CA2565219A1 - Selected cgrp antagonists, methods for the production thereof, and use thereof as medicaments - Google Patents

Info

Publication number

CA2565219A1

CA2565219A1 CA002565219A CA2565219A CA2565219A1 CA 2565219 A1 CA2565219 A1 CA 2565219A1 CA 002565219 A CA002565219 A CA 002565219A CA 2565219 A CA2565219 A CA 2565219A CA 2565219 A1 CA2565219 A1 CA 2565219A1

Authority

CA

Canada

Prior art keywords

alkyl

oxo

group

amino

methyl

Prior art date

2004-04-22

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 238000000034 method Methods 0.000 title claims abstract description 69
• 229940127597 CGRP antagonist Drugs 0.000 title claims abstract description 22
• 238000004519 manufacturing process Methods 0.000 title claims abstract description 6
• 239000003814 drug Substances 0.000 title abstract description 3
• 150000003839 salts Chemical class 0.000 claims abstract description 122
• 150000001875 compounds Chemical class 0.000 claims abstract description 103
• 239000000203 mixture Substances 0.000 claims abstract description 81
• 150000004677 hydrates Chemical class 0.000 claims abstract description 68
• 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 abstract description 39
• 150000007522 mineralic acids Chemical class 0.000 claims abstract description 35
• 150000007524 organic acids Chemical class 0.000 claims abstract description 34
• 235000005985 organic acids Nutrition 0.000 claims abstract description 34
• -1 biphenylyl Chemical group 0.000 claims description 990
• 229910052757 nitrogen Inorganic materials 0.000 claims description 229
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 200
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 199
• 229910052799 carbon Inorganic materials 0.000 claims description 153
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 141
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 99
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 86
• 125000000623 heterocyclic group Chemical group 0.000 claims description 85
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 84
• 229910052760 oxygen Inorganic materials 0.000 claims description 81
• 150000001721 carbon Chemical group 0.000 claims description 78
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 77
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 73
• 239000001301 oxygen Substances 0.000 claims description 73
• 238000006243 chemical reaction Methods 0.000 claims description 71
• 125000004076 pyridyl group Chemical group 0.000 claims description 67
• 125000001424 substituent group Chemical group 0.000 claims description 62
• 125000001153 fluoro group Chemical group F* 0.000 claims description 55
• 125000004432 carbon atom Chemical group C* 0.000 claims description 51
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 51
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 50
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 47
• 229920006395 saturated elastomer Polymers 0.000 claims description 46
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 45
• 125000000217 alkyl group Chemical group 0.000 claims description 44
• 229910052731 fluorine Inorganic materials 0.000 claims description 44
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 43
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 43
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 41
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 41
• 229910052736 halogen Inorganic materials 0.000 claims description 41
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 40
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 40
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 37
• 125000005843 halogen group Chemical group 0.000 claims description 37
• ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 36
• 150000002367 halogens Chemical class 0.000 claims description 34
• 125000005331 diazinyl group Chemical group N1=NC(=CC=C1)* 0.000 claims description 32
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 32
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 31
• 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 30
• 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 30
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 28
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 28
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 26
• 125000006239 protecting group Chemical group 0.000 claims description 25
• 239000003574 free electron Substances 0.000 claims description 24
• 125000005842 heteroatom Chemical group 0.000 claims description 22
• 239000011737 fluorine Substances 0.000 claims description 21
• 125000001544 thienyl group Chemical group 0.000 claims description 20
• 125000003342 alkenyl group Chemical group 0.000 claims description 18
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 18
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 18
• 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 17
• 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 16
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 16
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 15
• 150000001412 amines Chemical class 0.000 claims description 15
• 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 15
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 15
• 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims description 13
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 13
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 13
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 13
• 125000003118 aryl group Chemical group 0.000 claims description 13
• 125000001072 heteroaryl group Chemical group 0.000 claims description 13
• 125000006598 aminocarbonylamino group Chemical group 0.000 claims description 12
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 12
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 12
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 12
• 125000003386 piperidinyl group Chemical group 0.000 claims description 12
• 125000006168 tricyclic group Chemical group 0.000 claims description 12
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 11
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 11
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 11
• 125000006563 (C1-3) alkylaminocarbonyl group Chemical group 0.000 claims description 10
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 10
• 125000001624 naphthyl group Chemical group 0.000 claims description 10
• 125000006592 (C2-C3) alkenyl group Chemical group 0.000 claims description 9
• 125000006593 (C2-C3) alkynyl group Chemical group 0.000 claims description 9
• 125000006529 (C3-C6) alkyl group Chemical group 0.000 claims description 9
• 125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims description 9
• 125000000304 alkynyl group Chemical group 0.000 claims description 9
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 9
• 238000005859 coupling reaction Methods 0.000 claims description 9
• 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims description 8
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 8
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 8
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 8
• 125000002541 furyl group Chemical group 0.000 claims description 8
• 125000002883 imidazolyl group Chemical group 0.000 claims description 8
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 8
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 8
• 229910052717 sulfur Inorganic materials 0.000 claims description 8
• 125000006597 (C1-C3) alkylcarbonylamino group Chemical group 0.000 claims description 7
• 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims description 7
• 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 7
• 125000006576 di-(C1-C3-alkyl)-aminocarbonyl group Chemical group 0.000 claims description 7
• 125000005605 benzo group Chemical group 0.000 claims description 6
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 6
• 239000000126 substance Substances 0.000 claims description 6
• SEEPANYCNGTZFQ-UHFFFAOYSA-N sulfadiazine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=NC=CC=N1 SEEPANYCNGTZFQ-UHFFFAOYSA-N 0.000 claims description 6
• 125000000169 tricyclic heterocycle group Chemical group 0.000 claims description 6
• 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 5
• BNEZSFLIEKRBGF-WJOKGBTCSA-N [(2r)-3-(3,4-diamino-5-methylphenyl)-1-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C)CCN1C1CCN(C(=O)[C@@H](CC=2C=C(N)C(N)=C(C)C=2)OC(=O)N2CCC(CC2)N2C(NC3=CC=CC=C3CC2)=O)CC1 BNEZSFLIEKRBGF-WJOKGBTCSA-N 0.000 claims description 5
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 5
• 239000008194 pharmaceutical composition Substances 0.000 claims description 5
• 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 5
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 4
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 4
• 208000023890 Complex Regional Pain Syndromes Diseases 0.000 claims description 4
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 4
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 4
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 4
• 206010047141 Vasodilatation Diseases 0.000 claims description 4
• AECMEUANQPRNNI-MGBGTMOVSA-N [(2r)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C)CCN1C1CCN(C(=O)[C@@H](CC=2C=C3OCCOC3=CC=2)OC(=O)N2CCC(CC2)N2C(NC3=CC=CC=C3CC2)=O)CC1 AECMEUANQPRNNI-MGBGTMOVSA-N 0.000 claims description 4
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
• 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 4
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 4
• 125000004122 cyclic group Chemical group 0.000 claims description 4
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
• 229910052805 deuterium Inorganic materials 0.000 claims description 4
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 4
• 229940088597 hormone Drugs 0.000 claims description 4
• 239000005556 hormone Substances 0.000 claims description 4
• 208000027866 inflammatory disease Diseases 0.000 claims description 4
• 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 claims description 4
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 4
• BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 claims description 4
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 4
• 125000005400 pyridylcarbonyl group Chemical group N1=C(C=CC=C1)C(=O)* 0.000 claims description 4
• 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 4
• 125000005190 thiohydroxy group Chemical group 0.000 claims description 4
• 238000011282 treatment Methods 0.000 claims description 4
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 4
• 230000024883 vasodilation Effects 0.000 claims description 4
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
• 208000019695 Migraine disease Diseases 0.000 claims description 3
• PKXAXZYEFWEZBA-WJOKGBTCSA-N [(2r)-3-(4-amino-3-methyl-5-nitrophenyl)-1-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C)CCN1C1CCN(C(=O)[C@@H](CC=2C=C(C(N)=C(C)C=2)[N+]([O-])=O)OC(=O)N2CCC(CC2)N2C(NC3=CC=CC=C3CC2)=O)CC1 PKXAXZYEFWEZBA-WJOKGBTCSA-N 0.000 claims description 3
• NZSUJWLKHMZKHF-WJOKGBTCSA-N [(2r)-3-(7-methyl-2-oxo-1,3-dihydrobenzimidazol-5-yl)-1-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C)CCN1C1CCN(C(=O)[C@@H](CC=2C=C3NC(=O)NC3=C(C)C=2)OC(=O)N2CCC(CC2)N2C(NC3=CC=CC=C3CC2)=O)CC1 NZSUJWLKHMZKHF-WJOKGBTCSA-N 0.000 claims description 3
• GGUSJTBWUSYIOG-MGBGTMOVSA-N [(2r)-3-(7-methyl-3h-benzimidazol-5-yl)-1-[4-(1-methylsulfonylpiperidin-4-yl)piperidin-1-yl]-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound O=C([C@H](OC(=O)N1CCC(CC1)N1C(NC2=CC=CC=C2CC1)=O)CC=1C=C(C=2NC=NC=2C=1)C)N(CC1)CCC1C1CCN(S(C)(=O)=O)CC1 GGUSJTBWUSYIOG-MGBGTMOVSA-N 0.000 claims description 3
• 230000001154 acute effect Effects 0.000 claims description 3
• 125000003545 alkoxy group Chemical group 0.000 claims description 3
• 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• 201000010099 disease Diseases 0.000 claims description 3
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
• 239000007858 starting material Substances 0.000 claims description 3
• OFIKHTJARNIHLG-MGBGTMOVSA-N 2-[4-[1-[(2r)-3-(3,4-dimethyl-2-oxo-1,3-benzoxazol-6-yl)-2-[4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carbonyl]oxypropanoyl]piperidin-4-yl]piperidin-1-yl]acetic acid Chemical compound O=C([C@H](OC(=O)N1CCC(CC1)N1C(NC2=CC=CC=C2CC1)=O)CC=1C=C(C=2N(C)C(=O)OC=2C=1)C)N(CC1)CCC1C1CCN(CC(O)=O)CC1 OFIKHTJARNIHLG-MGBGTMOVSA-N 0.000 claims description 2
• PLIASGGSSQMDAP-UUWRZZSWSA-N 2-[4-[1-[(2r)-3-(5-methyl-2,3-dihydro-1,4-benzodioxin-7-yl)-2-[4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carbonyl]oxypropanoyl]piperidin-4-yl]piperidin-1-yl]acetic acid Chemical compound O=C([C@H](OC(=O)N1CCC(CC1)N1C(NC2=CC=CC=C2CC1)=O)CC=1C=C(C=2OCCOC=2C=1)C)N(CC1)CCC1C1CCN(CC(O)=O)CC1 PLIASGGSSQMDAP-UUWRZZSWSA-N 0.000 claims description 2
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
• 241000193403 Clostridium Species 0.000 claims description 2
• 208000006561 Cluster Headache Diseases 0.000 claims description 2
• 206010012735 Diarrhoea Diseases 0.000 claims description 2
• 206010019233 Headaches Diseases 0.000 claims description 2
• 208000019693 Lung disease Diseases 0.000 claims description 2
• 206010027304 Menopausal symptoms Diseases 0.000 claims description 2
• 206010027603 Migraine headaches Diseases 0.000 claims description 2
• 208000007920 Neurogenic Inflammation Diseases 0.000 claims description 2
• 208000002193 Pain Diseases 0.000 claims description 2
• 206010060862 Prostate cancer Diseases 0.000 claims description 2
• 206010039085 Rhinitis allergic Diseases 0.000 claims description 2
• 206010040047 Sepsis Diseases 0.000 claims description 2
• 206010042496 Sunburn Diseases 0.000 claims description 2
• HEZAIZYSLNSWGX-WJOKGBTCSA-N [(2r)-1-[4-(4-amino-4-methylpiperidin-1-yl)piperidin-1-yl]-3-(4-methyl-2-oxo-3h-1,3-benzoxazol-6-yl)-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound O=C([C@H](OC(=O)N1CCC(CC1)N1C(NC2=CC=CC=C2CC1)=O)CC=1C=C(C=2NC(=O)OC=2C=1)C)N(CC1)CCC1N1CCC(C)(N)CC1 HEZAIZYSLNSWGX-WJOKGBTCSA-N 0.000 claims description 2
• LDRSDFZPIRCQQI-MGBGTMOVSA-N [(2r)-1-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]-3-(8-methylquinoxalin-6-yl)-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C)CCN1C1CCN(C(=O)[C@@H](CC=2C=C3N=CC=NC3=C(C)C=2)OC(=O)N2CCC(CC2)N2C(NC3=CC=CC=C3CC2)=O)CC1 LDRSDFZPIRCQQI-MGBGTMOVSA-N 0.000 claims description 2
• WKOQKLIAEFGLCL-PSXMRANNSA-N [(2r)-1-[4-[1-(2-ethoxy-2-oxoethyl)piperidin-4-yl]piperidin-1-yl]-3-(5-methyl-2,3-dihydro-1,4-benzodioxin-7-yl)-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound C1CN(CC(=O)OCC)CCC1C1CCN(C(=O)[C@@H](CC=2C=C3OCCOC3=C(C)C=2)OC(=O)N2CCC(CC2)N2C(NC3=CC=CC=C3CC2)=O)CC1 WKOQKLIAEFGLCL-PSXMRANNSA-N 0.000 claims description 2
• QYSLNQNXIKLQPU-MGBGTMOVSA-N [(2r)-3-(2,7-dimethyl-3h-benzimidazol-5-yl)-1-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C)CCN1C1CCN(C(=O)[C@@H](CC=2C=C3N=C(C)NC3=C(C)C=2)OC(=O)N2CCC(CC2)N2C(NC3=CC=CC=C3CC2)=O)CC1 QYSLNQNXIKLQPU-MGBGTMOVSA-N 0.000 claims description 2
• HXODNDYZHJWCIJ-JGCGQSQUSA-N [(2r)-3-(2-methoxy-7-methyl-3h-benzimidazol-5-yl)-1-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound O=C([C@H](OC(=O)N1CCC(CC1)N1C(NC2=CC=CC=C2CC1)=O)CC=1C=C2N=C(NC2=C(C)C=1)OC)N(CC1)CCC1N1CCN(C)CC1 HXODNDYZHJWCIJ-JGCGQSQUSA-N 0.000 claims description 2
• GBVTXQXCFYJPNA-WJOKGBTCSA-N [(2r)-3-(3,4-dimethyl-2-oxo-1,3-benzoxazol-6-yl)-1-[4-(oxan-4-yl)piperazin-1-yl]-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound O=C([C@H](OC(=O)N1CCC(CC1)N1C(NC2=CC=CC=C2CC1)=O)CC=1C=C(C=2N(C)C(=O)OC=2C=1)C)N(CC1)CCN1C1CCOCC1 GBVTXQXCFYJPNA-WJOKGBTCSA-N 0.000 claims description 2
• XEOQNPBMKJKNHU-JGCGQSQUSA-N [(2r)-3-(3,4-dimethyl-2-oxo-1,3-benzoxazol-6-yl)-1-oxo-1-(4-piperidin-4-ylpiperidin-1-yl)propan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound O=C([C@H](OC(=O)N1CCC(CC1)N1C(NC2=CC=CC=C2CC1)=O)CC=1C=C(C=2N(C)C(=O)OC=2C=1)C)N(CC1)CCC1C1CCNCC1 XEOQNPBMKJKNHU-JGCGQSQUSA-N 0.000 claims description 2
• KDDCSDLRONNEDB-WJOKGBTCSA-N [(2r)-3-(4-methyl-2-oxo-3h-1,3-benzoxazol-6-yl)-1-[4-(1-methylpiperidin-4-yl)piperazin-1-yl]-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C)CCC1N1CCN(C(=O)[C@@H](CC=2C=C3OC(=O)NC3=C(C)C=2)OC(=O)N2CCC(CC2)N2C(NC3=CC=CC=C3CC2)=O)CC1 KDDCSDLRONNEDB-WJOKGBTCSA-N 0.000 claims description 2
• SQLKNITWVQMMMQ-WJOKGBTCSA-N [(2r)-3-(4-methyl-2-oxo-3h-1,3-benzoxazol-6-yl)-1-oxo-1-[4-(1-sulfamoylpiperidin-4-yl)piperidin-1-yl]propan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound O=C([C@H](OC(=O)N1CCC(CC1)N1C(NC2=CC=CC=C2CC1)=O)CC=1C=C(C=2NC(=O)OC=2C=1)C)N(CC1)CCC1C1CCN(S(N)(=O)=O)CC1 SQLKNITWVQMMMQ-WJOKGBTCSA-N 0.000 claims description 2
• BPKFHKHQSITQQA-JGCGQSQUSA-N [(2r)-3-(5-methyl-2,3-dihydro-1,4-benzodioxin-7-yl)-1-oxo-1-(4-piperazin-1-ylpiperidin-1-yl)propan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound O=C([C@H](OC(=O)N1CCC(CC1)N1C(NC2=CC=CC=C2CC1)=O)CC=1C=C(C=2OCCOC=2C=1)C)N(CC1)CCC1N1CCNCC1 BPKFHKHQSITQQA-JGCGQSQUSA-N 0.000 claims description 2
• QKAZDXPWIAOLGD-WJOKGBTCSA-N [(2r)-3-(7-methyl-2h-benzotriazol-5-yl)-1-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C)CCN1C1CCN(C(=O)[C@@H](CC=2C=C3N=NNC3=C(C)C=2)OC(=O)N2CCC(CC2)N2C(NC3=CC=CC=C3CC2)=O)CC1 QKAZDXPWIAOLGD-WJOKGBTCSA-N 0.000 claims description 2
• MIWJGPNAKBXEGY-JGCGQSQUSA-N [(2r)-3-(7-methyl-3h-benzimidazol-5-yl)-1-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C)CCN1C1CCN(C(=O)[C@@H](CC=2C=C3N=CNC3=C(C)C=2)OC(=O)N2CCC(CC2)N2C(NC3=CC=CC=C3CC2)=O)CC1 MIWJGPNAKBXEGY-JGCGQSQUSA-N 0.000 claims description 2
• ANUVRBSEHOOWNH-WJOKGBTCSA-N [(2r)-3-(7-methyl-3h-benzimidazol-5-yl)-1-oxo-1-(4-piperazin-1-ylpiperidin-1-yl)propan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound O=C([C@H](OC(=O)N1CCC(CC1)N1C(NC2=CC=CC=C2CC1)=O)CC=1C=C(C=2NC=NC=2C=1)C)N(CC1)CCC1N1CCNCC1 ANUVRBSEHOOWNH-WJOKGBTCSA-N 0.000 claims description 2
• ULXGBGHGIWBEAI-JGCGQSQUSA-N [(2r)-3-(7-methyl-3h-benzimidazol-5-yl)-1-oxo-1-(4-piperidin-4-ylpiperidin-1-yl)propan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound O=C([C@H](OC(=O)N1CCC(CC1)N1C(NC2=CC=CC=C2CC1)=O)CC=1C=C(C=2NC=NC=2C=1)C)N(CC1)CCC1C1CCNCC1 ULXGBGHGIWBEAI-JGCGQSQUSA-N 0.000 claims description 2
• 201000010105 allergic rhinitis Diseases 0.000 claims description 2
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• 230000017531 blood circulation Effects 0.000 claims description 2
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
• 230000002950 deficient Effects 0.000 claims description 2
• 239000000262 estrogen Substances 0.000 claims description 2
• 231100000869 headache Toxicity 0.000 claims description 2
• 230000002757 inflammatory effect Effects 0.000 claims description 2
• 229960005181 morphine Drugs 0.000 claims description 2
• 210000002200 mouth mucosa Anatomy 0.000 claims description 2
• 230000003449 preventive effect Effects 0.000 claims description 2
• 238000011321 prophylaxis Methods 0.000 claims description 2
• 201000001514 prostate carcinoma Diseases 0.000 claims description 2
• 230000005855 radiation Effects 0.000 claims description 2
• 230000002829 reductive effect Effects 0.000 claims description 2
• 230000035939 shock Effects 0.000 claims description 2
• 230000037380 skin damage Effects 0.000 claims description 2
• 208000017520 skin disease Diseases 0.000 claims description 2
• 208000024891 symptom Diseases 0.000 claims description 2
• 230000001225 therapeutic effect Effects 0.000 claims description 2
• 239000003053 toxin Substances 0.000 claims description 2
• 231100000765 toxin Toxicity 0.000 claims description 2
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
• LISFMEBWQUVKPJ-FOQJRBATSA-N 1H-quinolin-2-one Chemical group C1=CC=C2N[14C](=O)C=CC2=C1 LISFMEBWQUVKPJ-FOQJRBATSA-N 0.000 claims 3
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 2
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 2
• 239000000969 carrier Substances 0.000 claims 2
• ZWPGCDDQUIVDLH-SZFCLFMZSA-N [(2r)-1-[4-(1-azabicyclo[2.2.2]octan-3-yl)piperazin-1-yl]-3-(5-methyl-2,3-dihydro-1,4-benzodioxin-7-yl)-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound C1CC2=CC=CC=C2NC(=O)N1C(CC1)CCN1C(=O)O[C@@H](C(=O)N1CCN(CC1)C1C2CCN(CC2)C1)CC(C=C1C)=CC2=C1OCCO2 ZWPGCDDQUIVDLH-SZFCLFMZSA-N 0.000 claims 1
• MHHYQPHJVAOICI-JGCGQSQUSA-N [(2r)-1-[4-(4-amino-4-methylpiperidin-1-yl)piperidin-1-yl]-3-(3,4-dimethyl-2-oxo-1,3-benzoxazol-6-yl)-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound O=C([C@H](OC(=O)N1CCC(CC1)N1C(NC2=CC=CC=C2CC1)=O)CC=1C=C(C=2N(C)C(=O)OC=2C=1)C)N(CC1)CCC1N1CCC(C)(N)CC1 MHHYQPHJVAOICI-JGCGQSQUSA-N 0.000 claims 1
• OJBLBNPRVQSBIB-MGBGTMOVSA-N [(2r)-1-[4-(4-amino-4-methylpiperidin-1-yl)piperidin-1-yl]-3-(5-methyl-2,3-dihydro-1,4-benzodioxin-7-yl)-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound O=C([C@H](OC(=O)N1CCC(CC1)N1C(NC2=CC=CC=C2CC1)=O)CC=1C=C(C=2OCCOC=2C=1)C)N(CC1)CCC1N1CCC(C)(N)CC1 OJBLBNPRVQSBIB-MGBGTMOVSA-N 0.000 claims 1
• BZJYZJQBPXKFQD-MGBGTMOVSA-N [(2r)-1-[4-(4-hydroxypiperidin-1-yl)piperidin-1-yl]-3-(5-methyl-2,3-dihydro-1,4-benzodioxin-7-yl)-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound O=C([C@H](OC(=O)N1CCC(CC1)N1C(NC2=CC=CC=C2CC1)=O)CC=1C=C(C=2OCCOC=2C=1)C)N(CC1)CCC1N1CCC(O)CC1 BZJYZJQBPXKFQD-MGBGTMOVSA-N 0.000 claims 1
• JQGXYFNKCZBLSR-WJOKGBTCSA-N [(2r)-1-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]-3-[7-methyl-2-(trifluoromethyl)-3h-benzimidazol-5-yl]-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C)CCN1C1CCN(C(=O)[C@@H](CC=2C=C3N=C(NC3=C(C)C=2)C(F)(F)F)OC(=O)N2CCC(CC2)N2C(NC3=CC=CC=C3CC2)=O)CC1 JQGXYFNKCZBLSR-WJOKGBTCSA-N 0.000 claims 1
• ZCMLNRQTTQELTB-UUWRZZSWSA-N [(2r)-3-(2-cyclopropyl-7-methyl-3h-benzimidazol-5-yl)-1-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C)CCN1C1CCN(C(=O)[C@@H](CC=2C=C3N=C(NC3=C(C)C=2)C2CC2)OC(=O)N2CCC(CC2)N2C(NC3=CC=CC=C3CC2)=O)CC1 ZCMLNRQTTQELTB-UUWRZZSWSA-N 0.000 claims 1
• UZRJJOBLCALBCS-JGCGQSQUSA-N [(2r)-3-(3,4-dimethyl-2-oxo-1,3-benzoxazol-6-yl)-1-[4-(1-methylpiperidin-4-yl)piperazin-1-yl]-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C)CCC1N1CCN(C(=O)[C@@H](CC=2C=C3OC(=O)N(C)C3=C(C)C=2)OC(=O)N2CCC(CC2)N2C(NC3=CC=CC=C3CC2)=O)CC1 UZRJJOBLCALBCS-JGCGQSQUSA-N 0.000 claims 1
• GXGZOGIJVKRDGA-MGBGTMOVSA-N [(2r)-3-(3,4-dimethyl-2-oxo-1,3-benzoxazol-6-yl)-1-[4-(1-methylpiperidin-4-yl)piperidin-1-yl]-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C)CCC1C1CCN(C(=O)[C@@H](CC=2C=C3OC(=O)N(C)C3=C(C)C=2)OC(=O)N2CCC(CC2)N2C(NC3=CC=CC=C3CC2)=O)CC1 GXGZOGIJVKRDGA-MGBGTMOVSA-N 0.000 claims 1
• LPQYXAYUHLPXCW-MGBGTMOVSA-N [(2r)-3-(3,4-dimethyl-2-oxo-1,3-benzoxazol-6-yl)-1-[4-(1-methylsulfonylpiperidin-4-yl)piperidin-1-yl]-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound O=C([C@H](OC(=O)N1CCC(CC1)N1C(NC2=CC=CC=C2CC1)=O)CC=1C=C(C=2N(C)C(=O)OC=2C=1)C)N(CC1)CCC1C1CCN(S(C)(=O)=O)CC1 LPQYXAYUHLPXCW-MGBGTMOVSA-N 0.000 claims 1
• ULXLWKYAHFOPOR-JGCGQSQUSA-N [(2r)-3-(3,4-dimethyl-2-oxo-1,3-benzoxazol-6-yl)-1-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C)CCN1C1CCN(C(=O)[C@@H](CC=2C=C3OC(=O)N(C)C3=C(C)C=2)OC(=O)N2CCC(CC2)N2C(NC3=CC=CC=C3CC2)=O)CC1 ULXLWKYAHFOPOR-JGCGQSQUSA-N 0.000 claims 1
• XKONAUSRNZWWGX-JGCGQSQUSA-N [(2r)-3-(3,4-dimethyl-2-oxo-1,3-benzoxazol-6-yl)-1-oxo-1-[4-(1-sulfamoylpiperidin-4-yl)piperidin-1-yl]propan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound O=C([C@H](OC(=O)N1CCC(CC1)N1C(NC2=CC=CC=C2CC1)=O)CC=1C=C(C=2N(C)C(=O)OC=2C=1)C)N(CC1)CCC1C1CCN(S(N)(=O)=O)CC1 XKONAUSRNZWWGX-JGCGQSQUSA-N 0.000 claims 1
• QIPFGYIUIJIKDX-JGCGQSQUSA-N [(2r)-3-(4-methyl-2-oxo-3h-1,3-benzoxazol-6-yl)-1-[4-(1-methylsulfonylpiperidin-4-yl)piperidin-1-yl]-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound O=C([C@H](OC(=O)N1CCC(CC1)N1C(NC2=CC=CC=C2CC1)=O)CC=1C=C(C=2NC(=O)OC=2C=1)C)N(CC1)CCC1C1CCN(S(C)(=O)=O)CC1 QIPFGYIUIJIKDX-JGCGQSQUSA-N 0.000 claims 1
• PDLXZGJORSIUOT-WJOKGBTCSA-N [(2r)-3-(4-methyl-2-oxo-3h-1,3-benzoxazol-6-yl)-1-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C)CCN1C1CCN(C(=O)[C@@H](CC=2C=C3OC(=O)NC3=C(C)C=2)OC(=O)N2CCC(CC2)N2C(NC3=CC=CC=C3CC2)=O)CC1 PDLXZGJORSIUOT-WJOKGBTCSA-N 0.000 claims 1
• USLJFIXVLLOXKH-JGCGQSQUSA-N [(2r)-3-(5-methyl-2,3-dihydro-1,4-benzodioxin-7-yl)-1-(4-morpholin-4-ylpiperidin-1-yl)-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound O=C([C@H](OC(=O)N1CCC(CC1)N1C(NC2=CC=CC=C2CC1)=O)CC=1C=C(C=2OCCOC=2C=1)C)N(CC1)CCC1N1CCOCC1 USLJFIXVLLOXKH-JGCGQSQUSA-N 0.000 claims 1
• RUUASPAQWQSUMZ-UUWRZZSWSA-N [(2r)-3-(5-methyl-2,3-dihydro-1,4-benzodioxin-7-yl)-1-[4-(1-methylpiperidin-4-yl)piperidin-1-yl]-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C)CCC1C1CCN(C(=O)[C@@H](CC=2C=C3OCCOC3=C(C)C=2)OC(=O)N2CCC(CC2)N2C(NC3=CC=CC=C3CC2)=O)CC1 RUUASPAQWQSUMZ-UUWRZZSWSA-N 0.000 claims 1
• KYLIZPLUROFFHR-UUWRZZSWSA-N [(2r)-3-(5-methyl-2,3-dihydro-1,4-benzodioxin-7-yl)-1-[4-(1-methylsulfonylpiperidin-4-yl)piperidin-1-yl]-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound O=C([C@H](OC(=O)N1CCC(CC1)N1C(NC2=CC=CC=C2CC1)=O)CC=1C=C(C=2OCCOC=2C=1)C)N(CC1)CCC1C1CCN(S(C)(=O)=O)CC1 KYLIZPLUROFFHR-UUWRZZSWSA-N 0.000 claims 1
• VUDLAFDTWMCMJW-MGBGTMOVSA-N [(2r)-3-(5-methyl-2,3-dihydro-1,4-benzodioxin-7-yl)-1-oxo-1-(4-piperidin-1-ylpiperidin-1-yl)propan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound O=C([C@H](OC(=O)N1CCC(CC1)N1C(NC2=CC=CC=C2CC1)=O)CC=1C=C(C=2OCCOC=2C=1)C)N(CC1)CCC1N1CCCCC1 VUDLAFDTWMCMJW-MGBGTMOVSA-N 0.000 claims 1
• JSSFGZCDONDKEU-JGCGQSQUSA-N [(2r)-3-(5-methyl-2,3-dihydro-1,4-benzodioxin-7-yl)-1-oxo-1-(4-piperidin-4-ylpiperazin-1-yl)propan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound O=C([C@H](OC(=O)N1CCC(CC1)N1C(NC2=CC=CC=C2CC1)=O)CC=1C=C(C=2OCCOC=2C=1)C)N(CC1)CCN1C1CCNCC1 JSSFGZCDONDKEU-JGCGQSQUSA-N 0.000 claims 1
• GJWQZKYGOGOXJQ-JGCGQSQUSA-N [(2r)-3-(5-methyl-2,3-dihydro-1,4-benzodioxin-7-yl)-1-oxo-1-[4-(5-oxo-1,4-diazepan-1-yl)piperidin-1-yl]propan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound O=C([C@H](OC(=O)N1CCC(CC1)N1C(NC2=CC=CC=C2CC1)=O)CC=1C=C(C=2OCCOC=2C=1)C)N(CC1)CCC1N1CCNC(=O)CC1 GJWQZKYGOGOXJQ-JGCGQSQUSA-N 0.000 claims 1
• CYEMPCYRHCJVIR-JGCGQSQUSA-N [(2r)-3-(8-methylimidazo[1,2-a]pyridin-6-yl)-1-[4-(1-methylpiperidin-4-yl)piperazin-1-yl]-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C)CCC1N1CCN(C(=O)[C@@H](CC2=CN3C=CN=C3C(C)=C2)OC(=O)N2CCC(CC2)N2C(NC3=CC=CC=C3CC2)=O)CC1 CYEMPCYRHCJVIR-JGCGQSQUSA-N 0.000 claims 1
• ODWZLHZWZHVIAK-MGBGTMOVSA-N [(2r)-3-(8-methylimidazo[1,2-a]pyridin-6-yl)-1-[4-(1-methylpiperidin-4-yl)piperidin-1-yl]-1-oxopropan-2-yl] 4-(2-oxo-4,5-dihydro-1h-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C)CCC1C1CCN(C(=O)[C@@H](CC2=CN3C=CN=C3C(C)=C2)OC(=O)N2CCC(CC2)N2C(NC3=CC=CC=C3CC2)=O)CC1 ODWZLHZWZHVIAK-MGBGTMOVSA-N 0.000 claims 1
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• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 96
• DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 89
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 87
• 238000004128 high performance liquid chromatography Methods 0.000 description 75
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 74
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