CA2711614A1 - Pyrrolopyridines as kinase inhibitors - Google Patents

Info

Publication number

CA2711614A1

CA2711614A1 CA2711614A CA2711614A CA2711614A1 CA 2711614 A1 CA2711614 A1 CA 2711614A1 CA 2711614 A CA2711614 A CA 2711614A CA 2711614 A CA2711614 A CA 2711614A CA 2711614 A1 CA2711614 A1 CA 2711614A1

Authority

CA

Canada

Prior art keywords

compound

mmol

pyrrolo

reaction

phenyl

Prior art date

2008-01-08

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

• 150000005255 pyrrolopyridines Chemical class 0.000 title description 3
• 229940043355 kinase inhibitor Drugs 0.000 title description 2
• 239000003757 phosphotransferase inhibitor Substances 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 204
• 238000000034 method Methods 0.000 claims abstract description 81
• 150000003839 salts Chemical class 0.000 claims abstract description 71
• 238000011282 treatment Methods 0.000 claims abstract description 50
• 101000777277 Homo sapiens Serine/threonine-protein kinase Chk2 Proteins 0.000 claims abstract description 20
• 102100031075 Serine/threonine-protein kinase Chk2 Human genes 0.000 claims abstract description 20
• 101000777293 Homo sapiens Serine/threonine-protein kinase Chk1 Proteins 0.000 claims abstract description 19
• 102100031081 Serine/threonine-protein kinase Chk1 Human genes 0.000 claims abstract description 19
• -1 1-oxa-3,4-diazolyl Chemical group 0.000 claims description 84
• 229910052736 halogen Inorganic materials 0.000 claims description 84
• 150000002367 halogens Chemical group 0.000 claims description 84
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 73
• 239000001257 hydrogen Substances 0.000 claims description 69
• 229910052739 hydrogen Inorganic materials 0.000 claims description 69
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 53
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 39
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 39
• 201000010099 disease Diseases 0.000 claims description 38
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 35
• 125000000623 heterocyclic group Chemical group 0.000 claims description 33
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 31
• 241000124008 Mammalia Species 0.000 claims description 29
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 29
• 206010028980 Neoplasm Diseases 0.000 claims description 28
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 28
• 230000003463 hyperproliferative effect Effects 0.000 claims description 26
• 239000003112 inhibitor Substances 0.000 claims description 22
• 238000005859 coupling reaction Methods 0.000 claims description 21
• 229910052757 nitrogen Inorganic materials 0.000 claims description 21
• 201000011510 cancer Diseases 0.000 claims description 20
• 238000010168 coupling process Methods 0.000 claims description 19
• 125000001072 heteroaryl group Chemical group 0.000 claims description 19
• 230000008878 coupling Effects 0.000 claims description 18
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
• 238000010511 deprotection reaction Methods 0.000 claims description 15
• 208000035475 disorder Diseases 0.000 claims description 15
• 239000003814 drug Substances 0.000 claims description 14
• 239000008194 pharmaceutical composition Substances 0.000 claims description 14
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 13
• 239000003153 chemical reaction reagent Substances 0.000 claims description 13
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 12
• 238000004519 manufacturing process Methods 0.000 claims description 11
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 11
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 10
• 125000004429 atom Chemical group 0.000 claims description 8
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 7
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
• 230000010933 acylation Effects 0.000 claims description 6
• 238000005917 acylation reaction Methods 0.000 claims description 6
• 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 6
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
• 125000004076 pyridyl group Chemical group 0.000 claims description 6
• 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 5
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 4
• 238000011275 oncology therapy Methods 0.000 claims description 4
• 238000002560 therapeutic procedure Methods 0.000 claims description 4
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
• ZVXKYWHJBYIYNI-UHFFFAOYSA-N 1h-pyrazole-4-carboxamide Chemical compound NC(=O)C=1C=NNC=1 ZVXKYWHJBYIYNI-UHFFFAOYSA-N 0.000 claims description 3
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 3
• 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 3
• 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 3
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 3
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 3
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
• 230000001093 anti-cancer Effects 0.000 claims description 3
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
• CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 3
• 125000001544 thienyl group Chemical group 0.000 claims description 3
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
• LNNDTIIAQNGGPA-UHFFFAOYSA-N 5-chloropyridine-3-carboxamide Chemical compound NC(=O)C1=CN=CC(Cl)=C1 LNNDTIIAQNGGPA-UHFFFAOYSA-N 0.000 claims description 2
• BCCUXBGEPLKSEX-UHFFFAOYSA-N 5-methylpyridine-3-carboxamide Chemical compound CC1=CN=CC(C(N)=O)=C1 BCCUXBGEPLKSEX-UHFFFAOYSA-N 0.000 claims description 2
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
• 230000005764 inhibitory process Effects 0.000 abstract description 4
• 238000011065 in-situ storage Methods 0.000 abstract description 2
• 230000002265 prevention Effects 0.000 abstract description 2
• 238000003745 diagnosis Methods 0.000 abstract 1
• 238000000338 in vitro Methods 0.000 abstract 1
• 238000001727 in vivo Methods 0.000 abstract 1
• 210000004962 mammalian cell Anatomy 0.000 abstract 1
• 230000001575 pathological effect Effects 0.000 abstract 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 579
• 238000006243 chemical reaction Methods 0.000 description 327
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 216
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 182
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 148
• 239000000243 solution Substances 0.000 description 145
• 229910001868 water Inorganic materials 0.000 description 115
• 239000007787 solid Substances 0.000 description 86
• 239000000203 mixture Substances 0.000 description 81
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 81
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 77
• 125000000217 alkyl group Chemical group 0.000 description 75
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 71
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 63
• 238000003756 stirring Methods 0.000 description 63
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 62
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 58
• 235000019439 ethyl acetate Nutrition 0.000 description 55
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 52
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 47
• 238000004440 column chromatography Methods 0.000 description 43
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 42
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
• 239000012043 crude product Substances 0.000 description 32
• 239000003921 oil Substances 0.000 description 32
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 31
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 29
• 238000004587 chromatography analysis Methods 0.000 description 29
• 125000004043 oxo group Chemical group O=* 0.000 description 29
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 28
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 28
• 238000005160 1H NMR spectroscopy Methods 0.000 description 27
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 25
• 229910052740 iodine Inorganic materials 0.000 description 24
• 238000000746 purification Methods 0.000 description 24
• GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 22
• 239000000047 product Substances 0.000 description 21
• 239000012265 solid product Substances 0.000 description 21
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
• 239000002253 acid Substances 0.000 description 20
• 125000003118 aryl group Chemical group 0.000 description 20
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 19
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 19
• 210000004027 cell Anatomy 0.000 description 18
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 18
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 17
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
• 239000010410 layer Substances 0.000 description 16
• 229920006395 saturated elastomer Polymers 0.000 description 16
• 229910052938 sodium sulfate Inorganic materials 0.000 description 16
• 235000011152 sodium sulphate Nutrition 0.000 description 16
• GQWRBNJRKSPGTF-CQSZACIVSA-N (2s)-2-(4-chlorophenyl)-3-[(2-methylpropan-2-yl)oxycarbonyl-propan-2-ylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N(C(C)C)C[C@@H](C(O)=O)C1=CC=C(Cl)C=C1 GQWRBNJRKSPGTF-CQSZACIVSA-N 0.000 description 15
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
• 150000001413 amino acids Chemical class 0.000 description 15
• 150000002431 hydrogen Chemical group 0.000 description 15
• 238000000926 separation method Methods 0.000 description 15
• 239000012267 brine Substances 0.000 description 14
• 150000002148 esters Chemical class 0.000 description 14
• 235000019341 magnesium sulphate Nutrition 0.000 description 14
• 229910000029 sodium carbonate Inorganic materials 0.000 description 14
• 235000017550 sodium carbonate Nutrition 0.000 description 14
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
• 239000002904 solvent Substances 0.000 description 14
• 230000015572 biosynthetic process Effects 0.000 description 13
• 238000001914 filtration Methods 0.000 description 13
• 239000011541 reaction mixture Substances 0.000 description 13
• 238000003786 synthesis reaction Methods 0.000 description 13
• 239000012044 organic layer Substances 0.000 description 12
• 239000000543 intermediate Substances 0.000 description 11
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
• 229910000027 potassium carbonate Inorganic materials 0.000 description 11
• 125000006239 protecting group Chemical group 0.000 description 11
• DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 10
• 150000001412 amines Chemical class 0.000 description 10
• 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 description 9
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
• 239000007832 Na2SO4 Substances 0.000 description 9
• NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 9
• 125000000753 cycloalkyl group Chemical group 0.000 description 9
• 238000010992 reflux Methods 0.000 description 9
• 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 8
• 101150041968 CDC13 gene Proteins 0.000 description 8
• 206010025323 Lymphomas Diseases 0.000 description 8
• 206010039491 Sarcoma Diseases 0.000 description 8
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
• 208000009956 adenocarcinoma Diseases 0.000 description 8
• 238000009434 installation Methods 0.000 description 8
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 8
• 235000015320 potassium carbonate Nutrition 0.000 description 8
• 238000006722 reduction reaction Methods 0.000 description 8
• 206010041823 squamous cell carcinoma Diseases 0.000 description 8
• BETBOAZCLSJOBQ-LLVKDONJSA-N (2r)-3-(4-chlorophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](C(O)=O)CC1=CC=C(Cl)C=C1 BETBOAZCLSJOBQ-LLVKDONJSA-N 0.000 description 7
• 201000009030 Carcinoma Diseases 0.000 description 7
• 108091000080 Phosphotransferase Proteins 0.000 description 7
• HCBIBCJNVBAKAB-UHFFFAOYSA-N Procaine hydrochloride Chemical compound Cl.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 HCBIBCJNVBAKAB-UHFFFAOYSA-N 0.000 description 7
• 230000002159 abnormal effect Effects 0.000 description 7
• 150000001336 alkenes Chemical class 0.000 description 7
• 125000006242 amine protecting group Chemical group 0.000 description 7
• 239000003795 chemical substances by application Substances 0.000 description 7
• 239000010779 crude oil Substances 0.000 description 7
• 239000000706 filtrate Substances 0.000 description 7
• 230000007062 hydrolysis Effects 0.000 description 7
• 238000006460 hydrolysis reaction Methods 0.000 description 7
• 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 7
• JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 7
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• 150000003141 primary amines Chemical class 0.000 description 7
• 230000009467 reduction Effects 0.000 description 7
• 125000001424 substituent group Chemical group 0.000 description 7
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
• 238000004809 thin layer chromatography Methods 0.000 description 7
• MBYQIHCBCCZXDZ-UHFFFAOYSA-N 3-methyl-5-phenyl-4-piperazin-1-yl-1h-pyrrolo[2,3-b]pyridine Chemical compound C1CNCCN1C1=C2C(C)=CNC2=NC=C1C1=CC=CC=C1 MBYQIHCBCCZXDZ-UHFFFAOYSA-N 0.000 description 6
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• UBBFOEJAGGJZDA-UHFFFAOYSA-N 5-phenyl-4-piperazin-1-yl-1h-pyrrolo[2,3-b]pyridine;dihydrochloride Chemical compound Cl.Cl.C1CNCCN1C1=C(C=2C=CC=CC=2)C=NC2=C1C=CN2 UBBFOEJAGGJZDA-UHFFFAOYSA-N 0.000 description 6
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
• 239000002841 Lewis acid Substances 0.000 description 6
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 6
• 238000005984 hydrogenation reaction Methods 0.000 description 6
• 150000007517 lewis acids Chemical class 0.000 description 6
• 230000002829 reductive effect Effects 0.000 description 6
• 238000006467 substitution reaction Methods 0.000 description 6
• XDIQYLQINKZOHN-JOCHJYFZSA-N tert-butyl n-[(2s)-3-[4-(5-bromo-1h-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl]-2-(4-chlorophenyl)-3-oxopropyl]-n-propan-2-ylcarbamate Chemical compound C1([C@H](C(=O)N2CCN(CC2)C=2C=3C=CNC=3N=CC=2Br)CN(C(C)C)C(=O)OC(C)(C)C)=CC=C(Cl)C=C1 XDIQYLQINKZOHN-JOCHJYFZSA-N 0.000 description 6
• HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 6
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
• JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 5
• 125000003342 alkenyl group Chemical group 0.000 description 5
• 230000029936 alkylation Effects 0.000 description 5
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• 230000002401 inhibitory effect Effects 0.000 description 5
• WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 5
• MMGDUOFJZARVSP-UHFFFAOYSA-N n-(4-piperazin-1-yl-1h-pyrrolo[2,3-b]pyridin-3-yl)pyridine-3-carboxamide Chemical compound C=1C=CN=CC=1C(=O)NC(C=12)=CNC2=NC=CC=1N1CCNCC1 MMGDUOFJZARVSP-UHFFFAOYSA-N 0.000 description 5
• 235000005152 nicotinamide Nutrition 0.000 description 5
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• VWQMQFQSTACSGE-UHFFFAOYSA-N tert-butyl 4-[1-(benzenesulfonyl)-5-(3-fluorophenyl)pyrrolo[2,3-b]pyridin-4-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=C(C=2C=C(F)C=CC=2)C=NC2=C1C=CN2S(=O)(=O)C1=CC=CC=C1 VWQMQFQSTACSGE-UHFFFAOYSA-N 0.000 description 2
• VGROWXNMSBOHBT-UHFFFAOYSA-N tert-butyl 4-[1-(benzenesulfonyl)-5-(3-methoxyphenyl)pyrrolo[2,3-b]pyridin-4-yl]piperazine-1-carboxylate Chemical compound COC1=CC=CC(C=2C(=C3C=CN(C3=NC=2)S(=O)(=O)C=2C=CC=CC=2)N2CCN(CC2)C(=O)OC(C)(C)C)=C1 VGROWXNMSBOHBT-UHFFFAOYSA-N 0.000 description 2
• SDIZPSMYPTZRPI-UHFFFAOYSA-N tert-butyl 4-[1-(benzenesulfonyl)-5-phenylpyrrolo[2,3-b]pyridin-4-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=C(C=2C=CC=CC=2)C=NC2=C1C=CN2S(=O)(=O)C1=CC=CC=C1 SDIZPSMYPTZRPI-UHFFFAOYSA-N 0.000 description 2
• HNVXAZOETBPUQU-UHFFFAOYSA-N tert-butyl 4-[5-(2-fluorophenyl)-1h-pyrrolo[2,3-b]pyridin-4-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=C(C=2C(=CC=CC=2)F)C=NC2=C1C=CN2 HNVXAZOETBPUQU-UHFFFAOYSA-N 0.000 description 2
• FLDMLBQNZCOCAV-UHFFFAOYSA-N tert-butyl 4-[5-(3-fluorophenyl)-1h-pyrrolo[2,3-b]pyridin-4-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=C(C=2C=C(F)C=CC=2)C=NC2=C1C=CN2 FLDMLBQNZCOCAV-UHFFFAOYSA-N 0.000 description 2
• BDSDVXNAIIDSDB-UHFFFAOYSA-N tert-butyl 4-[5-(3-methoxyphenyl)-1h-pyrrolo[2,3-b]pyridin-4-yl]piperazine-1-carboxylate Chemical compound COC1=CC=CC(C=2C(=C3C=CNC3=NC=2)N2CCN(CC2)C(=O)OC(C)(C)C)=C1 BDSDVXNAIIDSDB-UHFFFAOYSA-N 0.000 description 2
• HZPXCPFTBDKJDG-UHFFFAOYSA-N tert-butyl 4-[5-(4-fluorophenyl)-1h-pyrrolo[2,3-b]pyridin-4-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=C(C=2C=CC(F)=CC=2)C=NC2=C1C=CN2 HZPXCPFTBDKJDG-UHFFFAOYSA-N 0.000 description 2
• PZQORKDZZKPENZ-UHFFFAOYSA-N tert-butyl 4-[5-(acetamidocarbamoyl)-1h-pyrrolo[2,3-b]pyridin-4-yl]piperazine-1-carboxylate Chemical compound CC(=O)NNC(=O)C1=CN=C2NC=CC2=C1N1CCN(C(=O)OC(C)(C)C)CC1 PZQORKDZZKPENZ-UHFFFAOYSA-N 0.000 description 2
• RVPSSWAOLWMIRO-GDLZYMKVSA-N tert-butyl N-[(2S)-2-(4-chlorophenyl)-3-[4-(3-methyl-5-phenyl-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl]-3-oxopropyl]-N-propan-2-ylcarbamate Chemical compound O=C([C@H](CN(C(C)C)C(=O)OC(C)(C)C)C=1C=CC(Cl)=CC=1)N(CC1)CCN1C(C=1C(C)=CNC=1N=C1)=C1C1=CC=CC=C1 RVPSSWAOLWMIRO-GDLZYMKVSA-N 0.000 description 2
• ATHGXEXHYXXBKB-LJQANCHMSA-N tert-butyl n-[(1r)-2-[4-(5-bromo-1h-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl]-1-cyclohexyl-2-oxoethyl]carbamate Chemical compound C1([C@@H](NC(=O)OC(C)(C)C)C(=O)N2CCN(CC2)C=2C=3C=CNC=3N=CC=2Br)CCCCC1 ATHGXEXHYXXBKB-LJQANCHMSA-N 0.000 description 2
• QDXAFSGDOIENRB-HXUWFJFHSA-N tert-butyl n-[(2r)-1-[4-(5-bromo-1h-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl]-3-(4-chlorophenyl)-1-oxopropan-2-yl]carbamate Chemical compound C([C@@H](NC(=O)OC(C)(C)C)C(=O)N1CCN(CC1)C=1C=2C=CNC=2N=CC=1Br)C1=CC=C(Cl)C=C1 QDXAFSGDOIENRB-HXUWFJFHSA-N 0.000 description 2
• MISDTTTWTYNDFM-HXUWFJFHSA-N tert-butyl n-[(2r)-1-[4-(5-carbamoyl-1h-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl]-3-(4-chlorophenyl)-1-oxopropan-2-yl]carbamate Chemical compound C([C@@H](NC(=O)OC(C)(C)C)C(=O)N1CCN(CC1)C=1C=2C=CNC=2N=CC=1C(N)=O)C1=CC=C(Cl)C=C1 MISDTTTWTYNDFM-HXUWFJFHSA-N 0.000 description 2
• PHKAEFFHMNGDGP-AREMUKBSSA-N tert-butyl n-[(2r)-3-(4-chlorophenyl)-1-[4-(3-methyl-5-phenyl-1h-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl]-1-oxopropan-2-yl]carbamate Chemical compound C1CN(C(=O)[C@@H](CC=2C=CC(Cl)=CC=2)NC(=O)OC(C)(C)C)CCN1C1=C2C(C)=CNC2=NC=C1C1=CC=CC=C1 PHKAEFFHMNGDGP-AREMUKBSSA-N 0.000 description 2
• CIXYYIWDZOUHAG-LJQANCHMSA-N tert-butyl n-[(2r)-3-(4-chlorophenyl)-1-[4-[3-[(2-hydroxyacetyl)amino]-1h-pyrrolo[2,3-b]pyridin-4-yl]piperazin-1-yl]-1-oxopropan-2-yl]carbamate Chemical compound C([C@@H](NC(=O)OC(C)(C)C)C(=O)N1CCN(CC1)C=1C=2C(NC(=O)CO)=CNC=2N=CC=1)C1=CC=C(Cl)C=C1 CIXYYIWDZOUHAG-LJQANCHMSA-N 0.000 description 2
• GPOJIQLAIYAZMS-AREMUKBSSA-N tert-butyl n-[(2r)-3-(4-chlorophenyl)-1-[4-[5-(3-fluorophenyl)-1h-pyrrolo[2,3-b]pyridin-4-yl]piperazin-1-yl]-1-oxopropan-2-yl]carbamate Chemical compound C([C@@H](NC(=O)OC(C)(C)C)C(=O)N1CCN(CC1)C=1C=2C=CNC=2N=CC=1C=1C=C(F)C=CC=1)C1=CC=C(Cl)C=C1 GPOJIQLAIYAZMS-AREMUKBSSA-N 0.000 description 2
• OCOKTHBJQGXPLE-HHHXNRCGSA-N tert-butyl n-[(2r)-3-(4-chlorophenyl)-1-[4-[5-(3-methoxyphenyl)-1h-pyrrolo[2,3-b]pyridin-4-yl]piperazin-1-yl]-1-oxopropan-2-yl]carbamate Chemical compound COC1=CC=CC(C=2C(=C3C=CNC3=NC=2)N2CCN(CC2)C(=O)[C@@H](CC=2C=CC(Cl)=CC=2)NC(=O)OC(C)(C)C)=C1 OCOKTHBJQGXPLE-HHHXNRCGSA-N 0.000 description 2
• PVIDBXQMEKGNGE-AREMUKBSSA-N tert-butyl n-[(2r)-3-(4-chlorophenyl)-1-oxo-1-[4-(5-phenyl-1h-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl]propan-2-yl]carbamate Chemical compound C([C@@H](NC(=O)OC(C)(C)C)C(=O)N1CCN(CC1)C=1C=2C=CNC=2N=CC=1C=1C=CC=CC=1)C1=CC=C(Cl)C=C1 PVIDBXQMEKGNGE-AREMUKBSSA-N 0.000 description 2
• UWFXXUYNXQZVEQ-JOCHJYFZSA-N tert-butyl n-[(2r)-3-methyl-1-oxo-1-[4-[3-(pyridine-3-carbonylamino)-1h-pyrrolo[2,3-b]pyridin-4-yl]piperazin-1-yl]butan-2-yl]carbamate Chemical compound C1CN(C(=O)[C@H](NC(=O)OC(C)(C)C)C(C)C)CCN1C1=CC=NC2=C1C(NC(=O)C=1C=NC=CC=1)=CN2 UWFXXUYNXQZVEQ-JOCHJYFZSA-N 0.000 description 2
• AJCKLGAKWMUEOZ-HHHXNRCGSA-N tert-butyl n-[(2s)-2-(4-chlorophenyl)-3-[4-[5-(1-methylpyrazol-4-yl)-1h-pyrrolo[2,3-b]pyridin-4-yl]piperazin-1-yl]-3-oxopropyl]-n-propan-2-ylcarbamate Chemical compound O=C([C@H](CN(C(C)C)C(=O)OC(C)(C)C)C=1C=CC(Cl)=CC=1)N(CC1)CCN1C(C=1C=CNC=1N=C1)=C1C=1C=NN(C)C=1 AJCKLGAKWMUEOZ-HHHXNRCGSA-N 0.000 description 2
• OHEDKSGSSWFMOU-GDLZYMKVSA-N tert-butyl n-[(2s)-2-(4-chlorophenyl)-3-[4-[5-(3,4-dimethoxyphenyl)-1h-pyrrolo[2,3-b]pyridin-4-yl]piperazin-1-yl]-3-oxopropyl]-n-propan-2-ylcarbamate Chemical compound C1=C(OC)C(OC)=CC=C1C1=CN=C(NC=C2)C2=C1N1CCN(C(=O)[C@H](CN(C(C)C)C(=O)OC(C)(C)C)C=2C=CC(Cl)=CC=2)CC1 OHEDKSGSSWFMOU-GDLZYMKVSA-N 0.000 description 2
• FVIXOAIFSVIEOO-GDLZYMKVSA-N tert-butyl n-[(2s)-2-(4-chlorophenyl)-3-[4-[5-(3-fluorophenyl)-1h-pyrrolo[2,3-b]pyridin-4-yl]piperazin-1-yl]-3-oxopropyl]-n-propan-2-ylcarbamate Chemical compound O=C([C@H](CN(C(C)C)C(=O)OC(C)(C)C)C=1C=CC(Cl)=CC=1)N(CC1)CCN1C(C=1C=CNC=1N=C1)=C1C1=CC=CC(F)=C1 FVIXOAIFSVIEOO-GDLZYMKVSA-N 0.000 description 2
• PSGDQZXBJLYBDO-SSEXGKCCSA-N tert-butyl n-[(2s)-2-(4-chlorophenyl)-3-[4-[5-(3-methoxyphenyl)-1h-pyrrolo[2,3-b]pyridin-4-yl]piperazin-1-yl]-3-oxopropyl]-n-propan-2-ylcarbamate Chemical compound COC1=CC=CC(C=2C(=C3C=CNC3=NC=2)N2CCN(CC2)C(=O)[C@H](CN(C(C)C)C(=O)OC(C)(C)C)C=2C=CC(Cl)=CC=2)=C1 PSGDQZXBJLYBDO-SSEXGKCCSA-N 0.000 description 2
• TZVRRLHIIXQNBQ-GDLZYMKVSA-N tert-butyl n-[(2s)-2-(4-chlorophenyl)-3-[4-[5-(4-fluorophenyl)-1h-pyrrolo[2,3-b]pyridin-4-yl]piperazin-1-yl]-3-oxopropyl]-n-propan-2-ylcarbamate Chemical compound O=C([C@H](CN(C(C)C)C(=O)OC(C)(C)C)C=1C=CC(Cl)=CC=1)N(CC1)CCN1C(C=1C=CNC=1N=C1)=C1C1=CC=C(F)C=C1 TZVRRLHIIXQNBQ-GDLZYMKVSA-N 0.000 description 2
• HZSIEJKTPKFYQP-GDLZYMKVSA-N tert-butyl n-[(2s)-2-(4-chlorophenyl)-3-oxo-3-[4-(5-phenyl-1h-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl]propyl]-n-propan-2-ylcarbamate Chemical compound O=C([C@H](CN(C(C)C)C(=O)OC(C)(C)C)C=1C=CC(Cl)=CC=1)N(CC1)CCN1C(C=1C=CNC=1N=C1)=C1C1=CC=CC=C1 HZSIEJKTPKFYQP-GDLZYMKVSA-N 0.000 description 2
• LSQTUNWGGMLKTE-RUZDIDTESA-N tert-butyl n-[(2s)-2-(4-chlorophenyl)-3-oxo-3-[4-(5-propan-2-yloxy-1h-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl]propyl]-n-propan-2-ylcarbamate Chemical compound C1([C@@H](CN(C(C)C)C(=O)OC(C)(C)C)C(=O)N2CCN(CC2)C2=C3C=CNC3=NC=C2OC(C)C)=CC=C(Cl)C=C1 LSQTUNWGGMLKTE-RUZDIDTESA-N 0.000 description 2
• JRURASQXRYMCNT-MUUNZHRXSA-N tert-butyl n-[(2s)-2-(4-chlorophenyl)-3-oxo-3-[4-(5-pyridin-3-yl-1h-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl]propyl]-n-propan-2-ylcarbamate Chemical compound O=C([C@H](CN(C(C)C)C(=O)OC(C)(C)C)C=1C=CC(Cl)=CC=1)N(CC1)CCN1C(C=1C=CNC=1N=C1)=C1C1=CC=CN=C1 JRURASQXRYMCNT-MUUNZHRXSA-N 0.000 description 2
• USXKZUXSNXNJAZ-XZOQPEGZSA-N tert-butyl n-[(2s)-3-[(4s)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]-2-(4-chlorophenyl)-3-oxopropyl]-n-propan-2-ylcarbamate Chemical compound C([C@@H]1N(C(OC1)=O)C(=O)[C@H](CN(C(C)C)C(=O)OC(C)(C)C)C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 USXKZUXSNXNJAZ-XZOQPEGZSA-N 0.000 description 2
• LTBXKLQTPVOLBL-HSZRJFAPSA-N tert-butyl n-[(2s)-3-[4-(3-acetamido-1h-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl]-2-(4-chlorophenyl)-3-oxopropyl]-n-propan-2-ylcarbamate Chemical compound C1([C@H](C(=O)N2CCN(CC2)C=2C=3C(NC(C)=O)=CNC=3N=CC=2)CN(C(C)C)C(=O)OC(C)(C)C)=CC=C(Cl)C=C1 LTBXKLQTPVOLBL-HSZRJFAPSA-N 0.000 description 2
• HWNOHQCQZVXKAK-HHHXNRCGSA-N tert-butyl n-[(4r)-4-(4-chlorophenyl)-2-methyl-5-[4-(3-methyl-5-phenyl-1h-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl]-5-oxopentan-2-yl]carbamate Chemical compound C1CN(C(=O)[C@H](CC(C)(C)NC(=O)OC(C)(C)C)C=2C=CC(Cl)=CC=2)CCN1C1=C2C(C)=CNC2=NC=C1C1=CC=CC=C1 HWNOHQCQZVXKAK-HHHXNRCGSA-N 0.000 description 2
• BMMJACRRGRLUTB-HHHXNRCGSA-N tert-butyl n-[(4r)-4-(4-chlorophenyl)-5-[4-[5-(3-fluorophenyl)-1h-pyrrolo[2,3-b]pyridin-4-yl]piperazin-1-yl]-2-methyl-5-oxopentan-2-yl]carbamate Chemical compound O=C([C@H](CC(C)(C)NC(=O)OC(C)(C)C)C=1C=CC(Cl)=CC=1)N(CC1)CCN1C(C=1C=CNC=1N=C1)=C1C1=CC=CC(F)=C1 BMMJACRRGRLUTB-HHHXNRCGSA-N 0.000 description 2
• JHCROLKRJACRMS-UHFFFAOYSA-N tert-butyl n-[2-[(4-chlorophenyl)methyl]-3-[4-(3-methyl-5-phenyl-1h-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl]-3-oxopropyl]carbamate Chemical compound C1CN(C(=O)C(CNC(=O)OC(C)(C)C)CC=2C=CC(Cl)=CC=2)CCN1C1=C2C(C)=CNC2=NC=C1C1=CC=CC=C1 JHCROLKRJACRMS-UHFFFAOYSA-N 0.000 description 2
• UIXGDOCDDAQMIX-UHFFFAOYSA-N tert-butyl n-[2-oxo-2-[4-[3-(pyridine-3-carbonylamino)-1h-pyrrolo[2,3-b]pyridin-4-yl]piperazin-1-yl]ethyl]carbamate Chemical compound C1CN(C(=O)CNC(=O)OC(C)(C)C)CCN1C1=CC=NC2=C1C(NC(=O)C=1C=NC=CC=1)=CN2 UIXGDOCDDAQMIX-UHFFFAOYSA-N 0.000 description 2
• VVACPLYJPBRJKI-UHFFFAOYSA-N tert-butyl n-[2-oxo-2-[4-[5-phenyl-3-(pyridine-3-carbonylamino)-1h-pyrrolo[2,3-b]pyridin-4-yl]piperazin-1-yl]ethyl]carbamate Chemical compound C1CN(C(=O)CNC(=O)OC(C)(C)C)CCN1C1=C(C=2C=CC=CC=2)C=NC2=C1C(NC(=O)C=1C=NC=CC=1)=CN2 VVACPLYJPBRJKI-UHFFFAOYSA-N 0.000 description 2
• LIEYFMWRSWEFGT-UHFFFAOYSA-N tert-butyl n-[3-[(4-chlorophenyl)methyl]-4-[4-(3-methyl-5-phenyl-1h-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl]-4-oxobutyl]carbamate Chemical compound C1CN(C(=O)C(CCNC(=O)OC(C)(C)C)CC=2C=CC(Cl)=CC=2)CCN1C1=C2C(C)=CNC2=NC=C1C1=CC=CC=C1 LIEYFMWRSWEFGT-UHFFFAOYSA-N 0.000 description 2
• CHPLBEGUIVPNCB-UHFFFAOYSA-N tert-butyl n-[3-[4-[5-bromo-3-(pyridine-3-carbonylamino)-1h-pyrrolo[2,3-b]pyridin-4-yl]piperazin-1-yl]-3-oxopropyl]carbamate Chemical compound C1CN(C(=O)CCNC(=O)OC(C)(C)C)CCN1C1=C(Br)C=NC2=C1C(NC(=O)C=1C=NC=CC=1)=CN2 CHPLBEGUIVPNCB-UHFFFAOYSA-N 0.000 description 2
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• YYNJIBHWVNKZCI-UHFFFAOYSA-N tert-butyl n-[3-oxo-3-[4-[3-(pyridine-3-carbonylamino)-1h-pyrrolo[2,3-b]pyridin-4-yl]piperazin-1-yl]propyl]carbamate Chemical compound C1CN(C(=O)CCNC(=O)OC(C)(C)C)CCN1C1=CC=NC2=C1C(NC(=O)C=1C=NC=CC=1)=CN2 YYNJIBHWVNKZCI-UHFFFAOYSA-N 0.000 description 2
• QLWDUWFAOSLGEA-UHFFFAOYSA-N tert-butyl n-[3-oxo-3-[4-[5-phenyl-3-(pyridine-3-carbonylamino)-1h-pyrrolo[2,3-b]pyridin-4-yl]piperazin-1-yl]propyl]carbamate Chemical compound C1CN(C(=O)CCNC(=O)OC(C)(C)C)CCN1C1=C(C=2C=CC=CC=2)C=NC2=C1C(NC(=O)C=1C=NC=CC=1)=CN2 QLWDUWFAOSLGEA-UHFFFAOYSA-N 0.000 description 2
• 150000003512 tertiary amines Chemical class 0.000 description 2
• 238000012360 testing method Methods 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
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• 229910052727 yttrium Inorganic materials 0.000 description 2
• 239000011701 zinc Substances 0.000 description 2
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