HRP20000520A2 - 1,2,4,5-TETRADYDRO-BENZO/d/AZEPINES - Google Patents

1,2,4,5-TETRADYDRO-BENZO/d/AZEPINES

Info

Publication number: HRP20000520A2
Authority: HR; Croatia
Prior art keywords: chr; tetrahydro; benzo; azepin; carbonitrile
Prior art date: 1999-08-06

Application number

HR20000520A

Other languages

English (en)

Croatian (hr)

Inventor

Adam Geo

Alfred Binggeli

Hans-Peter Maerki

Vincent Mutel

Maurice Wilhelm

Wolfgang Wostl

Original Assignee

Hoffmann La Roche

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1999-08-06

Filing date

2000-08-02

Publication date

2001-06-30

2000-08-02 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

2001-06-30 Publication of HRP20000520A2 publication Critical patent/HRP20000520A2/hr

Links

150000001538 azepines Chemical class 0.000 title 1
238000000034 method Methods 0.000 claims description 207
150000001875 compounds Chemical class 0.000 claims description 140
125000000217 alkyl group Chemical group 0.000 claims description 72
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 58
-1 or -OR Chemical group 0.000 claims description 58
LDUCGZQCFUMHIK-UHFFFAOYSA-N 2-methyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidin-4-one Chemical compound CC1=NC(O)=C([N+]([O-])=O)C(N2CCC3=CC=CC=C3CC2)=N1 LDUCGZQCFUMHIK-UHFFFAOYSA-N 0.000 claims description 38
125000003342 alkenyl group Chemical group 0.000 claims description 30
238000006243 chemical reaction Methods 0.000 claims description 30
125000003545 alkoxy group Chemical group 0.000 claims description 27
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 27
125000004093 cyano group Chemical group *C#N 0.000 claims description 24
150000003839 salts Chemical class 0.000 claims description 24
VXBNIUWMGBUTRT-UHFFFAOYSA-N 4-oxo-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidine-5-carbonitrile Chemical compound O=C1NC=NC(N2CCC3=CC=CC=C3CC2)=C1C#N VXBNIUWMGBUTRT-UHFFFAOYSA-N 0.000 claims description 23
229910052739 hydrogen Inorganic materials 0.000 claims description 23
239000001257 hydrogen Substances 0.000 claims description 23
OZQHSVVVDNQSDH-UHFFFAOYSA-N 2-amino-4-oxo-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidine-5-carbonitrile Chemical compound O=C1NC(N)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N OZQHSVVVDNQSDH-UHFFFAOYSA-N 0.000 claims description 21
125000000524 functional group Chemical group 0.000 claims description 20
229910052736 halogen Inorganic materials 0.000 claims description 19
150000002367 halogens Chemical class 0.000 claims description 19
150000002431 hydrogen Chemical class 0.000 claims description 18
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
UIMKJXDFYJRFQF-UHFFFAOYSA-N 1-amino-2-methyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(N)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N UIMKJXDFYJRFQF-UHFFFAOYSA-N 0.000 claims description 12
238000004519 manufacturing process Methods 0.000 claims description 12
150000003335 secondary amines Chemical class 0.000 claims description 11
125000001424 substituent group Chemical group 0.000 claims description 11
125000004432 carbon atom Chemical group C* 0.000 claims description 10
229910052801 chlorine Inorganic materials 0.000 claims description 10
230000001684 chronic effect Effects 0.000 claims description 10
229940079593 drug Drugs 0.000 claims description 10
239000003814 drug Substances 0.000 claims description 10
208000028017 Psychotic disease Diseases 0.000 claims description 9
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 9
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 8
208000002193 Pain Diseases 0.000 claims description 8
206010034010 Parkinsonism Diseases 0.000 claims description 8
WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 7
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
239000000460 chlorine Substances 0.000 claims description 7
125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 claims description 7
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
208000012902 Nervous system disease Diseases 0.000 claims description 6
208000025966 Neurological disease Diseases 0.000 claims description 6
YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 claims description 6
230000001154 acute effect Effects 0.000 claims description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
229910052794 bromium Inorganic materials 0.000 claims description 6
239000011737 fluorine Substances 0.000 claims description 6
229910052731 fluorine Inorganic materials 0.000 claims description 6
229930195712 glutamate Natural products 0.000 claims description 6
229910052757 nitrogen Inorganic materials 0.000 claims description 6
230000002265 prevention Effects 0.000 claims description 6
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
229910052722 tritium Inorganic materials 0.000 claims description 6
ADXRSPBNIFDIIL-UHFFFAOYSA-N 2-(2-hydroxyethyl)-4-oxo-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidine-5-carbonitrile Chemical compound O=C1NC(CCO)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N ADXRSPBNIFDIIL-UHFFFAOYSA-N 0.000 claims description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
208000027089 Parkinsonian disease Diseases 0.000 claims description 5
206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 5
230000027455 binding Effects 0.000 claims description 5
108010014719 metabotropic glutamate receptor type 1 Proteins 0.000 claims description 5
230000001629 suppression Effects 0.000 claims description 5
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
NWUORKWXEPJXQF-UHFFFAOYSA-N 1,2-dimethyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(C)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N NWUORKWXEPJXQF-UHFFFAOYSA-N 0.000 claims description 4
NEMPTYBDKRDGHY-UHFFFAOYSA-N 1-(2-hydroxyethyl)-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(CCO)C=NC(N2CCC3=CC=CC=C3CC2)=C1C#N NEMPTYBDKRDGHY-UHFFFAOYSA-N 0.000 claims description 4
NBSFMOFDESCFSH-UHFFFAOYSA-N 1-(cyanomethyl)-2-methyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(CC#N)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N NBSFMOFDESCFSH-UHFFFAOYSA-N 0.000 claims description 4
UTVWGQDJAYXQQP-UHFFFAOYSA-N 1-(cyclopropylmethyl)-2-methyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound CC1=NC(N2CCC3=CC=CC=C3CC2)=C(C#N)C(=O)N1CC1CC1 UTVWGQDJAYXQQP-UHFFFAOYSA-N 0.000 claims description 4
AHCLTTILLQXZBY-UHFFFAOYSA-N 1-[2-(dimethylamino)ethyl]-2-methyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(CCN(C)C)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N AHCLTTILLQXZBY-UHFFFAOYSA-N 0.000 claims description 4
QNUVWRAGDSGAKX-UHFFFAOYSA-N 1-ethyl-2-methyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(CC)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N QNUVWRAGDSGAKX-UHFFFAOYSA-N 0.000 claims description 4
BRJWSWOUTCHPTG-UHFFFAOYSA-N 2-(2-hydroxyethylamino)-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound OCCNC1=NC(OCC(F)(F)F)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 BRJWSWOUTCHPTG-UHFFFAOYSA-N 0.000 claims description 4
XTWMPGSNYMAJGI-UHFFFAOYSA-N 2-(3-imidazol-1-ylpropylamino)-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC3=CC=CC=C3CC2)=C(C#N)C(OCC(F)(F)F)=NC=1NCCCN1C=CN=C1 XTWMPGSNYMAJGI-UHFFFAOYSA-N 0.000 claims description 4
FYCSWLGBFSEWJQ-UHFFFAOYSA-N 2-(3-morpholin-4-ylpropylamino)-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC3=CC=CC=C3CC2)=C(C#N)C(OCC(F)(F)F)=NC=1NCCCN1CCOCC1 FYCSWLGBFSEWJQ-UHFFFAOYSA-N 0.000 claims description 4
TUCLALLSSVWYSE-UHFFFAOYSA-N 2-amino-1-ethyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(CC)C(N)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N TUCLALLSSVWYSE-UHFFFAOYSA-N 0.000 claims description 4
FHGDGVRNAVRKTO-UHFFFAOYSA-N 3-(2-fluoroethyl)-2-methyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-one Chemical compound O=C1N(CCF)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1[N+]([O-])=O FHGDGVRNAVRKTO-UHFFFAOYSA-N 0.000 claims description 4
XLYNPVUYKJFZME-UHFFFAOYSA-N 4-oxo-2-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-7,8,9,10-tetrahydro-6h-pyrimido[1,2-a]azepine-3-carbonitrile Chemical compound C1CC2=CC=CC=C2CCN1C1=C(C#N)C(=O)N2CCCCCC2=N1 XLYNPVUYKJFZME-UHFFFAOYSA-N 0.000 claims description 4
ILQVVUZJQWRAAZ-UHFFFAOYSA-N 6-oxo-1-propan-2-yl-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(C(C)C)C=NC(N2CCC3=CC=CC=C3CC2)=C1C#N ILQVVUZJQWRAAZ-UHFFFAOYSA-N 0.000 claims description 4
208000024827 Alzheimer disease Diseases 0.000 claims description 4
208000000044 Amnesia Diseases 0.000 claims description 4
208000019901 Anxiety disease Diseases 0.000 claims description 4
206010007559 Cardiac failure congestive Diseases 0.000 claims description 4
208000000094 Chronic Pain Diseases 0.000 claims description 4
206010010904 Convulsion Diseases 0.000 claims description 4
208000012661 Dyskinesia Diseases 0.000 claims description 4
208000020564 Eye injury Diseases 0.000 claims description 4
206010019196 Head injury Diseases 0.000 claims description 4
208000010496 Heart Arrest Diseases 0.000 claims description 4
208000023105 Huntington disease Diseases 0.000 claims description 4
208000013016 Hypoglycemia Diseases 0.000 claims description 4
206010021143 Hypoxia Diseases 0.000 claims description 4
208000026139 Memory disease Diseases 0.000 claims description 4
102100036834 Metabotropic glutamate receptor 1 Human genes 0.000 claims description 4
208000019695 Migraine disease Diseases 0.000 claims description 4
208000007101 Muscle Cramp Diseases 0.000 claims description 4
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
208000017442 Retinal disease Diseases 0.000 claims description 4
206010038923 Retinopathy Diseases 0.000 claims description 4
208000005392 Spasm Diseases 0.000 claims description 4
208000006011 Stroke Diseases 0.000 claims description 4
206010046543 Urinary incontinence Diseases 0.000 claims description 4
206010047700 Vomiting Diseases 0.000 claims description 4
208000005298 acute pain Diseases 0.000 claims description 4
125000004423 acyloxy group Chemical group 0.000 claims description 4
125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 4
230000029936 alkylation Effects 0.000 claims description 4
238000005804 alkylation reaction Methods 0.000 claims description 4
230000036506 anxiety Effects 0.000 claims description 4
230000036770 blood supply Effects 0.000 claims description 4
210000004556 brain Anatomy 0.000 claims description 4
230000003925 brain function Effects 0.000 claims description 4
208000010877 cognitive disease Diseases 0.000 claims description 4
230000036461 convulsion Effects 0.000 claims description 4
206010015037 epilepsy Diseases 0.000 claims description 4
230000006870 function Effects 0.000 claims description 4
230000002218 hypoglycaemic effect Effects 0.000 claims description 4
230000007954 hypoxia Effects 0.000 claims description 4
230000006984 memory degeneration Effects 0.000 claims description 4
208000023060 memory loss Diseases 0.000 claims description 4
206010027599 migraine Diseases 0.000 claims description 4
125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
229940127240 opiate Drugs 0.000 claims description 4
230000035935 pregnancy Effects 0.000 claims description 4
230000008569 process Effects 0.000 claims description 4
201000000980 schizophrenia Diseases 0.000 claims description 4
208000020431 spinal cord injury Diseases 0.000 claims description 4
230000008673 vomiting Effects 0.000 claims description 4
WYHIRKWDIUBMMH-UHFFFAOYSA-N 2-(ethylamino)-4-oxo-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidine-5-carbonitrile Chemical compound O=C1NC(NCC)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N WYHIRKWDIUBMMH-UHFFFAOYSA-N 0.000 claims description 3
TYQBSPNSNLZYMO-UHFFFAOYSA-N 2-methyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound O=C1N(OCC(F)(F)F)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N TYQBSPNSNLZYMO-UHFFFAOYSA-N 0.000 claims description 3
SRZSARYUDCDBIQ-UHFFFAOYSA-N 3-[2-methyl-5-nitro-6-[3-(1,2,4-triazol-1-yl)propoxy]pyrimidin-4-yl]-1,2,4,5-tetrahydro-3-benzazepine Chemical compound [O-][N+](=O)C=1C(N2CCC3=CC=CC=C3CC2)=NC(C)=NC=1OCCCN1C=NC=N1 SRZSARYUDCDBIQ-UHFFFAOYSA-N 0.000 claims description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
229910052760 oxygen Inorganic materials 0.000 claims description 3
239000001301 oxygen Substances 0.000 claims description 3
150000003141 primary amines Chemical class 0.000 claims description 3
229940044551 receptor antagonist Drugs 0.000 claims description 3
239000002464 receptor antagonist Substances 0.000 claims description 3
238000001356 surgical procedure Methods 0.000 claims description 3
238000012360 testing method Methods 0.000 claims description 3
150000003573 thiols Chemical class 0.000 claims description 3
125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims description 2
208000030507 AIDS Diseases 0.000 claims description 2
206010065040 AIDS dementia complex Diseases 0.000 claims description 2
206010012289 Dementia Diseases 0.000 claims description 2
229910006074 SO2NH2 Inorganic materials 0.000 claims description 2
230000003213 activating effect Effects 0.000 claims description 2
125000002252 acyl group Chemical group 0.000 claims description 2
230000007812 deficiency Effects 0.000 claims description 2
230000002950 deficient Effects 0.000 claims description 2
125000005675 difluoroethenyl group Chemical group [H]C(*)=C(F)F 0.000 claims description 2
230000006806 disease prevention Effects 0.000 claims description 2
125000004043 oxo group Chemical group O=* 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
125000006239 protecting group Chemical group 0.000 claims description 2
230000000391 smoking effect Effects 0.000 claims 2
125000001033 ether group Chemical group 0.000 claims 1
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 554
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 270
239000007787 solid Substances 0.000 description 262
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 213
230000008018 melting Effects 0.000 description 176
238000002844 melting Methods 0.000 description 176
229910000027 potassium carbonate Inorganic materials 0.000 description 136
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 110
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 90
239000000203 mixture Substances 0.000 description 67
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 63
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 60
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 55
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 52
239000003921 oil Substances 0.000 description 51
235000019198 oils Nutrition 0.000 description 51
239000000243 solution Substances 0.000 description 50
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 49
YRPSNQDCQZEXFQ-UHFFFAOYSA-N 2-methyl-4-oxo-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidine-5-carbonitrile Chemical compound O=C1NC(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N YRPSNQDCQZEXFQ-UHFFFAOYSA-N 0.000 description 47
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 46
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 45
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 44
MPUXFEGFHPCPLI-UHFFFAOYSA-N ethyl 2-cyano-3-methylsulfanyl-3-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)prop-2-enoate Chemical compound C1CN(C(SC)=C(C#N)C(=O)OCC)CCC2=CC=CC=C21 MPUXFEGFHPCPLI-UHFFFAOYSA-N 0.000 description 42
239000011541 reaction mixture Substances 0.000 description 42
JTKJTZIVKICTQS-UHFFFAOYSA-N 2-methylsulfonyl-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound CS(=O)(=O)C1=NC(OCC(F)(F)F)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 JTKJTZIVKICTQS-UHFFFAOYSA-N 0.000 description 35
229910000104 sodium hydride Inorganic materials 0.000 description 35
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 34
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 34
239000012312 sodium hydride Substances 0.000 description 34
XSFOFWOHPLLLKC-UHFFFAOYSA-N 4-chloro-2-methylsulfanyl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound CSC1=NC(Cl)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 XSFOFWOHPLLLKC-UHFFFAOYSA-N 0.000 description 31
230000002829 reductive effect Effects 0.000 description 31
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
238000010992 reflux Methods 0.000 description 28
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 27
239000000741 silica gel Substances 0.000 description 27
229910002027 silica gel Inorganic materials 0.000 description 27
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 26
229910052943 magnesium sulfate Inorganic materials 0.000 description 26
235000019341 magnesium sulphate Nutrition 0.000 description 26
239000003480 eluent Substances 0.000 description 25
239000002904 solvent Substances 0.000 description 24
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
239000012043 crude product Substances 0.000 description 23
239000012074 organic phase Substances 0.000 description 23
ZTUGICZMQIRBNP-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-3-benzazepin-3-ium;chloride Chemical compound Cl.C1CNCCC2=CC=CC=C21 ZTUGICZMQIRBNP-UHFFFAOYSA-N 0.000 description 21
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 19
238000004587 chromatography analysis Methods 0.000 description 19
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 19
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
239000002585 base Substances 0.000 description 16
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 15
RTMMSCJWQYWMNK-UHFFFAOYSA-N 2,2,2-trifluoroethyl trifluoromethanesulfonate Chemical compound FC(F)(F)COS(=O)(=O)C(F)(F)F RTMMSCJWQYWMNK-UHFFFAOYSA-N 0.000 description 14
RKSUYGSVBABZTL-UHFFFAOYSA-N 1-hydroxy-2-methyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(O)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N RKSUYGSVBABZTL-UHFFFAOYSA-N 0.000 description 13
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 13
125000005605 benzo group Chemical group 0.000 description 12
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 11
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 11
MFOQLXKMKRHLJD-UHFFFAOYSA-N tert-butyl n-[5-cyano-2-methyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-1-yl]carbamate Chemical compound O=C1N(NC(=O)OC(C)(C)C)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N MFOQLXKMKRHLJD-UHFFFAOYSA-N 0.000 description 11
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 11
LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 description 10
LDLCZOVUSADOIV-UHFFFAOYSA-N 2-bromoethanol Chemical compound OCCBr LDLCZOVUSADOIV-UHFFFAOYSA-N 0.000 description 10
XENBELIGWDKZOP-UHFFFAOYSA-N 4-chloro-6-methoxy-2-methyl-5-nitropyrimidine Chemical compound COC1=NC(C)=NC(Cl)=C1[N+]([O-])=O XENBELIGWDKZOP-UHFFFAOYSA-N 0.000 description 10
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 10
MGVLZTSOZFVVKR-UHFFFAOYSA-N 6-bromo-2-methyl-5-nitro-1h-pyrimidin-4-one Chemical compound CC1=NC(Br)=C([N+]([O-])=O)C(=O)N1 MGVLZTSOZFVVKR-UHFFFAOYSA-N 0.000 description 9
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
229910052799 carbon Inorganic materials 0.000 description 9
210000004027 cell Anatomy 0.000 description 9
XVIAPHVAGFEFFN-UHFFFAOYSA-N pyrimidine-5-carbonitrile Chemical compound N#CC1=CN=CN=C1 XVIAPHVAGFEFFN-UHFFFAOYSA-N 0.000 description 9
238000003756 stirring Methods 0.000 description 9
239000000725 suspension Substances 0.000 description 9
FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 9
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
238000002360 preparation method Methods 0.000 description 8
OLALZJUAVPQEHH-UHFFFAOYSA-N 3-[2-methyl-5-nitro-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-1-yl]propyl methanesulfonate Chemical compound O=C1N(CCCOS(C)(=O)=O)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1[N+]([O-])=O OLALZJUAVPQEHH-UHFFFAOYSA-N 0.000 description 7
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 7
LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 7
125000001309 chloro group Chemical group Cl* 0.000 description 7
VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical class OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 7
SOBVNIJFGSZGCK-UHFFFAOYSA-N 2-(oxan-2-yloxymethyl)-4-oxo-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC3=CC=CC=C3CC2)=C(C#N)C(=O)NC=1COC1CCCCO1 SOBVNIJFGSZGCK-UHFFFAOYSA-N 0.000 description 6
PLWWNYZBFPBLLP-UHFFFAOYSA-N 2-amino-4-methylsulfanyl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound CSC1=NC(N)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N PLWWNYZBFPBLLP-UHFFFAOYSA-N 0.000 description 6
WWMVHBWLJHOAQR-UHFFFAOYSA-N 4-oxo-2-propyl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidine-5-carbonitrile Chemical compound O=C1NC(CCC)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N WWMVHBWLJHOAQR-UHFFFAOYSA-N 0.000 description 6
DTCJTNVAMXQJQH-UHFFFAOYSA-N 6-(7-fluoro-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-2-methyl-5-nitro-1h-pyrimidin-4-one Chemical compound O=C1NC(C)=NC(N2CCC3=CC(F)=CC=C3CC2)=C1[N+]([O-])=O DTCJTNVAMXQJQH-UHFFFAOYSA-N 0.000 description 6
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
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 6
108010010914 Metabotropic glutamate receptors Proteins 0.000 description 6
102000016193 Metabotropic glutamate receptors Human genes 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
239000002253 acid Substances 0.000 description 6
239000000969 carrier Substances 0.000 description 6
239000012230 colorless oil Substances 0.000 description 6
239000006260 foam Substances 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
239000011734 sodium Substances 0.000 description 6
SEPUNCBGQVPMMR-UHFFFAOYSA-N 1-ethyl-2-[2-(oxan-2-yloxy)ethyl]-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC3=CC=CC=C3CC2)=C(C#N)C(=O)N(CC)C=1CCOC1CCCCO1 SEPUNCBGQVPMMR-UHFFFAOYSA-N 0.000 description 5
QETLZPKJMIGSJL-UHFFFAOYSA-N 2-(oxan-2-yloxymethyl)-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC3=CC=CC=C3CC2)=C(C#N)C(OCC(F)(F)F)=NC=1COC1CCCCO1 QETLZPKJMIGSJL-UHFFFAOYSA-N 0.000 description 5
FOLILDWKSJLNQB-UHFFFAOYSA-N 2-[2-(oxan-2-yloxy)ethyl]-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC3=CC=CC=C3CC2)=C(C#N)C(OCC(F)(F)F)=NC=1CCOC1CCCCO1 FOLILDWKSJLNQB-UHFFFAOYSA-N 0.000 description 5
FYCZAGJXNDSRHS-UHFFFAOYSA-N 3-(4-hydroxybutyl)-2-methyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-one Chemical compound O=C1N(CCCCO)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1[N+]([O-])=O FYCZAGJXNDSRHS-UHFFFAOYSA-N 0.000 description 5
GXSGFVHYUDOHKP-UHFFFAOYSA-N 3-[2-methyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-yl]oxypropan-1-ol Chemical compound CC1=NC(OCCCO)=C([N+]([O-])=O)C(N2CCC3=CC=CC=C3CC2)=N1 GXSGFVHYUDOHKP-UHFFFAOYSA-N 0.000 description 5
HQDKWBBCUWKSCE-UHFFFAOYSA-N 3-[2-methyl-5-nitro-6-(2,2,2-trifluoroethoxy)pyrimidin-4-yl]-1,2,4,5-tetrahydro-3-benzazepine Chemical compound CC1=NC(OCC(F)(F)F)=C([N+]([O-])=O)C(N2CCC3=CC=CC=C3CC2)=N1 HQDKWBBCUWKSCE-UHFFFAOYSA-N 0.000 description 5
MJDGOVVAESGYKW-UHFFFAOYSA-N 3-methyl-2,4-dioxo-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidine-5-carbonitrile Chemical compound O=C1N(C)C(=O)NC(N2CCC3=CC=CC=C3CC2)=C1C#N MJDGOVVAESGYKW-UHFFFAOYSA-N 0.000 description 5
BHYYZJOLOSEULL-UHFFFAOYSA-N 4-amino-2-methyl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound CC1=NC(N)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 BHYYZJOLOSEULL-UHFFFAOYSA-N 0.000 description 5
FRCMDUDKQOEZCW-UHFFFAOYSA-N 4-amino-2-methylsulfanyl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound CSC1=NC(N)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 FRCMDUDKQOEZCW-UHFFFAOYSA-N 0.000 description 5
DUSNFVAHWXVQIW-UHFFFAOYSA-N 4-amino-2-methylsulfonyl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound CS(=O)(=O)C1=NC(N)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 DUSNFVAHWXVQIW-UHFFFAOYSA-N 0.000 description 5
LHZOXSFSTRNMHK-UHFFFAOYSA-N 4-ethoxy-2-[2-(oxan-2-yloxy)ethyl]-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC3=CC=CC=C3CC2)=C(C#N)C(OCC)=NC=1CCOC1CCCCO1 LHZOXSFSTRNMHK-UHFFFAOYSA-N 0.000 description 5
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
239000004480 active ingredient Substances 0.000 description 5
BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 5
150000001412 amines Chemical class 0.000 description 5
239000005557 antagonist Substances 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
239000007903 gelatin capsule Substances 0.000 description 5
235000012907 honey Nutrition 0.000 description 5
239000012442 inert solvent Substances 0.000 description 5
239000008101 lactose Substances 0.000 description 5
229940098779 methanesulfonic acid Drugs 0.000 description 5
230000003647 oxidation Effects 0.000 description 5
238000007254 oxidation reaction Methods 0.000 description 5
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
102000005962 receptors Human genes 0.000 description 5
108020003175 receptors Proteins 0.000 description 5
238000010898 silica gel chromatography Methods 0.000 description 5
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 5
239000000126 substance Substances 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical class CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 5
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
RKOUFQLNMRAACI-UHFFFAOYSA-N 1,1,1-trifluoro-2-iodoethane Chemical compound FC(F)(F)CI RKOUFQLNMRAACI-UHFFFAOYSA-N 0.000 description 4
ARMSVRBUSGVGCO-UHFFFAOYSA-N 1-(5-bromo-1,2-dihydro-3-benzazepin-3-yl)ethanone Chemical compound BrC1=CN(C(=O)C)CCC2=CC=CC=C21 ARMSVRBUSGVGCO-UHFFFAOYSA-N 0.000 description 4
PXQYXQFJTCZUBJ-UHFFFAOYSA-N 2-(2-methylsulfanylethyl)-4-oxo-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidine-5-carbonitrile Chemical compound O=C1NC(CCSC)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N PXQYXQFJTCZUBJ-UHFFFAOYSA-N 0.000 description 4
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
KNPQWYHIRDHPNM-UHFFFAOYSA-N 2-[2-(oxan-2-yloxy)ethyl]-4-oxo-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC3=CC=CC=C3CC2)=C(C#N)C(=O)NC=1CCOC1CCCCO1 KNPQWYHIRDHPNM-UHFFFAOYSA-N 0.000 description 4
SRVXSISGYBMIHR-UHFFFAOYSA-N 3-[3-[3-(2-amino-2-oxoethyl)phenyl]-5-chlorophenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid Chemical compound S1C(C)=CN=C1C(CC(O)=O)C1=CC(Cl)=CC(C=2C=C(CC(N)=O)C=CC=2)=C1 SRVXSISGYBMIHR-UHFFFAOYSA-N 0.000 description 4
GDDNTTHUKVNJRA-UHFFFAOYSA-N 3-bromo-3,3-difluoroprop-1-ene Chemical compound FC(F)(Br)C=C GDDNTTHUKVNJRA-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
UYRXYSZUALFOLT-UHFFFAOYSA-N 3-ethyl-2-methyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-one Chemical compound O=C1N(CC)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1[N+]([O-])=O UYRXYSZUALFOLT-UHFFFAOYSA-N 0.000 description 4
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
MSHFRERJPWKJFX-UHFFFAOYSA-N 4-Methoxybenzyl alcohol Chemical compound COC1=CC=C(CO)C=C1 MSHFRERJPWKJFX-UHFFFAOYSA-N 0.000 description 4
BJEHWUQSTAPYQQ-UHFFFAOYSA-N 4-[2-methyl-5-nitro-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-1-yl]butyl methanesulfonate Chemical compound O=C1N(CCCCOS(C)(=O)=O)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1[N+]([O-])=O BJEHWUQSTAPYQQ-UHFFFAOYSA-N 0.000 description 4
SHDMCTOVONAMKO-UHFFFAOYSA-N 7-fluoro-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1CNCCC2=CC(F)=CC=C21 SHDMCTOVONAMKO-UHFFFAOYSA-N 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
239000012448 Lithium borohydride Substances 0.000 description 4
239000012359 Methanesulfonyl chloride Substances 0.000 description 4
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 4
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
239000013078 crystal Substances 0.000 description 4
239000006185 dispersion Substances 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
229940049906 glutamate Drugs 0.000 description 4
FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 4
FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 4
235000019359 magnesium stearate Nutrition 0.000 description 4
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
239000002480 mineral oil Substances 0.000 description 4
235000010446 mineral oil Nutrition 0.000 description 4
LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 4
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 4
239000000825 pharmaceutical preparation Substances 0.000 description 4
229920005862 polyol Polymers 0.000 description 4
150000003077 polyols Chemical class 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 3
NNKYGWCUSCESAJ-SFHVURJKSA-N 1-[[(4s)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-2-methyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound CC1=NC(N2CCC3=CC=CC=C3CC2)=C(C#N)C(=O)N1C[C@H]1COC(C)(C)O1 NNKYGWCUSCESAJ-SFHVURJKSA-N 0.000 description 3
SNEYLUPOGNOXCE-UHFFFAOYSA-N 2-(2-morpholin-4-ylethylamino)-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC3=CC=CC=C3CC2)=C(C#N)C(OCC(F)(F)F)=NC=1NCCN1CCOCC1 SNEYLUPOGNOXCE-UHFFFAOYSA-N 0.000 description 3
REXUYBKPWIPONM-UHFFFAOYSA-N 2-bromoacetonitrile Chemical compound BrCC#N REXUYBKPWIPONM-UHFFFAOYSA-N 0.000 description 3
LQLJZSJKRYTKTP-UHFFFAOYSA-N 2-dimethylaminoethyl chloride hydrochloride Chemical compound Cl.CN(C)CCCl LQLJZSJKRYTKTP-UHFFFAOYSA-N 0.000 description 3
VYODYBAKJVHDFG-UHFFFAOYSA-N 2-methyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1-(2,2,2-trifluoroethyl)pyrimidine-5-carbonitrile Chemical compound O=C1N(CC(F)(F)F)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N VYODYBAKJVHDFG-UHFFFAOYSA-N 0.000 description 3
MVIGBSFARJQYHH-UHFFFAOYSA-N 2-methylsulfanyl-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound CSC1=NC(OCC(F)(F)F)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 MVIGBSFARJQYHH-UHFFFAOYSA-N 0.000 description 3
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 3
JKWAQKNJFSGJKO-UHFFFAOYSA-N 3-(6-chloro-2-methyl-5-nitropyrimidin-4-yl)-1,2,4,5-tetrahydro-3-benzazepine Chemical compound CC1=NC(Cl)=C([N+]([O-])=O)C(N2CCC3=CC=CC=C3CC2)=N1 JKWAQKNJFSGJKO-UHFFFAOYSA-N 0.000 description 3
NVVCJHUBMDULHH-UHFFFAOYSA-N 3-[2-methyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-yl]oxypropyl methanesulfonate Chemical compound CC1=NC(OCCCOS(C)(=O)=O)=C([N+]([O-])=O)C(N2CCC3=CC=CC=C3CC2)=N1 NVVCJHUBMDULHH-UHFFFAOYSA-N 0.000 description 3
KDHWOCLBMVSZPG-UHFFFAOYSA-N 3-imidazol-1-ylpropan-1-amine Chemical compound NCCCN1C=CN=C1 KDHWOCLBMVSZPG-UHFFFAOYSA-N 0.000 description 3
PYANHFBJHGQVPZ-UHFFFAOYSA-N 4-[2-methyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-yl]oxybutan-1-ol Chemical compound CC1=NC(OCCCCO)=C([N+]([O-])=O)C(N2CCC3=CC=CC=C3CC2)=N1 PYANHFBJHGQVPZ-UHFFFAOYSA-N 0.000 description 3
VFPNSCPJKWZRHR-UHFFFAOYSA-N 4-chloro-2-(2-morpholin-4-ylethoxy)-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC3=CC=CC=C3CC2)=C(C#N)C(Cl)=NC=1OCCN1CCOCC1 VFPNSCPJKWZRHR-UHFFFAOYSA-N 0.000 description 3
IXFDNAUTJUBXMZ-UHFFFAOYSA-N 4-hydrazinyl-2-methylsulfanyl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound CSC1=NC(NN)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 IXFDNAUTJUBXMZ-UHFFFAOYSA-N 0.000 description 3
NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 3
VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 description 3
229920002261 Corn starch Polymers 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 3
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 3
RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 3
150000008038 benzoazepines Chemical class 0.000 description 3
239000002775 capsule Substances 0.000 description 3
210000003169 central nervous system Anatomy 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000008120 corn starch Substances 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical group C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 3
ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 3
239000005457 ice water Substances 0.000 description 3
125000000468 ketone group Chemical group 0.000 description 3
150000002576 ketones Chemical class 0.000 description 3
YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 3
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 3
RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical compound NCCN1CCOCC1 RWIVICVCHVMHMU-UHFFFAOYSA-N 0.000 description 3
PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 3
239000011591 potassium Substances 0.000 description 3
238000012545 processing Methods 0.000 description 3
239000000047 product Substances 0.000 description 3
238000006467 substitution reaction Methods 0.000 description 3
239000000454 talc Substances 0.000 description 3
229910052623 talc Inorganic materials 0.000 description 3
150000003512 tertiary amines Chemical class 0.000 description 3
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 3
238000005406 washing Methods 0.000 description 3
MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 2
BKXUMCAMNJQQDG-UHFFFAOYSA-N 1,2-bis(2-hydroxyethyl)-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(CCO)C(CCO)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N BKXUMCAMNJQQDG-UHFFFAOYSA-N 0.000 description 2
FNTZQUVCPPKULB-UHFFFAOYSA-N 1,2-diamino-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(N)C(N)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N FNTZQUVCPPKULB-UHFFFAOYSA-N 0.000 description 2
ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 description 2
NABUFFLEHQEQPH-UHFFFAOYSA-N 1-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)ethanone Chemical compound C1CN(C(=O)C)CCC2=CC=CC=C21 NABUFFLEHQEQPH-UHFFFAOYSA-N 0.000 description 2
SKJOOIMMJIPGPV-UHFFFAOYSA-N 1-(2-hydroxyethyl)-2-methyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(CCO)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N SKJOOIMMJIPGPV-UHFFFAOYSA-N 0.000 description 2
TWJJBJKCTCIOMD-UHFFFAOYSA-N 1-(7-amino-1,2,4,5-tetrahydro-3-benzazepin-3-yl)ethanone Chemical compound C1CN(C(=O)C)CCC2=CC=C(N)C=C21 TWJJBJKCTCIOMD-UHFFFAOYSA-N 0.000 description 2
RJSFXGOSASJMKR-UHFFFAOYSA-N 1-(7-fluoro-1,2,4,5-tetrahydro-3-benzazepin-3-yl)ethanone Chemical compound C1CN(C(=O)C)CCC2=CC=C(F)C=C21 RJSFXGOSASJMKR-UHFFFAOYSA-N 0.000 description 2
WZHKUTKSFHRWQX-UHFFFAOYSA-N 1-(difluoromethoxy)-2-methyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(OC(F)F)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N WZHKUTKSFHRWQX-UHFFFAOYSA-N 0.000 description 2
LCHGPMMXNOTQGS-UHFFFAOYSA-N 1-(methoxymethyl)-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(COC)C=NC(N2CCC3=CC=CC=C3CC2)=C1C#N LCHGPMMXNOTQGS-UHFFFAOYSA-N 0.000 description 2
RXNYTELQSLULTA-INIZCTEOSA-N 1-[(2s)-2,3-dihydroxypropyl]-2-methyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(C[C@H](O)CO)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N RXNYTELQSLULTA-INIZCTEOSA-N 0.000 description 2
KAZCPUGQEGUQIZ-UHFFFAOYSA-N 1-ethoxy-2-methyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(OCC)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N KAZCPUGQEGUQIZ-UHFFFAOYSA-N 0.000 description 2
KTVXETAMWVBIJG-UHFFFAOYSA-N 1-ethyl-2-(2-hydroxyethyl)-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(CC)C(CCO)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N KTVXETAMWVBIJG-UHFFFAOYSA-N 0.000 description 2
BNGKKCZSSGNTQX-UHFFFAOYSA-N 1-ethyl-2-(2-methylsulfanylethyl)-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(CC)C(CCSC)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N BNGKKCZSSGNTQX-UHFFFAOYSA-N 0.000 description 2
GWGGVKHMNWOPDF-UHFFFAOYSA-N 1-ethyl-2-(ethylamino)-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(CC)C(NCC)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N GWGGVKHMNWOPDF-UHFFFAOYSA-N 0.000 description 2
UIQOWFRNPQGBDO-UHFFFAOYSA-N 1-methoxy-2-methyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(OC)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N UIQOWFRNPQGBDO-UHFFFAOYSA-N 0.000 description 2
NEPSKPCEPGOSDF-UHFFFAOYSA-N 1-methyl-5-oxo-7-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-2,3-dihydroimidazo[1,2-a]pyrimidine-6-carbonitrile Chemical compound C1CC2=CC=CC=C2CCN1C1=C(C#N)C(=O)N2CCN(C)C2=N1 NEPSKPCEPGOSDF-UHFFFAOYSA-N 0.000 description 2
VYVGSWIZZJVLTQ-UHFFFAOYSA-N 2,3-diethyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-one Chemical compound O=C1N(CC)C(CC)=NC(N2CCC3=CC=CC=C3CC2)=C1[N+]([O-])=O VYVGSWIZZJVLTQ-UHFFFAOYSA-N 0.000 description 2
ACNBEQIADHCQRE-UHFFFAOYSA-N 2,3-dimethyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-one Chemical compound O=C1N(C)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1[N+]([O-])=O ACNBEQIADHCQRE-UHFFFAOYSA-N 0.000 description 2
HAKGTFGHMHCYFU-UHFFFAOYSA-N 2,4-dioxo-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidine-5-carbonitrile Chemical compound O=C1NC(=O)NC(N2CCC3=CC=CC=C3CC2)=C1C#N HAKGTFGHMHCYFU-UHFFFAOYSA-N 0.000 description 2
PAXXXPIAKABLCD-UHFFFAOYSA-N 2-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)benzonitrile Chemical compound N#CC1=CC=CC=C1N1CCC2=CC=CC=C2CC1 PAXXXPIAKABLCD-UHFFFAOYSA-N 0.000 description 2
WOEUHVIFVSNFJS-UHFFFAOYSA-N 2-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyridine-3-carbonitrile Chemical compound N#CC1=CC=CN=C1N1CCC2=CC=CC=C2CC1 WOEUHVIFVSNFJS-UHFFFAOYSA-N 0.000 description 2
TWSDUJLRBMMPSM-UHFFFAOYSA-N 2-(2-hydroxyethyl)-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound OCCC1=NC(OCC(F)(F)F)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 TWSDUJLRBMMPSM-UHFFFAOYSA-N 0.000 description 2
IZQOOTPAJCXYNC-UHFFFAOYSA-N 2-(2-methoxyethoxy)-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound COCCOC1=NC(OCC(F)(F)F)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 IZQOOTPAJCXYNC-UHFFFAOYSA-N 0.000 description 2
JBWXHNUBPBBHLW-UHFFFAOYSA-N 2-(2-methylsulfanylethyl)-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound CSCCC1=NC(OCC(F)(F)F)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 JBWXHNUBPBBHLW-UHFFFAOYSA-N 0.000 description 2
AJYJABRTGXSQJF-UHFFFAOYSA-N 2-(2-pyridin-2-yloxyethylamino)-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC3=CC=CC=C3CC2)=C(C#N)C(OCC(F)(F)F)=NC=1NCCOC1=CC=CC=N1 AJYJABRTGXSQJF-UHFFFAOYSA-N 0.000 description 2
AKFPUPPLSPVTER-UHFFFAOYSA-N 2-(2-pyridin-3-ylethylamino)-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC3=CC=CC=C3CC2)=C(C#N)C(OCC(F)(F)F)=NC=1NCCC1=CC=CN=C1 AKFPUPPLSPVTER-UHFFFAOYSA-N 0.000 description 2
GIUYCDJIZPSRMF-UHFFFAOYSA-N 2-(2-pyrrolidin-1-ylethylamino)-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC3=CC=CC=C3CC2)=C(C#N)C(OCC(F)(F)F)=NC=1NCCN1CCCC1 GIUYCDJIZPSRMF-UHFFFAOYSA-N 0.000 description 2
LDQXTBAOOPRWHW-UHFFFAOYSA-N 2-(3-hydroxypropylamino)-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound OCCCNC1=NC(OCC(F)(F)F)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 LDQXTBAOOPRWHW-UHFFFAOYSA-N 0.000 description 2
GSLUZGWRMCNRRZ-UHFFFAOYSA-N 2-(3-phenoxypropoxy)-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC3=CC=CC=C3CC2)=C(C#N)C(OCC(F)(F)F)=NC=1OCCCOC1=CC=CC=C1 GSLUZGWRMCNRRZ-UHFFFAOYSA-N 0.000 description 2
SEXLWYLUQGIFJC-UHFFFAOYSA-N 2-(3-pyridin-2-ylpropoxy)-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC3=CC=CC=C3CC2)=C(C#N)C(OCC(F)(F)F)=NC=1OCCCC1=CC=CC=N1 SEXLWYLUQGIFJC-UHFFFAOYSA-N 0.000 description 2
VASAZRIPGNYGFX-UHFFFAOYSA-N 2-(4-ethylpiperazin-1-yl)-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound C1CN(CC)CCN1C1=NC(OCC(F)(F)F)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 VASAZRIPGNYGFX-UHFFFAOYSA-N 0.000 description 2
NADSCGDQQVKIFV-UHFFFAOYSA-N 2-(hydroxymethyl)-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound OCC1=NC(OCC(F)(F)F)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 NADSCGDQQVKIFV-UHFFFAOYSA-N 0.000 description 2
HPACVCQJSTVCDV-UHFFFAOYSA-N 2-(hydroxymethyl)-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1-(2,2,2-trifluoroethyl)pyrimidine-5-carbonitrile Chemical compound O=C1N(CC(F)(F)F)C(CO)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N HPACVCQJSTVCDV-UHFFFAOYSA-N 0.000 description 2
KKFDCBRMNNSAAW-UHFFFAOYSA-N 2-(morpholin-4-yl)ethanol Chemical compound OCCN1CCOCC1 KKFDCBRMNNSAAW-UHFFFAOYSA-N 0.000 description 2
XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 2
FCWMOOUOGJDTJD-UHFFFAOYSA-N 2-[2-(1,3-dioxoisoindol-2-yl)ethyl]-4-oxo-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidine-5-carbonitrile Chemical compound C1CC2=CC=CC=C2CCN1C1=C(C#N)C(=O)NC(CCN2C(C3=CC=CC=C3C2=O)=O)=N1 FCWMOOUOGJDTJD-UHFFFAOYSA-N 0.000 description 2
YARLSKBCMUKFQA-UHFFFAOYSA-N 2-[2-(2-hydroxyethoxy)ethylamino]-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound OCCOCCNC1=NC(OCC(F)(F)F)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 YARLSKBCMUKFQA-UHFFFAOYSA-N 0.000 description 2
UIQWCLYOSGDDCK-UHFFFAOYSA-N 2-[2-methyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-yl]oxyethanamine Chemical compound CC1=NC(OCCN)=C([N+]([O-])=O)C(N2CCC3=CC=CC=C3CC2)=N1 UIQWCLYOSGDDCK-UHFFFAOYSA-N 0.000 description 2
YJVYDLDQWOONTO-UHFFFAOYSA-N 2-[2-methyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-yl]oxyethanol Chemical compound CC1=NC(OCCO)=C([N+]([O-])=O)C(N2CCC3=CC=CC=C3CC2)=N1 YJVYDLDQWOONTO-UHFFFAOYSA-N 0.000 description 2
SIAACNOVTAUDPJ-UHFFFAOYSA-N 2-[5-cyano-4-oxo-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidin-2-yl]acetamide Chemical compound O=C1NC(CC(=O)N)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N SIAACNOVTAUDPJ-UHFFFAOYSA-N 0.000 description 2
PTYWUCYGKUFEJB-UHFFFAOYSA-N 2-amino-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound NC1=NC(OCC(F)(F)F)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 PTYWUCYGKUFEJB-UHFFFAOYSA-N 0.000 description 2
NIGABBJLWQTUHQ-UHFFFAOYSA-N 2-amino-4-bromo-6-methylsulfanylpyrimidine-5-carbonitrile Chemical compound CSC1=NC(N)=NC(Br)=C1C#N NIGABBJLWQTUHQ-UHFFFAOYSA-N 0.000 description 2
UXKTWZCCVHMXFE-UHFFFAOYSA-N 2-amino-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidin-4-one Chemical compound O=C1NC(N)=NC(N2CCC3=CC=CC=C3CC2)=C1[N+]([O-])=O UXKTWZCCVHMXFE-UHFFFAOYSA-N 0.000 description 2
UJSGQQJJNNRLDL-UHFFFAOYSA-N 2-cyclopropyl-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC3=CC=CC=C3CC2)=C(C#N)C(OCC(F)(F)F)=NC=1C1CC1 UJSGQQJJNNRLDL-UHFFFAOYSA-N 0.000 description 2
IUKMELDXVWFKAH-UHFFFAOYSA-N 2-cyclopropyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1-(2,2,2-trifluoroethyl)pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC3=CC=CC=C3CC2)=C(C#N)C(=O)N(CC(F)(F)F)C=1C1CC1 IUKMELDXVWFKAH-UHFFFAOYSA-N 0.000 description 2
IKBMNSBCPQUFJK-UHFFFAOYSA-N 2-methyl-1-(methylamino)-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(NC)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N IKBMNSBCPQUFJK-UHFFFAOYSA-N 0.000 description 2
QVMANNHIYQCMDE-UHFFFAOYSA-N 2-methyl-3-(2-methylpropyl)-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-one Chemical compound O=C1N(CC(C)C)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1[N+]([O-])=O QVMANNHIYQCMDE-UHFFFAOYSA-N 0.000 description 2
IKQVJEBCZCQZDS-UHFFFAOYSA-N 2-methyl-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound CC1=NC(OCC(F)(F)F)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 IKQVJEBCZCQZDS-UHFFFAOYSA-N 0.000 description 2
RERCCSZNLYFAJW-UHFFFAOYSA-N 2-methyl-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethylamino)pyrimidine-5-carbonitrile Chemical compound CC1=NC(NCC(F)(F)F)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 RERCCSZNLYFAJW-UHFFFAOYSA-N 0.000 description 2
XOLZWZQRBFEBLF-UHFFFAOYSA-N 2-methyl-4-propoxy-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound CCCOC1=NC(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N XOLZWZQRBFEBLF-UHFFFAOYSA-N 0.000 description 2
CIVUNEMYGOPVEK-UHFFFAOYSA-N 2-methyl-5-nitro-3-(3-phenylpropyl)-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-one Chemical compound CC1=NC(N2CCC3=CC=CC=C3CC2)=C([N+]([O-])=O)C(=O)N1CCCC1=CC=CC=C1 CIVUNEMYGOPVEK-UHFFFAOYSA-N 0.000 description 2
FRXGWLQJALRSBC-UHFFFAOYSA-N 2-methyl-5-nitro-3-propan-2-yl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-one Chemical compound O=C1N(C(C)C)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1[N+]([O-])=O FRXGWLQJALRSBC-UHFFFAOYSA-N 0.000 description 2
OYXNDTYTTHMGFF-UHFFFAOYSA-N 2-methyl-5-nitro-3-propyl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-one Chemical compound O=C1N(CCC)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1[N+]([O-])=O OYXNDTYTTHMGFF-UHFFFAOYSA-N 0.000 description 2
PQNUWDYLPWUAMY-UHFFFAOYSA-N 2-methyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-3-(2,2,2-trifluoroethyl)pyrimidin-4-one Chemical compound O=C1N(CC(F)(F)F)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1[N+]([O-])=O PQNUWDYLPWUAMY-UHFFFAOYSA-N 0.000 description 2
GTZABUIRMQNXPO-UHFFFAOYSA-N 2-methyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-3-[3-(1,2,4-triazol-1-yl)propyl]pyrimidin-4-one Chemical compound CC1=NC(N2CCC3=CC=CC=C3CC2)=C([N+]([O-])=O)C(=O)N1CCCN1C=NC=N1 GTZABUIRMQNXPO-UHFFFAOYSA-N 0.000 description 2
WKYMXCBCUFXECY-UHFFFAOYSA-N 2-methyl-5-nitro-6-(5,6,8,9-tetrahydro-[1,3]dioxolo[4,5-h][3]benzazepin-7-yl)-1h-pyrimidin-4-one Chemical compound O=C1NC(C)=NC(N2CCC3=CC=4OCOC=4C=C3CC2)=C1[N+]([O-])=O WKYMXCBCUFXECY-UHFFFAOYSA-N 0.000 description 2
LNEIXWWXFNPPJR-UHFFFAOYSA-N 2-methyl-5-nitro-6-(7-nitro-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidin-4-one Chemical compound O=C1NC(C)=NC(N2CCC3=CC(=CC=C3CC2)[N+]([O-])=O)=C1[N+]([O-])=O LNEIXWWXFNPPJR-UHFFFAOYSA-N 0.000 description 2
HJEVHHWWINMDCC-UHFFFAOYSA-N 2-methyl-6-oxo-1-(propan-2-ylamino)-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(NC(C)C)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N HJEVHHWWINMDCC-UHFFFAOYSA-N 0.000 description 2
ARTMXGPVSFXQEO-UHFFFAOYSA-N 2-methyl-6-oxo-1-propan-2-yloxy-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(OC(C)C)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N ARTMXGPVSFXQEO-UHFFFAOYSA-N 0.000 description 2
LUFUUUCPAOWUFN-UHFFFAOYSA-N 2-methyl-6-oxo-1-propyl-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(CCC)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N LUFUUUCPAOWUFN-UHFFFAOYSA-N 0.000 description 2
FQGGLDSQSTXRLQ-UHFFFAOYSA-N 2-methyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1-(2,2,2-trifluoroethylamino)pyrimidine-5-carbonitrile Chemical compound O=C1N(NCC(F)(F)F)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N FQGGLDSQSTXRLQ-UHFFFAOYSA-N 0.000 description 2
BVVSFTGGHZTPOK-UHFFFAOYSA-N 2-methylsulfanyl-4-(2-morpholin-4-ylethoxy)-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound N#CC=1C(N2CCC3=CC=CC=C3CC2)=NC(SC)=NC=1OCCN1CCOCC1 BVVSFTGGHZTPOK-UHFFFAOYSA-N 0.000 description 2
XBOZMCIQYBLUNH-UHFFFAOYSA-N 2-methylsulfanyl-4-(3-pyridin-2-ylpropoxy)-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound N#CC=1C(N2CCC3=CC=CC=C3CC2)=NC(SC)=NC=1OCCCC1=CC=CC=N1 XBOZMCIQYBLUNH-UHFFFAOYSA-N 0.000 description 2
MHUQQSKESMQRRA-UHFFFAOYSA-N 2-methylsulfanyl-4-oxo-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidine-5-carbonitrile Chemical compound O=C1NC(SC)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N MHUQQSKESMQRRA-UHFFFAOYSA-N 0.000 description 2
MFNDMMTZVHYGIM-UHFFFAOYSA-N 3-(2-hydroxyethyl)-2-methyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-one Chemical compound O=C1N(CCO)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1[N+]([O-])=O MFNDMMTZVHYGIM-UHFFFAOYSA-N 0.000 description 2
ILSNINKODGAABT-UHFFFAOYSA-N 3-(2-methyl-5-nitro-4-oxo-1h-pyrimidin-6-yl)-1,2,4,5-tetrahydro-3-benzazepine-7-sulfonamide Chemical compound O=C1NC(C)=NC(N2CCC3=CC(=CC=C3CC2)S(N)(=O)=O)=C1[N+]([O-])=O ILSNINKODGAABT-UHFFFAOYSA-N 0.000 description 2
FIHNAIACDUQDLZ-UHFFFAOYSA-N 3-(2-methyl-5-nitro-4-oxo-1h-pyrimidin-6-yl)-2,4-dihydro-1h-3-benzazepin-5-one Chemical compound O=C1NC(C)=NC(N2CC(=O)C3=CC=CC=C3CC2)=C1[N+]([O-])=O FIHNAIACDUQDLZ-UHFFFAOYSA-N 0.000 description 2
BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 2
UTORWFJXEZVQIB-UHFFFAOYSA-N 3-(5-methyl-3-nitropyridin-2-yl)-1,2,4,5-tetrahydro-3-benzazepine Chemical compound [O-][N+](=O)C1=CC(C)=CN=C1N1CCC2=CC=CC=C2CC1 UTORWFJXEZVQIB-UHFFFAOYSA-N 0.000 description 2
YVRVWNRKCOROPH-UHFFFAOYSA-N 3-(6-chloro-5-nitropyrimidin-4-yl)-1,2,4,5-tetrahydro-3-benzazepine Chemical compound [O-][N+](=O)C1=C(Cl)N=CN=C1N1CCC2=CC=CC=C2CC1 YVRVWNRKCOROPH-UHFFFAOYSA-N 0.000 description 2
MIBFNCRIHFZGPJ-UHFFFAOYSA-N 3-(6-ethoxy-2-methyl-5-nitropyrimidin-4-yl)-7-fluoro-1,2,4,5-tetrahydro-3-benzazepine Chemical compound CCOC1=NC(C)=NC(N2CCC3=CC(F)=CC=C3CC2)=C1[N+]([O-])=O MIBFNCRIHFZGPJ-UHFFFAOYSA-N 0.000 description 2
RGAYNQSITJIMND-UHFFFAOYSA-N 3-(6-methoxy-5-nitropyrimidin-4-yl)-1,2,4,5-tetrahydro-3-benzazepine Chemical compound COC1=NC=NC(N2CCC3=CC=CC=C3CC2)=C1[N+]([O-])=O RGAYNQSITJIMND-UHFFFAOYSA-N 0.000 description 2
YSNKZNYALOGTQK-UHFFFAOYSA-N 3-[2-methyl-5-nitro-6-(3-phenylpropoxy)pyrimidin-4-yl]-1,2,4,5-tetrahydro-3-benzazepine Chemical compound [O-][N+](=O)C=1C(N2CCC3=CC=CC=C3CC2)=NC(C)=NC=1OCCCC1=CC=CC=C1 YSNKZNYALOGTQK-UHFFFAOYSA-N 0.000 description 2
ZIFBEOAVJKHTDU-UHFFFAOYSA-N 3-[2-methyl-5-nitro-6-(3-pyridin-2-ylpropoxy)pyrimidin-4-yl]-1,2,4,5-tetrahydro-3-benzazepine Chemical compound [O-][N+](=O)C=1C(N2CCC3=CC=CC=C3CC2)=NC(C)=NC=1OCCCC1=CC=CC=N1 ZIFBEOAVJKHTDU-UHFFFAOYSA-N 0.000 description 2
JQCBBTZJFVLVDH-UHFFFAOYSA-N 3-[2-methyl-5-nitro-6-(3-pyridin-4-ylpropoxy)pyrimidin-4-yl]-1,2,4,5-tetrahydro-3-benzazepine Chemical compound [O-][N+](=O)C=1C(N2CCC3=CC=CC=C3CC2)=NC(C)=NC=1OCCCC1=CC=NC=C1 JQCBBTZJFVLVDH-UHFFFAOYSA-N 0.000 description 2
UYDDGKDZVXFRPJ-UHFFFAOYSA-N 3-[2-methyl-5-nitro-6-[4-(1,2,4-triazol-1-yl)butoxy]pyrimidin-4-yl]-1,2,4,5-tetrahydro-3-benzazepine Chemical compound [O-][N+](=O)C=1C(N2CCC3=CC=CC=C3CC2)=NC(C)=NC=1OCCCCN1C=NC=N1 UYDDGKDZVXFRPJ-UHFFFAOYSA-N 0.000 description 2
WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 2
IMDLCOPMQQUEQL-LJQANCHMSA-N 3-[3-[(3r)-3-hydroxypyrrolidin-1-yl]propyl]-2-methyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-one Chemical compound CC1=NC(N2CCC3=CC=CC=C3CC2)=C([N+]([O-])=O)C(=O)N1CCCN1CC[C@@H](O)C1 IMDLCOPMQQUEQL-LJQANCHMSA-N 0.000 description 2
JJBJBPVDGTULOT-UHFFFAOYSA-N 3-[4-[tert-butyl(dimethyl)silyl]oxybutyl]-2-methyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-one Chemical compound O=C1N(CCCCO[Si](C)(C)C(C)(C)C)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1[N+]([O-])=O JJBJBPVDGTULOT-UHFFFAOYSA-N 0.000 description 2
KZSQNCCFGRCNPX-UHFFFAOYSA-N 3-[6-(3-imidazol-1-ylpropoxy)-2-methyl-5-nitropyrimidin-4-yl]-1,2,4,5-tetrahydro-3-benzazepine Chemical compound [O-][N+](=O)C=1C(N2CCC3=CC=CC=C3CC2)=NC(C)=NC=1OCCCN1C=CN=C1 KZSQNCCFGRCNPX-UHFFFAOYSA-N 0.000 description 2
XEHNDQIPKIOXEE-UHFFFAOYSA-N 3-[[2-methyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-yl]amino]propan-1-ol Chemical compound CC1=NC(NCCCO)=C([N+]([O-])=O)C(N2CCC3=CC=CC=C3CC2)=N1 XEHNDQIPKIOXEE-UHFFFAOYSA-N 0.000 description 2
NIDWUZTTXGJFNN-UHFFFAOYSA-N 3-bromopropoxybenzene Chemical compound BrCCCOC1=CC=CC=C1 NIDWUZTTXGJFNN-UHFFFAOYSA-N 0.000 description 2
LAMUXTNQCICZQX-UHFFFAOYSA-N 3-chloropropan-1-ol Chemical compound OCCCCl LAMUXTNQCICZQX-UHFFFAOYSA-N 0.000 description 2
XZBXAYCCBFTQHH-UHFFFAOYSA-N 3-chloropropylbenzene Chemical compound ClCCCC1=CC=CC=C1 XZBXAYCCBFTQHH-UHFFFAOYSA-N 0.000 description 2
LHKWHLPOHVOAIA-UHFFFAOYSA-N 3-ethyl-5-nitro-2-propan-2-yl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-one Chemical compound O=C1N(CC)C(C(C)C)=NC(N2CCC3=CC=CC=C3CC2)=C1[N+]([O-])=O LHKWHLPOHVOAIA-UHFFFAOYSA-N 0.000 description 2
LVUCVBRYYIBZHA-UHFFFAOYSA-N 3-hydroxypropanimidamide;hydrochloride Chemical compound Cl.NC(=N)CCO LVUCVBRYYIBZHA-UHFFFAOYSA-N 0.000 description 2
UIKUBYKUYUSRSM-UHFFFAOYSA-N 3-morpholinopropylamine Chemical compound NCCCN1CCOCC1 UIKUBYKUYUSRSM-UHFFFAOYSA-N 0.000 description 2
ZUGAIMFLQLPTKB-UHFFFAOYSA-N 3-pyridin-3-ylpropan-1-ol Chemical compound OCCCC1=CC=CN=C1 ZUGAIMFLQLPTKB-UHFFFAOYSA-N 0.000 description 2
JUCUDQWOSNXFQH-UHFFFAOYSA-N 4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-2,6-bis(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound FC(F)(F)COC1=NC(OCC(F)(F)F)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 JUCUDQWOSNXFQH-UHFFFAOYSA-N 0.000 description 2
NBJHDLKSWUDGJG-UHFFFAOYSA-N 4-(2-chloroethyl)morpholin-4-ium;chloride Chemical compound Cl.ClCCN1CCOCC1 NBJHDLKSWUDGJG-UHFFFAOYSA-N 0.000 description 2
CLANSGSVVKDSHX-UHFFFAOYSA-N 4-(2-hydroxyethoxy)-2-(2-hydroxyethyl)-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound OCCOC1=NC(CCO)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N CLANSGSVVKDSHX-UHFFFAOYSA-N 0.000 description 2
STKAECAMUIPMBA-UHFFFAOYSA-N 4-(2-hydroxyethoxy)-2-(2-methylsulfanylethyl)-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound CSCCC1=NC(OCCO)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 STKAECAMUIPMBA-UHFFFAOYSA-N 0.000 description 2
BCCDNRGWSGFPNE-UHFFFAOYSA-N 4-(2-hydroxyethoxy)-2-[2-(oxan-2-yloxy)ethyl]-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC3=CC=CC=C3CC2)=C(C#N)C(OCCO)=NC=1CCOC1CCCCO1 BCCDNRGWSGFPNE-UHFFFAOYSA-N 0.000 description 2
WYDVEVZOSCSAKJ-UHFFFAOYSA-N 4-(2-hydroxyethoxy)-2-methyl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound CC1=NC(OCCO)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 WYDVEVZOSCSAKJ-UHFFFAOYSA-N 0.000 description 2
RNSRTZWLMKMMSQ-UHFFFAOYSA-N 4-(3-imidazol-1-ylpropylamino)-2-methylsulfanyl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound N#CC=1C(N2CCC3=CC=CC=C3CC2)=NC(SC)=NC=1NCCCN1C=CN=C1 RNSRTZWLMKMMSQ-UHFFFAOYSA-N 0.000 description 2
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
XPLOJUYUFJAJKM-UHFFFAOYSA-N 4-(4-methylpentoxy)-2-methylsulfanyl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound CSC1=NC(OCCCC(C)C)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 XPLOJUYUFJAJKM-UHFFFAOYSA-N 0.000 description 2
KNDJKIVGCCYOTO-UHFFFAOYSA-N 4-(cyanomethoxy)-2-methyl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound CC1=NC(OCC#N)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 KNDJKIVGCCYOTO-UHFFFAOYSA-N 0.000 description 2
YCCNOZVJGPOAJN-UHFFFAOYSA-N 4-(difluoromethoxy)-2-methyl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound CC1=NC(OC(F)F)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 YCCNOZVJGPOAJN-UHFFFAOYSA-N 0.000 description 2
QMWJCHMSTDNFDI-MRXNPFEDSA-N 4-[(2r)-2,3-dihydroxypropoxy]-2-methyl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound CC1=NC(OC[C@H](O)CO)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 QMWJCHMSTDNFDI-MRXNPFEDSA-N 0.000 description 2
VJSKCMADFAYHBE-UHFFFAOYSA-N 4-[(4-methoxyphenyl)methoxy]-3-nitro-2-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6,7,8,9-tetrahydro-5h-cyclohepta[b]pyridine Chemical compound C1=CC(OC)=CC=C1COC1=C(CCCCC2)C2=NC(N2CCC3=CC=CC=C3CC2)=C1[N+]([O-])=O VJSKCMADFAYHBE-UHFFFAOYSA-N 0.000 description 2
YFCIFWOJYYFDQP-PTWZRHHISA-N 4-[3-amino-6-[(1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide Chemical compound CNC[C@@H](NC(=O)c1ccc(cc1F)-c1nc(cnc1N)[C@H]1CC[C@H](O)[C@@H](F)C1)c1cc(F)cc(Br)c1 YFCIFWOJYYFDQP-PTWZRHHISA-N 0.000 description 2
XYWIPYBIIRTJMM-IBGZPJMESA-N 4-[[(2S)-2-[4-[5-chloro-2-[4-(trifluoromethyl)triazol-1-yl]phenyl]-5-methoxy-2-oxopyridin-1-yl]butanoyl]amino]-2-fluorobenzamide Chemical compound CC[C@H](N1C=C(OC)C(=CC1=O)C1=C(C=CC(Cl)=C1)N1C=C(N=N1)C(F)(F)F)C(=O)NC1=CC(F)=C(C=C1)C(N)=O XYWIPYBIIRTJMM-IBGZPJMESA-N 0.000 description 2
MALKUIGNWOGYHK-GOSISDBHSA-N 4-[[(4r)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]-2-methyl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound N#CC=1C(N2CCC3=CC=CC=C3CC2)=NC(C)=NC=1OC[C@@H]1COC(C)(C)O1 MALKUIGNWOGYHK-GOSISDBHSA-N 0.000 description 2
LBWSGHLXEOETFG-UHFFFAOYSA-N 4-amino-2-(2-hydroxyethylamino)-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound NC1=NC(NCCO)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N LBWSGHLXEOETFG-UHFFFAOYSA-N 0.000 description 2
KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 2
MNZRMOSZXHSYLY-UHFFFAOYSA-N 4-chloro-2-methylsulfonyl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound CS(=O)(=O)C1=NC(Cl)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 MNZRMOSZXHSYLY-UHFFFAOYSA-N 0.000 description 2
VACMMQREPACPNH-UHFFFAOYSA-N 4-chloro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-2-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound FC(F)(F)COC1=NC(Cl)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 VACMMQREPACPNH-UHFFFAOYSA-N 0.000 description 2
WWNLACZGVXRJFU-UHFFFAOYSA-N 4-ethoxy-2-methyl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound CCOC1=NC(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N WWNLACZGVXRJFU-UHFFFAOYSA-N 0.000 description 2
RWUQCFRJEFQTKV-UHFFFAOYSA-N 4-ethoxy-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound CCOC1=NC=NC(N2CCC3=CC=CC=C3CC2)=C1C#N RWUQCFRJEFQTKV-UHFFFAOYSA-N 0.000 description 2
LKDAHNLFFBFTAV-UHFFFAOYSA-N 4-methoxy-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound COC1=NC=NC(N2CCC3=CC=CC=C3CC2)=C1C#N LKDAHNLFFBFTAV-UHFFFAOYSA-N 0.000 description 2
LZICCGYCKCTPPG-UHFFFAOYSA-N 4-oxo-2-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-3-carbonitrile Chemical compound C1CC2=CC=CC=C2CCN1C1=C(C#N)C(=O)N2CCCCC2=N1 LZICCGYCKCTPPG-UHFFFAOYSA-N 0.000 description 2
MMJZHUALIQIGOS-UHFFFAOYSA-N 4-oxo-2-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-7,8-dihydro-6h-pyrrolo[1,2-a]pyrimidine-3-carbonitrile Chemical compound C1CC2=CC=CC=C2CCN1C1=C(C#N)C(=O)N2CCCC2=N1 MMJZHUALIQIGOS-UHFFFAOYSA-N 0.000 description 2
BZSMZVVEBXNPPK-UHFFFAOYSA-N 4-oxo-2-(3-phenoxypropylamino)-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC3=CC=CC=C3CC2)=C(C#N)C(=O)NC=1NCCCOC1=CC=CC=C1 BZSMZVVEBXNPPK-UHFFFAOYSA-N 0.000 description 2
TVPLZIZESXOSID-UHFFFAOYSA-N 4-oxo-2-(phenylsulfanylmethyl)-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC3=CC=CC=C3CC2)=C(C#N)C(=O)NC=1CSC1=CC=CC=C1 TVPLZIZESXOSID-UHFFFAOYSA-N 0.000 description 2
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
CJFQSFZRPQSTCL-UHFFFAOYSA-N 5-ethyl-6-(hydroxymethyl)-2-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyridine-3-carbonitrile Chemical compound N1=C(CO)C(CC)=CC(C#N)=C1N1CCC2=CC=CC=C2CC1 CJFQSFZRPQSTCL-UHFFFAOYSA-N 0.000 description 2
VDGFOUYAVFLSRU-UHFFFAOYSA-N 5-methylsulfanyl-7-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-2,3-dihydroimidazo[1,2-c]pyrimidine-8-carbonitrile;hydrochloride Chemical compound Cl.C1CC2=CC=CC=C2CCN1C1=C(C#N)C2=NCCN2C(SC)=N1 VDGFOUYAVFLSRU-UHFFFAOYSA-N 0.000 description 2
QBMRZAWQUSEHEO-UHFFFAOYSA-N 5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidin-4-one Chemical compound OC1=NC=NC(N2CCC3=CC=CC=C3CC2)=C1[N+]([O-])=O QBMRZAWQUSEHEO-UHFFFAOYSA-N 0.000 description 2
IKBZKLCUIGRONE-UHFFFAOYSA-N 5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-amine Chemical compound NC1=NC=NC(N2CCC3=CC=CC=C3CC2)=C1[N+]([O-])=O IKBZKLCUIGRONE-UHFFFAOYSA-N 0.000 description 2
HEFHAEFYVYBIDW-UHFFFAOYSA-N 5-oxo-7-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-3,8-dihydro-2h-imidazo[1,2-a]pyrimidine-6-carbonitrile Chemical compound C1CC2=CC=CC=C2CCN1C1=C(C#N)C(=O)N2CCNC2=N1 HEFHAEFYVYBIDW-UHFFFAOYSA-N 0.000 description 2
MOFUFENEPZWIHP-UHFFFAOYSA-N 5-oxo-7-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-8h-imidazo[1,2-a]pyrimidine-6-carbonitrile Chemical compound C1CC2=CC=CC=C2CCN1C1=C(C#N)C(=O)N2C=CNC2=N1 MOFUFENEPZWIHP-UHFFFAOYSA-N 0.000 description 2
SSHDZLPJYABIAT-UHFFFAOYSA-N 6-(6-methoxy-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-2-methyl-5-nitro-1h-pyrimidin-4-one Chemical compound C1CC=2C(OC)=CC=CC=2CCN1C=1N=C(C)NC(=O)C=1[N+]([O-])=O SSHDZLPJYABIAT-UHFFFAOYSA-N 0.000 description 2
STJKRTWDNKRCFC-UHFFFAOYSA-N 6-(7,8-dimethoxy-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-2-methyl-5-nitro-1h-pyrimidin-4-one Chemical compound C1CC=2C=C(OC)C(OC)=CC=2CCN1C=1N=C(C)NC(=O)C=1[N+]([O-])=O STJKRTWDNKRCFC-UHFFFAOYSA-N 0.000 description 2
YCKOWZLFWDAONL-UHFFFAOYSA-N 6-(7-amino-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-2-methyl-5-nitro-1h-pyrimidin-4-one Chemical compound O=C1NC(C)=NC(N2CCC3=CC(N)=CC=C3CC2)=C1[N+]([O-])=O YCKOWZLFWDAONL-UHFFFAOYSA-N 0.000 description 2
DWPPFBNJNHQPBX-UHFFFAOYSA-N 6-(7-chloro-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-2-methyl-5-nitro-1h-pyrimidin-4-one Chemical compound O=C1NC(C)=NC(N2CCC3=CC(Cl)=CC=C3CC2)=C1[N+]([O-])=O DWPPFBNJNHQPBX-UHFFFAOYSA-N 0.000 description 2
KBBMMYXFJKTTBW-UHFFFAOYSA-N 6-(7-methoxy-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-2-methyl-5-nitro-1h-pyrimidin-4-one Chemical compound C1CC2=CC(OC)=CC=C2CCN1C=1N=C(C)NC(=O)C=1[N+]([O-])=O KBBMMYXFJKTTBW-UHFFFAOYSA-N 0.000 description 2
NGJMCWXMNHCDPF-UHFFFAOYSA-N 6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1-(2,2,2-trifluoroethyl)-2-(2,2,2-trifluoroethylamino)pyrimidine-5-carbonitrile Chemical compound O=C1N(CC(F)(F)F)C(NCC(F)(F)F)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N NGJMCWXMNHCDPF-UHFFFAOYSA-N 0.000 description 2
CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 2
HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 2
BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 2
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
229930194542 Keto Natural products 0.000 description 2
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
229920000168 Microcrystalline cellulose Polymers 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
LYIVRHZVMWBIMC-MBXJOHMKSA-N O=C1N(\C=C/C)C(N)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N Chemical compound O=C1N(\C=C/C)C(N)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N LYIVRHZVMWBIMC-MBXJOHMKSA-N 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-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
QDBGAZYKGABOFT-UHFFFAOYSA-N [5-cyano-3-ethyl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyridin-2-yl]methyl 2,2,2-trifluoroacetate Chemical compound N1=C(COC(=O)C(F)(F)F)C(CC)=CC(C#N)=C1N1CCC2=CC=CC=C2CC1 QDBGAZYKGABOFT-UHFFFAOYSA-N 0.000 description 2
XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 2
150000001409 amidines Chemical class 0.000 description 2
NMVVJCLUYUWBSZ-UHFFFAOYSA-N aminomethylideneazanium;chloride Chemical compound Cl.NC=N NMVVJCLUYUWBSZ-UHFFFAOYSA-N 0.000 description 2
235000011114 ammonium hydroxide Nutrition 0.000 description 2
230000003042 antagnostic effect Effects 0.000 description 2
239000012300 argon atmosphere Substances 0.000 description 2
XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 2
125000002785 azepinyl group Chemical group 0.000 description 2
235000019400 benzoyl peroxide Nutrition 0.000 description 2
239000012148 binding buffer Substances 0.000 description 2
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 2
ARUJJNVNLJPSDO-UHFFFAOYSA-N butanamide;hydrochloride Chemical compound Cl.CCCC(N)=O ARUJJNVNLJPSDO-UHFFFAOYSA-N 0.000 description 2
KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
DGLFSNZWRYADFC-UHFFFAOYSA-N chembl2334586 Chemical compound C1CCC2=CN=C(N)N=C2C2=C1NC1=CC=C(C#CC(C)(O)C)C=C12 DGLFSNZWRYADFC-UHFFFAOYSA-N 0.000 description 2
238000000354 decomposition reaction Methods 0.000 description 2
239000008298 dragée Substances 0.000 description 2
WCQOBLXWLRDEQA-UHFFFAOYSA-N ethanimidamide;hydrochloride Chemical compound Cl.CC(N)=N WCQOBLXWLRDEQA-UHFFFAOYSA-N 0.000 description 2
POABRARINOCORV-UHFFFAOYSA-N ethyl 2-cyano-3,3-bis(methylsulfanyl)prop-2-enoate Chemical compound CCOC(=O)C(C#N)=C(SC)SC POABRARINOCORV-UHFFFAOYSA-N 0.000 description 2
ZADTVBHVBMVDMU-UHFFFAOYSA-N ethyl 2-cyano-3-methylsulfonyl-3-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)prop-2-enoate Chemical compound C1CN(C(=C(C#N)C(=O)OCC)S(C)(=O)=O)CCC2=CC=CC=C21 ZADTVBHVBMVDMU-UHFFFAOYSA-N 0.000 description 2
239000003925 fat Substances 0.000 description 2
235000019253 formic acid Nutrition 0.000 description 2
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
229910000040 hydrogen fluoride Inorganic materials 0.000 description 2
238000005984 hydrogenation reaction Methods 0.000 description 2
238000011534 incubation Methods 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
239000011630 iodine Substances 0.000 description 2
239000007788 liquid Substances 0.000 description 2
238000005259 measurement Methods 0.000 description 2
LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
ZXOFXJZDKCXPTF-UHFFFAOYSA-N methyl 2-[5-cyano-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-1-yl]acetate Chemical compound O=C1N(CC(=O)OC)C=NC(N2CCC3=CC=CC=C3CC2)=C1C#N ZXOFXJZDKCXPTF-UHFFFAOYSA-N 0.000 description 2
AVAQLMHCQPNOHH-UHFFFAOYSA-N methyl 2-[5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-yl]sulfanylacetate Chemical compound COC(=O)CSC1=NC=NC(N2CCC3=CC=CC=C3CC2)=C1[N+]([O-])=O AVAQLMHCQPNOHH-UHFFFAOYSA-N 0.000 description 2
GUCYZAFJQRFYEY-UHFFFAOYSA-N methyl 2-[[5-cyano-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethoxy)pyrimidin-2-yl]amino]acetate Chemical compound COC(=O)CNC1=NC(OCC(F)(F)F)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 GUCYZAFJQRFYEY-UHFFFAOYSA-N 0.000 description 2
NNBBQNFHCVVQHZ-UHFFFAOYSA-N methyl carbamimidothioate;sulfuric acid Chemical compound CSC(N)=N.OS(O)(=O)=O NNBBQNFHCVVQHZ-UHFFFAOYSA-N 0.000 description 2
235000019813 microcrystalline cellulose Nutrition 0.000 description 2
239000008108 microcrystalline cellulose Substances 0.000 description 2
229940016286 microcrystalline cellulose Drugs 0.000 description 2
230000004048 modification Effects 0.000 description 2
238000012986 modification Methods 0.000 description 2
OIZOOFFSPOOOEX-UHFFFAOYSA-N n-[5-cyano-4-methylsulfanyl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-2-yl]acetamide Chemical compound CSC1=NC(NC(C)=O)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N OIZOOFFSPOOOEX-UHFFFAOYSA-N 0.000 description 2
JZKAXNYAXTZYCB-UHFFFAOYSA-N n-[5-nitro-4-oxo-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidin-2-yl]acetamide Chemical compound O=C1NC(NC(=O)C)=NC(N2CCC3=CC=CC=C3CC2)=C1[N+]([O-])=O JZKAXNYAXTZYCB-UHFFFAOYSA-N 0.000 description 2
QEYBDOPNYIXIPO-UHFFFAOYSA-N n-cyclopropyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-amine Chemical compound N1=CN=C(N2CCC3=CC=CC=C3CC2)C([N+](=O)[O-])=C1NC1CC1 QEYBDOPNYIXIPO-UHFFFAOYSA-N 0.000 description 2
239000002858 neurotransmitter agent Substances 0.000 description 2
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
239000012071 phase Substances 0.000 description 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
239000002243 precursor Substances 0.000 description 2
NITSAQJPBJYMFL-UHFFFAOYSA-N pyridin-4-ol Chemical compound O=C1C=[C]NC=C1 NITSAQJPBJYMFL-UHFFFAOYSA-N 0.000 description 2
150000003222 pyridines Chemical class 0.000 description 2
ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 2
230000009467 reduction Effects 0.000 description 2
238000006722 reduction reaction Methods 0.000 description 2
LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 2
229910001958 silver carbonate Inorganic materials 0.000 description 2
230000005586 smoking cessation Effects 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
239000000829 suppository Substances 0.000 description 2
KFOFAUBJBNNGEJ-UHFFFAOYSA-N tert-butyl 3-[[5-cyano-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethoxy)pyrimidin-2-yl]amino]propanoate Chemical compound CC(C)(C)OC(=O)CCNC1=NC(OCC(F)(F)F)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 KFOFAUBJBNNGEJ-UHFFFAOYSA-N 0.000 description 2
QQPNAPNJYAYVNU-UHFFFAOYSA-N tert-butyl n-[5-cyano-2-methyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-1-yl]-n-(2,2,2-trifluoroethyl)carbamate Chemical compound O=C1N(N(CC(F)(F)F)C(=O)OC(C)(C)C)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N QQPNAPNJYAYVNU-UHFFFAOYSA-N 0.000 description 2
CZULJCAECSOLRH-UHFFFAOYSA-N tert-butyl n-[5-cyano-2-methyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-1-yl]-n-ethylcarbamate Chemical compound O=C1N(N(C(=O)OC(C)(C)C)CC)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N CZULJCAECSOLRH-UHFFFAOYSA-N 0.000 description 2
MTQPZXNVDIKRAK-UHFFFAOYSA-N tert-butyl-(4-chlorobutoxy)-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OCCCCCl MTQPZXNVDIKRAK-UHFFFAOYSA-N 0.000 description 2
SOCVQZFVYZBJSQ-UHFFFAOYSA-N tert-butyl-dimethyl-[4-[2-methyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-yl]oxybutoxy]silane Chemical compound CC1=NC(OCCCCO[Si](C)(C)C(C)(C)C)=C([N+]([O-])=O)C(N2CCC3=CC=CC=C3CC2)=N1 SOCVQZFVYZBJSQ-UHFFFAOYSA-N 0.000 description 2
150000007944 thiolates Chemical class 0.000 description 2
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
239000005051 trimethylchlorosilane Substances 0.000 description 2
235000015112 vegetable and seed oil Nutrition 0.000 description 2
239000008158 vegetable oil Substances 0.000 description 2
239000001993 wax Substances 0.000 description 2
VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
VBDPZPFXKVVQRB-UHFFFAOYSA-N (2,2-dicyano-1-methylsulfanylethenyl)cyanamide Chemical compound N#CNC(SC)=C(C#N)C#N VBDPZPFXKVVQRB-UHFFFAOYSA-N 0.000 description 1
DOMQFIFVDIAOOT-ROUUACIJSA-N (2S,3R)-N-[4-(2,6-dimethoxyphenyl)-5-(5-methylpyridin-3-yl)-1,2,4-triazol-3-yl]-3-(5-methylpyrimidin-2-yl)butane-2-sulfonamide Chemical compound COC1=C(C(=CC=C1)OC)N1C(=NN=C1C=1C=NC=C(C=1)C)NS(=O)(=O)[C@@H](C)[C@H](C)C1=NC=C(C=N1)C DOMQFIFVDIAOOT-ROUUACIJSA-N 0.000 description 1
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
JHHZLHWJQPUNKB-SCSAIBSYSA-N (3r)-pyrrolidin-3-ol Chemical compound O[C@@H]1CCNC1 JHHZLHWJQPUNKB-SCSAIBSYSA-N 0.000 description 1
MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 1
UKGJZDSUJSPAJL-YPUOHESYSA-N (e)-n-[(1r)-1-[3,5-difluoro-4-(methanesulfonamido)phenyl]ethyl]-3-[2-propyl-6-(trifluoromethyl)pyridin-3-yl]prop-2-enamide Chemical compound CCCC1=NC(C(F)(F)F)=CC=C1\C=C\C(=O)N[C@H](C)C1=CC(F)=C(NS(C)(=O)=O)C(F)=C1 UKGJZDSUJSPAJL-YPUOHESYSA-N 0.000 description 1
ZGYIXVSQHOKQRZ-COIATFDQSA-N (e)-n-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-[(3s)-oxolan-3-yl]oxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N#CC1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZGYIXVSQHOKQRZ-COIATFDQSA-N 0.000 description 1
QPEJHYYABLMLIC-UHFFFAOYSA-N 1,1,5,5-tetramethyl-3,4-dihydro-2h-3-benzazepine Chemical compound CC1(C)CNCC(C)(C)C2=CC=CC=C12 QPEJHYYABLMLIC-UHFFFAOYSA-N 0.000 description 1
JKEAOQHKFOPGKZ-UHFFFAOYSA-N 1,2,3,4-tetrahydro-3-benzazepin-5-one;hydrochloride Chemical compound Cl.O=C1CNCCC2=CC=CC=C12 JKEAOQHKFOPGKZ-UHFFFAOYSA-N 0.000 description 1
APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 1
WCRIJEKRPPLAMH-UHFFFAOYSA-N 1-(2-hydroxyethyl)-2-(2-methylsulfanylethyl)-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(CCO)C(CCSC)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N WCRIJEKRPPLAMH-UHFFFAOYSA-N 0.000 description 1
WDQFELCEOPFLCZ-UHFFFAOYSA-N 1-(2-hydroxyethyl)pyrrolidin-2-one Chemical compound OCCN1CCCC1=O WDQFELCEOPFLCZ-UHFFFAOYSA-N 0.000 description 1
KFFQRIZBYSBIKP-UHFFFAOYSA-N 1-(7-nitro-1,2,4,5-tetrahydro-3-benzazepin-3-yl)ethanone Chemical compound C1CN(C(=O)C)CCC2=CC=C([N+]([O-])=O)C=C21 KFFQRIZBYSBIKP-UHFFFAOYSA-N 0.000 description 1
CSCIGXJYHRUVMF-UHFFFAOYSA-N 1-(difluoromethyl)-2-methyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(C(F)F)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N CSCIGXJYHRUVMF-UHFFFAOYSA-N 0.000 description 1
HDGOHNNGGIITPC-UHFFFAOYSA-N 1-(ethylamino)-2-methyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(NCC)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N HDGOHNNGGIITPC-UHFFFAOYSA-N 0.000 description 1
ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
ROLQJJUMJACOMH-UHFFFAOYSA-N 1-[3-[[2-methyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-yl]amino]propyl]pyrrolidin-2-one Chemical compound [O-][N+](=O)C=1C(N2CCC3=CC=CC=C3CC2)=NC(C)=NC=1NCCCN1CCCC1=O ROLQJJUMJACOMH-UHFFFAOYSA-N 0.000 description 1
WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 1
PNVRICPXAKNJHM-UHFFFAOYSA-N 1-methyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(C)C=NC(N2CCC3=CC=CC=C3CC2)=C1C#N PNVRICPXAKNJHM-UHFFFAOYSA-N 0.000 description 1
TUCYWBVWKLKPMG-UHFFFAOYSA-N 1h-1-benzazepin-2-ol Chemical class N1C(O)=CC=CC2=CC=CC=C21 TUCYWBVWKLKPMG-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
LOXPKSAIAHLVML-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-3-benzazepin-7-amine Chemical compound C1CNCCC2=CC(N)=CC=C21 LOXPKSAIAHLVML-UHFFFAOYSA-N 0.000 description 1
MWVMYAWMFTVYED-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1CNCCC2=CC=CC=C21 MWVMYAWMFTVYED-UHFFFAOYSA-N 0.000 description 1
IRUXSKJXJFMZPQ-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-3-benzazepine-7-sulfonamide Chemical compound C1CNCCC2=CC(S(=O)(=O)N)=CC=C21 IRUXSKJXJFMZPQ-UHFFFAOYSA-N 0.000 description 1
ZEZJPIDPVXJEME-UHFFFAOYSA-N 2,4-Dihydroxypyridine Chemical compound OC=1C=CNC(=O)C=1 ZEZJPIDPVXJEME-UHFFFAOYSA-N 0.000 description 1
GIAFURWZWWWBQT-UHFFFAOYSA-N 2-(2-aminoethoxy)ethanol Chemical compound NCCOCCO GIAFURWZWWWBQT-UHFFFAOYSA-N 0.000 description 1
HRGXKFNRGWHDHK-UHFFFAOYSA-N 2-(2-methoxyethoxy)-4-methylsulfanyl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound COCCOC1=NC(SC)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 HRGXKFNRGWHDHK-UHFFFAOYSA-N 0.000 description 1
SBASXUCJHJRPEV-UHFFFAOYSA-N 2-(2-methoxyethoxy)ethanol Chemical compound COCCOCCO SBASXUCJHJRPEV-UHFFFAOYSA-N 0.000 description 1
JTCWSPQFJFCKDB-UHFFFAOYSA-N 2-(2-morpholin-4-ylethoxy)-4-(2-morpholin-4-ylethylamino)-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound N1=C(OCCN2CCOCC2)N=C(N2CCC3=CC=CC=C3CC2)C(C#N)=C1NCCN1CCOCC1 JTCWSPQFJFCKDB-UHFFFAOYSA-N 0.000 description 1
HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
VHVXEJIHRDYTGM-UHFFFAOYSA-N 2-(cyanomethylamino)-4-oxo-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidine-5-carbonitrile Chemical compound O=C1NC(NCC#N)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N VHVXEJIHRDYTGM-UHFFFAOYSA-N 0.000 description 1
YMAQGZCGOAIAEY-UHFFFAOYSA-N 2-(dimethylamino)-4-oxo-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidine-5-carbonitrile Chemical compound O=C1NC(N(C)C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N YMAQGZCGOAIAEY-UHFFFAOYSA-N 0.000 description 1
QMPQFHSQSPSURC-UHFFFAOYSA-N 2-(hydroxymethyl)-4-oxo-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidine-5-carbonitrile Chemical compound O=C1NC(CO)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N QMPQFHSQSPSURC-UHFFFAOYSA-N 0.000 description 1
ODKPMJHFJPZGGA-UHFFFAOYSA-N 2-(oxan-2-yloxymethyl)-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1-(2,2,2-trifluoroethyl)pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC3=CC=CC=C3CC2)=C(C#N)C(=O)N(CC(F)(F)F)C=1COC1CCCCO1 ODKPMJHFJPZGGA-UHFFFAOYSA-N 0.000 description 1
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
METIWNNPHPBEHP-UHFFFAOYSA-N 2-[[4-[4-(4-methyl-n-(4-methylphenyl)anilino)phenyl]-2,1,3-benzothiadiazol-7-yl]methylidene]propanedinitrile Chemical compound C1=CC(C)=CC=C1N(C=1C=CC(=CC=1)C=1C2=NSN=C2C(C=C(C#N)C#N)=CC=1)C1=CC=C(C)C=C1 METIWNNPHPBEHP-UHFFFAOYSA-N 0.000 description 1
FICQFRCPSFCFBY-UHFFFAOYSA-N 2-[bis(methylsulfanyl)methylidene]propanedinitrile Chemical compound CSC(SC)=C(C#N)C#N FICQFRCPSFCFBY-UHFFFAOYSA-N 0.000 description 1
OEOSBSDFEMQOQA-UHFFFAOYSA-N 2-[methylsulfanyl(1,2,4,5-tetrahydro-3-benzazepin-3-yl)methylidene]propanedinitrile Chemical compound C1CN(C(SC)=C(C#N)C#N)CCC2=CC=CC=C21 OEOSBSDFEMQOQA-UHFFFAOYSA-N 0.000 description 1
QAQFTYDVWBOIRJ-UHFFFAOYSA-N 2-amino-4-ethoxy-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound CCOC1=NC(N)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N QAQFTYDVWBOIRJ-UHFFFAOYSA-N 0.000 description 1
UTTPUMOOQSNOHH-UHFFFAOYSA-N 2-amino-6-chloro-5-nitro-1h-pyrimidin-4-one Chemical compound NC1=NC(=O)C([N+]([O-])=O)=C(Cl)N1 UTTPUMOOQSNOHH-UHFFFAOYSA-N 0.000 description 1
WUXIMJNBCJLMEY-UHFFFAOYSA-N 2-amino-6-chloro-5-nitro-2,3-dihydro-1h-pyrimidin-4-one Chemical compound NC1NC(Cl)=C([N+]([O-])=O)C(=O)N1 WUXIMJNBCJLMEY-UHFFFAOYSA-N 0.000 description 1
QLHVJBXAQWPEDI-UHFFFAOYSA-N 2-chloro-3,5-dinitropyridine Chemical compound [O-][N+](=O)C1=CN=C(Cl)C([N+]([O-])=O)=C1 QLHVJBXAQWPEDI-UHFFFAOYSA-N 0.000 description 1
UUOLETYDNTVQDY-UHFFFAOYSA-N 2-chloro-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CN=C1Cl UUOLETYDNTVQDY-UHFFFAOYSA-N 0.000 description 1
CIAOWSZWDCTPPE-UHFFFAOYSA-N 2-chloro-5-ethyl-6-methylpyridine-3-carbonitrile Chemical compound CCC1=CC(C#N)=C(Cl)N=C1C CIAOWSZWDCTPPE-UHFFFAOYSA-N 0.000 description 1
LUAJUWOJEFFNFE-UHFFFAOYSA-N 2-chloro-5-methyl-3-nitropyridine Chemical compound CC1=CN=C(Cl)C([N+]([O-])=O)=C1 LUAJUWOJEFFNFE-UHFFFAOYSA-N 0.000 description 1
YSBNBAYNISAUIT-UHFFFAOYSA-N 2-chloro-6-methylpyridine-3-carbonitrile Chemical compound CC1=CC=C(C#N)C(Cl)=N1 YSBNBAYNISAUIT-UHFFFAOYSA-N 0.000 description 1
QSKPIOLLBIHNAC-UHFFFAOYSA-N 2-chloro-acetaldehyde Chemical compound ClCC=O QSKPIOLLBIHNAC-UHFFFAOYSA-N 0.000 description 1
JAUPUQRPBNDMDT-UHFFFAOYSA-N 2-chloropyridine-3-carbonitrile Chemical compound ClC1=NC=CC=C1C#N JAUPUQRPBNDMDT-UHFFFAOYSA-N 0.000 description 1
UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical class ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 1
ANGZCDWLJCLIGV-UHFFFAOYSA-N 2-cyclopropyl-4-oxo-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC3=CC=CC=C3CC2)=C(C#N)C(=O)NC=1C1CC1 ANGZCDWLJCLIGV-UHFFFAOYSA-N 0.000 description 1
NUJFCQFIGKZNJF-UHFFFAOYSA-N 2-ethoxyethyl methanesulfonate Chemical compound CCOCCOS(C)(=O)=O NUJFCQFIGKZNJF-UHFFFAOYSA-N 0.000 description 1
UKQVDMIAGTYDFN-UHFFFAOYSA-N 2-ethylguanidine;sulfuric acid Chemical compound OS(O)(=O)=O.CCN=C(N)N.CCN=C(N)N UKQVDMIAGTYDFN-UHFFFAOYSA-N 0.000 description 1
DRWDZFNIPARKSG-UHFFFAOYSA-N 2-hydroxyethanimidamide;hydrochloride Chemical compound Cl.NC(=N)CO DRWDZFNIPARKSG-UHFFFAOYSA-N 0.000 description 1
JJKWHOSQTYYFAE-UHFFFAOYSA-N 2-methoxyacetyl chloride Chemical compound COCC(Cl)=O JJKWHOSQTYYFAE-UHFFFAOYSA-N 0.000 description 1
NQAKPQQUYKJTFV-UHFFFAOYSA-N 2-methyl-3-(2-morpholin-4-ylethyl)-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-one Chemical compound CC1=NC(N2CCC3=CC=CC=C3CC2)=C([N+]([O-])=O)C(=O)N1CCN1CCOCC1 NQAKPQQUYKJTFV-UHFFFAOYSA-N 0.000 description 1
IESRCYMWAQMOFN-UHFFFAOYSA-N 2-methyl-5-nitro-3-(3-pyridin-3-ylpropyl)-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-one Chemical compound CC1=NC(N2CCC3=CC=CC=C3CC2)=C([N+]([O-])=O)C(=O)N1CCCC1=CC=CN=C1 IESRCYMWAQMOFN-UHFFFAOYSA-N 0.000 description 1
TZQQYJUVNSKTIO-UHFFFAOYSA-N 2-methyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-3-[4-(1,2,4-triazol-1-yl)butyl]pyrimidin-4-one Chemical compound CC1=NC(N2CCC3=CC=CC=C3CC2)=C([N+]([O-])=O)C(=O)N1CCCCN1C=NC=N1 TZQQYJUVNSKTIO-UHFFFAOYSA-N 0.000 description 1
HJEKMMPXQFROAK-UHFFFAOYSA-N 2-methyl-6-oxo-1-propoxy-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1N(OCCC)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N HJEKMMPXQFROAK-UHFFFAOYSA-N 0.000 description 1
VDHREJVCOCVJHW-UHFFFAOYSA-N 2-methyl-n-(3-morpholin-4-ylpropyl)-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-amine Chemical compound [O-][N+](=O)C=1C(N2CCC3=CC=CC=C3CC2)=NC(C)=NC=1NCCCN1CCOCC1 VDHREJVCOCVJHW-UHFFFAOYSA-N 0.000 description 1
DBXRADABDCPRKF-UHFFFAOYSA-N 2-methylsulfanyl-4-(2-morpholin-4-ylethylamino)-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound N#CC=1C(N2CCC3=CC=CC=C3CC2)=NC(SC)=NC=1NCCN1CCOCC1 DBXRADABDCPRKF-UHFFFAOYSA-N 0.000 description 1
FZCQSCYCTKISNO-UHFFFAOYSA-N 2-oxo-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-4-(2,2,2-trifluoroethoxy)-1h-pyrimidine-5-carbonitrile Chemical compound N#CC1=C(OCC(F)(F)F)NC(=O)N=C1N1CCC2=CC=CC=C2CC1 FZCQSCYCTKISNO-UHFFFAOYSA-N 0.000 description 1
DGHTUVZNKFCITB-UHFFFAOYSA-N 2-phenylsulfanylacetamide;hydrochloride Chemical compound Cl.NC(=O)CSC1=CC=CC=C1 DGHTUVZNKFCITB-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
NEKYYQMXIMPIMK-UHFFFAOYSA-N 2-propyl-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound CCCC1=NC(OCC(F)(F)F)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 NEKYYQMXIMPIMK-UHFFFAOYSA-N 0.000 description 1
TUVONOFKFDJHBJ-UHFFFAOYSA-N 2-pyridin-2-yloxyethanamine Chemical compound NCCOC1=CC=CC=N1 TUVONOFKFDJHBJ-UHFFFAOYSA-N 0.000 description 1
NAHHNSMHYCLMON-UHFFFAOYSA-N 2-pyridin-3-ylethanamine Chemical compound NCCC1=CC=CN=C1 NAHHNSMHYCLMON-UHFFFAOYSA-N 0.000 description 1
WRXNJTBODVGDRY-UHFFFAOYSA-N 2-pyrrolidin-1-ylethanamine Chemical compound NCCN1CCCC1 WRXNJTBODVGDRY-UHFFFAOYSA-N 0.000 description 1
QISBQTNZFZDBJQ-UHFFFAOYSA-N 2h-thieno[2,3-d]azepine Chemical class C1=NC=CC2=CCSC2=C1 QISBQTNZFZDBJQ-UHFFFAOYSA-N 0.000 description 1
VPWPSKAYUUPMLJ-UHFFFAOYSA-N 3,3-bis(methylsulfanyl)prop-2-enoic acid Chemical class CSC(SC)=CC(O)=O VPWPSKAYUUPMLJ-UHFFFAOYSA-N 0.000 description 1
QYMDLBQFLKOPGW-UHFFFAOYSA-N 3,4,5,6-tetrahydro-2h-azepin-7-amine;hydrochloride Chemical compound Cl.N=C1CCCCCN1 QYMDLBQFLKOPGW-UHFFFAOYSA-N 0.000 description 1
JEBHLIYFPKISBI-UHFFFAOYSA-N 3,4-dihydro-2h-pyrrol-5-amine;hydrochloride Chemical compound Cl.NC1=NCCC1 JEBHLIYFPKISBI-UHFFFAOYSA-N 0.000 description 1
ZLLFSWNFEMJNKW-UHFFFAOYSA-N 3-(1,3-dioxoisoindol-2-yl)propanimidamide;hydrochloride Chemical compound Cl.C1=CC=C2C(=O)N(CCC(=N)N)C(=O)C2=C1 ZLLFSWNFEMJNKW-UHFFFAOYSA-N 0.000 description 1
HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
NORFJAOFJZYXFH-UHFFFAOYSA-N 3-(3-hydroxypropyl)-2-methyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-one Chemical compound O=C1N(CCCO)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1[N+]([O-])=O NORFJAOFJZYXFH-UHFFFAOYSA-N 0.000 description 1
UZGLOGCJCWBBIV-UHFFFAOYSA-N 3-(chloromethyl)pyridin-1-ium;chloride Chemical compound Cl.ClCC1=CC=CN=C1 UZGLOGCJCWBBIV-UHFFFAOYSA-N 0.000 description 1
YGYGASJNJTYNOL-CQSZACIVSA-N 3-[(4r)-2,2-dimethyl-1,1-dioxothian-4-yl]-5-(4-fluorophenyl)-1h-indole-7-carboxamide Chemical compound C1CS(=O)(=O)C(C)(C)C[C@@H]1C1=CNC2=C(C(N)=O)C=C(C=3C=CC(F)=CC=3)C=C12 YGYGASJNJTYNOL-CQSZACIVSA-N 0.000 description 1
LBGSFZHTUUQHQX-UHFFFAOYSA-N 3-[2-(dimethylamino)ethyl]-2-methyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-one Chemical compound O=C1N(CCN(C)C)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1[N+]([O-])=O LBGSFZHTUUQHQX-UHFFFAOYSA-N 0.000 description 1
VNXIZGKIMUMQPX-UHFFFAOYSA-N 3-[2-methyl-5-nitro-6-(3-pyridin-3-ylpropoxy)pyrimidin-4-yl]-1,2,4,5-tetrahydro-3-benzazepine Chemical compound [O-][N+](=O)C=1C(N2CCC3=CC=CC=C3CC2)=NC(C)=NC=1OCCCC1=CC=CN=C1 VNXIZGKIMUMQPX-UHFFFAOYSA-N 0.000 description 1
OPYLVJWCBUBXHE-HXUWFJFHSA-N 3-[3-[(2r)-2-(hydroxymethyl)pyrrolidin-1-yl]propyl]-2-methyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-one Chemical compound CC1=NC(N2CCC3=CC=CC=C3CC2)=C([N+]([O-])=O)C(=O)N1CCCN1CCC[C@@H]1CO OPYLVJWCBUBXHE-HXUWFJFHSA-N 0.000 description 1
ZWVGHIXAMLHDTE-UHFFFAOYSA-N 3-butyl-2-methyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-one Chemical compound O=C1N(CCCC)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1[N+]([O-])=O ZWVGHIXAMLHDTE-UHFFFAOYSA-N 0.000 description 1
WFWPCYGOUPSZSY-UHFFFAOYSA-N 3-ethyl-6-(7-fluoro-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-2-methyl-5-nitropyrimidin-4-one Chemical compound O=C1N(CC)C(C)=NC(N2CCC3=CC(F)=CC=C3CC2)=C1[N+]([O-])=O WFWPCYGOUPSZSY-UHFFFAOYSA-N 0.000 description 1
ISULZYQDGYXDFW-UHFFFAOYSA-N 3-methylbutanoyl chloride Chemical compound CC(C)CC(Cl)=O ISULZYQDGYXDFW-UHFFFAOYSA-N 0.000 description 1
BOAFCICMVMFLIT-UHFFFAOYSA-N 3-nitro-1h-pyridin-2-one Chemical class OC1=NC=CC=C1[N+]([O-])=O BOAFCICMVMFLIT-UHFFFAOYSA-N 0.000 description 1
AWVDYRFLCAZENH-UHFFFAOYSA-N 3-phenoxypropan-1-ol Chemical compound OCCCOC1=CC=CC=C1 AWVDYRFLCAZENH-UHFFFAOYSA-N 0.000 description 1
FVZXYJDGVYLMDB-UHFFFAOYSA-N 3-pyridin-2-ylpropan-1-ol Chemical compound OCCCC1=CC=CC=N1 FVZXYJDGVYLMDB-UHFFFAOYSA-N 0.000 description 1
PZVZGDBCMQBRMA-UHFFFAOYSA-N 3-pyridin-4-ylpropan-1-ol Chemical compound OCCCC1=CC=NC=C1 PZVZGDBCMQBRMA-UHFFFAOYSA-N 0.000 description 1
TXJXCXSFIVCGDS-UHFFFAOYSA-N 34583-83-0 Chemical compound C1CNCCC2=CC([N+](=O)[O-])=CC=C21 TXJXCXSFIVCGDS-UHFFFAOYSA-N 0.000 description 1
WKRLLZZGRLNCQP-UHFFFAOYSA-N 4,5-dihydro-1h-imidazol-2-amine;hydrobromide Chemical compound Br.NC1=NCCN1 WKRLLZZGRLNCQP-UHFFFAOYSA-N 0.000 description 1
GLOOTGZVAHKTJS-UHFFFAOYSA-N 4,6-dichloro-2-methylsulfanylpyrimidine-5-carbonitrile Chemical compound CSC1=NC(Cl)=C(C#N)C(Cl)=N1 GLOOTGZVAHKTJS-UHFFFAOYSA-N 0.000 description 1
HCTISZQLTGAYOX-UHFFFAOYSA-N 4,6-dichloro-5-nitropyrimidine Chemical compound [O-][N+](=O)C1=C(Cl)N=CN=C1Cl HCTISZQLTGAYOX-UHFFFAOYSA-N 0.000 description 1
XJPZKYIHCLDXST-UHFFFAOYSA-N 4,6-dichloropyrimidine Chemical group ClC1=CC(Cl)=NC=N1 XJPZKYIHCLDXST-UHFFFAOYSA-N 0.000 description 1
IPEBKIMUIHKZJP-UHFFFAOYSA-N 4,6-dichloropyrimidine-5-carbonitrile Chemical compound ClC1=NC=NC(Cl)=C1C#N IPEBKIMUIHKZJP-UHFFFAOYSA-N 0.000 description 1
PPSBQPLBPWUUNS-UHFFFAOYSA-N 4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound N#CC1=CN=CN=C1N1CCC2=CC=CC=C2CC1 PPSBQPLBPWUUNS-UHFFFAOYSA-N 0.000 description 1
URSLSOKOGMHRKO-UHFFFAOYSA-N 4-(2-hydroxyethylamino)-2-methylsulfanyl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound CSC1=NC(NCCO)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 URSLSOKOGMHRKO-UHFFFAOYSA-N 0.000 description 1
KRQHKVGKSMBHML-UHFFFAOYSA-N 4-(2-methoxyethoxy)-2-methylsulfanyl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound COCCOC1=NC(SC)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N KRQHKVGKSMBHML-UHFFFAOYSA-N 0.000 description 1
VJPPLCNBDLZIFG-ZDUSSCGKSA-N 4-[(3S)-3-(but-2-ynoylamino)piperidin-1-yl]-5-fluoro-2,3-dimethyl-1H-indole-7-carboxamide Chemical compound C(C#CC)(=O)N[C@@H]1CN(CCC1)C1=C2C(=C(NC2=C(C=C1F)C(=O)N)C)C VJPPLCNBDLZIFG-ZDUSSCGKSA-N 0.000 description 1
HMULOIBWQOIKFR-UHFFFAOYSA-N 4-[2-methyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-yl]oxybutyl methanesulfonate Chemical compound CC1=NC(OCCCCOS(C)(=O)=O)=C([N+]([O-])=O)C(N2CCC3=CC=CC=C3CC2)=N1 HMULOIBWQOIKFR-UHFFFAOYSA-N 0.000 description 1
PNCWVUCBFXXYKA-UHFFFAOYSA-N 4-[bromo(difluoro)methoxy]-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound FC(F)(Br)OC1=NC=NC(N2CCC3=CC=CC=C3CC2)=C1C#N PNCWVUCBFXXYKA-UHFFFAOYSA-N 0.000 description 1
BLFRQYKZFKYQLO-UHFFFAOYSA-N 4-aminobutan-1-ol Chemical compound NCCCCO BLFRQYKZFKYQLO-UHFFFAOYSA-N 0.000 description 1
ZVJJQADVZUHQTR-UHFFFAOYSA-N 4-chloropyrimidine-5-carbonitrile Chemical compound ClC1=NC=NC=C1C#N ZVJJQADVZUHQTR-UHFFFAOYSA-N 0.000 description 1
HBLXILCOKGRHMY-UHFFFAOYSA-N 4-ethoxy-2-(2-hydroxyethyl)-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound CCOC1=NC(CCO)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N HBLXILCOKGRHMY-UHFFFAOYSA-N 0.000 description 1
RNFNHFHDYDYRJL-UHFFFAOYSA-N 4-ethoxy-2-(2-methylsulfanylethyl)-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound CCOC1=NC(CCSC)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N RNFNHFHDYDYRJL-UHFFFAOYSA-N 0.000 description 1
LFTCMRLJEQHKJN-UHFFFAOYSA-N 4-fluoro-2-methyl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound CC1=NC(F)=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 LFTCMRLJEQHKJN-UHFFFAOYSA-N 0.000 description 1
BKLDFBXZCKWOSZ-UHFFFAOYSA-N 4-methoxy-2-methyl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound COC1=NC(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N BKLDFBXZCKWOSZ-UHFFFAOYSA-N 0.000 description 1
PCWGTDULNUVNBN-UHFFFAOYSA-N 4-methylpentan-1-ol Chemical compound CC(C)CCCO PCWGTDULNUVNBN-UHFFFAOYSA-N 0.000 description 1
WYJONKLPESDZOA-UHFFFAOYSA-N 4-oxo-2-(2-phenoxyethylamino)-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC3=CC=CC=C3CC2)=C(C#N)C(=O)NC=1NCCOC1=CC=CC=C1 WYJONKLPESDZOA-UHFFFAOYSA-N 0.000 description 1
CVJSUVPDRXQTJH-UHFFFAOYSA-N 4-oxo-2-sulfanylidene-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1h-pyrimidine-5-carbonitrile Chemical compound O=C1NC(=S)NC(N2CCC3=CC=CC=C3CC2)=C1C#N CVJSUVPDRXQTJH-UHFFFAOYSA-N 0.000 description 1
IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 1
NXSVNZLOPNKRTH-UHFFFAOYSA-N 5-ethyl-6-methyl-2-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyridine-3-carbonitrile Chemical compound N1=C(C)C(CC)=CC(C#N)=C1N1CCC2=CC=CC=C2CC1 NXSVNZLOPNKRTH-UHFFFAOYSA-N 0.000 description 1
QFHOTEDYSYZFMJ-UHFFFAOYSA-N 5-methylsulfanyl-7-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-[1,2,4]triazolo[4,3-c]pyrimidine-8-carbonitrile Chemical compound C1CC2=CC=CC=C2CCN1C1=C(C#N)C2=NN=CN2C(SC)=N1 QFHOTEDYSYZFMJ-UHFFFAOYSA-N 0.000 description 1
LLVGNTFQVMZZPW-UHFFFAOYSA-N 5-nitro-1h-pyrimidin-6-one Chemical compound [O-][N+](=O)C1=CN=CNC1=O LLVGNTFQVMZZPW-UHFFFAOYSA-N 0.000 description 1
BUDWOYMADQZCFL-UHFFFAOYSA-N 6,7,8,9-tetrahydro-5h-[1,3]dioxolo[4,5-h][3]benzazepine;hydrochloride Chemical compound Cl.C1CNCCC2=C1C=C1OCOC1=C2 BUDWOYMADQZCFL-UHFFFAOYSA-N 0.000 description 1
KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
XLOJPRJMBDTXTC-UHFFFAOYSA-N 6-methoxy-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1CNCCC2=C1C=CC=C2OC XLOJPRJMBDTXTC-UHFFFAOYSA-N 0.000 description 1
PBTVIAYFENAMOJ-UHFFFAOYSA-N 6-methyl-2-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyridine-3-carbonitrile Chemical compound CC1=CC=C(C#N)C(N2CCC3=CC=CC=C3CC2)=N1 PBTVIAYFENAMOJ-UHFFFAOYSA-N 0.000 description 1
TZNQDEHNAXCCQV-UHFFFAOYSA-N 6-oxo-1-[3-(2-oxoazepan-1-yl)propyl]-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrile Chemical compound O=C1CCCCCN1CCCN1C(=O)C(C#N)=C(N2CCC3=CC=CC=C3CC2)N=C1 TZNQDEHNAXCCQV-UHFFFAOYSA-N 0.000 description 1
SVOQOFSQLVVHKQ-UHFFFAOYSA-N 6-oxo-1h-pyrimidine-5-carbonitrile Chemical compound O=C1NC=NC=C1C#N SVOQOFSQLVVHKQ-UHFFFAOYSA-N 0.000 description 1
GBTCPUUOVINMHY-UHFFFAOYSA-N 6-oxo-2-propyl-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-1-(2,2,2-trifluoroethyl)pyrimidine-5-carbonitrile Chemical compound O=C1N(CC(F)(F)F)C(CCC)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N GBTCPUUOVINMHY-UHFFFAOYSA-N 0.000 description 1
RJSLVOHVHJUPNE-UHFFFAOYSA-N 7,8-dimethoxy-2,3,4,5-tetrahydro-1h-3-benzazepine;hydrochloride Chemical compound Cl.C1CNCCC2=C1C=C(OC)C(OC)=C2 RJSLVOHVHJUPNE-UHFFFAOYSA-N 0.000 description 1
ZJIUEDYXZUIMNV-UHFFFAOYSA-N 7-chloro-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1CNCCC2=CC(Cl)=CC=C21 ZJIUEDYXZUIMNV-UHFFFAOYSA-N 0.000 description 1
VWLWWBQMNIAARP-UHFFFAOYSA-N 7-methoxy-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1CNCCC2=CC(OC)=CC=C21 VWLWWBQMNIAARP-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
ZRPZPNYZFSJUPA-UHFFFAOYSA-N ARS-1620 Chemical compound Oc1cccc(F)c1-c1c(Cl)cc2c(ncnc2c1F)N1CCN(CC1)C(=O)C=C ZRPZPNYZFSJUPA-UHFFFAOYSA-N 0.000 description 1
IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 1
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
PCQUJGCGOKMOEE-UHFFFAOYSA-N CC1N=C(C(=C(N1)OCCCCOS(=O)(=O)C)[N+](=O)[O-])N1CCC2=C(CC1)C=CC=C2 Chemical compound CC1N=C(C(=C(N1)OCCCCOS(=O)(=O)C)[N+](=O)[O-])N1CCC2=C(CC1)C=CC=C2 PCQUJGCGOKMOEE-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
QDHHCQZDFGDHMP-UHFFFAOYSA-N Chloramine Chemical compound ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 description 1
HVVNJUAVDAZWCB-RXMQYKEDSA-N D-prolinol Chemical compound OC[C@H]1CCCN1 HVVNJUAVDAZWCB-RXMQYKEDSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 1
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
GISRWBROCYNDME-PELMWDNLSA-N F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C Chemical compound F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C GISRWBROCYNDME-PELMWDNLSA-N 0.000 description 1
102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
239000007995 HEPES buffer Substances 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
108090000543 Ligand-Gated Ion Channels Proteins 0.000 description 1
102000004086 Ligand-Gated Ion Channels Human genes 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 description 1
102100038352 Metabotropic glutamate receptor 3 Human genes 0.000 description 1
102100038357 Metabotropic glutamate receptor 5 Human genes 0.000 description 1
102100038300 Metabotropic glutamate receptor 6 Human genes 0.000 description 1
102100038294 Metabotropic glutamate receptor 7 Human genes 0.000 description 1
AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
FEYNFHSRETUBEM-UHFFFAOYSA-N N-[3-(1,1-difluoroethyl)phenyl]-1-(4-methoxyphenyl)-3-methyl-5-oxo-4H-pyrazole-4-carboxamide Chemical compound COc1ccc(cc1)N1N=C(C)C(C(=O)Nc2cccc(c2)C(C)(F)F)C1=O FEYNFHSRETUBEM-UHFFFAOYSA-N 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 1
235000019502 Orange oil Nutrition 0.000 description 1
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
239000007868 Raney catalyst Substances 0.000 description 1
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
229910000564 Raney nickel Inorganic materials 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
KITGYVIOYOCIIE-QNMAEOQASA-N [(z)-hex-3-enyl] (e)-but-2-enoate Chemical compound CC\C=C/CCOC(=O)\C=C\C KITGYVIOYOCIIE-QNMAEOQASA-N 0.000 description 1
JEDZLBFUGJTJGQ-UHFFFAOYSA-N [Na].COCCO[AlH]OCCOC Chemical compound [Na].COCCO[AlH]OCCOC JEDZLBFUGJTJGQ-UHFFFAOYSA-N 0.000 description 1
QSCPQKVWSNUJLJ-UHFFFAOYSA-N [amino(methoxy)methylidene]azanium;sulfate Chemical compound COC(N)=N.COC(N)=N.OS(O)(=O)=O QSCPQKVWSNUJLJ-UHFFFAOYSA-N 0.000 description 1
KYIKRXIYLAGAKQ-UHFFFAOYSA-N abcn Chemical compound C1CCCCC1(C#N)N=NC1(C#N)CCCCC1 KYIKRXIYLAGAKQ-UHFFFAOYSA-N 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
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
239000013543 active substance Substances 0.000 description 1
239000000556 agonist Substances 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
239000003513 alkali Substances 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
229910000102 alkali metal hydride Inorganic materials 0.000 description 1
150000008046 alkali metal hydrides Chemical class 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
125000004414 alkyl thio group Chemical group 0.000 description 1
230000002152 alkylating effect Effects 0.000 description 1
125000002947 alkylene group Chemical group 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 1
CHKQALUEEULCPZ-UHFFFAOYSA-N amino 2,4,6-trimethylbenzenesulfonate Chemical compound CC1=CC(C)=C(S(=O)(=O)ON)C(C)=C1 CHKQALUEEULCPZ-UHFFFAOYSA-N 0.000 description 1
229940024606 amino acid Drugs 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
239000012131 assay buffer Substances 0.000 description 1
150000007514 bases Chemical class 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
150000001555 benzenes Chemical class 0.000 description 1
150000008359 benzonitriles Chemical class 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
KXHPPCXNWTUNSB-UHFFFAOYSA-M benzyl(trimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)CC1=CC=CC=C1 KXHPPCXNWTUNSB-UHFFFAOYSA-M 0.000 description 1
230000005540 biological transmission Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
239000000872 buffer Substances 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
229910000024 caesium carbonate Inorganic materials 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
150000004649 carbonic acid derivatives Chemical class 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
238000010531 catalytic reduction reaction Methods 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
239000012459 cleaning agent Substances 0.000 description 1
239000002299 complementary DNA Substances 0.000 description 1
229940125904 compound 1 Drugs 0.000 description 1
238000012937 correction Methods 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
ACPFLXJEPKOPGF-UHFFFAOYSA-N diaminomethylidene(dimethyl)azanium;hydrogen sulfate Chemical compound [O-]S([O-])(=O)=O.C[NH+](C)C([NH3+])=N ACPFLXJEPKOPGF-UHFFFAOYSA-N 0.000 description 1
239000012954 diazonium Substances 0.000 description 1
IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 1
AZSZCFSOHXEJQE-UHFFFAOYSA-N dibromodifluoromethane Chemical compound FC(F)(Br)Br AZSZCFSOHXEJQE-UHFFFAOYSA-N 0.000 description 1
150000005690 diesters Chemical class 0.000 description 1
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
150000002009 diols Chemical class 0.000 description 1
WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000000975 dye Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
FLJVEUZHQBPWNL-UHFFFAOYSA-N ethyl n-[5-cyano-2-methyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-1-yl]-n-ethylcarbamate Chemical compound O=C1N(N(CC)C(=O)OCC)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N FLJVEUZHQBPWNL-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
230000002964 excitative effect Effects 0.000 description 1
239000000284 extract Substances 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000003365 glass fiber Substances 0.000 description 1
239000008103 glucose Substances 0.000 description 1
229960002989 glutamic acid Drugs 0.000 description 1
NDEMNVPZDAFUKN-UHFFFAOYSA-N guanidine;nitric acid Chemical compound NC(N)=N.O[N+]([O-])=O.O[N+]([O-])=O NDEMNVPZDAFUKN-UHFFFAOYSA-N 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
150000002430 hydrocarbons Chemical group 0.000 description 1
LEUJVEZIEALICS-UHFFFAOYSA-N hydrogen sulfate;1h-imidazol-2-ylazanium Chemical compound OS(O)(=O)=O.NC1=NC=CN1 LEUJVEZIEALICS-UHFFFAOYSA-N 0.000 description 1
COQRGFWWJBEXRC-UHFFFAOYSA-N hydron;methyl 2-aminoacetate;chloride Chemical compound Cl.COC(=O)CN COQRGFWWJBEXRC-UHFFFAOYSA-N 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
239000003999 initiator Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
230000003993 interaction Effects 0.000 description 1
229960004903 invert sugar Drugs 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000011968 lewis acid catalyst Substances 0.000 description 1
239000003446 ligand Substances 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
229940124807 mGLUR antagonist Drugs 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
230000000873 masking effect Effects 0.000 description 1
239000012528 membrane Substances 0.000 description 1
108010038445 metabotropic glutamate receptor 3 Proteins 0.000 description 1
108010038450 metabotropic glutamate receptor 6 Proteins 0.000 description 1
108010038449 metabotropic glutamate receptor 7 Proteins 0.000 description 1
YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
DCSBPJSFBUGYTP-UHFFFAOYSA-N methyl n-[5-cyano-2-methyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-1-yl]-n-methylcarbamate Chemical compound O=C1N(N(C)C(=O)OC)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N DCSBPJSFBUGYTP-UHFFFAOYSA-N 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
GDZAKQKPIRLJTP-UHFFFAOYSA-N n'-cyclopropylethanimidamide;hydrochloride Chemical compound Cl.CC(=N)NC1CC1 GDZAKQKPIRLJTP-UHFFFAOYSA-N 0.000 description 1
QADUTEYALNXTFB-UHFFFAOYSA-N n,n-dimethyl-2-[2-methyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-yl]oxyethanamine Chemical compound CN(C)CCOC1=NC(C)=NC(N2CCC3=CC=CC=C3CC2)=C1[N+]([O-])=O QADUTEYALNXTFB-UHFFFAOYSA-N 0.000 description 1
FMASTMURQSHELY-UHFFFAOYSA-N n-(4-fluoro-2-methylphenyl)-3-methyl-n-[(2-methyl-1h-indol-4-yl)methyl]pyridine-4-carboxamide Chemical compound C1=CC=C2NC(C)=CC2=C1CN(C=1C(=CC(F)=CC=1)C)C(=O)C1=CC=NC=C1C FMASTMURQSHELY-UHFFFAOYSA-N 0.000 description 1
OSFLVGYBNNKVRL-UHFFFAOYSA-N n-[5-cyano-1-ethyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-2-yl]formamide Chemical compound O=C1N(CC)C(NC=O)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N OSFLVGYBNNKVRL-UHFFFAOYSA-N 0.000 description 1
NNKPHNTWNILINE-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-[3-[[1-[2-[2-(methylamino)ethoxy]phenyl]cyclopropyl]amino]-2-oxopyrazin-1-yl]benzamide Chemical compound CNCCOC1=CC=CC=C1C1(NC=2C(N(C=3C(=C(F)C=C(C=3)C(=O)NC3CC3)C)C=CN=2)=O)CC1 NNKPHNTWNILINE-UHFFFAOYSA-N 0.000 description 1
RRPKGUUYTHFUPN-UHFFFAOYSA-N n-hydroxy-2,4,6-trimethylbenzenesulfonamide Chemical compound CC1=CC(C)=C(S(=O)(=O)NO)C(C)=C1 RRPKGUUYTHFUPN-UHFFFAOYSA-N 0.000 description 1
LFOCFUWHCCANGL-UHFFFAOYSA-N n-methyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-amine Chemical compound CNC1=NC=NC(N2CCC3=CC=CC=C3CC2)=C1[N+]([O-])=O LFOCFUWHCCANGL-UHFFFAOYSA-N 0.000 description 1
XVTVJNXKVZQUSM-UHFFFAOYSA-N n-nitroacetamide Chemical class CC(=O)N[N+]([O-])=O XVTVJNXKVZQUSM-UHFFFAOYSA-N 0.000 description 1
SNMVRZFUUCLYTO-UHFFFAOYSA-N n-propyl chloride Chemical compound CCCCl SNMVRZFUUCLYTO-UHFFFAOYSA-N 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
210000005036 nerve Anatomy 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
125000004355 nitrogen functional group Chemical group 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
239000012038 nucleophile Substances 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000002245 particle Substances 0.000 description 1
239000008188 pellet Substances 0.000 description 1
239000003444 phase transfer catalyst Substances 0.000 description 1
LGRFSURHDFAFJT-UHFFFAOYSA-N phthalic anhydride Chemical class C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 1
230000035790 physiological processes and functions Effects 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
LZMJNVRJMFMYQS-UHFFFAOYSA-N poseltinib Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC(OC=2C=C(NC(=O)C=C)C=CC=2)=C(OC=C2)C2=N1 LZMJNVRJMFMYQS-UHFFFAOYSA-N 0.000 description 1
NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
KHOSTBIBDFQLGJ-UHFFFAOYSA-N propanediamide;hydrochloride Chemical compound Cl.NC(=O)CC(N)=O KHOSTBIBDFQLGJ-UHFFFAOYSA-N 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
238000000159 protein binding assay Methods 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical class OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
IIHQNAXFIODVDU-UHFFFAOYSA-N pyrimidine-2-carbonitrile Chemical class N#CC1=NC=CC=N1 IIHQNAXFIODVDU-UHFFFAOYSA-N 0.000 description 1
150000003230 pyrimidines Chemical class 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
238000006476 reductive cyclization reaction Methods 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
210000002265 sensory receptor cell Anatomy 0.000 description 1
230000019491 signal transduction Effects 0.000 description 1
XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
239000002002 slurry Substances 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
ZNJHFNUEQDVFCJ-UHFFFAOYSA-M sodium;2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid;hydroxide Chemical compound [OH-].[Na+].OCCN1CCN(CCS(O)(=O)=O)CC1 ZNJHFNUEQDVFCJ-UHFFFAOYSA-M 0.000 description 1
235000013599 spices Nutrition 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
ZJXHVYSDMUKUCA-UHFFFAOYSA-N tert-butyl 3-aminopropanoate Chemical compound CC(C)(C)OC(=O)CCN ZJXHVYSDMUKUCA-UHFFFAOYSA-N 0.000 description 1
FZMZNAWBMQKJRL-UHFFFAOYSA-N tert-butyl n-(1-hydroxyethyl)carbamate Chemical compound CC(O)NC(=O)OC(C)(C)C FZMZNAWBMQKJRL-UHFFFAOYSA-N 0.000 description 1
QNLCTIFJTPWCDT-UHFFFAOYSA-N tert-butyl n-(2,4,6-trimethylphenyl)sulfonylcarbamate Chemical compound CC1=CC(C)=C(S(=O)(=O)NC(=O)OC(C)(C)C)C(C)=C1 QNLCTIFJTPWCDT-UHFFFAOYSA-N 0.000 description 1
QKSQWQOAUQFORH-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylimino]carbamate Chemical compound CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C QKSQWQOAUQFORH-UHFFFAOYSA-N 0.000 description 1
PDJALHZSIRSFBO-UHFFFAOYSA-N tert-butyl n-[2-[2-methyl-5-nitro-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-yl]oxyethyl]carbamate Chemical compound CC1=NC(OCCNC(=O)OC(C)(C)C)=C([N+]([O-])=O)C(N2CCC3=CC=CC=C3CC2)=N1 PDJALHZSIRSFBO-UHFFFAOYSA-N 0.000 description 1
OIPJYRGCJUGRNL-UHFFFAOYSA-N tert-butyl n-[5-cyano-2-methyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-1-yl]-n-propan-2-ylcarbamate Chemical compound O=C1N(N(C(=O)OC(C)(C)C)C(C)C)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N OIPJYRGCJUGRNL-UHFFFAOYSA-N 0.000 description 1
RHTNWWCBZRYVAK-UHFFFAOYSA-N tert-butyl n-[[5-cyano-2-methyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-1-yl]amino]carbamate Chemical compound O=C1N(NNC(=O)OC(C)(C)C)C(C)=NC(N2CCC3=CC=CC=C3CC2)=C1C#N RHTNWWCBZRYVAK-UHFFFAOYSA-N 0.000 description 1
BFKJFAAPBSQJPD-UHFFFAOYSA-N tetrafluoroethene Chemical group FC(F)=C(F)F BFKJFAAPBSQJPD-UHFFFAOYSA-N 0.000 description 1
150000003585 thioureas Chemical class 0.000 description 1
125000005490 tosylate group Chemical group 0.000 description 1
125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
238000012546 transfer Methods 0.000 description 1
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
150000008648 triflates Chemical class 0.000 description 1
229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
150000003672 ureas Chemical class 0.000 description 1
229910052720 vanadium Inorganic materials 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- 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
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Hospice & Palliative Care (AREA)
Addiction (AREA)
Cardiology (AREA)
Diabetes (AREA)
Urology & Nephrology (AREA)
Heart & Thoracic Surgery (AREA)
Psychology (AREA)
Vascular Medicine (AREA)
Obesity (AREA)
Emergency Medicine (AREA)
Endocrinology (AREA)
Ophthalmology & Optometry (AREA)
Hematology (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Otolaryngology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)
Other In-Based Heterocyclic Compounds (AREA)

HR20000520A 1999-08-06 2000-08-02 1,2,4,5-TETRADYDRO-BENZO/d/AZEPINES HRP20000520A2 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
EP99115557		1999-08-06

Publications (1)

Publication Number	Publication Date
HRP20000520A2 true HRP20000520A2 (en)	2001-06-30

Family

ID=8238742

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HR20000520A HRP20000520A2 (en)	1999-08-06	2000-08-02	1,2,4,5-TETRADYDRO-BENZO/d/AZEPINES

Country Status (27)

Country	Link
US (1)	US6218385B1 (de)
JP (1)	JP3260350B2 (de)
KR (1)	KR100390116B1 (de)
CN (1)	CN1146455C (de)
AR (1)	AR025035A1 (de)
AT (1)	ATE254614T1 (de)
AU (1)	AU774485B2 (de)
BR (1)	BR0003375A (de)
CA (1)	CA2314798A1 (de)
CO (1)	CO5180625A1 (de)
DE (1)	DE60006618T2 (de)
ES (1)	ES2209728T3 (de)
HR (1)	HRP20000520A2 (de)
HU (1)	HUP0003112A3 (de)
ID (1)	ID26743A (de)
IL (1)	IL137688A0 (de)
MA (1)	MA26748A1 (de)
NO (1)	NO20003966L (de)
NZ (1)	NZ506096A (de)
PE (1)	PE20010467A1 (de)
PL (1)	PL341890A1 (de)
RU (1)	RU2240317C2 (de)
SG (1)	SG93251A1 (de)
TR (1)	TR200002298A2 (de)
UY (1)	UY26276A1 (de)
YU (1)	YU49700A (de)
ZA (1)	ZA200003927B (de)

Families Citing this family (35)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
KR100545906B1 (ko) *	2000-12-22	2006-01-26	에프. 호프만-라 로슈 아게	ｍＧｌｕＲ 1 길항물질로서의 테트라하이드로-(벤조 또는티에노)-아제핀-피라진 및 트리아진 유도체
US6953787B2 (en)	2002-04-12	2005-10-11	Arena Pharmaceuticals, Inc.	5HT2C receptor modulators
KR100897642B1 (ko) *	2002-12-20	2009-05-14	글락소 그룹 리미티드	신경 장애 치료용 벤즈아제핀 유도체
CN1805938B (zh) *	2003-06-17	2010-06-16	艾尼纳制药公司	用于治疗5ht2c受体相关疾病的苯并氮杂卓衍生物
PL2332921T3 (pl) *	2003-06-17	2016-08-31	Arena Pharm Inc	Chlorowodorek 8-chloro-1-metylo-2,3,4,5-tetrahydro-1H-3-benzazepiny
WO2005042490A1 (en) *	2003-10-22	2005-05-12	Arena Pharmaceuticals, Inc.	Benzazepine derivatives and methods of prophylaxis or treatment of 5ht2c receptor associated diseases
US20080009478A1 (en) *	2003-10-22	2008-01-10	Arena Pharmaceuticals, Inc.	Benzazepine Derivatives and Methods of Prophylaxis or Treatment of 5Ht2c Receptor Associated Diseases
NZ555981A (en)	2004-12-21	2011-01-28	Arena Pharm Inc	Crystalline forms of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride
BRPI0515862A2 (pt)	2004-12-23	2011-10-11	Arena Pharm Inc	uso de fentermina e agonista seletivo do receptor de 5ht-2c na preparação de composições, composições moduladoras do receptor de 5ht-2c e forma de dosagem unitária compreendendo as mesmas
EP2275095A3 (de)	2005-08-26	2011-08-17	Braincells, Inc.	Neurogenese durch modulation des Muscarinrezeptors
EP2258358A3 (de)	2005-08-26	2011-09-07	Braincells, Inc.	Neurogenese mit Acetylcholinesterasehemmer
EP1940389A2 (de)	2005-10-21	2008-07-09	Braincells, Inc.	Modulation von neurogenese durch pde-hemmung
AU2006308889A1 (en)	2005-10-31	2007-05-10	Braincells, Inc.	GABA receptor mediated modulation of neurogenesis
US20100216734A1 (en)	2006-03-08	2010-08-26	Braincells, Inc.	Modulation of neurogenesis by nootropic agents
EP2001852A2 (de)	2006-04-03	2008-12-17	Arena Pharmaceuticals, Inc.	Verfahren zur herstellung von 8-chlor-1-methyl-2,3,4,5-tetrahydro-1h-3-benzazepin und entsprechenden zwischenprodukten
JP2009536667A (ja)	2006-05-09	2009-10-15	ブレインセルス，インコーポレイティド	５ｈｔ受容体介在性の神経新生
EP2382975A3 (de)	2006-05-09	2012-02-29	Braincells, Inc.	Neurogenese mittels Angiotensin-Modulation
EP1873527A1 (de) *	2006-06-30	2008-01-02	Schwarz Pharma Ag	Verfahren zur Identifizierung von CRMP-Modulatoren
AU2007292848A1 (en)	2006-09-08	2008-03-13	Braincells, Inc.	Combinations containing a 4-acylaminopyridine derivative
US20100184806A1 (en)	2006-09-19	2010-07-22	Braincells, Inc.	Modulation of neurogenesis by ppar agents
PL2083811T3 (pl)	2006-11-22	2017-05-31	Clinical Research Associates, Llc	Sposoby leczenia zespołu downa, zespołu łamliwego chromosomu x oraz autyzmu
CN101547892B (zh) *	2006-12-05	2014-08-20	艾尼纳制药公司	制备(r)-8-氯-1-甲基-2,3,4,5-四氢-1h-3-苯并氮杂卓的方法和其中间体
TW200845978A (en) *	2007-03-07	2008-12-01	Janssen Pharmaceutica Nv	3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives
EP2288585A1 (de)	2008-03-04	2011-03-02	Arena Pharmaceuticals, Inc.	Verfahren zur herstellung von mit dem 5-ht2c-agonisten (r)-8-chlor-1-methyl-2,3,4,5-tetrahydro-1h-3-benzazepin verwandten zwischenprodukten
WO2010099217A1 (en)	2009-02-25	2010-09-02	Braincells, Inc.	Modulation of neurogenesis using d-cycloserine combinations
US8952197B2 (en)	2009-06-18	2015-02-10	Arena Pharmaceuticals, Inc.	Processes for the preparation of 5-HT2C receptor agonists
WO2011109398A2 (en)	2010-03-02	2011-09-09	President And Fellows Of Harvard College	Methods and compositions for treatment of angelman syndrome and autism spectrum disorders
US20110294879A1 (en)	2010-05-28	2011-12-01	Xenoport, Inc.	Method of treatment of fragile x syndrome, down's syndrome, autism and related disorders
US9045431B2 (en)	2010-06-02	2015-06-02	Arena Pharmaceuticals, Inc.	Processes for the preparation of 5-HT2C receptor agonists
WO2012009646A1 (en)	2010-07-15	2012-01-19	Xenoport, Inc.	Methods of treating fragile x syndrome, down's syndrome, autism and related disorders
JP2013536859A (ja)	2010-09-01	2013-09-26	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	５−ｈｔ２ｃアゴニストの非吸湿性塩
JP6272695B2 (ja)	2010-09-01	2018-01-31	エーザイ・アール・アンド・ディー・マネジメント株式会社	体重管理のために有用な５−ｈｔ２ｃアゴニストの改変放出剤形
AU2011296015B2 (en)	2010-09-01	2015-11-12	Arena Pharmaceuticals, Inc.	Administration of lorcaserin to individuals with renal impairment
KR20130138770A (ko)	2010-09-01	2013-12-19	아레나 파마슈티칼스, 인크.	광학적으로 활성 산을 갖는 로르카세린의 염
JP2015534563A (ja)	2012-10-09	2015-12-03	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	体重管理の方法

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4206210A (en) *	1977-01-19	1980-06-03	Smithkline Corporation	Alkylthio-7,8-dihdroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines having dopaminergic activity
DK0556310T3 (da) *	1990-11-06	1995-08-21	Pfizer	Quinazolinderivater til forhøjelse af antitumoraktivitet
US5241065A (en) *	1992-02-25	1993-08-31	Schering Corporation	2,3,4,5-tetrahydro-1h-3-benzazepines having anti-psychotic activity
AU678503B2 (en) *	1993-09-24	1997-05-29	Takeda Chemical Industries Ltd.	Condensed heterocyclic compounds and their use as squalene synthetase inhibitors

2000
- 2000-07-27 ES ES00116091T patent/ES2209728T3/es not_active Expired - Lifetime
- 2000-07-27 DE DE60006618T patent/DE60006618T2/de not_active Expired - Fee Related
- 2000-07-27 AT AT00116091T patent/ATE254614T1/de not_active IP Right Cessation
- 2000-08-01 NZ NZ506096A patent/NZ506096A/xx unknown
- 2000-08-01 US US09/630,702 patent/US6218385B1/en not_active Expired - Fee Related
- 2000-08-01 CA CA002314798A patent/CA2314798A1/en not_active Abandoned
- 2000-08-01 MA MA26033A patent/MA26748A1/fr unknown
- 2000-08-02 ID IDP20000655A patent/ID26743A/id unknown
- 2000-08-02 AU AU48979/00A patent/AU774485B2/en not_active Ceased
- 2000-08-02 SG SG200004344A patent/SG93251A1/en unknown
- 2000-08-02 HR HR20000520A patent/HRP20000520A2/hr not_active Application Discontinuation
- 2000-08-02 ZA ZA200003927A patent/ZA200003927B/xx unknown
- 2000-08-02 PE PE2000000768A patent/PE20010467A1/es not_active Application Discontinuation
- 2000-08-03 CO CO00058410A patent/CO5180625A1/es not_active Application Discontinuation
- 2000-08-03 IL IL13768800A patent/IL137688A0/xx unknown
- 2000-08-04 HU HU0003112A patent/HUP0003112A3/hu unknown
- 2000-08-04 RU RU2000120522/04A patent/RU2240317C2/ru not_active IP Right Cessation
- 2000-08-04 TR TR2000/02298A patent/TR200002298A2/xx unknown
- 2000-08-04 KR KR10-2000-0045324A patent/KR100390116B1/ko not_active Expired - Fee Related
- 2000-08-04 CN CNB001225235A patent/CN1146455C/zh not_active Expired - Fee Related
- 2000-08-04 AR ARP000104022A patent/AR025035A1/es not_active Application Discontinuation
- 2000-08-04 NO NO20003966A patent/NO20003966L/no not_active Application Discontinuation
- 2000-08-04 JP JP2000236848A patent/JP3260350B2/ja not_active Expired - Fee Related
- 2000-08-04 UY UY26276A patent/UY26276A1/es not_active Application Discontinuation
- 2000-08-07 PL PL00341890A patent/PL341890A1/xx unknown
- 2000-08-07 YU YU49700A patent/YU49700A/sh unknown
- 2000-08-07 BR BR0003375-8A patent/BR0003375A/pt not_active Application Discontinuation

Also Published As

Publication number	Publication date
NZ506096A (en)	2002-08-28
DE60006618D1 (de)	2003-12-24
TR200002298A3 (tr)	2001-03-21
NO20003966L (no)	2001-02-07
KR20010082510A (ko)	2001-08-30
PE20010467A1 (es)	2001-04-17
SG93251A1 (en)	2002-12-17
US6218385B1 (en)	2001-04-17
AR025035A1 (es)	2002-11-06
ES2209728T3 (es)	2004-07-01
HUP0003112A2 (hu)	2002-11-28
DE60006618T2 (de)	2004-09-23
KR100390116B1 (ko)	2003-07-04
ID26743A (id)	2001-02-08
BR0003375A (pt)	2001-03-13
NO20003966D0 (no)	2000-08-04
ATE254614T1 (de)	2003-12-15
CA2314798A1 (en)	2001-02-06
UY26276A1 (es)	2000-10-31
CN1283623A (zh)	2001-02-14
AU774485B2 (en)	2004-07-01
RU2240317C2 (ru)	2004-11-20
HUP0003112A3 (en)	2003-07-28
HU0003112D0 (en)	2000-10-28
JP2001089472A (ja)	2001-04-03
TR200002298A2 (tr)	2001-03-21
JP3260350B2 (ja)	2002-02-25
YU49700A (sh)	2003-04-30
IL137688A0 (en)	2001-10-31
CN1146455C (zh)	2004-04-21
CO5180625A1 (es)	2002-07-30
PL341890A1 (en)	2001-02-12
MA26748A1 (fr)	2004-12-20
AU4897900A (en)	2001-02-08
ZA200003927B (en)	2001-02-06

Legal Events

Date	Code	Title
2001-06-30	A1OB	Publication of a patent application
2001-12-05	AIPI	Request for the grant of a patent on the basis of a substantive examination of a patent application
2004-09-30	ODBC	Application rejected

Publication	Publication Date	Title
HRP20000520A2 (en)	2001-06-30	1,2,4,5-TETRADYDRO-BENZO/d/AZEPINES
EP1074549B1 (de)	2003-11-19	Tetrahydro-benzo(d)azepine und deren Verwendung als metabotrope Glutamatrezeptor-Antagonisten
JP3398152B2 (ja)	2003-04-21	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
US6107301A (en)	2000-08-22	1N-alkyl-N-arylpyrimidinamines and derivatives thereof
ES2313110T3 (es)	2009-03-01	Compuestos de cetolactama y su utilizacion.
CA2689989A1 (en)	2008-12-11	Heterocyclic compounds and uses thereof
EP1646389A1 (de)	2006-04-19	Pyrimidin-2,4-dion-derivate als gonadotropin freisetzende hormon-rezeptor-antagonisten
JPH0597851A (ja)	1993-04-20	窒素含有６員環複素環を結合させるアンギオテンシンｉｉ拮抗薬
CA2296014A1 (en)	1999-01-14	Aryl-and arylamino-substituted heterocycles as corticotropin releasing hormone antagonists
KR20140103996A (ko)	2014-08-27	Lrrk2 조절제로서 아미노피리미딘 유도체
ES2340941T3 (es)	2010-06-11	Compuestos de 4-piperazinil-pirimidina adecuados para tretar trastornos que responden a modulacion del receptor d 3 de dopamina.
EP1644342A1 (de)	2006-04-12	Antagonisten des gonadotropin-releasing hormone rezeptors und damit in zusammenhang stehende verfahren
MXPA00007661A (en)	2002-07-25	Tetrahydro-benzo(d)azepines and their use as antagonists at metabotropic glutamate receptors
CZ20002831A3 (cs)	2001-03-14	1.2.4.5-Tetrahydrobenzo/d/azepinové deriváty, způsob jejich přípravy a jejich použití
TW200303316A (en)	2003-09-01	Substituted indolizine-like compounds and methods of use