AU2006278759B2 - Pyrimidine compounds as serotonin receptor modulators - Google Patents

Info

Publication number

AU2006278759B2

AU2006278759B2 AU2006278759A AU2006278759A AU2006278759B2 AU 2006278759 B2 AU2006278759 B2 AU 2006278759B2 AU 2006278759 A AU2006278759 A AU 2006278759A AU 2006278759 A AU2006278759 A AU 2006278759A AU 2006278759 B2 AU2006278759 B2 AU 2006278759B2

Authority

AU

Australia

Prior art keywords

alkyl

phenyl

substituted

pyrido

group

Prior art date

2005-08-04

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

Ceased

Links

• Espacenet
• Global Dossier
• Discuss

• 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 title abstract description 17
• 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 title abstract description 17
• 150000003230 pyrimidines Chemical class 0.000 title description 16
• 150000001875 compounds Chemical class 0.000 claims abstract description 202
• QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims abstract description 88
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 73
• 201000010099 disease Diseases 0.000 claims abstract description 26
• 230000001404 mediated effect Effects 0.000 claims abstract description 22
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims abstract description 19
• 229940076279 serotonin Drugs 0.000 claims abstract description 10
• 125000000217 alkyl group Chemical group 0.000 claims description 823
• -1 lactiobionate Chemical compound 0.000 claims description 221
• 229910052799 carbon Inorganic materials 0.000 claims description 194
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 170
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 160
• 150000001721 carbon Chemical group 0.000 claims description 138
• 125000005843 halogen group Chemical group 0.000 claims description 120
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 111
• 125000001424 substituent group Chemical group 0.000 claims description 108
• 125000003342 alkenyl group Chemical group 0.000 claims description 95
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 85
• 229910052757 nitrogen Inorganic materials 0.000 claims description 85
• 238000000034 method Methods 0.000 claims description 83
• 125000003386 piperidinyl group Chemical group 0.000 claims description 83
• 125000002757 morpholinyl group Chemical group 0.000 claims description 82
• 125000004193 piperazinyl group Chemical group 0.000 claims description 82
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 82
• 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 81
• 125000004432 carbon atom Chemical group C* 0.000 claims description 80
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 80
• 125000006413 ring segment Chemical group 0.000 claims description 80
• 125000002029 aromatic hydrocarbon group Chemical group 0.000 claims description 79
• 125000002950 monocyclic group Chemical group 0.000 claims description 79
• 125000000304 alkynyl group Chemical group 0.000 claims description 75
• 150000001408 amides Chemical class 0.000 claims description 71
• 239000000203 mixture Substances 0.000 claims description 64
• 150000003839 salts Chemical class 0.000 claims description 52
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 50
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 50
• 208000035475 disorder Diseases 0.000 claims description 47
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 43
• 125000001931 aliphatic group Chemical group 0.000 claims description 40
• 125000002947 alkylene group Chemical group 0.000 claims description 39
• 150000002148 esters Chemical class 0.000 claims description 34
• 241000124008 Mammalia Species 0.000 claims description 32
• 230000002265 prevention Effects 0.000 claims description 27
• 125000004076 pyridyl group Chemical group 0.000 claims description 25
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 24
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 23
• 229910052739 hydrogen Inorganic materials 0.000 claims description 22
• 125000002971 oxazolyl group Chemical group 0.000 claims description 22
• 125000001544 thienyl group Chemical group 0.000 claims description 22
• 125000004122 cyclic group Chemical group 0.000 claims description 21
• 125000001072 heteroaryl group Chemical group 0.000 claims description 21
• 125000005842 heteroatom Chemical group 0.000 claims description 21
• 239000012453 solvate Substances 0.000 claims description 21
• 125000004450 alkenylene group Chemical group 0.000 claims description 20
• 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 20
• 125000003118 aryl group Chemical group 0.000 claims description 20
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 20
• 150000004677 hydrates Chemical class 0.000 claims description 20
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 20
• 208000019901 Anxiety disease Diseases 0.000 claims description 19
• 125000004419 alkynylene group Chemical group 0.000 claims description 19
• 230000036506 anxiety Effects 0.000 claims description 19
• 125000002993 cycloalkylene group Chemical group 0.000 claims description 19
• 239000003814 drug Substances 0.000 claims description 19
• 208000019695 Migraine disease Diseases 0.000 claims description 18
• 125000005724 cycloalkenylene group Chemical group 0.000 claims description 18
• 206010027599 migraine Diseases 0.000 claims description 18
• 208000002551 irritable bowel syndrome Diseases 0.000 claims description 17
• 229910052701 rubidium Inorganic materials 0.000 claims description 15
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 13
• 201000000980 schizophrenia Diseases 0.000 claims description 13
• 208000030814 Eating disease Diseases 0.000 claims description 12
• 208000019454 Feeding and Eating disease Diseases 0.000 claims description 12
• 208000018262 Peripheral vascular disease Diseases 0.000 claims description 12
• 206010046543 Urinary incontinence Diseases 0.000 claims description 12
• 235000014632 disordered eating Nutrition 0.000 claims description 12
• 230000030135 gastric motility Effects 0.000 claims description 12
• PLZDHJUUEGCXJH-UHFFFAOYSA-N pyrido[4,3-d]pyrimidine Chemical compound C1=NC=C2C=NC=CC2=N1 PLZDHJUUEGCXJH-UHFFFAOYSA-N 0.000 claims description 12
• 208000019116 sleep disease Diseases 0.000 claims description 12
• 208000020925 Bipolar disease Diseases 0.000 claims description 11
• 208000019888 Circadian rhythm sleep disease Diseases 0.000 claims description 11
• 208000011688 Generalised anxiety disease Diseases 0.000 claims description 11
• 208000001456 Jet Lag Syndrome Diseases 0.000 claims description 11
• 208000019022 Mood disease Diseases 0.000 claims description 11
• 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 11
• 208000028017 Psychotic disease Diseases 0.000 claims description 11
• 201000001880 Sexual dysfunction Diseases 0.000 claims description 11
• 208000029364 generalized anxiety disease Diseases 0.000 claims description 11
• 208000033915 jet lag type circadian rhythm sleep disease Diseases 0.000 claims description 11
• 231100000872 sexual dysfunction Toxicity 0.000 claims description 11
• 238000004519 manufacturing process Methods 0.000 claims description 10
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 10
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 9
• 239000003937 drug carrier Substances 0.000 claims description 8
• 208000015114 central nervous system disease Diseases 0.000 claims description 7
• 239000008194 pharmaceutical composition Substances 0.000 claims description 7
• 238000002600 positron emission tomography Methods 0.000 claims description 7
• RKPRFJORBOCCDX-UHFFFAOYSA-N 4-(4-fluorophenyl)-2-propan-2-yl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine Chemical group N=1C(C(C)C)=NC=2CCNCC=2C=1C1=CC=C(F)C=C1 RKPRFJORBOCCDX-UHFFFAOYSA-N 0.000 claims description 6
• 208000007848 Alcoholism Diseases 0.000 claims description 6
• 206010012735 Diarrhoea Diseases 0.000 claims description 6
• 208000001953 Hypotension Diseases 0.000 claims description 6
• 208000022873 Ocular disease Diseases 0.000 claims description 6
• 208000002193 Pain Diseases 0.000 claims description 6
• 206010040070 Septic Shock Diseases 0.000 claims description 6
• 230000005856 abnormality Effects 0.000 claims description 6
• 230000027288 circadian rhythm Effects 0.000 claims description 6
• 230000002526 effect on cardiovascular system Effects 0.000 claims description 6
• 230000002496 gastric effect Effects 0.000 claims description 6
• 230000036543 hypotension Effects 0.000 claims description 6
• 208000028867 ischemia Diseases 0.000 claims description 6
• 208000017169 kidney disease Diseases 0.000 claims description 6
• 230000002503 metabolic effect Effects 0.000 claims description 6
• 208000028173 post-traumatic stress disease Diseases 0.000 claims description 6
• 230000036303 septic shock Effects 0.000 claims description 6
• 230000035939 shock Effects 0.000 claims description 6
• 208000022925 sleep disturbance Diseases 0.000 claims description 6
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 6
• 230000002792 vascular Effects 0.000 claims description 6
• LKGBTCMMESGPGL-UHFFFAOYSA-N 4-(4-fluorophenyl)-2-phenyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine Chemical compound C1=CC(F)=CC=C1C1=NC(C=2C=CC=CC=2)=NC2=C1CNCC2 LKGBTCMMESGPGL-UHFFFAOYSA-N 0.000 claims description 5
• 206010012688 Diabetic retinal oedema Diseases 0.000 claims description 5
• 206010012689 Diabetic retinopathy Diseases 0.000 claims description 5
• 208000010412 Glaucoma Diseases 0.000 claims description 5
• 206010020772 Hypertension Diseases 0.000 claims description 5
• 206010061218 Inflammation Diseases 0.000 claims description 5
• 206010028813 Nausea Diseases 0.000 claims description 5
• 208000008589 Obesity Diseases 0.000 claims description 5
• 208000003435 Optic Neuritis Diseases 0.000 claims description 5
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 5
• 206010064930 age-related macular degeneration Diseases 0.000 claims description 5
• 206010001584 alcohol abuse Diseases 0.000 claims description 5
• 208000025746 alcohol use disease Diseases 0.000 claims description 5
• 230000003054 hormonal effect Effects 0.000 claims description 5
• 230000004054 inflammatory process Effects 0.000 claims description 5
• 208000002780 macular degeneration Diseases 0.000 claims description 5
• 239000003068 molecular probe Substances 0.000 claims description 5
• 230000008693 nausea Effects 0.000 claims description 5
• 235000020824 obesity Nutrition 0.000 claims description 5
• RYTJQWWDIOORSK-UHFFFAOYSA-N 2-benzyl-4-(4-fluorophenyl)-6,7,8,9-tetrahydro-5h-pyrimido[5,4-c]azepine;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1C1=NC(CC=2C=CC=CC=2)=NC2=C1CNCCC2 RYTJQWWDIOORSK-UHFFFAOYSA-N 0.000 claims description 4
• TVFDKRFXXSXNQG-UHFFFAOYSA-N 2-benzyl-7-methyl-4-(4-methylphenyl)-5,6,8,9-tetrahydropyrimido[4,5-d]azepine Chemical compound N=1C(C=2C=CC(C)=CC=2)=C2CCN(C)CCC2=NC=1CC1=CC=CC=C1 TVFDKRFXXSXNQG-UHFFFAOYSA-N 0.000 claims description 4
• AFXYGEHWOKMZQS-UHFFFAOYSA-N 2-butan-2-yl-4-(4-fluorophenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine;hydrochloride Chemical compound Cl.N=1C(C(C)CC)=NC=2CCNCC=2C=1C1=CC=C(F)C=C1 AFXYGEHWOKMZQS-UHFFFAOYSA-N 0.000 claims description 4
• YXTJOVZVHZIUNM-UHFFFAOYSA-N 2-tert-butyl-4-(4-fluorophenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine Chemical compound N=1C(C(C)(C)C)=NC=2CCNCC=2C=1C1=CC=C(F)C=C1 YXTJOVZVHZIUNM-UHFFFAOYSA-N 0.000 claims description 4
• UBXFSHYTJMAJGS-UHFFFAOYSA-N 4-(4-fluorophenyl)-2-(2-methoxyethyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine Chemical compound N=1C(CCOC)=NC=2CCNCC=2C=1C1=CC=C(F)C=C1 UBXFSHYTJMAJGS-UHFFFAOYSA-N 0.000 claims description 4
• CZFYSRJTOJIVPQ-UHFFFAOYSA-N 4-(4-fluorophenyl)-2-propan-2-yl-5,6,7,8-tetrahydroquinazoline Chemical compound N=1C(C(C)C)=NC=2CCCCC=2C=1C1=CC=C(F)C=C1 CZFYSRJTOJIVPQ-UHFFFAOYSA-N 0.000 claims description 4
• AIUMOQLDWXLQDO-UHFFFAOYSA-N 4-phenyl-2-propan-2-yl-6,7,8,9-tetrahydro-5h-pyrimido[4,5-c]azepine Chemical compound N=1C(C(C)C)=NC=2CNCCCC=2C=1C1=CC=CC=C1 AIUMOQLDWXLQDO-UHFFFAOYSA-N 0.000 claims description 4
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 4
• 125000004429 atom Chemical group 0.000 claims description 4
• XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 claims description 4
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 4
• NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 4
• ZCPJSJOPVXVKAG-UHFFFAOYSA-N 2-[4-(4-fluorophenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl]propanoic acid Chemical compound N=1C(C(C(O)=O)C)=NC=2CCNCC=2C=1C1=CC=C(F)C=C1 ZCPJSJOPVXVKAG-UHFFFAOYSA-N 0.000 claims description 3
• ZUHRRJVOTSODOR-UHFFFAOYSA-N 2-benzyl-4-(4-fluorophenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine Chemical compound C1=CC(F)=CC=C1C1=NC(CC=2C=CC=CC=2)=NC2=C1CNCC2 ZUHRRJVOTSODOR-UHFFFAOYSA-N 0.000 claims description 3
• ZKSMAPWVBJQLNO-UHFFFAOYSA-N 2-benzyl-4-(4-methylphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine Chemical compound C1=CC(C)=CC=C1C1=NC(CC=2C=CC=CC=2)=NC2=C1CNCC2 ZKSMAPWVBJQLNO-UHFFFAOYSA-N 0.000 claims description 3
• KPAGUIDGAONHKM-UHFFFAOYSA-N 2-benzyl-4-phenyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine Chemical compound N=1C=2CNCCC=2C(C=2C=CC=CC=2)=NC=1CC1=CC=CC=C1 KPAGUIDGAONHKM-UHFFFAOYSA-N 0.000 claims description 3
• VPCIQDQLKTYYFI-UHFFFAOYSA-N 2-butan-2-yl-4-(4-methylphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine;hydrochloride Chemical compound Cl.N=1C(C(C)CC)=NC=2CCNCC=2C=1C1=CC=C(C)C=C1 VPCIQDQLKTYYFI-UHFFFAOYSA-N 0.000 claims description 3
• VAIXQGRVMRRZAE-UHFFFAOYSA-N 2-cyclobutyl-4-(4-methylphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine Chemical compound C1=CC(C)=CC=C1C1=NC(C2CCC2)=NC2=C1CNCC2 VAIXQGRVMRRZAE-UHFFFAOYSA-N 0.000 claims description 3
• ZFKHQIZFZFIFOQ-UHFFFAOYSA-N 2-cyclopentyl-4-(4-fluorophenyl)-6,7,8,9-tetrahydro-5h-pyrimido[4,5-d]azepine Chemical compound C1=CC(F)=CC=C1C1=NC(C2CCCC2)=NC2=C1CCNCC2 ZFKHQIZFZFIFOQ-UHFFFAOYSA-N 0.000 claims description 3
• UDWHMLMQXNEKBD-UHFFFAOYSA-N 4-(4-fluorophenyl)-2-(1,1,1,3,3,3-hexafluoropropan-2-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine Chemical compound C1=CC(F)=CC=C1C1=NC(C(C(F)(F)F)C(F)(F)F)=NC2=C1CNCC2 UDWHMLMQXNEKBD-UHFFFAOYSA-N 0.000 claims description 3
• VEBIPTDXWIUNHW-UHFFFAOYSA-N 4-(4-fluorophenyl)-2-(1-methylcyclopropyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine Chemical compound N=1C=2CCNCC=2C(C=2C=CC(F)=CC=2)=NC=1C1(C)CC1 VEBIPTDXWIUNHW-UHFFFAOYSA-N 0.000 claims description 3
• KAKBJMZQEXHHAS-UHFFFAOYSA-N 4-(4-fluorophenyl)-2-(1-methylpiperidin-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine Chemical compound C1CN(C)CCC1C(N=C1C=2C=CC(F)=CC=2)=NC2=C1CNCC2 KAKBJMZQEXHHAS-UHFFFAOYSA-N 0.000 claims description 3
• JQQWHVUKYBIUGY-UHFFFAOYSA-N 4-(4-fluorophenyl)-2-(4-methoxyphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine Chemical compound C1=CC(OC)=CC=C1C(N=C1C=2C=CC(F)=CC=2)=NC2=C1CNCC2 JQQWHVUKYBIUGY-UHFFFAOYSA-N 0.000 claims description 3
• BTOLKTWDIBDQQP-UHFFFAOYSA-N 7-benzyl-4-phenyl-2-propan-2-yl-6,8-dihydro-5h-pyrido[3,4-d]pyrimidine Chemical compound C1CC=2C(C=3C=CC=CC=3)=NC(C(C)C)=NC=2CN1CC1=CC=CC=C1 BTOLKTWDIBDQQP-UHFFFAOYSA-N 0.000 claims description 3
• SEFYFAHQQLNRGX-UHFFFAOYSA-N 7h-pyrimido[4,5-d]azepine Chemical compound C1=CNC=CC2=CN=CN=C21 SEFYFAHQQLNRGX-UHFFFAOYSA-N 0.000 claims description 3
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 3
• 150000001860 citric acid derivatives Chemical class 0.000 claims description 3
• AKCLJLKZMKSIRX-UHFFFAOYSA-N dodeca-2,4,6-triene Chemical compound CCCCCC=CC=CC=CC AKCLJLKZMKSIRX-UHFFFAOYSA-N 0.000 claims description 3
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 3
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 3
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 3
• LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 claims description 2
• NQFBXIROFMVGNW-UHFFFAOYSA-N 2,7-dibenzyl-4-phenyl-6,8-dihydro-5h-pyrido[3,4-d]pyrimidine Chemical compound C=1C=CC=CC=1CN(C1)CCC(C(=N2)C=3C=CC=CC=3)=C1N=C2CC1=CC=CC=C1 NQFBXIROFMVGNW-UHFFFAOYSA-N 0.000 claims description 2
• XHSCZYJVMANUEJ-UHFFFAOYSA-N 2-(2-propan-2-yl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-1,3-thiazole Chemical compound N=1C(C(C)C)=NC=2CCNCC=2C=1C1=NC=CS1 XHSCZYJVMANUEJ-UHFFFAOYSA-N 0.000 claims description 2
• NEAQVXCKMIBFBH-UHFFFAOYSA-N 2-(4-fluorocyclohexyl)-4-(4-fluorophenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine Chemical compound C1CC(F)CCC1C(N=C1C=2C=CC(F)=CC=2)=NC2=C1CNCC2 NEAQVXCKMIBFBH-UHFFFAOYSA-N 0.000 claims description 2
• UTWOKDMZZMEEIR-UHFFFAOYSA-N 2-benzyl-4-(3,4-difluorophenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine Chemical compound C1=C(F)C(F)=CC=C1C1=NC(CC=2C=CC=CC=2)=NC2=C1CNCC2 UTWOKDMZZMEEIR-UHFFFAOYSA-N 0.000 claims description 2
• HWTYXTNYMDWWFE-UHFFFAOYSA-N 2-benzyl-4-(3-fluorophenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine Chemical compound FC1=CC=CC(C=2C=3CNCCC=3N=C(CC=3C=CC=CC=3)N=2)=C1 HWTYXTNYMDWWFE-UHFFFAOYSA-N 0.000 claims description 2
• XNOSXOVNQUXCIU-UHFFFAOYSA-N 2-benzyl-4-phenyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine Chemical compound N=1C=2CCNCC=2C(C=2C=CC=CC=2)=NC=1CC1=CC=CC=C1 XNOSXOVNQUXCIU-UHFFFAOYSA-N 0.000 claims description 2
• YWDIQXUBGTZIJI-UHFFFAOYSA-N 2-cyclobutyl-4-(4-fluorophenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1C1=NC(C2CCC2)=NC2=C1CNCC2 YWDIQXUBGTZIJI-UHFFFAOYSA-N 0.000 claims description 2
• RMODCJATEPQNLZ-UHFFFAOYSA-N 2-cyclopent-3-en-1-yl-4-(4-fluorophenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine Chemical compound C1=CC(F)=CC=C1C1=NC(C2CC=CC2)=NC2=C1CNCC2 RMODCJATEPQNLZ-UHFFFAOYSA-N 0.000 claims description 2
• JHWYCTGSHIXUNV-UHFFFAOYSA-N 2-cyclopentyl-4-(4-fluorophenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine Chemical compound C1=CC(F)=CC=C1C1=NC(C2CCCC2)=NC2=C1CNCC2 JHWYCTGSHIXUNV-UHFFFAOYSA-N 0.000 claims description 2
• NCYDQOYVSVVPGD-UHFFFAOYSA-N 2-cyclopentyl-4-(4-methoxyphenyl)-7-methyl-5,6,8,9-tetrahydropyrimido[4,5-d]azepine Chemical compound C1=CC(OC)=CC=C1C1=NC(C2CCCC2)=NC2=C1CCN(C)CC2 NCYDQOYVSVVPGD-UHFFFAOYSA-N 0.000 claims description 2
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• DEBCZTRGKYYNFB-UHFFFAOYSA-N tert-butyl 4-(4-fluorophenyl)-2-[(4-fluorophenyl)methyl]-5,6,8,9-tetrahydropyrimido[4,5-d]azepine-7-carboxylate Chemical compound N=1C(C=2C=CC(F)=CC=2)=C2CCN(C(=O)OC(C)(C)C)CCC2=NC=1CC1=CC=C(F)C=C1 DEBCZTRGKYYNFB-UHFFFAOYSA-N 0.000 description 1
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• 150000003510 tertiary aliphatic amines Chemical class 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• 238000012360 testing method Methods 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
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• 238000002560 therapeutic procedure Methods 0.000 description 1
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• 230000001988 toxicity Effects 0.000 description 1
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• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
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• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
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• UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1
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• 229940007718 zinc hydroxide Drugs 0.000 description 1