HRP970413A2 - Azolo triazines and pyrimidines - Google Patents

Azolo triazines and pyrimidines

Info

Publication number: HRP970413A2
Authority: HR; Croatia
Prior art keywords: compound; formula; stereoisomeric forms; alkyl; cycloalkyl
Prior art date: 1996-07-24

Application number

Other languages

English (en)

Croatian (hr)

Inventor

Argyrios Georgious Arvanitis

Robert John Chorvat

Original Assignee

Du Pont Pharm Co

Priority date (The priority date 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 date listed.)

1996-07-24

Filing date

1997-07-24

Publication date

1998-10-31

1997-07-23 Priority claimed from US08/899,242 external-priority patent/US6124289A/en

1997-07-24 Application filed by Du Pont Pharm Co filed Critical Du Pont Pharm Co

1998-10-31 Publication of HRP970413A2 publication Critical patent/HRP970413A2/hr

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
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
RXQZLSRIOOYKLF-UHFFFAOYSA-N 5H-pyrazolo[4,3-d]triazine Chemical compound N1=NN=C2C=NNC2=C1 RXQZLSRIOOYKLF-UHFFFAOYSA-N 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
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239000011780 sodium chloride Substances 0.000 description 1
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239000008117 stearic acid Substances 0.000 description 1
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125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
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239000001226 triphosphate Substances 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
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Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)
Polymers With Sulfur, Phosphorus Or Metals In The Main Chain (AREA)
Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)
Detergent Compositions (AREA)
Coloring (AREA)

HRP970413 1996-07-24 1997-07-24 Azolo triazines and pyrimidines HRP970413A2 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US68604796A	1996-07-24	1996-07-24
US2329096P	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 (sk)
CN (3)	CN1104432C (sk)
AR (1)	AR049583A2 (sk)
BR (1)	BR9710544A (sk)
CA (1)	CA2259583C (sk)
CZ (1)	CZ299451B6 (sk)
EA (1)	EA004403B1 (sk)
EE (1)	EE04316B1 (sk)
HR (1)	HRP970413A2 (sk)
IL (4)	IL127871A0 (sk)
NO (1)	NO315610B1 (sk)
NZ (1)	NZ333777A (sk)
PL (1)	PL195762B1 (sk)
SI (1)	SI9720045B (sk)
SK (1)	SK286461B6 (sk)

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* Cited by examiner, † Cited by third party
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
ATE481405T1 (de) *	2006-09-20	2010-10-15	Lilly Co Eli	Thiazolpyrazolopyrimidine als antagonisten des crf1-rezeptors
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
AU2018317398A1 (en)	2017-08-14	2019-11-21	Spruce Biosciences, Inc.	Corticotropin releasing factor receptor antagonists
CN112592346B (zh) *	2019-07-30	2022-04-26	厦门宝太生物科技股份有限公司	一种a2a和/或a2b抑制剂中间体的制备方法
MX2023001688A (es)	2020-08-12	2023-02-22	Spruce Biosciences Inc	Metodos y composiciones para tratar el sindrome de ovario poliquistico.
US11708372B2 (en)	2021-11-19	2023-07-25	Spruce Biosciences, Inc.	Crystalline composition of tildacerfont and methods of use and preparation thereof

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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
AU639615B2 (en) *	1990-10-09	1993-07-29	Otsuka Pharmaceutical Co., Ltd.	Pyrimidine derivative, production thereof, and androgen inhibitor
CA2107479C (en) *	1991-04-22	1997-12-16	Makoto Inoue	Pyrazolo[1,5-a]pyrimidine derivatives and anti-inflammatory agent containing the same
US5356897A (en) *	1991-09-09	1994-10-18	Fujisawa Pharmaceutical Co., Ltd.	3-(heteroaryl)-pyrazololi[1,5-a]pyrimidines

1997
- 1997-07-23 SI SI9720045A patent/SI9720045B/sl active Search and Examination
- 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 CZ CZ0018499A patent/CZ299451B6/cs not_active IP Right Cessation
- 1997-07-23 NZ NZ333777A patent/NZ333777A/en not_active IP Right Cessation
- 1997-07-23 PL PL97331523A patent/PL195762B1/pl unknown
- 1997-07-23 IL IL12787197A patent/IL127871A0/xx unknown
- 1997-07-23 EE EEP199900019A patent/EE04316B1/xx unknown
- 1997-07-23 CA CA002259583A patent/CA2259583C/en not_active Expired - Lifetime
- 1997-07-23 JP JP50723398A patent/JP4704521B2/ja not_active Expired - Fee Related
- 1997-07-23 EA EA199900158A patent/EA004403B1/ru not_active IP Right Cessation
- 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
1999
- 1999-01-21 NO NO19990264A patent/NO315610B1/no not_active IP Right Cessation
2001
- 2001-05-30 CN CN 01120849 patent/CN1250223C/zh not_active Expired - Lifetime
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
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
PL195762B1 (pl)	2007-10-31
IL150163A (en)	2010-12-30
IL127871A (en)	2010-04-29
JP2002513382A (ja)	2002-05-08
NO315610B3 (no)	2003-09-29
SI9720045B (sl)	2008-02-29
CN1225637A (zh)	1999-08-11
NO990264L (no)	1999-03-10
SK9799A3 (sk)	2005-04-01
IL164513A0 (en)	2005-12-18
CZ18499A3 (cs)	1999-11-17
EE04316B1 (et)	2004-06-15
SI9720045A (sl)	1999-10-31
NO315610B1 (no)	2003-09-29
IL127871A0 (en)	1999-10-28
NO990264D0 (no)	1999-01-21
JP4194539B2 (ja)	2008-12-10
CN1104432C (zh)	2003-04-02
EA199900158A1 (ru)	1999-10-28
CN1388126A (zh)	2003-01-01
EA004403B1 (ru)	2004-04-29
AR049583A2 (es)	2006-08-16
CA2259583A1 (en)	1998-01-29
CZ299451B6 (cs)	2008-07-30
PL331523A1 (en)	1999-07-19
EE9900019A (et)	1999-08-16
IL164513A (en)	2010-04-29
JP4704521B2 (ja)	2011-06-15
NZ333777A (en)	2000-07-28
BR9710544A (pt)	1999-08-17
SK286461B6 (sk)	2008-10-07
CN1327793A (zh)	2001-12-26
CN1250223C (zh)	2006-04-12
JP2005097257A (ja)	2005-04-14
CA2259583C (en)	2009-11-17

Publication	Publication Date	Title
CA2614603C (en)	2011-08-16	Azolo triazines and pyrimidines
ES2294800T3 (es)	2008-04-01	Azolo triazinas y pirimidinas.
US6191131B1 (en)	2001-02-20	Azolo triazines and pyrimidines
LT4680B (lt)	2000-07-25	Azolo triazinai ir pirimidinai
US6313124B1 (en)	2001-11-06	Tetrazine bicyclic compounds
US6960583B2 (en)	2005-11-01	Pyrazolotriazines as CRF antagonists
US6734185B2 (en)	2004-05-11	Pyrrolo[3,4-d]pyrimidines as corticotropin releasing factor (CRF) antagonists
HRP970413A2 (en)	1998-10-31	Azolo triazines and pyrimidines
US20030008885A1 (en)	2003-01-09	Azolo triazines and pyrimidines
US7678793B2 (en)	2010-03-16	Azolo triazines and pyrimidines
CA2532925C (en)	2009-10-20	Azolo triazines and pyrimidines

Legal Events

Date	Code	Title
1998-10-31	A1OB	Publication of a patent application
1999-04-30	AIPI	Request for the grant of a patent on the basis of a substantive examination of a patent application
2008-05-06	ODBI	Application refused