HRP940664A2 - 1n-alkyl-n-arylpyrimidinamines and derivatives thereof - Google Patents
1n-alkyl-n-arylpyrimidinamines and derivatives thereof Download PDFInfo
- Publication number
- HRP940664A2 HRP940664A2 HR08/315,660A HRP940664A HRP940664A2 HR P940664 A2 HRP940664 A2 HR P940664A2 HR P940664 A HRP940664 A HR P940664A HR P940664 A2 HRP940664 A2 HR P940664A2
- Authority
- HR
- Croatia
- Prior art keywords
- alkyl
- methyl
- ethyl
- bromo
- phenyl
- Prior art date
Links
- -1 2-pyridinyl Chemical group 0.000 claims description 574
- 150000001875 compounds Chemical class 0.000 claims description 200
- 229910052739 hydrogen Inorganic materials 0.000 claims description 182
- 239000001257 hydrogen Substances 0.000 claims description 170
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 154
- 150000002431 hydrogen Chemical class 0.000 claims description 116
- 125000000217 alkyl group Chemical group 0.000 claims description 111
- 125000003118 aryl group Chemical group 0.000 claims description 99
- 229910052736 halogen Inorganic materials 0.000 claims description 92
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 89
- 229910052799 carbon Inorganic materials 0.000 claims description 85
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 84
- 150000002367 halogens Chemical class 0.000 claims description 84
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 81
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 80
- 229910020008 S(O) Inorganic materials 0.000 claims description 79
- 239000000203 mixture Substances 0.000 claims description 71
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 63
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 57
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 54
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 51
- 125000001424 substituent group Chemical group 0.000 claims description 51
- 125000005843 halogen group Chemical group 0.000 claims description 49
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 48
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 48
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 48
- 238000006467 substitution reaction Methods 0.000 claims description 46
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 45
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 44
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical group [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 42
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 39
- 229910052757 nitrogen Inorganic materials 0.000 claims description 39
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 38
- 238000000034 method Methods 0.000 claims description 38
- 125000001072 heteroaryl group Chemical group 0.000 claims description 36
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 35
- 125000003545 alkoxy group Chemical group 0.000 claims description 35
- 125000002883 imidazolyl group Chemical group 0.000 claims description 35
- 229910052720 vanadium Inorganic materials 0.000 claims description 35
- 229910052727 yttrium Inorganic materials 0.000 claims description 35
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 34
- 229910052794 bromium Inorganic materials 0.000 claims description 34
- 125000001041 indolyl group Chemical group 0.000 claims description 34
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 33
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 32
- 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 claims description 31
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 30
- 125000002541 furyl group Chemical group 0.000 claims description 30
- 125000003386 piperidinyl group Chemical group 0.000 claims description 30
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 30
- 125000004193 piperazinyl group Chemical group 0.000 claims description 29
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 28
- 125000001188 haloalkyl group Chemical group 0.000 claims description 28
- 229910052740 iodine Inorganic materials 0.000 claims description 28
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 27
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 26
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 26
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 26
- 125000001422 pyrrolinyl group Chemical group 0.000 claims description 26
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 25
- 125000006373 (C2-C10) alkyl group Chemical group 0.000 claims description 25
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 25
- 125000000160 oxazolidinyl group Chemical group 0.000 claims description 25
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 25
- 125000003072 pyrazolidinyl group Chemical group 0.000 claims description 25
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 25
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 25
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 25
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 25
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 25
- XCUAIINAJCDIPM-XVFCMESISA-N N(4)-hydroxycytidine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=NO)C=C1 XCUAIINAJCDIPM-XVFCMESISA-N 0.000 claims description 24
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 24
- 125000004970 halomethyl group Chemical group 0.000 claims description 24
- 125000000623 heterocyclic group Chemical group 0.000 claims description 24
- 125000002971 oxazolyl group Chemical group 0.000 claims description 24
- 125000000335 thiazolyl group Chemical group 0.000 claims description 24
- 125000004306 triazinyl group Chemical group 0.000 claims description 24
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 23
- 125000005955 1H-indazolyl group Chemical group 0.000 claims description 23
- 229930194542 Keto Natural products 0.000 claims description 23
- 229910052801 chlorine Inorganic materials 0.000 claims description 23
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 23
- 125000002757 morpholinyl group Chemical group 0.000 claims description 23
- 125000004930 octahydroisoquinolinyl group Chemical group C1(NCCC2CCCC=C12)* 0.000 claims description 23
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 claims description 23
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 23
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 23
- 125000004933 β-carbolinyl group Chemical group C1(=NC=CC=2C3=CC=CC=C3NC12)* 0.000 claims description 23
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 22
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 22
- 125000005865 C2-C10alkynyl group Chemical group 0.000 claims description 21
- 125000000468 ketone group Chemical group 0.000 claims description 21
- 125000002471 4H-quinolizinyl group Chemical group C=1(C=CCN2C=CC=CC12)* 0.000 claims description 20
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 20
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 20
- 125000003838 furazanyl group Chemical group 0.000 claims description 20
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 claims description 20
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 claims description 20
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 20
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 19
- 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 claims description 19
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 19
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims description 19
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 19
- 125000005986 4-piperidonyl group Chemical group 0.000 claims description 18
- 125000004931 azocinyl group Chemical group N1=C(C=CC=CC=C1)* 0.000 claims description 18
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 18
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 claims description 18
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 17
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims description 17
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 17
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 claims description 17
- 125000002393 azetidinyl group Chemical group 0.000 claims description 16
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 claims description 16
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 14
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 13
- 239000002253 acid Substances 0.000 claims description 12
- 125000002785 azepinyl group Chemical group 0.000 claims description 12
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 12
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 12
- 125000004076 pyridyl group Chemical group 0.000 claims description 12
- 125000001544 thienyl group Chemical group 0.000 claims description 12
- 208000019901 Anxiety disease Diseases 0.000 claims description 11
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 claims description 11
- 125000001246 bromo group Chemical group Br* 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 claims description 11
- 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 claims description 11
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 claims description 11
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 claims description 11
- 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 claims description 11
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 10
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 10
- 125000005954 phenoxathiinyl group Chemical group 0.000 claims description 10
- 239000000651 prodrug Substances 0.000 claims description 10
- 229940002612 prodrug Drugs 0.000 claims description 10
- 125000002755 pyrazolinyl group Chemical group 0.000 claims description 10
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 claims description 9
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 8
- 125000006242 amine protecting group Chemical group 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 8
- 208000024827 Alzheimer disease Diseases 0.000 claims description 7
- 208000019022 Mood disease Diseases 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- KSBRTKROJARSOL-UHFFFAOYSA-N n-ethyl-4,6-dimethyl-n-(2-methylsulfanyl-4-propan-2-ylphenyl)pyrimidin-2-amine Chemical compound C=1C=C(C(C)C)C=C(SC)C=1N(CC)C1=NC(C)=CC(C)=N1 KSBRTKROJARSOL-UHFFFAOYSA-N 0.000 claims description 7
- 206010053164 Alcohol withdrawal syndrome Diseases 0.000 claims description 6
- 206010013754 Drug withdrawal syndrome Diseases 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 6
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 208000029650 alcohol withdrawal Diseases 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 230000036506 anxiety Effects 0.000 claims description 6
- 230000035558 fertility Effects 0.000 claims description 6
- 208000027866 inflammatory disease Diseases 0.000 claims description 6
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 6
- KPARZMBGRLAYAL-UHFFFAOYSA-N 1-(2-bromo-4,6-dimethoxyphenyl)-4,6-dimethylpyrrolo[2,3-b]pyridine Chemical compound COC1=CC(OC)=CC(Br)=C1N1C2=NC(C)=CC(C)=C2C=C1 KPARZMBGRLAYAL-UHFFFAOYSA-N 0.000 claims description 5
- ZMXAHDWFFGRSOY-UHFFFAOYSA-N 1-(2-bromo-4,6-dimethoxyphenyl)-4,6-dimethylpyrrolo[2,3-b]pyridine-3-carbonitrile Chemical compound COC1=CC(OC)=CC(Br)=C1N1C2=NC(C)=CC(C)=C2C(C#N)=C1 ZMXAHDWFFGRSOY-UHFFFAOYSA-N 0.000 claims description 5
- NIQBQCGMLBLOAL-UHFFFAOYSA-N 1-(2-bromo-4-propan-2-ylphenyl)-6-methyl-4-phenylpyrrolo[2,3-b]pyridine Chemical compound BrC1=CC(C(C)C)=CC=C1N1C2=NC(C)=CC(C=3C=CC=CC=3)=C2C=C1 NIQBQCGMLBLOAL-UHFFFAOYSA-N 0.000 claims description 5
- IZPTWDGBBSSUFN-UHFFFAOYSA-N 1-(2-bromo-4-propan-2-ylphenyl)-6-methyl-4-phenylpyrrolo[2,3-b]pyridine-3-carbonitrile Chemical compound BrC1=CC(C(C)C)=CC=C1N1C2=NC(C)=CC(C=3C=CC=CC=3)=C2C(C#N)=C1 IZPTWDGBBSSUFN-UHFFFAOYSA-N 0.000 claims description 5
- 125000004104 aryloxy group Chemical group 0.000 claims description 5
- 125000006244 carboxylic acid protecting group Chemical group 0.000 claims description 5
- 206010013663 drug dependence Diseases 0.000 claims description 5
- DZRAIVUEAUXHQH-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-n-ethyl-4-methyl-6-phenylmethoxy-1,3,5-triazin-2-amine Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C(N=1)=NC(C)=NC=1OCC1=CC=CC=C1 DZRAIVUEAUXHQH-UHFFFAOYSA-N 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 claims description 5
- 208000011117 substance-related disease Diseases 0.000 claims description 5
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 4
- 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 4
- QFPQNRRUWQDVHQ-UHFFFAOYSA-N 1-(2-bromo-4-propan-2-ylphenyl)-4,6-dimethylpyrrolo[2,3-b]pyridine Chemical compound BrC1=CC(C(C)C)=CC=C1N1C2=NC(C)=CC(C)=C2C=C1 QFPQNRRUWQDVHQ-UHFFFAOYSA-N 0.000 claims description 4
- PIGVJMHCKKTORD-UHFFFAOYSA-N 1-(2-bromo-4-propan-2-ylphenyl)-4,6-dimethylpyrrolo[2,3-b]pyridine-3-carbonitrile Chemical compound BrC1=CC(C(C)C)=CC=C1N1C2=NC(C)=CC(C)=C2C(C#N)=C1 PIGVJMHCKKTORD-UHFFFAOYSA-N 0.000 claims description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 4
- 125000006725 C1-C10 alkenyl group Chemical group 0.000 claims description 4
- 208000030814 Eating disease Diseases 0.000 claims description 4
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- AKUOZFAOUIQUKF-UHFFFAOYSA-N [2-(2-bromo-n-ethyl-4-propan-2-ylanilino)-6-methylpyrimidin-4-yl]-morpholin-4-ylmethanone Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C(N=1)=NC(C)=CC=1C(=O)N1CCOCC1 AKUOZFAOUIQUKF-UHFFFAOYSA-N 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 4
- 125000004367 cycloalkylaryl group Chemical group 0.000 claims description 4
- 208000010643 digestive system disease Diseases 0.000 claims description 4
- 235000014632 disordered eating Nutrition 0.000 claims description 4
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 4
- VMWJCFLUSKZZDX-UHFFFAOYSA-N n,n-dimethylmethanamine Chemical compound [CH2]N(C)C VMWJCFLUSKZZDX-UHFFFAOYSA-N 0.000 claims description 4
- DJPDZZNMXCMJGS-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-n-ethyl-4-methylpyrimidin-2-amine Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C1=NC=CC(C)=N1 DJPDZZNMXCMJGS-UHFFFAOYSA-N 0.000 claims description 4
- PJFOPDCUBUCCSE-UHFFFAOYSA-N n-ethyl-n-[2-iodo-4-(methoxymethyl)phenyl]-4,6-dimethylpyrimidin-2-amine Chemical compound C=1C=C(COC)C=C(I)C=1N(CC)C1=NC(C)=CC(C)=N1 PJFOPDCUBUCCSE-UHFFFAOYSA-N 0.000 claims description 4
- 230000001629 suppression Effects 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000006763 (C3-C9) cycloalkyl group Chemical group 0.000 claims description 3
- JYYZIQYKFUXTNM-UHFFFAOYSA-N 2-[4-(2-bromo-n-ethyl-4,6-dimethoxyanilino)-6-methyl-1,3,5-triazin-2-yl]-2-phenylacetonitrile Chemical compound BrC=1C=C(OC)C=C(OC)C=1N(CC)C(N=1)=NC(C)=NC=1C(C#N)C1=CC=CC=C1 JYYZIQYKFUXTNM-UHFFFAOYSA-N 0.000 claims description 3
- SNPCWSQESDMCAG-UHFFFAOYSA-N 2-[[2-(2-bromo-n-ethyl-4-propan-2-ylanilino)-6-methylpyrimidin-4-yl]-methylamino]ethanol Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C1=NC(C)=CC(N(C)CCO)=N1 SNPCWSQESDMCAG-UHFFFAOYSA-N 0.000 claims description 3
- QJRSSLRLXNELDQ-UHFFFAOYSA-N 4-chloro-n-ethyl-n-(2-iodo-4-propan-2-ylphenyl)-6-methylpyrimidin-2-amine Chemical compound C=1C=C(C(C)C)C=C(I)C=1N(CC)C1=NC(C)=CC(Cl)=N1 QJRSSLRLXNELDQ-UHFFFAOYSA-N 0.000 claims description 3
- 206010048327 Supranuclear palsy Diseases 0.000 claims description 3
- 125000003368 amide group Chemical group 0.000 claims description 3
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 3
- 210000000987 immune system Anatomy 0.000 claims description 3
- NDMWEDHNQDKEOR-UHFFFAOYSA-N methyl 2-[2-(2-bromo-4-propan-2-ylphenyl)ethylamino]-6-methylpyrimidine-4-carboxylate Chemical compound COC(=O)C1=CC(C)=NC(NCCC=2C(=CC(=CC=2)C(C)C)Br)=N1 NDMWEDHNQDKEOR-UHFFFAOYSA-N 0.000 claims description 3
- IGKKAHZACZTWNL-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-4,6-dimethyl-n-prop-2-ynylpyrimidin-2-amine Chemical compound BrC1=CC(C(C)C)=CC=C1N(CC#C)C1=NC(C)=CC(C)=N1 IGKKAHZACZTWNL-UHFFFAOYSA-N 0.000 claims description 3
- NZHPYWKTCLZWBM-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-n,4,6-trimethylpyrimidin-2-amine Chemical compound BrC1=CC(C(C)C)=CC=C1N(C)C1=NC(C)=CC(C)=N1 NZHPYWKTCLZWBM-UHFFFAOYSA-N 0.000 claims description 3
- IUNYNCQHIRZDOR-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-n-ethyl-4-methyl-6-(morpholin-4-ylmethyl)pyrimidin-2-amine Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C(N=1)=NC(C)=CC=1CN1CCOCC1 IUNYNCQHIRZDOR-UHFFFAOYSA-N 0.000 claims description 3
- RIGHNPNQDCAARO-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-n-ethyl-4-methyl-6-phenoxy-1,3,5-triazin-2-amine Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C(N=1)=NC(C)=NC=1OC1=CC=CC=C1 RIGHNPNQDCAARO-UHFFFAOYSA-N 0.000 claims description 3
- RBDRJBIKURSTPZ-UHFFFAOYSA-N n-ethyl-4-methyl-6-morpholin-4-yl-n-(2,4,6-trimethoxyphenyl)-1,3,5-triazin-2-amine Chemical compound COC=1C=C(OC)C=C(OC)C=1N(CC)C(N=1)=NC(C)=NC=1N1CCOCC1 RBDRJBIKURSTPZ-UHFFFAOYSA-N 0.000 claims description 3
- IQYYNCCRMAFRHD-UHFFFAOYSA-N n-ethyl-n-(2-iodo-4-propan-2-ylphenyl)-4-methyl-6-morpholin-4-ylpyrimidin-2-amine Chemical compound C=1C=C(C(C)C)C=C(I)C=1N(CC)C(N=1)=NC(C)=CC=1N1CCOCC1 IQYYNCCRMAFRHD-UHFFFAOYSA-N 0.000 claims description 3
- FRRZGNDQWVABDX-UHFFFAOYSA-N n-ethyl-n-(2-iodo-4-propan-2-ylphenyl)-4-methyl-6-thiomorpholin-4-ylpyrimidin-2-amine Chemical compound C=1C=C(C(C)C)C=C(I)C=1N(CC)C(N=1)=NC(C)=CC=1N1CCSCC1 FRRZGNDQWVABDX-UHFFFAOYSA-N 0.000 claims description 3
- ANUIPSUUNJVURM-UHFFFAOYSA-N n-ethyl-n-[2-iodo-4-(2-methoxyethyl)phenyl]-4,6-dimethylpyrimidin-2-amine Chemical compound C=1C=C(CCOC)C=C(I)C=1N(CC)C1=NC(C)=CC(C)=N1 ANUIPSUUNJVURM-UHFFFAOYSA-N 0.000 claims description 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 3
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 208000028173 post-traumatic stress disease Diseases 0.000 claims description 3
- 125000006728 (C1-C6) alkynyl group Chemical group 0.000 claims description 2
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 2
- PUXGFALKNTZHGS-UHFFFAOYSA-N 1-(2-bromo-4-propan-2-ylphenyl)-4-chloro-6-methylpyrrolo[2,3-b]pyridine Chemical compound BrC1=CC(C(C)C)=CC=C1N1C2=NC(C)=CC(Cl)=C2C=C1 PUXGFALKNTZHGS-UHFFFAOYSA-N 0.000 claims description 2
- PRRTYZKNYJKSNF-UHFFFAOYSA-N 1-(2-bromo-4-propan-2-ylphenyl)-4-chloro-6-methylpyrrolo[2,3-b]pyridine-3-carbonitrile Chemical compound BrC1=CC(C(C)C)=CC=C1N1C2=NC(C)=CC(Cl)=C2C(C#N)=C1 PRRTYZKNYJKSNF-UHFFFAOYSA-N 0.000 claims description 2
- PNGHDPQUCWMVKJ-UHFFFAOYSA-N 1-(2-bromo-4-propan-2-ylphenyl)-6-chloro-4-methylpyrrolo[2,3-b]pyridine Chemical compound BrC1=CC(C(C)C)=CC=C1N1C2=NC(Cl)=CC(C)=C2C=C1 PNGHDPQUCWMVKJ-UHFFFAOYSA-N 0.000 claims description 2
- QHJTVYSIDYDLIS-UHFFFAOYSA-N 1-(2-bromo-4-propan-2-ylphenyl)-6-chloro-4-methylpyrrolo[2,3-b]pyridine-3-carbonitrile Chemical compound BrC1=CC(C(C)C)=CC=C1N1C2=NC(Cl)=CC(C)=C2C(C#N)=C1 QHJTVYSIDYDLIS-UHFFFAOYSA-N 0.000 claims description 2
- OJPWZKPOSBKZNX-UHFFFAOYSA-N 1-[2-(2-bromo-n-ethyl-4-propan-2-ylanilino)-6-methylpyrimidin-4-yl]ethanone Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C1=NC(C)=CC(C(C)=O)=N1 OJPWZKPOSBKZNX-UHFFFAOYSA-N 0.000 claims description 2
- JQFDDHMCJFUXTP-UHFFFAOYSA-N 1-[4-[(4,6-dimethylpyrimidin-2-yl)-ethylamino]-3-methylsulfanylphenyl]ethanone Chemical compound C=1C=C(C(C)=O)C=C(SC)C=1N(CC)C1=NC(C)=CC(C)=N1 JQFDDHMCJFUXTP-UHFFFAOYSA-N 0.000 claims description 2
- RSJRQOHBJCAGIG-UHFFFAOYSA-N 1-[4-[(4,6-dimethylpyrimidin-2-yl)-ethylamino]-3-methylsulfanylphenyl]propan-1-one Chemical compound C=1C=C(C(=O)CC)C=C(SC)C=1N(CC)C1=NC(C)=CC(C)=N1 RSJRQOHBJCAGIG-UHFFFAOYSA-N 0.000 claims description 2
- PWEWKCNBZXTYBW-UHFFFAOYSA-N 1-[[2-(2-bromo-n-ethyl-4-propan-2-ylanilino)-6-methylpyrimidin-4-yl]methyl]piperidin-4-one Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C(N=1)=NC(C)=CC=1CN1CCC(=O)CC1 PWEWKCNBZXTYBW-UHFFFAOYSA-N 0.000 claims description 2
- LXWXAMUYNYXVDT-UHFFFAOYSA-N 1-n-(4,6-dimethylpyrimidin-2-yl)-1-n-ethyl-2-n,2-n-dimethyl-4-propan-2-ylbenzene-1,2-diamine Chemical compound C=1C=C(C(C)C)C=C(N(C)C)C=1N(CC)C1=NC(C)=CC(C)=N1 LXWXAMUYNYXVDT-UHFFFAOYSA-N 0.000 claims description 2
- ONNRAZUNJFTCGK-UHFFFAOYSA-N 1-n-(4,6-dimethylpyrimidin-2-yl)-1-n-ethyl-4-(methoxymethyl)-2-n,2-n-dimethylbenzene-1,2-diamine Chemical compound C=1C=C(COC)C=C(N(C)C)C=1N(CC)C1=NC(C)=CC(C)=N1 ONNRAZUNJFTCGK-UHFFFAOYSA-N 0.000 claims description 2
- YGJOIWOQULEABB-UHFFFAOYSA-N 1-n-(4,6-dimethylpyrimidin-2-yl)-1-n-ethyl-4-n,4-n-dimethyl-2-methylsulfanylbenzene-1,4-diamine Chemical compound C=1C=C(N(C)C)C=C(SC)C=1N(CC)C1=NC(C)=CC(C)=N1 YGJOIWOQULEABB-UHFFFAOYSA-N 0.000 claims description 2
- NDACBNVVBBIMHD-UHFFFAOYSA-N 1-n-(4,6-dimethylpyrimidin-2-yl)-1-n-ethyl-4-n-methyl-2-methylsulfanylbenzene-1,4-diamine Chemical compound C=1C=C(NC)C=C(SC)C=1N(CC)C1=NC(C)=CC(C)=N1 NDACBNVVBBIMHD-UHFFFAOYSA-N 0.000 claims description 2
- JUWHXSVDTHQDGB-UHFFFAOYSA-N 2-(2-bromo-n-(4,6-dimethylpyrimidin-2-yl)-4-propan-2-ylanilino)acetonitrile Chemical compound BrC1=CC(C(C)C)=CC=C1N(CC#N)C1=NC(C)=CC(C)=N1 JUWHXSVDTHQDGB-UHFFFAOYSA-N 0.000 claims description 2
- DPBXAOTWLIPGDT-UHFFFAOYSA-N 2-(2-bromo-n-ethyl-4-propan-2-ylanilino)-6-methylpyrimidine-4-carbaldehyde Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C1=NC(C)=CC(C=O)=N1 DPBXAOTWLIPGDT-UHFFFAOYSA-N 0.000 claims description 2
- DYJHRWLGWVAIJS-UHFFFAOYSA-N 2-(2-bromo-n-ethyl-4-propan-2-ylanilino)-6-methylpyrimidine-4-carboxylic acid Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C1=NC(C)=CC(C(O)=O)=N1 DYJHRWLGWVAIJS-UHFFFAOYSA-N 0.000 claims description 2
- YMWAKAQQEROJPM-UHFFFAOYSA-N 2-[2-(2-bromo-4-propan-2-ylphenyl)ethylamino]-n-cyclohexyl-6-methylpyrimidine-4-carboxamide Chemical compound BrC1=CC(C(C)C)=CC=C1CCNC1=NC(C)=CC(C(=O)NC2CCCCC2)=N1 YMWAKAQQEROJPM-UHFFFAOYSA-N 0.000 claims description 2
- LBHGKBHPZPOQFE-UHFFFAOYSA-N 2-[[2-(2-bromo-n-ethyl-4-propan-2-ylanilino)-6-methylpyrimidin-4-yl]methoxy]ethanol Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C1=NC(C)=CC(COCCO)=N1 LBHGKBHPZPOQFE-UHFFFAOYSA-N 0.000 claims description 2
- SZLBKNWFAIDLEM-UHFFFAOYSA-N 3-bromo-2-[(4,6-dimethylpyrimidin-2-yl)-ethylamino]-5-methoxyphenol Chemical compound OC=1C=C(OC)C=C(Br)C=1N(CC)C1=NC(C)=CC(C)=N1 SZLBKNWFAIDLEM-UHFFFAOYSA-N 0.000 claims description 2
- YQUOEIRBYAHBRN-UHFFFAOYSA-N 4-(1-aminoethyl)-n-(2-bromo-4-propan-2-ylphenyl)-n-ethyl-6-methylpyrimidin-2-amine Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C1=NC(C)=CC(C(C)N)=N1 YQUOEIRBYAHBRN-UHFFFAOYSA-N 0.000 claims description 2
- COPLUXHWFGDYHM-UHFFFAOYSA-N 4-[(4,6-dimethylpyrimidin-2-yl)-ethylamino]-3-methylsulfanylbenzonitrile Chemical compound C=1C=C(C#N)C=C(SC)C=1N(CC)C1=NC(C)=CC(C)=N1 COPLUXHWFGDYHM-UHFFFAOYSA-N 0.000 claims description 2
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims description 2
- BEEQPDJBYLPCQQ-UHFFFAOYSA-N [2-(2-bromo-n-ethyl-4-propan-2-ylanilino)-6-methylpyrimidin-4-yl]-(1,3-thiazol-2-yl)methanone Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C(N=1)=NC(C)=CC=1C(=O)C1=NC=CS1 BEEQPDJBYLPCQQ-UHFFFAOYSA-N 0.000 claims description 2
- CGVQIEMHKVIXNC-UHFFFAOYSA-N [2-(2-bromo-n-ethyl-4-propan-2-ylanilino)-6-methylpyrimidin-4-yl]-(1h-imidazol-2-yl)methanone Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C(N=1)=NC(C)=CC=1C(=O)C1=NC=CN1 CGVQIEMHKVIXNC-UHFFFAOYSA-N 0.000 claims description 2
- AYVGIQGVWAKYKW-UHFFFAOYSA-N [2-(2-bromo-n-ethyl-4-propan-2-ylanilino)-6-methylpyrimidin-4-yl]-(1h-indol-5-yl)methanone Chemical compound N=1C(C)=CC(C(=O)C=2C=C3C=CNC3=CC=2)=NC=1N(CC)C1=CC=C(C(C)C)C=C1Br AYVGIQGVWAKYKW-UHFFFAOYSA-N 0.000 claims description 2
- FUPULONIXXFNOA-UHFFFAOYSA-N [2-(2-bromo-n-ethyl-4-propan-2-ylanilino)-6-methylpyrimidin-4-yl]-(4-fluorophenyl)methanone Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C(N=1)=NC(C)=CC=1C(=O)C1=CC=C(F)C=C1 FUPULONIXXFNOA-UHFFFAOYSA-N 0.000 claims description 2
- WTIKCYJJWAXEJL-UHFFFAOYSA-N [2-(2-bromo-n-ethyl-4-propan-2-ylanilino)-6-methylpyrimidin-4-yl]-(4-methylpiperazin-1-yl)methanone Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C(N=1)=NC(C)=CC=1C(=O)N1CCN(C)CC1 WTIKCYJJWAXEJL-UHFFFAOYSA-N 0.000 claims description 2
- CCYHKRLBCGGAJA-UHFFFAOYSA-N [2-(2-bromo-n-ethyl-4-propan-2-ylanilino)-6-methylpyrimidin-4-yl]-[4-(2-methoxyphenyl)pyridin-3-yl]methanol Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C(N=1)=NC(C)=CC=1C(O)C1=CN=CC=C1C1=CC=CC=C1OC CCYHKRLBCGGAJA-UHFFFAOYSA-N 0.000 claims description 2
- MEYBTSNXBGNEML-UHFFFAOYSA-N [2-(2-bromo-n-ethyl-4-propan-2-ylanilino)-6-methylpyrimidin-4-yl]-piperidin-1-ylmethanone Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C(N=1)=NC(C)=CC=1C(=O)N1CCCCC1 MEYBTSNXBGNEML-UHFFFAOYSA-N 0.000 claims description 2
- BZSZSXJEMJIAGI-UHFFFAOYSA-N [2-(2-bromo-n-ethyl-4-propan-2-ylanilino)-6-methylpyrimidin-4-yl]-pyridin-3-ylmethanol Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C(N=1)=NC(C)=CC=1C(O)C1=CC=CN=C1 BZSZSXJEMJIAGI-UHFFFAOYSA-N 0.000 claims description 2
- RQWXMDAWDLDRLW-UHFFFAOYSA-N ethyl 4-[(4,6-dimethylpyrimidin-2-yl)-ethylamino]-3-methylsulfanylbenzoate Chemical compound CSC1=CC(C(=O)OCC)=CC=C1N(CC)C1=NC(C)=CC(C)=N1 RQWXMDAWDLDRLW-UHFFFAOYSA-N 0.000 claims description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
- ABOFQKIATQSBJH-UHFFFAOYSA-N n-(2,3-dibromo-4,6-dimethoxyphenyl)-n-ethyl-4,6-dimethylpyrimidin-2-amine Chemical compound COC=1C=C(OC)C(Br)=C(Br)C=1N(CC)C1=NC(C)=CC(C)=N1 ABOFQKIATQSBJH-UHFFFAOYSA-N 0.000 claims description 2
- KXUFDJBMSMCPNA-UHFFFAOYSA-N n-(2,4-dibromophenyl)-n,4,6-trimethylpyrimidin-2-amine Chemical compound N=1C(C)=CC(C)=NC=1N(C)C1=CC=C(Br)C=C1Br KXUFDJBMSMCPNA-UHFFFAOYSA-N 0.000 claims description 2
- PKLVIMXOKYZBAT-UHFFFAOYSA-N n-(2,4-diiodophenyl)-n-ethyl-4,6-dimethylpyrimidin-2-amine Chemical compound C=1C=C(I)C=C(I)C=1N(CC)C1=NC(C)=CC(C)=N1 PKLVIMXOKYZBAT-UHFFFAOYSA-N 0.000 claims description 2
- RJPDHWPEJHNYMI-UHFFFAOYSA-N n-(2,4-diiodophenyl)-n-ethyl-4-methyl-6-morpholin-4-ylpyrimidin-2-amine Chemical compound C=1C=C(I)C=C(I)C=1N(CC)C(N=1)=NC(C)=CC=1N1CCOCC1 RJPDHWPEJHNYMI-UHFFFAOYSA-N 0.000 claims description 2
- JEZVFXSFRJJBMI-UHFFFAOYSA-N n-(2,4-dimethoxyphenyl)-n,4,6-trimethylpyrimidin-2-amine Chemical compound COC1=CC(OC)=CC=C1N(C)C1=NC(C)=CC(C)=N1 JEZVFXSFRJJBMI-UHFFFAOYSA-N 0.000 claims description 2
- UAMZBRAQVITBBX-UHFFFAOYSA-N n-(2,4-dimethoxyphenyl)-n-ethyl-4,6-dimethylpyrimidin-2-amine Chemical compound C=1C=C(OC)C=C(OC)C=1N(CC)C1=NC(C)=CC(C)=N1 UAMZBRAQVITBBX-UHFFFAOYSA-N 0.000 claims description 2
- UBKRTZQGBSWLGT-UHFFFAOYSA-N n-(2,6-dibromo-4-ethoxyphenyl)-n-ethyl-4,6-dimethylpyrimidin-2-amine Chemical compound BrC1=CC(OCC)=CC(Br)=C1N(CC)C1=NC(C)=CC(C)=N1 UBKRTZQGBSWLGT-UHFFFAOYSA-N 0.000 claims description 2
- RYKFCXUCBJBZRD-UHFFFAOYSA-N n-(2,6-dibromo-4-propan-2-ylphenyl)-n-ethyl-4,6-dimethylpyrimidin-2-amine Chemical compound BrC=1C=C(C(C)C)C=C(Br)C=1N(CC)C1=NC(C)=CC(C)=N1 RYKFCXUCBJBZRD-UHFFFAOYSA-N 0.000 claims description 2
- KOQQQRALSQNXMO-UHFFFAOYSA-N n-(2,6-dibromo-4-propan-2-ylphenyl)-n-ethyl-4-methyl-6-thiomorpholin-4-ylpyrimidin-2-amine Chemical compound BrC=1C=C(C(C)C)C=C(Br)C=1N(CC)C(N=1)=NC(C)=CC=1N1CCSCC1 KOQQQRALSQNXMO-UHFFFAOYSA-N 0.000 claims description 2
- QQCOTSNFRWWJQB-UHFFFAOYSA-N n-(2,6-dimethoxy-4-methylphenyl)-n-ethyl-4,6-dimethylpyrimidin-2-amine Chemical compound COC=1C=C(C)C=C(OC)C=1N(CC)C1=NC(C)=CC(C)=N1 QQCOTSNFRWWJQB-UHFFFAOYSA-N 0.000 claims description 2
- BJBJQLPFJLBRHO-UHFFFAOYSA-N n-(2-bromo-4-ethylphenyl)-n,4,6-trimethylpyrimidin-2-amine Chemical compound BrC1=CC(CC)=CC=C1N(C)C1=NC(C)=CC(C)=N1 BJBJQLPFJLBRHO-UHFFFAOYSA-N 0.000 claims description 2
- YSWFQSVVSGMIRX-UHFFFAOYSA-N n-(2-bromo-4-methylphenyl)-n,4-dimethyl-6-morpholin-4-ylpyrimidin-2-amine Chemical compound C=1C=C(C)C=C(Br)C=1N(C)C(N=1)=NC(C)=CC=1N1CCOCC1 YSWFQSVVSGMIRX-UHFFFAOYSA-N 0.000 claims description 2
- UTNHLYVEOWYOTE-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-2,6-dimethylpyridin-4-amine Chemical compound BrC1=CC(C(C)C)=CC=C1NC1=CC(C)=NC(C)=C1 UTNHLYVEOWYOTE-UHFFFAOYSA-N 0.000 claims description 2
- KNUVQRQAICYVGN-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-n-(cyclopropylmethyl)-4,6-dimethylpyrimidin-2-amine Chemical compound BrC1=CC(C(C)C)=CC=C1N(C=1N=C(C)C=C(C)N=1)CC1CC1 KNUVQRQAICYVGN-UHFFFAOYSA-N 0.000 claims description 2
- LBJIYJWNCJMEQK-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-n-ethyl-2,6-dimethoxypyrimidin-4-amine Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C1=CC(OC)=NC(OC)=N1 LBJIYJWNCJMEQK-UHFFFAOYSA-N 0.000 claims description 2
- GMHLYIACCFSORE-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-n-ethyl-4,6-dimethyl-1,3,5-triazin-2-amine Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C1=NC(C)=NC(C)=N1 GMHLYIACCFSORE-UHFFFAOYSA-N 0.000 claims description 2
- FUWKBQSIOZJUBG-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-n-ethyl-4,6-dimethylpyridin-2-amine Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C1=CC(C)=CC(C)=N1 FUWKBQSIOZJUBG-UHFFFAOYSA-N 0.000 claims description 2
- YUEVFPATPSQDPG-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-n-ethyl-4,6-dimethylpyrimidin-2-amine Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C1=NC(C)=CC(C)=N1 YUEVFPATPSQDPG-UHFFFAOYSA-N 0.000 claims description 2
- IOJVECJASZTMAS-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-n-ethyl-4-(imidazol-1-ylmethyl)-6-methylpyrimidin-2-amine Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C(N=1)=NC(C)=CC=1CN1C=CN=C1 IOJVECJASZTMAS-UHFFFAOYSA-N 0.000 claims description 2
- AGKKIZIQXYXPCL-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-n-ethyl-4-methyl-6-(1h-pyrazol-5-yl)pyrimidin-2-amine Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C(N=1)=NC(C)=CC=1C=1C=CNN=1 AGKKIZIQXYXPCL-UHFFFAOYSA-N 0.000 claims description 2
- WYMCYSIIURANEB-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-n-ethyl-4-methyl-6-[1-(tetrazol-1-yl)propan-2-yl]pyrimidin-2-amine Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C(N=1)=NC(C)=CC=1C(C)CN1C=NN=N1 WYMCYSIIURANEB-UHFFFAOYSA-N 0.000 claims description 2
- WYIRCVYFLFJCDG-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-n-ethyl-4-methyl-6-methylsulfinylpyrimidin-2-amine Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C1=NC(C)=CC(S(C)=O)=N1 WYIRCVYFLFJCDG-UHFFFAOYSA-N 0.000 claims description 2
- BGFZZBKGHDEVEO-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-n-ethyl-4-methyl-6-methylsulfonylpyrimidin-2-amine Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C1=NC(C)=CC(S(C)(=O)=O)=N1 BGFZZBKGHDEVEO-UHFFFAOYSA-N 0.000 claims description 2
- JSQBMLUAUMFMRO-UHFFFAOYSA-N n-(2-bromo-6-methoxypyridin-3-yl)-n-ethyl-4,6-dimethylpyrimidin-2-amine Chemical compound C=1C=C(OC)N=C(Br)C=1N(CC)C1=NC(C)=CC(C)=N1 JSQBMLUAUMFMRO-UHFFFAOYSA-N 0.000 claims description 2
- SHJIJQWPWZCYHT-UHFFFAOYSA-N n-(2-bromo-6-methoxypyridin-3-yl)-n-ethyl-4-methyl-6-morpholin-4-yl-1,3,5-triazin-2-amine Chemical compound C=1C=C(OC)N=C(Br)C=1N(CC)C(N=1)=NC(C)=NC=1N1CCOCC1 SHJIJQWPWZCYHT-UHFFFAOYSA-N 0.000 claims description 2
- AFIAMYYTCNEEFL-UHFFFAOYSA-N n-(2-bromophenyl)-n-ethyl-4,6-dimethylpyrimidin-2-amine Chemical compound C=1C=CC=C(Br)C=1N(CC)C1=NC(C)=CC(C)=N1 AFIAMYYTCNEEFL-UHFFFAOYSA-N 0.000 claims description 2
- DHEBTQDTWJTIKX-UHFFFAOYSA-N n-(3-bromo-5-methylpyridin-2-yl)-n-ethyl-4,6-dimethylpyrimidin-2-amine Chemical compound N=1C=C(C)C=C(Br)C=1N(CC)C1=NC(C)=CC(C)=N1 DHEBTQDTWJTIKX-UHFFFAOYSA-N 0.000 claims description 2
- ROQNBOKIGVCZTB-UHFFFAOYSA-N n-(4-bromo-2-methylsulfanylphenyl)-n-ethyl-4,6-dimethylpyrimidin-2-amine Chemical compound C=1C=C(Br)C=C(SC)C=1N(CC)C1=NC(C)=CC(C)=N1 ROQNBOKIGVCZTB-UHFFFAOYSA-N 0.000 claims description 2
- AQVHCVRNRPRBIV-UHFFFAOYSA-N n-(4-ethyl-2-methylsulfanylphenyl)-4,6-dimethyl-n-propan-2-ylpyrimidin-2-amine Chemical compound CSC1=CC(CC)=CC=C1N(C(C)C)C1=NC(C)=CC(C)=N1 AQVHCVRNRPRBIV-UHFFFAOYSA-N 0.000 claims description 2
- PLXSHEVPAMKUPJ-UHFFFAOYSA-N n-[2,4-bis(methylsulfanyl)phenyl]-n-ethyl-4,6-dimethylpyrimidin-2-amine Chemical compound C=1C=C(SC)C=C(SC)C=1N(CC)C1=NC(C)=CC(C)=N1 PLXSHEVPAMKUPJ-UHFFFAOYSA-N 0.000 claims description 2
- FVMZEEHAOSJIEZ-UHFFFAOYSA-N n-[4-[(4,6-dimethylpyrimidin-2-yl)-ethylamino]-3-methylsulfanylphenyl]-n-methylacetamide Chemical compound C=1C=C(N(C)C(C)=O)C=C(SC)C=1N(CC)C1=NC(C)=CC(C)=N1 FVMZEEHAOSJIEZ-UHFFFAOYSA-N 0.000 claims description 2
- FMRVWRISEDIGCW-UHFFFAOYSA-N n-ethyl-4,6-dimethyl-n-(2-methylsulfinyl-4-propan-2-ylphenyl)pyrimidin-2-amine Chemical compound C=1C=C(C(C)C)C=C(S(C)=O)C=1N(CC)C1=NC(C)=CC(C)=N1 FMRVWRISEDIGCW-UHFFFAOYSA-N 0.000 claims description 2
- KPUHYYABTLEMQX-UHFFFAOYSA-N n-ethyl-4,6-dimethyl-n-(2-methylsulfonyl-4-propan-2-ylphenyl)pyrimidin-2-amine Chemical compound C=1C=C(C(C)C)C=C(S(C)(=O)=O)C=1N(CC)C1=NC(C)=CC(C)=N1 KPUHYYABTLEMQX-UHFFFAOYSA-N 0.000 claims description 2
- BJXVREHQPJOWOC-UHFFFAOYSA-N n-ethyl-4,6-dimethyl-n-[2-methylsulfanyl-4-(methylsulfanylmethyl)phenyl]pyrimidin-2-amine Chemical compound C=1C=C(CSC)C=C(SC)C=1N(CC)C1=NC(C)=CC(C)=N1 BJXVREHQPJOWOC-UHFFFAOYSA-N 0.000 claims description 2
- SVMBICKJCCGZQN-UHFFFAOYSA-N n-ethyl-n-(2-ethylsulfanyl-4-propan-2-ylphenyl)-4,6-dimethylpyrimidin-2-amine Chemical compound CCSC1=CC(C(C)C)=CC=C1N(CC)C1=NC(C)=CC(C)=N1 SVMBICKJCCGZQN-UHFFFAOYSA-N 0.000 claims description 2
- KWLHXYDCNRTMJQ-UHFFFAOYSA-N n-ethyl-n-(2-iodo-4-propan-2-ylphenyl)-4-methyl-6-morpholin-4-yl-1,3,5-triazin-2-amine Chemical compound C=1C=C(C(C)C)C=C(I)C=1N(CC)C(N=1)=NC(C)=NC=1N1CCOCC1 KWLHXYDCNRTMJQ-UHFFFAOYSA-N 0.000 claims description 2
- ZTFNHTMCJRKQPL-UHFFFAOYSA-N n-ethyl-n-(2-iodo-4-propan-2-ylphenyl)-4-methyl-6-piperidin-1-yl-1,3,5-triazin-2-amine Chemical compound C=1C=C(C(C)C)C=C(I)C=1N(CC)C(N=1)=NC(C)=NC=1N1CCCCC1 ZTFNHTMCJRKQPL-UHFFFAOYSA-N 0.000 claims description 2
- TWNLYTJTOOUNAA-UHFFFAOYSA-N n-ethyl-n-(2-iodo-4-propan-2-ylphenyl)-4-methyl-6-thiomorpholin-4-yl-1,3,5-triazin-2-amine Chemical compound C=1C=C(C(C)C)C=C(I)C=1N(CC)C(N=1)=NC(C)=NC=1N1CCSCC1 TWNLYTJTOOUNAA-UHFFFAOYSA-N 0.000 claims description 2
- XTYYREGYXWTHSW-UHFFFAOYSA-N n-ethyl-n-(4-ethyl-2-methylsulfanylphenyl)-4,6-dimethylpyrimidin-2-amine Chemical compound C=1C=C(CC)C=C(SC)C=1N(CC)C1=NC(C)=CC(C)=N1 XTYYREGYXWTHSW-UHFFFAOYSA-N 0.000 claims description 2
- RLJLNYOWGVLUFS-UHFFFAOYSA-N n-ethyl-n-(4-methoxy-2-methylsulfanylphenyl)-4,6-dimethylpyrimidin-2-amine Chemical compound C=1C=C(OC)C=C(SC)C=1N(CC)C1=NC(C)=CC(C)=N1 RLJLNYOWGVLUFS-UHFFFAOYSA-N 0.000 claims description 2
- GIDSXEJZZSPYJR-UHFFFAOYSA-N n-ethyl-n-(6-methoxypyridin-3-yl)-4,6-dimethylpyrimidin-2-amine Chemical compound N=1C(C)=CC(C)=NC=1N(CC)C1=CC=C(OC)N=C1 GIDSXEJZZSPYJR-UHFFFAOYSA-N 0.000 claims description 2
- PATXQBVHAQVHNY-UHFFFAOYSA-N n-ethyl-n-[2-ethylsulfanyl-4-(2-methoxyiminoethyl)phenyl]-4,6-dimethylpyrimidin-2-amine Chemical compound CCSC1=CC(CC=NOC)=CC=C1N(CC)C1=NC(C)=CC(C)=N1 PATXQBVHAQVHNY-UHFFFAOYSA-N 0.000 claims description 2
- XQQSZYFVTOOPMW-UHFFFAOYSA-N n-ethyl-n-[2-iodo-4-(2-methoxyethyl)phenyl]-4-methyl-6-morpholin-4-ylpyrimidin-2-amine Chemical compound C=1C=C(CCOC)C=C(I)C=1N(CC)C(N=1)=NC(C)=CC=1N1CCOCC1 XQQSZYFVTOOPMW-UHFFFAOYSA-N 0.000 claims description 2
- MPTIXHAOHVSASV-UHFFFAOYSA-N n-ethyl-n-[2-iodo-4-(methoxymethyl)phenyl]-4-methyl-6-morpholin-4-ylpyrimidin-2-amine Chemical compound C=1C=C(COC)C=C(I)C=1N(CC)C(N=1)=NC(C)=CC=1N1CCOCC1 MPTIXHAOHVSASV-UHFFFAOYSA-N 0.000 claims description 2
- ASZCNSFDUUHRGV-UHFFFAOYSA-N n-ethyl-n-[4-(1-methoxyethyl)-2-methylsulfanylphenyl]-4,6-dimethylpyrimidin-2-amine Chemical compound C=1C=C(C(C)OC)C=C(SC)C=1N(CC)C1=NC(C)=CC(C)=N1 ASZCNSFDUUHRGV-UHFFFAOYSA-N 0.000 claims description 2
- YRZKRQVVTHRMCA-UHFFFAOYSA-N n-ethyl-n-[4-(2-methoxyiminoethyl)-2-methylsulfanylphenyl]-4,6-dimethylpyrimidin-2-amine Chemical compound C=1C=C(CC=NOC)C=C(SC)C=1N(CC)C1=NC(C)=CC(C)=N1 YRZKRQVVTHRMCA-UHFFFAOYSA-N 0.000 claims description 2
- FCLIMOBCZCCTTE-UHFFFAOYSA-N n-ethyl-n-[4-(2-methoxyiminoethyl)-2-methylsulfonylphenyl]-4,6-dimethylpyrimidin-2-amine Chemical compound C=1C=C(CC=NOC)C=C(S(C)(=O)=O)C=1N(CC)C1=NC(C)=CC(C)=N1 FCLIMOBCZCCTTE-UHFFFAOYSA-N 0.000 claims description 2
- IIAFCXIPTAPLJO-UHFFFAOYSA-N n-ethyl-n-[4-(methoxymethyl)-2-methylsulfanylphenyl]-4,6-dimethylpyrimidin-2-amine Chemical compound C=1C=C(COC)C=C(SC)C=1N(CC)C1=NC(C)=CC(C)=N1 IIAFCXIPTAPLJO-UHFFFAOYSA-N 0.000 claims description 2
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 2
- 150000005208 1,4-dihydroxybenzenes Chemical class 0.000 claims 1
- SQGCKGUUABDNTQ-UHFFFAOYSA-N 1-[2-(2-bromo-n-ethyl-4-propan-2-ylanilino)-6-methylpyrimidine-4-carbonyl]piperidin-4-one Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C(N=1)=NC(C)=CC=1C(=O)N1CCC(=O)CC1 SQGCKGUUABDNTQ-UHFFFAOYSA-N 0.000 claims 1
- HCBCZCRQCBOFFD-UHFFFAOYSA-N 4-[2-(2-bromo-n-ethyl-4-propan-2-ylanilino)-6-methylpyrimidin-4-yl]piperazine-1-carbaldehyde Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C(N=1)=NC(C)=CC=1N1CCN(C=O)CC1 HCBCZCRQCBOFFD-UHFFFAOYSA-N 0.000 claims 1
- 206010029216 Nervousness Diseases 0.000 claims 1
- 208000022531 anorexia Diseases 0.000 claims 1
- 206010061428 decreased appetite Diseases 0.000 claims 1
- FWTDYVGFVHHPNU-UHFFFAOYSA-N n,4,6-trimethyl-n-(2,4,6-trimethoxyphenyl)pyrimidin-2-amine Chemical compound COC1=CC(OC)=CC(OC)=C1N(C)C1=NC(C)=CC(C)=N1 FWTDYVGFVHHPNU-UHFFFAOYSA-N 0.000 claims 1
- PIDAXQHBSKRJBP-UHFFFAOYSA-N n-(2-bromo-4,6-dimethoxyphenyl)-4-methyl-6-morpholin-4-yl-n-propan-2-yl-1,3,5-triazin-2-amine Chemical compound COC1=CC(OC)=CC(Br)=C1N(C(C)C)C1=NC(C)=NC(N2CCOCC2)=N1 PIDAXQHBSKRJBP-UHFFFAOYSA-N 0.000 claims 1
- FMNFRYBKQKPRAB-UHFFFAOYSA-N n-(2-bromo-4-butylphenyl)-4,6-dimethyl-n-propylpyrimidin-2-amine Chemical compound BrC1=CC(CCCC)=CC=C1N(CCC)C1=NC(C)=CC(C)=N1 FMNFRYBKQKPRAB-UHFFFAOYSA-N 0.000 claims 1
- RNYRYIVVVBXSRR-UHFFFAOYSA-N n-(2-bromo-4-butylphenyl)-n-ethyl-4,6-dimethylpyrimidin-2-amine Chemical compound BrC1=CC(CCCC)=CC=C1N(CC)C1=NC(C)=CC(C)=N1 RNYRYIVVVBXSRR-UHFFFAOYSA-N 0.000 claims 1
- PVKUTXRKMKETMN-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-n,4,6-triethylpyrimidin-2-amine Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C1=NC(CC)=CC(CC)=N1 PVKUTXRKMKETMN-UHFFFAOYSA-N 0.000 claims 1
- WNJVEQNHWLZFEY-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-n-ethyl-4-methyl-6-(trifluoromethyl)pyrimidin-2-amine Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C1=NC(C)=CC(C(F)(F)F)=N1 WNJVEQNHWLZFEY-UHFFFAOYSA-N 0.000 claims 1
- DQSVEQFHEZHQRX-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-n-ethyl-4-methyl-6-morpholin-4-ylpyrimidin-2-amine Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C(N=1)=NC(C)=CC=1N1CCOCC1 DQSVEQFHEZHQRX-UHFFFAOYSA-N 0.000 claims 1
- ROLHLGPRMAVQAE-UHFFFAOYSA-N n-(2-bromo-4-tert-butylphenyl)-n,4,6-trimethylpyrimidin-2-amine Chemical compound N=1C(C)=CC(C)=NC=1N(C)C1=CC=C(C(C)(C)C)C=C1Br ROLHLGPRMAVQAE-UHFFFAOYSA-N 0.000 claims 1
- BXGUUWNBLCCDDR-UHFFFAOYSA-N n-(2-bromo-4-tert-butylphenyl)-n-ethyl-4,6-dimethylpyrimidin-2-amine Chemical compound C=1C=C(C(C)(C)C)C=C(Br)C=1N(CC)C1=NC(C)=CC(C)=N1 BXGUUWNBLCCDDR-UHFFFAOYSA-N 0.000 claims 1
- NBECXEMALXBXPQ-UHFFFAOYSA-N n-(5-bromo-2,4-dimethoxyphenyl)-n-ethyl-4,6-dimethylpyrimidin-2-amine Chemical compound C=1C(Br)=C(OC)C=C(OC)C=1N(CC)C1=NC(C)=CC(C)=N1 NBECXEMALXBXPQ-UHFFFAOYSA-N 0.000 claims 1
- MXRMYSLQSZCSIR-UHFFFAOYSA-N n-[2-bromo-4-(trifluoromethyl)phenyl]-n,4,6-trimethylpyrimidin-2-amine Chemical compound C=1C=C(C(F)(F)F)C=C(Br)C=1N(C)C1=NC(C)=CC(C)=N1 MXRMYSLQSZCSIR-UHFFFAOYSA-N 0.000 claims 1
- JJHVVGHTEHHRPW-UHFFFAOYSA-N n-[2-bromo-4-(trifluoromethyl)phenyl]-n-ethyl-4,6-dimethylpyrimidin-2-amine Chemical compound C=1C=C(C(F)(F)F)C=C(Br)C=1N(CC)C1=NC(C)=CC(C)=N1 JJHVVGHTEHHRPW-UHFFFAOYSA-N 0.000 claims 1
- NAVWHRLGMUCGFU-UHFFFAOYSA-N n-ethyl-4,6-dimethyl-n-(2,4,6-trimethoxyphenyl)pyrimidin-2-amine Chemical compound COC=1C=C(OC)C=C(OC)C=1N(CC)C1=NC(C)=CC(C)=N1 NAVWHRLGMUCGFU-UHFFFAOYSA-N 0.000 claims 1
- XQPGFRBWNCMCSY-UHFFFAOYSA-N n-ethyl-n-(2-iodo-4-propan-2-ylphenyl)-4,6-dimethylpyrimidin-2-amine Chemical compound C=1C=C(C(C)C)C=C(I)C=1N(CC)C1=NC(C)=CC(C)=N1 XQPGFRBWNCMCSY-UHFFFAOYSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 232
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 132
- 235000019439 ethyl acetate Nutrition 0.000 description 94
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 88
- 239000000047 product Substances 0.000 description 71
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 57
- 239000002904 solvent Substances 0.000 description 51
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 51
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 49
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
- 229940093499 ethyl acetate Drugs 0.000 description 44
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 44
- 239000002585 base Substances 0.000 description 34
- 239000000741 silica gel Substances 0.000 description 33
- 229910002027 silica gel Inorganic materials 0.000 description 33
- 229910000104 sodium hydride Inorganic materials 0.000 description 33
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 32
- 238000006243 chemical reaction Methods 0.000 description 32
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 32
- 239000003921 oil Substances 0.000 description 31
- 235000019198 oils Nutrition 0.000 description 31
- 239000011541 reaction mixture Substances 0.000 description 30
- 239000012442 inert solvent Substances 0.000 description 28
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 27
- 239000000460 chlorine Substances 0.000 description 27
- 239000000243 solution Substances 0.000 description 27
- 102100021752 Corticoliberin Human genes 0.000 description 26
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 25
- 239000012267 brine Substances 0.000 description 25
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 25
- 101710113174 Corticoliberin Proteins 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
- 238000010992 reflux Methods 0.000 description 23
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 22
- 229910052783 alkali metal Inorganic materials 0.000 description 22
- 239000012312 sodium hydride Substances 0.000 description 22
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 20
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 19
- 238000003786 synthesis reaction Methods 0.000 description 19
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 18
- 230000015572 biosynthetic process Effects 0.000 description 18
- 239000012044 organic layer Substances 0.000 description 17
- 239000007787 solid Substances 0.000 description 17
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 16
- 239000000543 intermediate Substances 0.000 description 16
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 16
- 235000019341 magnesium sulphate Nutrition 0.000 description 16
- 150000001340 alkali metals Chemical class 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 239000000284 extract Substances 0.000 description 14
- 101100366282 Mus musculus Spats1 gene Proteins 0.000 description 13
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 13
- 239000003153 chemical reaction reagent Substances 0.000 description 13
- 239000010410 layer Substances 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 150000001413 amino acids Chemical class 0.000 description 12
- 238000001816 cooling Methods 0.000 description 12
- 239000012458 free base Substances 0.000 description 12
- 238000001819 mass spectrum Methods 0.000 description 12
- DFYFVOCFSGCVDH-UHFFFAOYSA-N methyl 2-(2-bromo-n-ethyl-4-propan-2-ylanilino)-6-methylpyrimidine-4-carboxylate Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C1=NC(C)=CC(C(=O)OC)=N1 DFYFVOCFSGCVDH-UHFFFAOYSA-N 0.000 description 12
- 108090000765 processed proteins & peptides Proteins 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 10
- 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 10
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
- 150000004703 alkoxides Chemical class 0.000 description 10
- 125000005233 alkylalcohol group Chemical group 0.000 description 10
- 235000011089 carbon dioxide Nutrition 0.000 description 10
- 239000003638 chemical reducing agent Substances 0.000 description 10
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 10
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 10
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 10
- 239000012299 nitrogen atmosphere Substances 0.000 description 10
- 229910000027 potassium carbonate Inorganic materials 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 9
- 150000001448 anilines Chemical class 0.000 description 9
- 150000004292 cyclic ethers Chemical class 0.000 description 9
- 150000001983 dialkylethers Chemical class 0.000 description 9
- 238000003818 flash chromatography Methods 0.000 description 9
- 238000010438 heat treatment Methods 0.000 description 9
- 150000004678 hydrides Chemical class 0.000 description 9
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 8
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 230000009467 reduction Effects 0.000 description 8
- 238000006722 reduction reaction Methods 0.000 description 8
- 239000000377 silicon dioxide Substances 0.000 description 8
- 108010056643 Corticotropin-Releasing Hormone Receptors Proteins 0.000 description 7
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- 229960000583 acetic acid Drugs 0.000 description 7
- 150000001298 alcohols Chemical class 0.000 description 7
- 150000001408 amides Chemical class 0.000 description 7
- 150000005005 aminopyrimidines Chemical class 0.000 description 7
- 150000003950 cyclic amides Chemical class 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 230000002140 halogenating effect Effects 0.000 description 7
- 150000002430 hydrocarbons Chemical group 0.000 description 7
- 125000001979 organolithium group Chemical group 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- WEMDUNBELVTSRP-UHFFFAOYSA-N 2-bromo-4-propan-2-ylaniline Chemical compound CC(C)C1=CC=C(N)C(Br)=C1 WEMDUNBELVTSRP-UHFFFAOYSA-N 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 6
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 6
- 150000008041 alkali metal carbonates Chemical class 0.000 description 6
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 6
- 150000008046 alkali metal hydrides Chemical class 0.000 description 6
- 150000004982 aromatic amines Chemical class 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- 150000002576 ketones Chemical class 0.000 description 6
- 239000012038 nucleophile Substances 0.000 description 6
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 6
- 208000000103 Anorexia Nervosa Diseases 0.000 description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 229940049706 benzodiazepine Drugs 0.000 description 5
- 125000002619 bicyclic group Chemical group 0.000 description 5
- 150000002357 guanidines Chemical class 0.000 description 5
- 229930195733 hydrocarbon Natural products 0.000 description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
- 229910052744 lithium Inorganic materials 0.000 description 5
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 5
- NSPJNIDYTSSIIY-UHFFFAOYSA-N methoxy(methoxymethoxy)methane Chemical compound COCOCOC NSPJNIDYTSSIIY-UHFFFAOYSA-N 0.000 description 5
- 239000011591 potassium Substances 0.000 description 5
- 235000011181 potassium carbonates Nutrition 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- 238000012552 review Methods 0.000 description 5
- 150000003335 secondary amines Chemical class 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 150000003462 sulfoxides Chemical class 0.000 description 5
- 125000005270 trialkylamine group Chemical group 0.000 description 5
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 5
- MVXVYAKCVDQRLW-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine Chemical class C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 description 4
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 4
- UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 4
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 4
- 208000012902 Nervous system disease Diseases 0.000 description 4
- 208000025966 Neurological disease Diseases 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 230000000949 anxiolytic effect Effects 0.000 description 4
- 239000000010 aprotic solvent Substances 0.000 description 4
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 4
- 229910000085 borane Inorganic materials 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000013058 crude material Substances 0.000 description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 150000008282 halocarbons Chemical class 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 4
- 235000015320 potassium carbonate Nutrition 0.000 description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 150000003212 purines Chemical class 0.000 description 4
- 239000012266 salt solution Substances 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- 235000011149 sulphuric acid Nutrition 0.000 description 4
- 150000003512 tertiary amines Chemical class 0.000 description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 3
- RZVPFDOTMFYQHR-UHFFFAOYSA-N 2-chloro-4,6-dimethylpyrimidine Chemical compound CC1=CC(C)=NC(Cl)=N1 RZVPFDOTMFYQHR-UHFFFAOYSA-N 0.000 description 3
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 3
- GIIGHSIIKVOWKZ-UHFFFAOYSA-N 2h-triazolo[4,5-d]pyrimidine Chemical compound N1=CN=CC2=NNN=C21 GIIGHSIIKVOWKZ-UHFFFAOYSA-N 0.000 description 3
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 3
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- JJTNLWSCFYERCK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine Chemical class N1=CN=C2NC=CC2=C1 JJTNLWSCFYERCK-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 3
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- 239000012448 Lithium borohydride Substances 0.000 description 3
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 3
- 102100027467 Pro-opiomelanocortin Human genes 0.000 description 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 239000003377 acid catalyst Substances 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 239000002168 alkylating agent Substances 0.000 description 3
- 229940100198 alkylating agent Drugs 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 239000002249 anxiolytic agent Substances 0.000 description 3
- 229940005530 anxiolytics Drugs 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 230000003542 behavioural effect Effects 0.000 description 3
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 3
- CDSGJHCARATGKG-UHFFFAOYSA-N bis(3-methylbutyl)borane Chemical compound CC(C)CCBCCC(C)C CDSGJHCARATGKG-UHFFFAOYSA-N 0.000 description 3
- 150000001728 carbonyl compounds Chemical class 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000010779 crude oil Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 238000006073 displacement reaction Methods 0.000 description 3
- 239000002024 ethyl acetate extract Substances 0.000 description 3
- 230000026030 halogenation Effects 0.000 description 3
- 238000005658 halogenation reaction Methods 0.000 description 3
- 239000004009 herbicide Substances 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 230000008629 immune suppression Effects 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 208000024714 major depressive disease Diseases 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 3
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 208000020016 psychiatric disease Diseases 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 3
- SSUJUUNLZQVZMO-UHFFFAOYSA-N 1,2,3,4,8,9,10,10a-octahydropyrimido[1,2-a]azepine Chemical compound C1CCC=CN2CCCNC21 SSUJUUNLZQVZMO-UHFFFAOYSA-N 0.000 description 2
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 2
- PAJPWUMXBYXFCZ-UHFFFAOYSA-N 1-aminocyclopropanecarboxylic acid Chemical compound OC(=O)C1(N)CC1 PAJPWUMXBYXFCZ-UHFFFAOYSA-N 0.000 description 2
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 2
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 2
- BTLKROSJMNFSQZ-UHFFFAOYSA-N 2,4-dichloro-6-methylpyrimidine Chemical compound CC1=CC(Cl)=NC(Cl)=N1 BTLKROSJMNFSQZ-UHFFFAOYSA-N 0.000 description 2
- QXHDYMUPPXAMPQ-UHFFFAOYSA-N 2-(4-aminophenyl)ethanol Chemical compound NC1=CC=C(CCO)C=C1 QXHDYMUPPXAMPQ-UHFFFAOYSA-N 0.000 description 2
- OBRGJCLVVJPXAU-UHFFFAOYSA-N 2-chloro-4-methyl-6-thiophen-2-ylpyrimidine Chemical compound ClC1=NC(C)=CC(C=2SC=CC=2)=N1 OBRGJCLVVJPXAU-UHFFFAOYSA-N 0.000 description 2
- BHAKRVSCGILCEW-UHFFFAOYSA-N 2-chloro-4-methylpyrimidine Chemical compound CC1=CC=NC(Cl)=N1 BHAKRVSCGILCEW-UHFFFAOYSA-N 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical class C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 2
- DBPKMSBWOKAKLA-UHFFFAOYSA-N 4-chloropyrimidine Chemical compound ClC1=CC=NC=N1 DBPKMSBWOKAKLA-UHFFFAOYSA-N 0.000 description 2
- TUARVSWVPPVUGS-UHFFFAOYSA-N 5-nitrouracil Chemical compound [O-][N+](=O)C1=CNC(=O)NC1=O TUARVSWVPPVUGS-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 101800000414 Corticotropin Proteins 0.000 description 2
- 108010022152 Corticotropin-Releasing Hormone Proteins 0.000 description 2
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 2
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 2
- 108010069820 Pro-Opiomelanocortin Proteins 0.000 description 2
- 239000000683 Pro-Opiomelanocortin Substances 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- SZPWXAOBLNYOHY-UHFFFAOYSA-N [C]1=CC=NC2=CC=CC=C12 Chemical group [C]1=CC=NC2=CC=CC=C12 SZPWXAOBLNYOHY-UHFFFAOYSA-N 0.000 description 2
- 150000001241 acetals Chemical class 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 229910001615 alkaline earth metal halide Inorganic materials 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 230000000338 anxiogenic effect Effects 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 239000000749 benzodiazepine receptor blocking agent Substances 0.000 description 2
- KTLFENNEPHBKJD-UHFFFAOYSA-K benzyl(trimethyl)azanium;tribromide Chemical compound [Br-].[Br-].[Br-].C[N+](C)(C)CC1=CC=CC=C1.C[N+](C)(C)CC1=CC=CC=C1.C[N+](C)(C)CC1=CC=CC=C1 KTLFENNEPHBKJD-UHFFFAOYSA-K 0.000 description 2
- NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 2
- 230000027455 binding Effects 0.000 description 2
- 235000010290 biphenyl Nutrition 0.000 description 2
- 239000004305 biphenyl Substances 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L calcium carbonate Substances [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 2
- 229960000258 corticotropin Drugs 0.000 description 2
- 239000002769 corticotropin releasing factor antagonist Substances 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
- 125000005266 diarylamine group Chemical group 0.000 description 2
- 210000002249 digestive system Anatomy 0.000 description 2
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 230000002124 endocrine Effects 0.000 description 2
- UYMKPFRHYYNDTL-UHFFFAOYSA-N ethenamine Chemical class NC=C UYMKPFRHYYNDTL-UHFFFAOYSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000000417 fungicide Substances 0.000 description 2
- 125000005283 haloketone group Chemical group 0.000 description 2
- RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 229910000103 lithium hydride Inorganic materials 0.000 description 2
- OHZZTXYKLXZFSZ-UHFFFAOYSA-I manganese(3+) 5,10,15-tris(1-methylpyridin-1-ium-4-yl)-20-(1-methylpyridin-4-ylidene)porphyrin-22-ide pentachloride Chemical compound [Cl-].[Cl-].[Cl-].[Cl-].[Cl-].[Mn+3].C1=CN(C)C=CC1=C1C(C=C2)=NC2=C(C=2C=C[N+](C)=CC=2)C([N-]2)=CC=C2C(C=2C=C[N+](C)=CC=2)=C(C=C2)N=C2C(C=2C=C[N+](C)=CC=2)=C2N=C1C=C2 OHZZTXYKLXZFSZ-UHFFFAOYSA-I 0.000 description 2
- RVADGLMNXSPVRI-UHFFFAOYSA-N methyl 2-(2-bromo-4-propan-2-ylanilino)-6-methylpyrimidine-4-carboxylate Chemical compound COC(=O)C1=CC(C)=NC(NC=2C(=CC(=CC=2)C(C)C)Br)=N1 RVADGLMNXSPVRI-UHFFFAOYSA-N 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- IRAITQYOQFRTSV-UHFFFAOYSA-N n-(2,6-dibromo-4-propan-2-ylphenyl)-4-methyl-6-thiomorpholin-4-ylpyrimidin-2-amine Chemical compound BrC1=CC(C(C)C)=CC(Br)=C1NC1=NC(C)=CC(N2CCSCC2)=N1 IRAITQYOQFRTSV-UHFFFAOYSA-N 0.000 description 2
- FKWFEXHQWCTXFD-UHFFFAOYSA-N n-(2-bromo-4,6-dimethoxyphenyl)-n-ethyl-4-methyl-6-morpholin-4-yl-1,3,5-triazin-2-amine Chemical compound BrC=1C=C(OC)C=C(OC)C=1N(CC)C(N=1)=NC(C)=NC=1N1CCOCC1 FKWFEXHQWCTXFD-UHFFFAOYSA-N 0.000 description 2
- IBTQKVWQCABYBS-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-4,6-dichloro-n-ethyl-1,3,5-triazin-2-amine Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C1=NC(Cl)=NC(Cl)=N1 IBTQKVWQCABYBS-UHFFFAOYSA-N 0.000 description 2
- YQAFFHYPUXODMI-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-4,6-dimethylpyrimidin-2-amine Chemical compound BrC1=CC(C(C)C)=CC=C1NC1=NC(C)=CC(C)=N1 YQAFFHYPUXODMI-UHFFFAOYSA-N 0.000 description 2
- PHTRTYQHMPWPED-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-n-ethyl-4,6-dimethoxy-1,3,5-triazin-2-amine Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C1=NC(OC)=NC(OC)=N1 PHTRTYQHMPWPED-UHFFFAOYSA-N 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 238000006396 nitration reaction Methods 0.000 description 2
- 125000002560 nitrile group Chemical group 0.000 description 2
- 125000002524 organometallic group Chemical group 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- 229910000105 potassium hydride Inorganic materials 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical group NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 2
- 150000003230 pyrimidines Chemical class 0.000 description 2
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 102220207965 rs778468876 Human genes 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 235000017550 sodium carbonate Nutrition 0.000 description 2
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- 235000010265 sodium sulphite Nutrition 0.000 description 2
- 150000003457 sulfones Chemical class 0.000 description 2
- 230000006103 sulfonylation Effects 0.000 description 2
- 238000005694 sulfonylation reaction Methods 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 150000003536 tetrazoles Chemical class 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- QQOWHRYOXYEMTL-UHFFFAOYSA-N triazin-4-amine Chemical compound N=C1C=CN=NN1 QQOWHRYOXYEMTL-UHFFFAOYSA-N 0.000 description 2
- 150000003918 triazines Chemical class 0.000 description 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 2
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- FPDYKABXINADKS-LURJTMIESA-N (2s)-2-(methylazaniumyl)hexanoate Chemical compound CCCC[C@H](NC)C(O)=O FPDYKABXINADKS-LURJTMIESA-N 0.000 description 1
- IYKLZBIWFXPUCS-VIFPVBQESA-N (2s)-2-(naphthalen-1-ylamino)propanoic acid Chemical compound C1=CC=C2C(N[C@@H](C)C(O)=O)=CC=CC2=C1 IYKLZBIWFXPUCS-VIFPVBQESA-N 0.000 description 1
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 description 1
- DEIBXAPEZDJDRC-UHFFFAOYSA-M (dimethylaminomethylideneamino)methylidene-dimethylazanium;chloride Chemical compound [Cl-].CN(C)C=NC=[N+](C)C DEIBXAPEZDJDRC-UHFFFAOYSA-M 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- POTIYWUALSJREP-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7,8,8a-decahydroquinoline Chemical compound N1CCCC2CCCCC21 POTIYWUALSJREP-UHFFFAOYSA-N 0.000 description 1
- YHRUOJUYPBUZOS-UHFFFAOYSA-N 1,3-dichloropropane Chemical compound ClCCCCl YHRUOJUYPBUZOS-UHFFFAOYSA-N 0.000 description 1
- SXYRTDICSOVQNZ-UHFFFAOYSA-N 1-(2-methoxyethoxy)ethanol Chemical compound COCCOC(C)O SXYRTDICSOVQNZ-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- NILQLFBWTXNUOE-UHFFFAOYSA-N 1-aminocyclopentanecarboxylic acid Chemical compound OC(=O)C1(N)CCCC1 NILQLFBWTXNUOE-UHFFFAOYSA-N 0.000 description 1
- 125000004173 1-benzimidazolyl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N1* 0.000 description 1
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
- 150000008319 1H-pyrimidin-2-ones Chemical class 0.000 description 1
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 1
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 1
- HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 1
- ZFFYPGZDXUPKNK-UHFFFAOYSA-N 2,3-dihydro-1h-pyrrolo[2,3-b]pyridine Chemical compound C1=CN=C2NCCC2=C1 ZFFYPGZDXUPKNK-UHFFFAOYSA-N 0.000 description 1
- OGNSCSPNOLGXSM-UHFFFAOYSA-N 2,4-diaminobutyric acid Chemical compound NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
- KRRJTUULKUAAOM-UHFFFAOYSA-N 2,4-dichloro-6-methyl-1h-triazine Chemical compound CC1=CC(Cl)=NN(Cl)N1 KRRJTUULKUAAOM-UHFFFAOYSA-N 0.000 description 1
- OMGHIGVFLOPEHJ-UHFFFAOYSA-N 2,5-dihydro-1h-pyrrol-1-ium-2-carboxylate Chemical compound OC(=O)C1NCC=C1 OMGHIGVFLOPEHJ-UHFFFAOYSA-N 0.000 description 1
- CJEBZUFROMNDEK-UHFFFAOYSA-N 2,6-dibromo-4-propan-2-ylaniline Chemical compound CC(C)C1=CC(Br)=C(N)C(Br)=C1 CJEBZUFROMNDEK-UHFFFAOYSA-N 0.000 description 1
- VYCNOBNEBXGHKT-UHFFFAOYSA-N 2-(2-methylhydrazinyl)acetic acid Chemical compound CNNCC(O)=O VYCNOBNEBXGHKT-UHFFFAOYSA-N 0.000 description 1
- OFWWMIZKFZGJDY-UHFFFAOYSA-N 2-(4-amino-3-bromophenyl)ethanol Chemical compound NC1=CC=C(CCO)C=C1Br OFWWMIZKFZGJDY-UHFFFAOYSA-N 0.000 description 1
- CLTMYNWFSDZKKI-UHFFFAOYSA-N 2-(aminomethyl)benzoic acid Chemical compound NCC1=CC=CC=C1C(O)=O CLTMYNWFSDZKKI-UHFFFAOYSA-N 0.000 description 1
- CQJAWZCYNRBZDL-UHFFFAOYSA-N 2-(methylazaniumyl)butanoate Chemical compound CCC(NC)C(O)=O CQJAWZCYNRBZDL-UHFFFAOYSA-N 0.000 description 1
- VRBILEJXCPNMNK-UHFFFAOYSA-N 2-[(2-chloro-6-methylpyrimidin-4-yl)-methylamino]ethanol Chemical compound OCCN(C)C1=CC(C)=NC(Cl)=N1 VRBILEJXCPNMNK-UHFFFAOYSA-N 0.000 description 1
- MIRIVTQQOKRWPV-UHFFFAOYSA-N 2-[3-bromo-4-[(4,6-dimethylpyrimidin-2-yl)-ethylamino]phenyl]ethanol Chemical compound C=1C=C(CCO)C=C(Br)C=1N(CC)C1=NC(C)=CC(C)=N1 MIRIVTQQOKRWPV-UHFFFAOYSA-N 0.000 description 1
- GBUGXAULUBTJFM-UHFFFAOYSA-N 2-[bis(methylamino)amino]acetic acid Chemical compound CNN(NC)CC(O)=O GBUGXAULUBTJFM-UHFFFAOYSA-N 0.000 description 1
- HCPJEHJGFKWRFM-UHFFFAOYSA-N 2-amino-5-methylphenol Chemical class CC1=CC=C(N)C(O)=C1 HCPJEHJGFKWRFM-UHFFFAOYSA-N 0.000 description 1
- 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- UVRRJILIXQAAFK-UHFFFAOYSA-N 2-bromo-4-methylaniline Chemical compound CC1=CC=C(N)C(Br)=C1 UVRRJILIXQAAFK-UHFFFAOYSA-N 0.000 description 1
- HIHIRNZVMBCSOF-UHFFFAOYSA-N 2-bromo-4-propan-2-yloxyaniline Chemical compound CC(C)OC1=CC=C(N)C(Br)=C1 HIHIRNZVMBCSOF-UHFFFAOYSA-N 0.000 description 1
- HQEMCIJMQLYVEL-UHFFFAOYSA-N 2-bromo-n-ethyl-4-propan-2-ylaniline Chemical compound CCNC1=CC=C(C(C)C)C=C1Br HQEMCIJMQLYVEL-UHFFFAOYSA-N 0.000 description 1
- RIYFONBSYWACFF-UHFFFAOYSA-N 2-bromoethylcyclopropane Chemical group BrCCC1CC1 RIYFONBSYWACFF-UHFFFAOYSA-N 0.000 description 1
- MARXMDRWROUXMD-UHFFFAOYSA-N 2-bromoisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(Br)C(=O)C2=C1 MARXMDRWROUXMD-UHFFFAOYSA-N 0.000 description 1
- JBMBVWROWJGFMG-UHFFFAOYSA-N 2-chloro-7h-purine Chemical compound ClC1=NC=C2NC=NC2=N1 JBMBVWROWJGFMG-UHFFFAOYSA-N 0.000 description 1
- MPBITFKSUGIJHH-UHFFFAOYSA-N 2-formylbutanedinitrile Chemical compound O=CC(C#N)CC#N MPBITFKSUGIJHH-UHFFFAOYSA-N 0.000 description 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
- GSWYUZQBLVUEPH-UHFFFAOYSA-N 3-(azaniumylmethyl)benzoate Chemical compound NCC1=CC=CC(C(O)=O)=C1 GSWYUZQBLVUEPH-UHFFFAOYSA-N 0.000 description 1
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- XJPZKYIHCLDXST-UHFFFAOYSA-N 4,6-dichloropyrimidine Chemical compound ClC1=CC(Cl)=NC=N1 XJPZKYIHCLDXST-UHFFFAOYSA-N 0.000 description 1
- WHEQVHAIRSPYDK-UHFFFAOYSA-N 4,6-dimethyl-1h-pyrimidin-2-one Chemical compound CC1=CC(C)=NC(O)=N1 WHEQVHAIRSPYDK-UHFFFAOYSA-N 0.000 description 1
- ZUEQJIULCHIIPF-UHFFFAOYSA-N 4-(2-chloro-6-methylpyrimidin-4-yl)thiomorpholine Chemical compound ClC1=NC(C)=CC(N2CCSCC2)=N1 ZUEQJIULCHIIPF-UHFFFAOYSA-N 0.000 description 1
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 1
- KHABBYNLBYZCKP-UHFFFAOYSA-N 4-aminopiperidin-1-ium-4-carboxylate Chemical compound OC(=O)C1(N)CCNCC1 KHABBYNLBYZCKP-UHFFFAOYSA-N 0.000 description 1
- SGLSTFIXVDSVNV-UHFFFAOYSA-N 4-iodobut-1-yne Chemical class ICCC#C SGLSTFIXVDSVNV-UHFFFAOYSA-N 0.000 description 1
- MLNFMFAMNBGAQT-UHFFFAOYSA-N 4-propan-2-yloxyaniline Chemical compound CC(C)OC1=CC=C(N)C=C1 MLNFMFAMNBGAQT-UHFFFAOYSA-N 0.000 description 1
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical compound [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
- HFKRAQJDTVSWNX-UHFFFAOYSA-N 5-amino-2-benzylpentanoic acid Chemical compound NCCCC(C(O)=O)CC1=CC=CC=C1 HFKRAQJDTVSWNX-UHFFFAOYSA-N 0.000 description 1
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 1
- USVZHTBPMMSRHY-UHFFFAOYSA-N 8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9-[2-(2-chlorophenyl)ethyl]purin-6-amine Chemical compound C=1C=2OCOC=2C=C(Br)C=1SC1=NC=2C(N)=NC=NC=2N1CCC1=CC=CC=C1Cl USVZHTBPMMSRHY-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical group CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000017194 Affective disease Diseases 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 101100509371 Arabidopsis thaliana CHR11 gene Proteins 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 229940110385 Benzodiazepine receptor antagonist Drugs 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 229910004664 Cerium(III) chloride Inorganic materials 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 229910020314 ClBr Inorganic materials 0.000 description 1
- 241001625326 Commellus colon Species 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 102400000739 Corticotropin Human genes 0.000 description 1
- 229940122010 Corticotropin releasing factor antagonist Drugs 0.000 description 1
- 150000008574 D-amino acids Chemical class 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- PNKUSGQVOMIXLU-UHFFFAOYSA-N Formamidine Chemical compound NC=N PNKUSGQVOMIXLU-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical group [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- LCWXJXMHJVIJFK-UHFFFAOYSA-N Hydroxylysine Natural products NCC(O)CC(N)CC(O)=O LCWXJXMHJVIJFK-UHFFFAOYSA-N 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- 206010062767 Hypophysitis Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- QUOGESRFPZDMMT-UHFFFAOYSA-N L-Homoarginine Natural products OC(=O)C(N)CCCCNC(N)=N QUOGESRFPZDMMT-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- QUOGESRFPZDMMT-YFKPBYRVSA-N L-homoarginine Chemical compound OC(=O)[C@@H](N)CCCCNC(N)=N QUOGESRFPZDMMT-YFKPBYRVSA-N 0.000 description 1
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
- QMCOPDWHWYSJSA-UHFFFAOYSA-N N-methyl-9H-pyrido[3,4-b]indole-3-carboxamide Chemical compound N1C2=CC=CC=C2C2=C1C=NC(C(=O)NC)=C2 QMCOPDWHWYSJSA-UHFFFAOYSA-N 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- OPKOKAMJFNKNAS-UHFFFAOYSA-N N-methylethanolamine Chemical compound CNCCO OPKOKAMJFNKNAS-UHFFFAOYSA-N 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- 102000003797 Neuropeptides Human genes 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
- 229910020656 PBr5 Inorganic materials 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 229940123924 Protein kinase C inhibitor Drugs 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 229910006124 SOCl2 Inorganic materials 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 101150095510 TMEM35A gene Proteins 0.000 description 1
- GYDJEQRTZSCIOI-UHFFFAOYSA-N Tranexamic acid Chemical compound NCC1CCC(C(O)=O)CC1 GYDJEQRTZSCIOI-UHFFFAOYSA-N 0.000 description 1
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
- 238000007239 Wittig reaction Methods 0.000 description 1
- 238000005644 Wolff-Kishner reduction reaction Methods 0.000 description 1
- VCOJPHPOVDIRJK-LURJTMIESA-N [(2s)-1-methylpyrrolidin-2-yl]methanol Chemical compound CN1CCC[C@H]1CO VCOJPHPOVDIRJK-LURJTMIESA-N 0.000 description 1
- UJEOXCFMQPCGTI-UHFFFAOYSA-N [2-(2-bromo-n-ethyl-4-propan-2-ylanilino)-6-methylpyrimidin-4-yl]-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)methanone Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C(N=1)=NC(C)=CC=1C(=O)N(CC1)CCC21OCCO2 UJEOXCFMQPCGTI-UHFFFAOYSA-N 0.000 description 1
- YCWYMXQIVILODJ-UHFFFAOYSA-N [2-(2-bromo-n-ethyl-4-propan-2-ylanilino)-6-methylpyrimidin-4-yl]methanol Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C1=NC(C)=CC(CO)=N1 YCWYMXQIVILODJ-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 150000003869 acetamides Chemical class 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 150000008043 acidic salts Chemical class 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 125000005076 adamantyloxycarbonyl group Chemical group C12(CC3CC(CC(C1)C3)C2)OC(=O)* 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 150000001351 alkyl iodides Chemical class 0.000 description 1
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 229940064734 aminobenzoate Drugs 0.000 description 1
- 229960002684 aminocaproic acid Drugs 0.000 description 1
- QCTBMLYLENLHLA-UHFFFAOYSA-N aminomethylbenzoic acid Chemical compound NCC1=CC=C(C(O)=O)C=C1 QCTBMLYLENLHLA-UHFFFAOYSA-N 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 150000003931 anilides Chemical class 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000003092 anti-cytokine Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003699 antiulcer agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000001543 aryl boronic acids Chemical class 0.000 description 1
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000002567 autonomic effect Effects 0.000 description 1
- 125000005604 azodicarboxylate group Chemical group 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical class ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
- AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 1
- XGIUDIMNNMKGDE-UHFFFAOYSA-N bis(trimethylsilyl)azanide Chemical compound C[Si](C)(C)[N-][Si](C)(C)C XGIUDIMNNMKGDE-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- JAMFGQBENKSWOF-UHFFFAOYSA-N bromo(methoxy)methane Chemical compound COCBr JAMFGQBENKSWOF-UHFFFAOYSA-N 0.000 description 1
- APJYYFNGGGLDJF-UHFFFAOYSA-N but-3-ynyl methanesulfonate Chemical compound CS(=O)(=O)OCCC#C APJYYFNGGGLDJF-UHFFFAOYSA-N 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 238000004177 carbon cycle Methods 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- VZGDMQKNWNREIO-UHFFFAOYSA-N carbon tetrachloride Substances ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- VYLVYHXQOHJDJL-UHFFFAOYSA-K cerium trichloride Chemical compound Cl[Ce](Cl)Cl VYLVYHXQOHJDJL-UHFFFAOYSA-K 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- ANTSCNMPPGJYLG-UHFFFAOYSA-N chlordiazepoxide Chemical compound O=N=1CC(NC)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 ANTSCNMPPGJYLG-UHFFFAOYSA-N 0.000 description 1
- 229960004782 chlordiazepoxide Drugs 0.000 description 1
- KWTSZCJMWHGPOS-UHFFFAOYSA-M chloro(trimethyl)stannane Chemical compound C[Sn](C)(C)Cl KWTSZCJMWHGPOS-UHFFFAOYSA-M 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- 108010050742 corticotropin releasing hormone (9-41) Proteins 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 125000006266 dimethyl hydroxy methyl group Chemical group [H]OC(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000012039 electrophile Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- ICFCBYVKPRHTPR-UHFFFAOYSA-N ethyl 4-amino-3-iodobenzoate Chemical compound CCOC(=O)C1=CC=C(N)C(I)=C1 ICFCBYVKPRHTPR-UHFFFAOYSA-N 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- OFBIFZUFASYYRE-UHFFFAOYSA-N flumazenil Chemical compound C1N(C)C(=O)C2=CC(F)=CC=C2N2C=NC(C(=O)OCC)=C21 OFBIFZUFASYYRE-UHFFFAOYSA-N 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 210000005153 frontal cortex Anatomy 0.000 description 1
- 244000000004 fungal plant pathogen Species 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000027119 gastric acid secretion Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 159000000011 group IA salts Chemical class 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000005280 halo alkyl sulfonyloxy group Chemical group 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 238000006197 hydroboration reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000002440 hydroxy compounds Chemical class 0.000 description 1
- QJHBJHUKURJDLG-UHFFFAOYSA-N hydroxy-L-lysine Natural products NCCCCC(NO)C(O)=O QJHBJHUKURJDLG-UHFFFAOYSA-N 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 230000000899 immune system response Effects 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 229940088592 immunologic factor Drugs 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000004926 indolenyl group Chemical group 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
- 229910052808 lithium carbonate Inorganic materials 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- HHQJWDKIRXRTLS-UHFFFAOYSA-N n'-bromobutanediamide Chemical compound NC(=O)CCC(=O)NBr HHQJWDKIRXRTLS-UHFFFAOYSA-N 0.000 description 1
- VEAUGEBKCBFOFE-UHFFFAOYSA-N n-(2-bromo-4-methylphenyl)-4,6-dimethylpyrimidin-2-amine Chemical compound BrC1=CC(C)=CC=C1NC1=NC(C)=CC(C)=N1 VEAUGEBKCBFOFE-UHFFFAOYSA-N 0.000 description 1
- DQJAOZSMMOFFFK-UHFFFAOYSA-N n-(2-bromo-4-methylphenyl)-n,4,6-trimethylpyrimidin-2-amine Chemical compound N=1C(C)=CC(C)=NC=1N(C)C1=CC=C(C)C=C1Br DQJAOZSMMOFFFK-UHFFFAOYSA-N 0.000 description 1
- PNKMNQFKXBLSTK-UHFFFAOYSA-N n-(2-bromo-4-propan-2-yloxyphenyl)-n-ethyl-4,6-dimethylpyrimidin-2-amine Chemical compound C=1C=C(OC(C)C)C=C(Br)C=1N(CC)C1=NC(C)=CC(C)=N1 PNKMNQFKXBLSTK-UHFFFAOYSA-N 0.000 description 1
- YTIFIMLEGCABCM-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-4-methyl-6-morpholin-4-ylpyrimidin-2-amine Chemical compound BrC1=CC(C(C)C)=CC=C1NC1=NC(C)=CC(N2CCOCC2)=N1 YTIFIMLEGCABCM-UHFFFAOYSA-N 0.000 description 1
- KCRDZKRDVBGAGX-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-4-methyl-6-thiophen-2-ylpyrimidin-2-amine Chemical compound BrC1=CC(C(C)C)=CC=C1NC1=NC(C)=CC(C=2SC=CC=2)=N1 KCRDZKRDVBGAGX-UHFFFAOYSA-N 0.000 description 1
- HAAFQZOMTAPHNO-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-4-methylpyrimidin-2-amine Chemical compound BrC1=CC(C(C)C)=CC=C1NC1=NC=CC(C)=N1 HAAFQZOMTAPHNO-UHFFFAOYSA-N 0.000 description 1
- QNKLCGGMUMYSHV-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-n-ethyl-4-(methoxymethyl)-6-methylpyrimidin-2-amine Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C1=NC(C)=CC(COC)=N1 QNKLCGGMUMYSHV-UHFFFAOYSA-N 0.000 description 1
- HDEREWFVKKZHLL-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-n-ethyl-4-methyl-6-morpholin-4-yl-1,3,5-triazin-2-amine Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C(N=1)=NC(C)=NC=1N1CCOCC1 HDEREWFVKKZHLL-UHFFFAOYSA-N 0.000 description 1
- FMAPHUUNNLPWTB-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)-n-ethyl-4-methyl-6-thiophen-2-ylpyrimidin-2-amine Chemical compound C=1C=C(C(C)C)C=C(Br)C=1N(CC)C(N=1)=NC(C)=CC=1C1=CC=CS1 FMAPHUUNNLPWTB-UHFFFAOYSA-N 0.000 description 1
- POSZCEYBZADKJL-UHFFFAOYSA-N n-(2-bromo-4-propan-2-ylphenyl)pyrimidin-2-amine Chemical class BrC1=CC(C(C)C)=CC=C1NC1=NC=CC=N1 POSZCEYBZADKJL-UHFFFAOYSA-N 0.000 description 1
- PUKALTSYVNBVNZ-UHFFFAOYSA-N n-[2-bromo-4-(2-methoxyethyl)phenyl]-n-ethyl-4-methyl-6-morpholin-4-ylpyrimidin-2-amine Chemical compound C=1C=C(CCOC)C=C(Br)C=1N(CC)C(N=1)=NC(C)=CC=1N1CCOCC1 PUKALTSYVNBVNZ-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- GRFFSCNZSVHVEX-UHFFFAOYSA-N n-ethyl-n-(2-methoxy-4-propan-2-ylphenyl)-4,6-dimethylpyrimidin-2-amine Chemical compound C=1C=C(C(C)C)C=C(OC)C=1N(CC)C1=NC(C)=CC(C)=N1 GRFFSCNZSVHVEX-UHFFFAOYSA-N 0.000 description 1
- XGXNTJHZPBRBHJ-UHFFFAOYSA-N n-phenylpyrimidin-2-amine Chemical compound N=1C=CC=NC=1NC1=CC=CC=C1 XGXNTJHZPBRBHJ-UHFFFAOYSA-N 0.000 description 1
- 230000001722 neurochemical effect Effects 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 230000003227 neuromodulating effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical group 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 150000004967 organic peroxy acids Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000002734 organomagnesium group Chemical group 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- WURFKUQACINBSI-UHFFFAOYSA-M ozonide Chemical compound [O]O[O-] WURFKUQACINBSI-UHFFFAOYSA-M 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 125000005327 perimidinyl group Chemical group N1C(=NC2=CC=CC3=CC=CC1=C23)* 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 229950000688 phenothiazine Drugs 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 1
- LJZPPWWHKPGCHS-UHFFFAOYSA-N propargyl chloride Chemical class ClCC#C LJZPPWWHKPGCHS-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 239000003881 protein kinase C inhibitor Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical class OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- FVLAYJRLBLHIPV-UHFFFAOYSA-N pyrimidin-5-amine Chemical compound NC1=CN=CN=C1 FVLAYJRLBLHIPV-UHFFFAOYSA-N 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- HBCQSNAFLVXVAY-UHFFFAOYSA-N pyrimidine-2-thiol Chemical class SC1=NC=CC=N1 HBCQSNAFLVXVAY-UHFFFAOYSA-N 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 229910052705 radium Inorganic materials 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010405 reoxidation reaction Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 102220024172 rs397515479 Human genes 0.000 description 1
- 229910052701 rubidium Inorganic materials 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 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 1
- 239000011780 sodium chloride Substances 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 150000003413 spiro compounds Chemical class 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 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
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- WTVXIBRMWGUIMI-UHFFFAOYSA-N trifluoro($l^{1}-oxidanylsulfonyl)methane Chemical group [O]S(=O)(=O)C(F)(F)F WTVXIBRMWGUIMI-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 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
- 238000010792 warming Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 150000003738 xylenes Chemical class 0.000 description 1
- LJGOZJHDEQHJRI-SITYYSIOSA-N α-helical crf Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(O)=O)[C@@H](C)CC)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(O)=O)[C@@H](C)O)C(C)C)C1=CNC=N1 LJGOZJHDEQHJRI-SITYYSIOSA-N 0.000 description 1
- MMSLSKDMIZOHRX-WYDAWZGFSA-N α-helical crf(9-41) Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(N)=O MMSLSKDMIZOHRX-WYDAWZGFSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
- C07D251/16—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to only one ring carbon atom
- C07D251/18—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to only one ring carbon atom with nitrogen atoms directly attached to the two other ring carbon atoms, e.g. guanamines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/40—Heterocyclic compounds containing purine ring systems with halogen atoms or perhalogeno-alkyl radicals directly attached in position 2 or 6
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US13420993A | 1993-10-12 | 1993-10-12 | |
US29727494A | 1994-08-26 | 1994-08-26 | |
US31566094A | 1994-09-29 | 1994-09-29 |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP940664A2 true HRP940664A2 (en) | 1996-12-31 |
Family
ID=27384537
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR08/315,660A HRP940664A2 (en) | 1993-10-12 | 1994-10-11 | 1n-alkyl-n-arylpyrimidinamines and derivatives thereof |
Country Status (14)
Country | Link |
---|---|
US (2) | US6107301A (ko) |
EP (1) | EP0723533A1 (ko) |
KR (1) | KR960704855A (ko) |
AU (1) | AU692484B2 (ko) |
BR (1) | BR9407799A (ko) |
CA (1) | CA2174080A1 (ko) |
CZ (1) | CZ101496A3 (ko) |
HR (1) | HRP940664A2 (ko) |
HU (1) | HUT74464A (ko) |
IL (1) | IL111221A0 (ko) |
NO (1) | NO961425L (ko) |
NZ (1) | NZ274978A (ko) |
PL (1) | PL313973A1 (ko) |
SK (1) | SK47096A3 (ko) |
Families Citing this family (106)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU738304B2 (en) * | 1995-10-13 | 2001-09-13 | Neurogen Corporation | Certain pyrrolopyridine derivatives; novel CRF 1 specific ligands |
EP0945447A1 (en) | 1998-03-27 | 1999-09-29 | Janssen Pharmaceutica N.V. | Trisubstituted 1,3,5-triazine derivatives for treatment of HIV infections |
TWI241298B (en) * | 1998-09-25 | 2005-10-11 | Mitsubishi Chem Corp | Pyrimidone derivatives |
EP1129079B1 (en) | 1998-11-10 | 2006-01-04 | Janssen Pharmaceutica N.V. | 2,4-disubstituded triazine derivatives with anti hiv activity |
SK285240B6 (sk) | 1999-09-24 | 2006-09-07 | Janssen Pharmaceutica N. V. | Antivírusové prostriedky |
CN1429222A (zh) * | 2000-02-17 | 2003-07-09 | 安姆根有限公司 | 激酶抑制剂 |
CN100355751C (zh) | 2000-03-29 | 2007-12-19 | 西克拉塞尔有限公司 | 2-取代的4-杂芳基-嘧啶、其组合物及其用途 |
ATE398109T1 (de) * | 2000-08-08 | 2008-07-15 | Ortho Mcneil Pharm Inc | 4-pyrimidinamine derivate, pharmazeutische zusammenstellungen und verwandte methoden |
US20050203092A1 (en) * | 2000-08-08 | 2005-09-15 | Benjamin Elfrida R. | 4-Pyrimidinamine derivatives, pharmaceutical compositions and related methods |
GB0100624D0 (en) * | 2001-01-10 | 2001-02-21 | Vernalis Res Ltd | Chemical compounds VII |
US20040157855A1 (en) * | 2001-04-05 | 2004-08-12 | Michael Heinrich | Use of n-phenyl-2-pyrimidineamine derivativea against mast cell-based diseases like allergic disorders |
ATE331519T1 (de) * | 2001-05-16 | 2006-07-15 | Gpc Biotech Ag | Pyridylpyrimidin-derivate als wirksame verbindungen gegen prionen-krankheiten |
WO2003000186A2 (en) | 2001-06-21 | 2003-01-03 | Ariad Pharmaceuticals, Inc. | Novel phenylamino-pyrimidines and uses thereof |
US6825198B2 (en) * | 2001-06-21 | 2004-11-30 | Pfizer Inc | 5-HT receptor ligands and uses thereof |
CA2451128A1 (en) | 2001-06-26 | 2003-01-09 | Bristol-Myers Squibb Company | N-heterocyclic inhibitors of tnf-alpha expression |
GB0117396D0 (en) * | 2001-07-17 | 2001-09-05 | Glaxo Group Ltd | Chemical compounds |
AU2002337498B2 (en) * | 2001-09-21 | 2006-08-10 | Mitsubishi Pharma Corporation | 3-substituted-4-pyrimidone derivatives |
WO2003037888A1 (en) * | 2001-09-21 | 2003-05-08 | Mitsubishi Pharma Corporation | 3-substituted-4-pyrimidone derivatives |
US7910586B2 (en) * | 2002-01-04 | 2011-03-22 | The Rockefeller University | Compositions and methods for prevention and treatment of amyloid-β peptide-related disorders |
US20030149052A1 (en) * | 2002-01-22 | 2003-08-07 | Memory Pharmaceuticals Corp. | Phosphodiesterase 4 inhibitors |
AR038368A1 (es) * | 2002-02-01 | 2005-01-12 | Novartis Ag | Compuestos n-pirimidin-2-il-aminas sustituidas como inhibidores de ige, una composicion farmaceutica y el uso de dichos compuestos para la preparacion de un medicamento |
TWI329105B (en) | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
TW200409629A (en) * | 2002-06-27 | 2004-06-16 | Bristol Myers Squibb Co | 2,4-disubstituted-pyridine N-oxides useful as HIV reverse transcriptase inhibitors |
BR0313000A (pt) | 2002-07-19 | 2005-07-12 | Memory Pharm Corp | Compostos, composição farmacêutica e método para efetuar a inibição da enzima pde4, realçar a cognição e/ou tratar a psicose em um paciente |
ES2445208T3 (es) | 2002-07-29 | 2014-02-28 | Rigel Pharmaceuticals, Inc. | Compuestos de 2,4-pirimidindiamina para uso en métodos para tratar o prevenir enfermedades autoinmunitarias |
DE60308699T2 (de) * | 2002-08-21 | 2007-08-23 | Glaxo Group Ltd., Greenford | 2-phenylamino-4-trifluoromethyl-5-(benzyl- oder pyridin-4-ylmethyl)carbamoylpyrimidin-derivate als selektive cb2 cannabinoid-rezeptor modulatoren |
UY27939A1 (es) * | 2002-08-21 | 2004-03-31 | Glaxo Group Ltd | Compuestos |
GB0219746D0 (en) * | 2002-08-23 | 2002-10-02 | Inst Of Ex Botany Ascr | Azapurine derivatives |
GB0222495D0 (en) * | 2002-09-27 | 2002-11-06 | Glaxo Group Ltd | Compounds |
MXPA05005547A (es) * | 2002-11-28 | 2005-07-26 | Schering Ag | Pirimidinas inhibidoras de chk, pdk y akt, su produccion y uso como agentes farmaceuticos. |
US7683069B2 (en) * | 2002-12-16 | 2010-03-23 | Mitsubishi Tanabe Pharma Corporation | 3-substituted-4-pyrimidone derivatives |
DK1599468T3 (da) | 2003-01-14 | 2008-02-04 | Arena Pharm Inc | 1,2,3-trisubstituerede aryl- og heteroarylderivater som modulatorer af metabolisme og forebyggelse og behandling af forstyrrelser forbundet dermed såsom diabetes og hyperglykæmi |
TWI357408B (en) * | 2003-03-26 | 2012-02-01 | Mitsubishi Tanabe Pharma Corp | 3-substituted-4-pyrimidone derivatives |
US20050014753A1 (en) * | 2003-04-04 | 2005-01-20 | Irm Llc | Novel compounds and compositions as protein kinase inhibitors |
WO2004092170A2 (en) * | 2003-04-09 | 2004-10-28 | Biogen Idec Ma Inc. | Triazolotriazines and pyrazolotriazines useful as a2a adenosine receptor antagon ists |
WO2004092172A2 (en) * | 2003-04-09 | 2004-10-28 | Biogen Idec Ma Inc. | Triazolo[1,5-c]pyrimidines and pyrazolo[1,5-c]pyrimidines useful as a2a adenosin e receptor antagonists |
US20070021429A1 (en) * | 2003-04-09 | 2007-01-25 | Yves St-Denis | Condensed n-heterocyclic compounds and their use as crf receptor antagonists |
GB0308208D0 (en) * | 2003-04-09 | 2003-05-14 | Glaxo Group Ltd | Chemical compounds |
US7834014B2 (en) * | 2003-04-09 | 2010-11-16 | Biogen Idec Ma Inc. | A2a adenosine receptor antagonists |
EP1618108A2 (en) * | 2003-04-09 | 2006-01-25 | Biogen Idec MA Inc. | Triazolo[1,5-a]pyrimidines and pyrazolo[1,5-a]pyrimidines useful as a2a adenosine receptor antagonists |
EP1615931A1 (en) * | 2003-04-09 | 2006-01-18 | Biogen Idec MA Inc. | Triazolopyrazines and methods of making and using the same |
EP2287166A3 (en) * | 2003-07-14 | 2011-06-22 | Arena Pharmaceuticals, Inc. | Fused-aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto |
KR101201603B1 (ko) * | 2003-07-30 | 2012-11-14 | 리겔 파마슈티칼스, 인크. | 자가면역 질환의 치료 또는 예방에 사용하기 위한2,4-피리미딘디아민 화합물 |
BRPI0413563A (pt) * | 2003-08-15 | 2006-10-17 | Irm Llc | compostos e composições como inibidores de atividade do receptor de quìnase de tirosina |
JP4866610B2 (ja) | 2003-08-18 | 2012-02-01 | 富士フイルムファインケミカルズ株式会社 | ピリジルテトラヒドロピリジン類およびピリジルピペリジン類 |
JP4800216B2 (ja) * | 2003-10-24 | 2011-10-26 | エグゼリクシス, インコーポレイテッド | p70S6キナーゼモジュレーターおよび使用方法 |
US7714009B2 (en) * | 2003-10-31 | 2010-05-11 | Takeda Pharmaceutical Company Limited | Nitrogen-containing fused heterocyclic compounds |
PT1686997E (pt) | 2003-11-18 | 2009-07-17 | Novartis Ag | Inibidores da forma mutante de kit |
MY141255A (en) * | 2003-12-11 | 2010-03-31 | Memory Pharm Corp | Phosphodiesterase 4 inhibitors, including n-substituted diarylamine analogs |
AU2005206557A1 (en) * | 2004-01-22 | 2005-08-04 | Amgen Inc. | Substituted heterocyclic compounds and methods of use |
GB0402653D0 (en) * | 2004-02-06 | 2004-03-10 | Cyclacel Ltd | Compounds |
US7534798B2 (en) * | 2004-02-11 | 2009-05-19 | Amgen Inc. | Vanilloid receptor ligands and their use in treatments |
CA2557667A1 (en) * | 2004-03-02 | 2005-09-15 | Neurogen Corporation | Aryl substituted purine analogues |
EP1763514A2 (en) | 2004-05-18 | 2007-03-21 | Rigel Pharmaceuticals, Inc. | Cycloalkyl substituted pyrimidinediamine compounds and their uses |
GB0411791D0 (en) * | 2004-05-26 | 2004-06-30 | Cyclacel Ltd | Compounds |
AU2005276231A1 (en) * | 2004-08-27 | 2006-03-02 | Cyclacel Limited | Purine and pyrimidine CDK inhibitors and their use for the treatment of autoimmune diseases |
US20080167321A1 (en) | 2004-09-20 | 2008-07-10 | Xenon Pharmaceuticals Inc. | Pyridine Derivatives For Inhibiting Human Stearoyl-Coa-Desaturase |
KR20070084067A (ko) * | 2004-10-13 | 2007-08-24 | 와이어쓰 | N-벤젠설포닐 치환 아닐리노-피리미딘 동족체 |
GB2420559B (en) * | 2004-11-15 | 2008-08-06 | Rigel Pharmaceuticals Inc | Stereoisomerically enriched 3-aminocarbonyl bicycloheptene pyrimidinediamine compounds and their uses |
EP1814878B1 (en) * | 2004-11-24 | 2012-01-04 | Rigel Pharmaceuticals, Inc. | Spiro-2, 4-pyrimidinediamine compounds and their uses |
ATE451381T1 (de) * | 2005-01-19 | 2009-12-15 | Rigel Pharmaceuticals Inc | Prodrugs aus 2,4-pyrimidindiamin-verbindungen und ihre verwendungen |
CA2606716C (en) * | 2005-05-02 | 2013-07-23 | Novartis Ag | Use of pyrimidylaminobenzamide derivatives for the treatment of systematic mastocytosis |
JP2008540436A (ja) * | 2005-05-03 | 2008-11-20 | ライジェル ファーマシューティカルズ, インコーポレイテッド | Jakキナーゼインヒビターおよびそれらの使用 |
US20060293343A1 (en) * | 2005-05-18 | 2006-12-28 | Asahi Kasei Pharma Corporation | Pyrimidine derivatives |
US7491732B2 (en) | 2005-06-08 | 2009-02-17 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the JAK pathway |
US20070203161A1 (en) * | 2006-02-24 | 2007-08-30 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the jak pathway |
EP1931668A2 (en) * | 2005-09-16 | 2008-06-18 | Ranbaxy Laboratories Limited | Substituted pyrazolo [3,4-b]pyridines as phosphodiesterase inhibitors |
US7915286B2 (en) | 2005-09-16 | 2011-03-29 | Ranbaxy Laboratories Limited | Substituted pyrazolo [3,4-b] pyridines as phosphodiesterase inhibitors |
US8153791B2 (en) | 2005-12-21 | 2012-04-10 | Janssen Pharmaceutica N.V. | Substituted pyrimidinyl oxime kinase inhibitors |
WO2007109783A2 (en) * | 2006-03-23 | 2007-09-27 | Janssen Pharmaceutica, N.V. | Substituted pyrimidine kinase inhibitors |
DK2133332T3 (da) * | 2007-04-11 | 2013-09-30 | Kissei Pharmaceutical | (aza)indolderivat og anvendelse deraf til medicinske formål |
WO2008157302A2 (en) * | 2007-06-13 | 2008-12-24 | Research Development Foundation | Methods for treatment and prevention of tauopathies and amyloid beta amyloidosis by modulating crf receptor signaling |
DK2300013T3 (en) | 2008-05-21 | 2017-12-04 | Ariad Pharma Inc | PHOSPHORUS DERIVATIVES AS KINASE INHIBITORS |
US9273077B2 (en) | 2008-05-21 | 2016-03-01 | Ariad Pharmaceuticals, Inc. | Phosphorus derivatives as kinase inhibitors |
WO2009144632A1 (en) * | 2008-05-30 | 2009-12-03 | Pfizer Limited | Novel compounds |
GB0906579D0 (en) | 2009-04-16 | 2009-05-20 | Vernalis R&D Ltd | Pharmaceuticals, compositions and methods of making and using the same |
US20100029689A1 (en) * | 2008-07-02 | 2010-02-04 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors |
US20100113523A1 (en) * | 2008-10-30 | 2010-05-06 | Alberte Randall S | Tryptase Enzyme Inhibiting Aminopyridines |
EP2459195A1 (en) * | 2009-07-28 | 2012-06-06 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the jak pathway |
SG10201507362TA (en) | 2009-08-05 | 2015-10-29 | Intra Cellular Therapies Inc | Novel Regulatory Proteins And Inhibitors |
MX353747B (es) | 2009-08-17 | 2018-01-26 | Memorial Sloan Kettering Cancer Center Star | Compuesto de union a proteina de choque termico, composiciones, y metodos para producir y usar los mismos. |
ES2937386T3 (es) | 2010-01-27 | 2023-03-28 | Arena Pharm Inc | Procesos para la preparación de ácido (R)-2-(7-(4-ciclopentil-3-(trifluorometil)benciloxi)-1,2,3,4-tetrahidrociclopenta[b]indol-3-il)acético y sales del mismo |
CA2797947C (en) | 2010-06-04 | 2019-07-09 | Charles Baker-Glenn | Aminopyrimidine derivatives as lrrk2 modulators |
SG188548A1 (en) | 2010-09-22 | 2013-04-30 | Arena Pharm Inc | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
HUE037844T2 (hu) | 2010-11-10 | 2018-09-28 | Genentech Inc | Pirazol-aminopirimidin-származékok mint LRRK2 modulátorok |
AU2012221927B2 (en) * | 2011-02-25 | 2016-04-28 | Yuhan Corporation | Diaminopyrimidine derivatives and processes for the preparation thereof |
AU2012250517B2 (en) | 2011-05-04 | 2016-05-19 | Takeda Pharmaceutical Company Limited | Compounds for inhibiting cell proliferation in EGFR-driven cancers |
WO2012167053A1 (en) * | 2011-06-01 | 2012-12-06 | Janus Biotherapeutics, Inc. | Novel immune system modulators |
GB201113538D0 (en) | 2011-08-04 | 2011-09-21 | Karobio Ab | Novel estrogen receptor ligands |
UA111640C2 (uk) * | 2011-11-08 | 2016-05-25 | Ф. Хоффманн-Ля Рош Аг | ПОХІДНІ [1,2,3]ТРИАЗОЛО[4,5-d]ПІРИМІДИНУ ЯК АГОНІСТИ КАНАБІНОЇДНОГО РЕЦЕПТОРА 2 |
WO2013160317A2 (en) * | 2012-04-23 | 2013-10-31 | Holsboermaschmeyer Neurochemie Gmbh | Crhr1 antagonists for use in the treatment of patients having crh overactivity |
AU2013204563B2 (en) | 2012-05-05 | 2016-05-19 | Takeda Pharmaceutical Company Limited | Compounds for inhibiting cell proliferation in EGFR-driven cancers |
GB201210686D0 (en) | 2012-06-15 | 2012-08-01 | Holsboermaschmeyer Neurochemie Gmbh | V1B receptor antagonist for use in the treatment of patients having an elevated AVP level and/or an elevated copeptin level |
US9611283B1 (en) | 2013-04-10 | 2017-04-04 | Ariad Pharmaceuticals, Inc. | Methods for inhibiting cell proliferation in ALK-driven cancers |
GB201310782D0 (en) | 2013-06-17 | 2013-07-31 | Max Planck Innovation Gmbh | Method for predicting a treatment response to a CRHR1 antagonist and/or V1B antagonist in a patient with depressive and/or anxiety symptoms |
US9878987B2 (en) | 2014-05-13 | 2018-01-30 | Memorial Sloan Kettering Cancer Center | HSP70 modulators and methods for making and using the same |
EP3242666A1 (en) | 2015-01-06 | 2017-11-15 | Arena Pharmaceuticals, Inc. | Methods of treating conditions related to the s1p1 receptor |
AU2016220049C1 (en) * | 2015-02-18 | 2021-02-25 | Buck Institute For Research On Aging | Triazolopyridines and triazolopyrimidines that lower stress-induced p-tau |
JP6838744B2 (ja) | 2015-06-22 | 2021-03-03 | アリーナ ファーマシューティカルズ, インコーポレイテッド | S1P1レセプター関連障害における使用のための(R)−2−(7−(4−シクロペンチル−3−(トリフルオロメチル)ベンジルオキシ)−1,2,3,4−テトラヒドロシクロペンタ[b]インドール−3−イル)酢酸(化合物1)の結晶性L−アルギニン塩 |
US11370793B2 (en) * | 2015-08-27 | 2022-06-28 | Nantneuro, Llc | Triazolopyridines and triazolopyrimidines that lower stress-induced p-tau |
CN106596830B (zh) * | 2017-01-16 | 2018-09-28 | 河北丰源环保科技股份有限公司 | 工业生产中2,4-二氨基甲苯浓度快速检测法 |
KR20190116416A (ko) | 2017-02-16 | 2019-10-14 | 아레나 파마슈티칼스, 인크. | 원발 담즙성 담관염을 치료하기 위한 화합물 및 방법 |
WO2018187652A1 (en) | 2017-04-06 | 2018-10-11 | Janssen Pharmaceutica Nv | 2,4-diaminopyrimidine derivatives as histamine h4 modulators |
CN111138413B (zh) * | 2018-11-01 | 2022-11-04 | 江苏豪森药业集团有限公司 | 一种细胞周期蛋白依赖性激酶抑制剂的制备方法及其中间体 |
CN114989795A (zh) * | 2021-03-02 | 2022-09-02 | 中国石油天然气集团有限公司 | 锯齿状金属螯合物堵漏剂、制备方法及应用 |
WO2023233130A1 (en) | 2022-05-30 | 2023-12-07 | AdoRx Therapeutics Limited | Cd73 inhibitor compounds |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CH513937A (de) * | 1968-08-30 | 1971-10-15 | Ciba Geigy Ag | Verfahren zur Herstellung vernetzter Polydimercapto-s-triazine und deren Verwendung als Klebstoffe und Lacke |
DE2818676A1 (de) * | 1978-04-27 | 1979-11-08 | Troponwerke Gmbh & Co Kg | Substituierte 5,6-dimethylpyrrolo 2,3-d pyrimidine, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
AU5319479A (en) * | 1978-12-22 | 1980-06-26 | Ici Australia Limited | Pyrimidinyl amino phenoxy carboxylate derivatives |
DE3111155A1 (de) * | 1981-03-21 | 1982-09-30 | Troponwerke GmbH & Co KG, 5000 Köln | 5,6-dimethyl-pyrrolo (2,3-b)pyridine, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
EP0155911A1 (de) * | 1984-03-19 | 1985-09-25 | Ciba-Geigy Ag | Purinderivate zur Regulierung des Pflanzenwachstums |
US4876252A (en) * | 1986-01-13 | 1989-10-24 | American Cyanamid Company | 4,5,6-substituted-N-(substituted-phenyl)-2-pyrimidinamines |
US4788195A (en) * | 1986-01-13 | 1988-11-29 | American Cyanamid Company | 4,5,6-substituted-N-(substituted-phenyl)-2-pyrimidinamines |
DE3614060A1 (de) * | 1986-04-23 | 1987-10-29 | Schering Ag | Pyrimidin-derivate, verfahren zu ihrer herstellung und ihre verwendung als fungizide |
JPH0784445B2 (ja) * | 1986-12-03 | 1995-09-13 | クミアイ化学工業株式会社 | ピリミジン誘導体および農園芸用殺菌剤 |
CA1336904C (en) * | 1987-08-26 | 1995-09-05 | Mitsuyuki Takesue | Pyrimidines and their pharmaceutically acceptable salts thereof |
GB8808071D0 (en) * | 1988-04-07 | 1988-05-11 | Shell Int Research | Triazine herbicides |
US5063245A (en) * | 1990-03-28 | 1991-11-05 | Nova Pharmaceutical Corporation | Corticotropin-releasing factor antagonism compounds |
GB9012592D0 (en) * | 1990-06-06 | 1990-07-25 | Smithkline Beecham Intercredit | Compounds |
DK40192D0 (da) * | 1992-03-26 | 1992-03-26 | Neurosearch As | Imidazolforbindelser, deres fremstilling og anvendelse |
US5516775A (en) * | 1992-08-31 | 1996-05-14 | Ciba-Geigy Corporation | Further use of pyrimidine derivatives |
DE69323212T2 (de) * | 1992-12-17 | 1999-05-27 | Pfizer | Pyrazole mit crf antagonistischer aktivität |
TW336932B (en) * | 1992-12-17 | 1998-07-21 | Pfizer | Amino-substituted pyrazoles |
TW444018B (en) * | 1992-12-17 | 2001-07-01 | Pfizer | Pyrazolopyrimidines |
DK0674641T3 (da) * | 1992-12-17 | 1999-09-27 | Pfizer | Pyrrolopyrimidiner som CRF-antagonister |
RU2130453C1 (ru) * | 1992-12-17 | 1999-05-20 | Пфайзер Инк. | Замещенные пиразолы, фармацевтическая композиция на их основе, способ лечения, промежуточный продукт |
CA2148931A1 (en) * | 1993-10-01 | 1995-04-13 | Jurg Zimmermann | Pyrimidineamine derivatives and processes for the preparation thereof |
-
1994
- 1994-10-06 PL PL94313973A patent/PL313973A1/xx unknown
- 1994-10-06 AU AU80122/94A patent/AU692484B2/en not_active Ceased
- 1994-10-06 KR KR1019960701900A patent/KR960704855A/ko not_active Application Discontinuation
- 1994-10-06 BR BR9407799A patent/BR9407799A/pt not_active Application Discontinuation
- 1994-10-06 CZ CZ961014A patent/CZ101496A3/cs unknown
- 1994-10-06 SK SK470-96A patent/SK47096A3/sk unknown
- 1994-10-06 NZ NZ274978A patent/NZ274978A/en unknown
- 1994-10-06 EP EP94931298A patent/EP0723533A1/en not_active Withdrawn
- 1994-10-06 CA CA002174080A patent/CA2174080A1/en not_active Abandoned
- 1994-10-06 HU HU9600932A patent/HUT74464A/hu unknown
- 1994-10-10 IL IL11122194A patent/IL111221A0/xx unknown
- 1994-10-11 HR HR08/315,660A patent/HRP940664A2/hr not_active Application Discontinuation
-
1996
- 1996-04-11 NO NO961425A patent/NO961425L/no not_active Application Discontinuation
-
1997
- 1997-08-05 US US08/906,349 patent/US6107301A/en not_active Expired - Lifetime
-
1998
- 1998-01-07 US US09/004,150 patent/US6342503B1/en not_active Expired - Lifetime
Also Published As
Publication number | Publication date |
---|---|
PL313973A1 (en) | 1996-08-05 |
SK47096A3 (en) | 1996-10-02 |
AU8012294A (en) | 1995-05-04 |
CA2174080A1 (en) | 1995-04-20 |
BR9407799A (pt) | 1997-05-06 |
HU9600932D0 (en) | 1996-06-28 |
NO961425D0 (no) | 1996-04-11 |
AU692484B2 (en) | 1998-06-11 |
EP0723533A1 (en) | 1996-07-31 |
HUT74464A (en) | 1996-12-30 |
US6107301A (en) | 2000-08-22 |
NZ274978A (en) | 1998-04-27 |
NO961425L (no) | 1996-06-12 |
US6342503B1 (en) | 2002-01-29 |
KR960704855A (ko) | 1996-10-09 |
CZ101496A3 (en) | 1996-11-13 |
IL111221A0 (en) | 1995-01-24 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
HRP940664A2 (en) | 1n-alkyl-n-arylpyrimidinamines and derivatives thereof | |
JP3398152B2 (ja) | 1n−アルキル−n−アリールピリミジンアミンおよびその誘導体 | |
US6103737A (en) | Aryl- and arylamino- substituted heterocycles as corticotropin releasing hormone antagonists | |
US6525056B2 (en) | Heterocyclyl-substituted ring-fused pyridines and pyrimidines as corticotropin releasing hormone (CRH) antagonists, useful for treating cns and stress-related disorders | |
AU739269B2 (en) | Tetrahydropteridines and pyridylpiperazines for treatment of neurological disorders | |
KR20000005037A (ko) | 아릴아미노 융합된 피리딘 및 피리미딘 | |
HRP20000520A2 (en) | 1,2,4,5-TETRADYDRO-BENZO/d/AZEPINES | |
US6107294A (en) | Thiazolo[4,5-d]pyrimidines and pyridines as corticotropin releasing factor (CRF) antagonists | |
EP2041132A2 (en) | New compounds | |
US20030171380A1 (en) | Substituted pyrazinones, pyridines and pyrimidines as corticotropin releasing factor ligands | |
CA2689989A1 (en) | Heterocyclic compounds and uses thereof | |
CA2729990A1 (en) | New chemical compounds | |
KR20140103996A (ko) | Lrrk2 조절제로서 아미노피리미딘 유도체 | |
CZ20023199A3 (cs) | Modulátory receptoru adenosinu | |
CA2729986A1 (en) | New chemical compounds | |
US6174912B1 (en) | Nitrogen substituted imidazo[4,5-C]pyrazoles as corticotropin releasing hormone antagonists | |
AU9021598A (en) | Nitrogen substituted imidazo{4,5-c}pyrazoles as corticotropin relea sing hormone antagonists | |
MXPA00002156A (en) | Heterocyclyl-substituted ring-fused pyridines and pyrimidines as corticotropin releasing hormone (crh) antagonists, useful for treating cns and stress-related disorders | |
MXPA00007661A (en) | Tetrahydro-benzo(d)azepines and their use as antagonists at metabotropic glutamate receptors | |
TW200303316A (en) | Substituted indolizine-like compounds and methods of use | |
LT4533B (lt) | Kondensuoti arilaminopiridinai ir pirimidinai |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A1OB | Publication of a patent application | ||
AIPI | Request for the grant of a patent on the basis of a substantive examination of a patent application | ||
ODBI | Application refused |