.000 claims description 108
- 125000001424 substituent group Chemical group 0.000 claims description 104
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 103
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 82
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 75
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 72
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 67
- 102100021752 Corticoliberin Human genes 0.000 claims description 56
- 229910052736 halogen Inorganic materials 0.000 claims description 56
- 150000002367 halogens Chemical class 0.000 claims description 56
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 52
- 125000000217 alkyl group Chemical group 0.000 claims description 48
- 125000004076 pyridyl group Chemical group 0.000 claims description 42
- 238000000034 method Methods 0.000 claims description 41
- 229910052799 carbon Inorganic materials 0.000 claims description 38
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 35
- 208000035475 disorder Diseases 0.000 claims description 34
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 30
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 30
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 26
- 101100440695 Dictyostelium discoideum corB gene Proteins 0.000 claims description 25
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 24
- 125000000304 alkynyl group Chemical group 0.000 claims description 23
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 22
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 21
- 239000003814 drug Substances 0.000 claims description 21
- 208000019901 Anxiety disease Diseases 0.000 claims description 20
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 20
- 241000124008 Mammalia Species 0.000 claims description 18
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 18
- 201000010099 disease Diseases 0.000 claims description 18
- 229940079593 drug Drugs 0.000 claims description 18
- 230000036506 anxiety Effects 0.000 claims description 17
- QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical group C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 claims description 17
- 125000001188 haloalkyl group Chemical group 0.000 claims description 17
- 125000001624 naphthyl group Chemical group 0.000 claims description 17
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 16
- 208000030814 Eating disease Diseases 0.000 claims description 16
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 16
- 208000019022 Mood disease Diseases 0.000 claims description 16
- 235000014632 disordered eating Nutrition 0.000 claims description 16
- 208000024827 Alzheimer disease Diseases 0.000 claims description 15
- 208000028173 post-traumatic stress disease Diseases 0.000 claims description 15
- 208000024891 symptom Diseases 0.000 claims description 15
- 208000017194 Affective disease Diseases 0.000 claims description 14
- 206010048327 Supranuclear palsy Diseases 0.000 claims description 14
- 239000003937 drug carrier Substances 0.000 claims description 14
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 14
- 208000000103 Anorexia Nervosa Diseases 0.000 claims description 13
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 13
- 230000003042 antagnostic effect Effects 0.000 claims description 13
- 208000019622 heart disease Diseases 0.000 claims description 13
- 208000027866 inflammatory disease Diseases 0.000 claims description 13
- 125000001544 thienyl group Chemical group 0.000 claims description 13
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 12
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 12
- 125000005865 C2-C10alkynyl group Chemical group 0.000 claims description 12
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 12
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 12
- 206010019233 Headaches Diseases 0.000 claims description 12
- 241000725303 Human immunodeficiency virus Species 0.000 claims description 12
- 208000013016 Hypoglycemia Diseases 0.000 claims description 12
- 208000008589 Obesity Diseases 0.000 claims description 12
- 208000006011 Stroke Diseases 0.000 claims description 12
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 12
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 12
- 206010015037 epilepsy Diseases 0.000 claims description 12
- 230000035558 fertility Effects 0.000 claims description 12
- 125000002541 furyl group Chemical group 0.000 claims description 12
- 231100000869 headache Toxicity 0.000 claims description 12
- 230000002008 hemorrhagic effect Effects 0.000 claims description 12
- 230000002218 hypoglycaemic effect Effects 0.000 claims description 12
- 230000008629 immune suppression Effects 0.000 claims description 12
- 208000015181 infectious disease Diseases 0.000 claims description 12
- 208000000509 infertility Diseases 0.000 claims description 12
- 230000036512 infertility Effects 0.000 claims description 12
- 231100000535 infertility Toxicity 0.000 claims description 12
- 208000014674 injury Diseases 0.000 claims description 12
- 235000020824 obesity Nutrition 0.000 claims description 12
- 210000000278 spinal cord Anatomy 0.000 claims description 12
- 230000008733 trauma Effects 0.000 claims description 12
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 11
- 206010013663 drug dependence Diseases 0.000 claims description 11
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 11
- 208000011117 substance-related disease Diseases 0.000 claims description 11
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 10
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 8
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 8
- PIGFYZPCRLYGLF-UHFFFAOYSA-N Aluminum nitride Chemical compound [Al]#N PIGFYZPCRLYGLF-UHFFFAOYSA-N 0.000 claims description 8
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000001041 indolyl group Chemical group 0.000 claims description 8
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000004306 triazinyl group Chemical group 0.000 claims description 8
- 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 7
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 7
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 6
- 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 claims description 6
- OCBFFGCSTGGPSQ-UHFFFAOYSA-N [CH2]CC Chemical compound [CH2]CC OCBFFGCSTGGPSQ-UHFFFAOYSA-N 0.000 claims description 6
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 5
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 5
- 229910052786 argon Inorganic materials 0.000 claims description 5
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 4
- 125000000081 (C5-C8) cycloalkenyl group Chemical group 0.000 claims description 4
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 4
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 4
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000005493 quinolyl group Chemical group 0.000 claims description 4
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- WPWHSFAFEBZWBB-UHFFFAOYSA-N 1-butyl radical Chemical compound [CH2]CCC WPWHSFAFEBZWBB-UHFFFAOYSA-N 0.000 claims description 3
- HNUALPPJLMYHDK-UHFFFAOYSA-N C[CH]C Chemical compound C[CH]C HNUALPPJLMYHDK-UHFFFAOYSA-N 0.000 claims description 3
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 3
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
- 125000006317 cyclopropyl amino group Chemical group 0.000 claims description 2
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 claims description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 49
- 239000000460 chlorine Substances 0.000 description 94
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 89
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 84
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 81
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 78
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 72
- 239000012442 inert solvent Substances 0.000 description 71
- 239000002585 base Substances 0.000 description 65
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 64
- 238000006243 chemical reaction Methods 0.000 description 62
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 58
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 58
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 52
- 150000008064 anhydrides Chemical class 0.000 description 50
- 125000005843 halogen group Chemical group 0.000 description 50
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 48
- 229910052751 metal Inorganic materials 0.000 description 46
- 239000002184 metal Substances 0.000 description 46
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 41
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 40
- 239000002253 acid Substances 0.000 description 38
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 34
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 32
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 29
- 150000004292 cyclic ethers Chemical class 0.000 description 27
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 26
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 25
- 239000003513 alkali Substances 0.000 description 25
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 25
- 150000001983 dialkylethers Chemical class 0.000 description 25
- 239000000543 intermediate Substances 0.000 description 25
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 24
- 150000007513 acids Chemical class 0.000 description 24
- 150000003950 cyclic amides Chemical class 0.000 description 24
- 229940113088 dimethylacetamide Drugs 0.000 description 24
- 239000003795 chemical substances by application Substances 0.000 description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 125000005233 alkylalcohol group Chemical group 0.000 description 21
- 235000019439 ethyl acetate Nutrition 0.000 description 21
- 150000004820 halides Chemical class 0.000 description 21
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 19
- 229910052783 alkali metal Inorganic materials 0.000 description 19
- 239000002904 solvent Substances 0.000 description 19
- 238000012360 testing method Methods 0.000 description 18
- 125000005270 trialkylamine group Chemical group 0.000 description 18
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 17
- 150000001340 alkali metals Chemical class 0.000 description 17
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 17
- 229910000104 sodium hydride Inorganic materials 0.000 description 17
- 239000012312 sodium hydride Substances 0.000 description 17
- 239000007787 solid Substances 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- 150000004982 aromatic amines Chemical class 0.000 description 16
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 16
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 15
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 15
- 150000001342 alkaline earth metals Chemical class 0.000 description 15
- 150000004703 alkoxides Chemical class 0.000 description 15
- 150000001408 amides Chemical class 0.000 description 15
- 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 15
- 239000000243 solution Substances 0.000 description 15
- 239000003153 chemical reaction reagent Substances 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 150000001350 alkyl halides Chemical class 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 11
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- 235000019198 oils Nutrition 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 11
- 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
- 229910052987 metal hydride Inorganic materials 0.000 description 10
- 150000004681 metal hydrides Chemical class 0.000 description 10
- 229910052760 oxygen Inorganic materials 0.000 description 10
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 10
- 229910052717 sulfur Inorganic materials 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
- 239000013543 active substance Substances 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- 230000002140 halogenating effect Effects 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 235000019341 magnesium sulphate Nutrition 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 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 7
- 229960000583 acetic acid Drugs 0.000 description 7
- 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
- 210000004027 cell Anatomy 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 6
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 6
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 6
- 150000008046 alkali metal hydrides Chemical class 0.000 description 6
- 229940049706 benzodiazepine Drugs 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 108010056643 Corticotropin-Releasing Hormone Receptors Proteins 0.000 description 5
- 208000012902 Nervous system disease Diseases 0.000 description 5
- 208000025966 Neurological disease Diseases 0.000 description 5
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 5
- 150000008041 alkali metal carbonates Chemical class 0.000 description 5
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 5
- 230000000949 anxiolytic effect Effects 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
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 229940098779 methanesulfonic acid Drugs 0.000 description 5
- 239000007800 oxidant agent Substances 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
- 238000003756 stirring Methods 0.000 description 5
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2329096P | 1996-07-24 | 1996-07-24 | |
| US68604796A | 1996-07-24 | 1996-07-24 | |
| US08/899,242 US6124289A (en) | 1996-07-24 | 1997-07-23 | Azolo triazines and pyrimidines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP970413A2 true HRP970413A2 (en) | 1998-10-31 |
Family
ID=27362048
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP970413 HRP970413A2 (en) | 1996-07-24 | 1997-07-24 | Azolo triazines and pyrimidines |
Country Status (15)
| Country | Link |
|---|---|
| JP (2) | JP4704521B2 (zh) |
| CN (3) | CN1104432C (zh) |
| AR (1) | AR049583A2 (zh) |
| BR (1) | BR9710544A (zh) |
| CA (1) | CA2259583C (zh) |
| CZ (1) | CZ299451B6 (zh) |
| EA (1) | EA004403B1 (zh) |
| EE (1) | EE04316B1 (zh) |
| HR (1) | HRP970413A2 (zh) |
| IL (4) | IL127871A0 (zh) |
| NO (1) | NO315610B3 (zh) |
| NZ (1) | NZ333777A (zh) |
| PL (1) | PL195762B1 (zh) |
| SI (1) | SI9720045B (zh) |
| SK (1) | SK286461B6 (zh) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030125330A1 (en) * | 2001-03-13 | 2003-07-03 | Gilligan Paul J. | 4 - (2-butylamino) - 2, 7-dimethyl-8- (2-methyl-6-methoxypyrid-3-yl) pyrazolo- [1,5-A] - 1,3,5-triazine, its enantiomers and pharmaceutically acceptable salts as corticotropin releasing factor receptor ligands |
| WO2004110454A1 (ja) * | 2003-06-13 | 2004-12-23 | Ishihara Sangyo Kaisha, Ltd. | アデノシンＡ2ａ受容体アゴニストの投与が必要な疾患を治療又は予防するための組成物 |
| US7329662B2 (en) * | 2003-10-03 | 2008-02-12 | Hoffmann-La Roche Inc. | Pyrazolo-pyridine |
| GB0519957D0 (en) * | 2005-09-30 | 2005-11-09 | Sb Pharmco Inc | Chemical compound |
| US8030304B2 (en) * | 2006-09-20 | 2011-10-04 | Eli Lilly And Company | Thiazole pyrazolopyrimidines CRF1 receptor antagonists |
| CN103694242B (zh) * | 2013-12-10 | 2016-01-06 | 昆明翔昊科技有限公司 | 吡唑并嘧啶类化合物及其药物组合物和其在制药中的应用 |
| CN112608316B (zh) * | 2019-07-30 | 2022-10-21 | 厦门宝太生物科技股份有限公司 | 一种吡唑并三嗪类腺苷受体拮抗剂 |
| BR112023002497A2 (pt) | 2020-08-12 | 2023-05-02 | Spruce Biosciences Inc | Métodos e composições para tratamento da síndrome dos ovários policísticos |
| US11708372B2 (en) | 2021-11-19 | 2023-07-25 | Spruce Biosciences, Inc. | Crystalline composition of tildacerfont and methods of use and preparation thereof |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3995039A (en) * | 1975-05-27 | 1976-11-30 | Merck & Co., Inc. | Pyrazolo [1,5-a] [1,3,5] triazines |
| JPS6157587A (ja) * | 1984-08-29 | 1986-03-24 | Shionogi & Co Ltd | 縮合複素環誘導体および抗潰瘍剤 |
| US4824834A (en) * | 1986-10-31 | 1989-04-25 | Otsuka Pharmaceutical Company, Limited | Pyrazolotriazine compounds |
| JP2691317B2 (ja) * | 1989-08-25 | 1997-12-17 | 株式会社大塚製薬工場 | ４―ヒドロキシ―８―（３―低級アルコキシ―４―フェニルスルフィニルフェニル）ピラゾロ〔１，５―ａ〕―１，３，５―トリアジン光学活性体の塩類及びその製造方法 |
| US5420128A (en) * | 1990-10-09 | 1995-05-30 | Otsuka Pharmaceutical Co., Ltd. | Pyrimidine derivatives, method of manufacturing the same, and androgen inhibitor |
| KR100191774B1 (ko) * | 1991-04-22 | 1999-06-15 | 오스카 아끼히꼬 | 피라졸로[1,5-알파] 피리미딘 유도체 및 이것을 함유하는 항염증제 |
| US5356897A (en) * | 1991-09-09 | 1994-10-18 | Fujisawa Pharmaceutical Co., Ltd. | 3-(heteroaryl)-pyrazololi[1,5-a]pyrimidines |
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1997
- 1997-07-23 PL PL97331523A patent/PL195762B1/pl unknown
- 1997-07-23 NZ NZ333777A patent/NZ333777A/en not_active IP Right Cessation
- 1997-07-23 CA CA002259583A patent/CA2259583C/en not_active Expired - Lifetime
- 1997-07-23 EE EEP199900019A patent/EE04316B1/xx unknown
- 1997-07-23 CZ CZ0018499A patent/CZ299451B6/cs not_active IP Right Cessation
- 1997-07-23 SI SI9720045A patent/SI9720045B/sl active Search and Examination
- 1997-07-23 EA EA199900158A patent/EA004403B1/ru not_active IP Right Cessation
- 1997-07-23 IL IL12787197A patent/IL127871A0/xx unknown
- 1997-07-23 SK SK97-99A patent/SK286461B6/sk not_active IP Right Cessation
- 1997-07-23 CN CN97196525A patent/CN1104432C/zh not_active Expired - Lifetime
- 1997-07-23 JP JP50723398A patent/JP4704521B2/ja not_active Expired - Fee Related
- 1997-07-23 BR BR9710544A patent/BR9710544A/pt not_active IP Right Cessation
- 1997-07-24 HR HRP970413 patent/HRP970413A2/hr not_active Application Discontinuation
-
1998
- 1998-12-30 IL IL127871A patent/IL127871A/en not_active IP Right Cessation
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1999
- 1999-01-21 NO NO19990264A patent/NO315610B3/no not_active IP Right Cessation
-
2001
- 2001-05-30 CN CN 01120849 patent/CN1250223C/zh not_active Expired - Lifetime
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2002
- 2002-04-25 CN CN 02118589 patent/CN1388126A/zh active Pending
- 2002-06-11 IL IL150163A patent/IL150163A/en not_active IP Right Cessation
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2004
- 2004-07-23 JP JP2004216483A patent/JP4194539B2/ja not_active Expired - Fee Related
- 2004-10-12 IL IL164513A patent/IL164513A/en not_active IP Right Cessation
-
2005
- 2005-07-11 AR ARP050102868A patent/AR049583A2/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| NZ333777A (en) | 2000-07-28 |
| NO990264L (no) | 1999-03-10 |
| JP2005097257A (ja) | 2005-04-14 |
| SI9720045A (sl) | 1999-10-31 |
| CA2259583A1 (en) | 1998-01-29 |
| EE04316B1 (et) | 2004-06-15 |
| CZ18499A3 (cs) | 1999-11-17 |
| AR049583A2 (es) | 2006-08-16 |
| NO990264D0 (no) | 1999-01-21 |
| PL195762B1 (pl) | 2007-10-31 |
| CA2259583C (en) | 2009-11-17 |
| CN1250223C (zh) | 2006-04-12 |
| EE9900019A (et) | 1999-08-16 |
| BR9710544A (pt) | 1999-08-17 |
| IL150163A (en) | 2010-12-30 |
| SK286461B6 (sk) | 2008-10-07 |
| SI9720045B (sl) | 2008-02-29 |
| JP2002513382A (ja) | 2002-05-08 |
| JP4704521B2 (ja) | 2011-06-15 |
| IL164513A0 (en) | 2005-12-18 |
| IL164513A (en) | 2010-04-29 |
| CN1104432C (zh) | 2003-04-02 |
| NO315610B1 (no) | 2003-09-29 |
| PL331523A1 (en) | 1999-07-19 |
| EA004403B1 (ru) | 2004-04-29 |
| CN1225637A (zh) | 1999-08-11 |
| IL127871A (en) | 2010-04-29 |
| IL127871A0 (en) | 1999-10-28 |
| EA199900158A1 (ru) | 1999-10-28 |
| CN1327793A (zh) | 2001-12-26 |
| SK9799A3 (sk) | 2005-04-01 |
| NO315610B3 (no) | 2003-09-29 |
| CN1388126A (zh) | 2003-01-01 |
| JP4194539B2 (ja) | 2008-12-10 |
| CZ299451B6 (cs) | 2008-07-30 |
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