KR20200034781A - 1,2-다이하이드로-3H-피라졸로[3,4-d]피리미딘-3-온 유사체 - Google Patents
1,2-다이하이드로-3H-피라졸로[3,4-d]피리미딘-3-온 유사체 Download PDFInfo
- Publication number
- KR20200034781A KR20200034781A KR1020207005636A KR20207005636A KR20200034781A KR 20200034781 A KR20200034781 A KR 20200034781A KR 1020207005636 A KR1020207005636 A KR 1020207005636A KR 20207005636 A KR20207005636 A KR 20207005636A KR 20200034781 A KR20200034781 A KR 20200034781A
- Authority
- KR
- South Korea
- Prior art keywords
- cancer
- alkyl
- optionally substituted
- compound
- unsubstituted
- Prior art date
- 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
- JTNQNHQPENYUGB-UHFFFAOYSA-N 1,2-dihydropyrazolo[3,4-d]pyrimidin-3-one Chemical class C1=NC=C2C(O)=NNC2=N1 JTNQNHQPENYUGB-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 292
- 150000003839 salts Chemical class 0.000 claims abstract description 125
- 206010006187 Breast cancer Diseases 0.000 claims abstract description 10
- 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 230
- 206010028980 Neoplasm Diseases 0.000 claims description 126
- 201000011510 cancer Diseases 0.000 claims description 121
- -1 cyano, amino Chemical group 0.000 claims description 104
- 101000621390 Homo sapiens Wee1-like protein kinase Proteins 0.000 claims description 100
- 102100023037 Wee1-like protein kinase Human genes 0.000 claims description 100
- 230000000694 effects Effects 0.000 claims description 83
- 238000000034 method Methods 0.000 claims description 69
- 125000000623 heterocyclic group Chemical group 0.000 claims description 58
- 125000001072 heteroaryl group Chemical group 0.000 claims description 57
- 239000008194 pharmaceutical composition Substances 0.000 claims description 50
- 230000002401 inhibitory effect Effects 0.000 claims description 49
- 125000003118 aryl group Chemical group 0.000 claims description 48
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 40
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 39
- 229910052739 hydrogen Inorganic materials 0.000 claims description 36
- 239000001257 hydrogen Substances 0.000 claims description 36
- 229910052736 halogen Inorganic materials 0.000 claims description 33
- 150000002367 halogens Chemical class 0.000 claims description 33
- 125000001424 substituent group Chemical group 0.000 claims description 32
- 150000001412 amines Chemical class 0.000 claims description 27
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 25
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 25
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 25
- 201000010881 cervical cancer Diseases 0.000 claims description 25
- 125000003342 alkenyl group Chemical group 0.000 claims description 24
- 125000000304 alkynyl group Chemical group 0.000 claims description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims description 23
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 22
- 229910052799 carbon Inorganic materials 0.000 claims description 20
- 150000002431 hydrogen Chemical class 0.000 claims description 20
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 18
- 208000000649 small cell carcinoma Diseases 0.000 claims description 18
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 238000004519 manufacturing process Methods 0.000 claims description 15
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 14
- 125000002252 acyl group Chemical group 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- 125000003107 substituted aryl group Chemical group 0.000 claims description 12
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 10
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 10
- 239000003085 diluting agent Substances 0.000 claims description 10
- 201000005202 lung cancer Diseases 0.000 claims description 10
- 208000020816 lung neoplasm Diseases 0.000 claims description 10
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 9
- 206010000830 Acute leukaemia Diseases 0.000 claims description 9
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 9
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 9
- 206010005003 Bladder cancer Diseases 0.000 claims description 9
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 9
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims description 9
- 206010009944 Colon cancer Diseases 0.000 claims description 9
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 9
- 208000006168 Ewing Sarcoma Diseases 0.000 claims description 9
- 208000017604 Hodgkin disease Diseases 0.000 claims description 9
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims description 9
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 9
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 9
- 206010025323 Lymphomas Diseases 0.000 claims description 9
- 208000032271 Malignant tumor of penis Diseases 0.000 claims description 9
- 208000034578 Multiple myelomas Diseases 0.000 claims description 9
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims description 9
- 206010029260 Neuroblastoma Diseases 0.000 claims description 9
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 9
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 9
- 206010033128 Ovarian cancer Diseases 0.000 claims description 9
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 9
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 9
- 208000002471 Penile Neoplasms Diseases 0.000 claims description 9
- 206010034299 Penile cancer Diseases 0.000 claims description 9
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 9
- 206010060862 Prostate cancer Diseases 0.000 claims description 9
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 9
- 208000015634 Rectal Neoplasms Diseases 0.000 claims description 9
- 206010039491 Sarcoma Diseases 0.000 claims description 9
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 9
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 9
- 208000024313 Testicular Neoplasms Diseases 0.000 claims description 9
- 206010057644 Testis cancer Diseases 0.000 claims description 9
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 9
- 208000023915 Ureteral Neoplasms Diseases 0.000 claims description 9
- 206010046392 Ureteric cancer Diseases 0.000 claims description 9
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 9
- 208000017733 acquired polycythemia vera Diseases 0.000 claims description 9
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 9
- 208000029742 colonic neoplasm Diseases 0.000 claims description 9
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 claims description 9
- 201000004101 esophageal cancer Diseases 0.000 claims description 9
- 230000001605 fetal effect Effects 0.000 claims description 9
- 206010017758 gastric cancer Diseases 0.000 claims description 9
- 201000007270 liver cancer Diseases 0.000 claims description 9
- 208000014018 liver neoplasm Diseases 0.000 claims description 9
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 9
- 201000001441 melanoma Diseases 0.000 claims description 9
- 201000008968 osteosarcoma Diseases 0.000 claims description 9
- 201000002528 pancreatic cancer Diseases 0.000 claims description 9
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 9
- 208000037244 polycythemia vera Diseases 0.000 claims description 9
- 206010038038 rectal cancer Diseases 0.000 claims description 9
- 201000001275 rectum cancer Diseases 0.000 claims description 9
- 201000000849 skin cancer Diseases 0.000 claims description 9
- 201000011549 stomach cancer Diseases 0.000 claims description 9
- 201000003120 testicular cancer Diseases 0.000 claims description 9
- 201000002510 thyroid cancer Diseases 0.000 claims description 9
- 201000011294 ureter cancer Diseases 0.000 claims description 9
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 9
- 150000003973 alkyl amines Chemical class 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 230000010076 replication Effects 0.000 claims description 8
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
- 125000004122 cyclic group Chemical group 0.000 claims description 7
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- 125000001188 haloalkyl group Chemical group 0.000 claims description 6
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 3
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 3
- 125000004434 sulfur atom Chemical group 0.000 claims description 3
- 210000000232 gallbladder Anatomy 0.000 claims 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 6
- 230000001747 exhibiting effect Effects 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 87
- 201000010099 disease Diseases 0.000 abstract description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 14
- 230000004663 cell proliferation Effects 0.000 abstract description 2
- 238000006243 chemical reaction Methods 0.000 description 156
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 120
- 239000000243 solution Substances 0.000 description 85
- 210000004027 cell Anatomy 0.000 description 77
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 69
- 239000007787 solid Substances 0.000 description 56
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 55
- 230000002829 reductive effect Effects 0.000 description 52
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 52
- 239000011734 sodium Substances 0.000 description 49
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 45
- 239000012044 organic layer Substances 0.000 description 38
- 125000004432 carbon atom Chemical group C* 0.000 description 34
- 238000005481 NMR spectroscopy Methods 0.000 description 33
- 108010078814 Tumor Suppressor Protein p53 Proteins 0.000 description 30
- 125000004429 atom Chemical group 0.000 description 29
- 229920006395 saturated elastomer Polymers 0.000 description 29
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 29
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 28
- 125000005842 heteroatom Chemical group 0.000 description 27
- 229910004298 SiO 2 Inorganic materials 0.000 description 26
- 238000004440 column chromatography Methods 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 23
- 239000012267 brine Substances 0.000 description 21
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 21
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 21
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 21
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 20
- 239000002904 solvent Substances 0.000 description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 125000000392 cycloalkenyl group Chemical group 0.000 description 18
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 18
- 239000003208 petroleum Substances 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 230000002950 deficient Effects 0.000 description 15
- 239000000460 chlorine Substances 0.000 description 14
- 239000000706 filtrate Substances 0.000 description 14
- 230000002018 overexpression Effects 0.000 description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 11
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 11
- 125000002947 alkylene group Chemical group 0.000 description 11
- 239000003112 inhibitor Substances 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 9
- YPRWYZSUBZXORL-UHFFFAOYSA-N 7-nitro-1,2,3,4-tetrahydroisoquinoline Chemical compound C1CNCC2=CC([N+](=O)[O-])=CC=C21 YPRWYZSUBZXORL-UHFFFAOYSA-N 0.000 description 8
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- 150000003254 radicals Chemical class 0.000 description 8
- 125000003003 spiro group Chemical group 0.000 description 8
- 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 8
- BKWJAKQVGHWELA-UHFFFAOYSA-N 1-[6-(2-hydroxypropan-2-yl)-2-pyridinyl]-6-[4-(4-methyl-1-piperazinyl)anilino]-2-prop-2-enyl-3-pyrazolo[3,4-d]pyrimidinone Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=C2C(=O)N(CC=C)N(C=3N=C(C=CC=3)C(C)(C)O)C2=N1 BKWJAKQVGHWELA-UHFFFAOYSA-N 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- 239000012298 atmosphere Substances 0.000 description 7
- 230000037396 body weight Effects 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 125000002950 monocyclic group Chemical group 0.000 description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
- 238000004007 reversed phase HPLC Methods 0.000 description 7
- 231100000419 toxicity Toxicity 0.000 description 7
- 230000001988 toxicity Effects 0.000 description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 229950009557 adavosertib Drugs 0.000 description 6
- 125000003277 amino group Chemical class 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- PYMKGCGDRBMJOA-UHFFFAOYSA-N 7-nitrospiro[2,3-dihydro-1h-isoquinoline-4,1'-cyclopropane] Chemical compound C=1C([N+](=O)[O-])=CC=C2C=1CNCC21CC1 PYMKGCGDRBMJOA-UHFFFAOYSA-N 0.000 description 5
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- 125000002619 bicyclic group Chemical group 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- SWMOAMVNXFVLII-UHFFFAOYSA-N 4,4-dimethyl-7-nitro-2,3-dihydro-1h-isoquinoline Chemical compound [O-][N+](=O)C1=CC=C2C(C)(C)CNCC2=C1 SWMOAMVNXFVLII-UHFFFAOYSA-N 0.000 description 4
- 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 4
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 108091000080 Phosphotransferase Proteins 0.000 description 4
- YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- 235000019253 formic acid Nutrition 0.000 description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 230000026731 phosphorylation Effects 0.000 description 4
- 238000006366 phosphorylation reaction Methods 0.000 description 4
- 102000020233 phosphotransferase Human genes 0.000 description 4
- 230000036470 plasma concentration Effects 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- LRIVVMZEHDTDGA-UHFFFAOYSA-N 7-amino-2-methyl-3,4-dihydroisoquinolin-1-one Chemical compound C1=C(N)C=C2C(=O)N(C)CCC2=C1 LRIVVMZEHDTDGA-UHFFFAOYSA-N 0.000 description 3
- AKSXJLVHPONQIP-UHFFFAOYSA-N 7-chloro-4,4-difluoro-2,3-dihydro-1h-isoquinoline Chemical compound ClC1=CC=C2C(F)(F)CNCC2=C1 AKSXJLVHPONQIP-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 102100032857 Cyclin-dependent kinase 1 Human genes 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 125000005631 S-sulfonamido group Chemical group 0.000 description 3
- 229910000831 Steel Inorganic materials 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 3
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 3
- 101150040313 Wee1 gene Proteins 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
- 150000001721 carbon Chemical group 0.000 description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 description 3
- 238000012054 celltiter-glo Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000013626 chemical specie 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
- 239000013058 crude material Substances 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
- 229910052805 deuterium Inorganic materials 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- PSBAIJVSCTZDDB-UHFFFAOYSA-N phenyl acetylsalicylate Chemical compound CC(=O)OC1=CC=CC=C1C(=O)OC1=CC=CC=C1 PSBAIJVSCTZDDB-UHFFFAOYSA-N 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000010959 steel Substances 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- OLOIFCYZWOTWRO-UHFFFAOYSA-N tert-butyl 6-amino-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound NC1=CC=C2CN(C(=O)OC(C)(C)C)CCC2=C1 OLOIFCYZWOTWRO-UHFFFAOYSA-N 0.000 description 3
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 3
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 2
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- FLXFRSZKOVKKPQ-UHFFFAOYSA-N 1,2-dihydroquinoline-2-carboxylic acid Chemical compound C1=CC=C2C=CC(C(=O)O)NC2=C1 FLXFRSZKOVKKPQ-UHFFFAOYSA-N 0.000 description 2
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 2
- WFCIESMNRLUMTR-UHFFFAOYSA-N 1,4,4-trimethyl-2,3-dihydro-1h-isoquinoline Chemical compound C1=CC=C2C(C)NCC(C)(C)C2=C1 WFCIESMNRLUMTR-UHFFFAOYSA-N 0.000 description 2
- JBYHSSAVUBIJMK-UHFFFAOYSA-N 1,4-oxathiane Chemical compound C1CSCCO1 JBYHSSAVUBIJMK-UHFFFAOYSA-N 0.000 description 2
- BKJRHIYYEKJYTP-UHFFFAOYSA-N 1-(7-nitro-3,4-dihydro-1h-isoquinolin-2-yl)ethanone Chemical compound C1=C([N+]([O-])=O)C=C2CN(C(=O)C)CCC2=C1 BKJRHIYYEKJYTP-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 2
- FQAJSEWFBJSSOY-UHFFFAOYSA-N 1h-1,7-naphthyridin-2-one Chemical compound C1=CN=CC2=NC(O)=CC=C21 FQAJSEWFBJSSOY-UHFFFAOYSA-N 0.000 description 2
- OALLDAHSJSVVQO-UHFFFAOYSA-N 2,2,2-trifluoro-n-(1,2,3,4-tetrahydroisoquinolin-6-yl)acetamide Chemical compound C1NCCC2=CC(NC(=O)C(F)(F)F)=CC=C21 OALLDAHSJSVVQO-UHFFFAOYSA-N 0.000 description 2
- HMDMSALIWQEZAX-UHFFFAOYSA-N 2,4,4-trimethyl-1,3-dihydroisoquinolin-7-amine Chemical compound NC1=CC=C2C(C)(C)CN(C)CC2=C1 HMDMSALIWQEZAX-UHFFFAOYSA-N 0.000 description 2
- OSZFZDTXPJJVBM-UHFFFAOYSA-N 2,4,4-trimethyl-7-nitro-1,3-dihydroisoquinoline Chemical compound [O-][N+](=O)C1=CC=C2C(C)(C)CN(C)CC2=C1 OSZFZDTXPJJVBM-UHFFFAOYSA-N 0.000 description 2
- JBKINHFZTVLNEM-UHFFFAOYSA-N 2-bromoethoxy-tert-butyl-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OCCBr JBKINHFZTVLNEM-UHFFFAOYSA-N 0.000 description 2
- WKTIBTBCLWOTJN-UHFFFAOYSA-N 2-chloro-7-methyl-6,8-dihydro-5h-1,7-naphthyridine Chemical compound C1=C(Cl)N=C2CN(C)CCC2=C1 WKTIBTBCLWOTJN-UHFFFAOYSA-N 0.000 description 2
- WYGYMIKICPQWCH-UHFFFAOYSA-N 2-ethyl-7-nitro-3,4-dihydro-1h-isoquinoline Chemical compound C1=C([N+]([O-])=O)C=C2CN(CC)CCC2=C1 WYGYMIKICPQWCH-UHFFFAOYSA-N 0.000 description 2
- PWHRVVMNFQGSJQ-UHFFFAOYSA-N 2-methyl-3,4-dihydro-1h-isoquinolin-6-amine Chemical compound NC1=CC=C2CN(C)CCC2=C1 PWHRVVMNFQGSJQ-UHFFFAOYSA-N 0.000 description 2
- VRKLIVSHUQSRNF-UHFFFAOYSA-N 2-methyl-3,4-dihydro-1h-isoquinolin-7-amine Chemical compound C1=C(N)C=C2CN(C)CCC2=C1 VRKLIVSHUQSRNF-UHFFFAOYSA-N 0.000 description 2
- PUMCPMLEPPOZRX-UHFFFAOYSA-N 2-methyl-7-nitro-3,4-dihydro-1h-isoquinoline Chemical compound C1=C([N+]([O-])=O)C=C2CN(C)CCC2=C1 PUMCPMLEPPOZRX-UHFFFAOYSA-N 0.000 description 2
- GXUFVBWYQHTXDP-UHFFFAOYSA-N 2-methylspiro[1,3-dihydroisoquinoline-4,1'-cyclopropane]-7-amine Chemical compound C1N(C)CC2=CC(N)=CC=C2C21CC2 GXUFVBWYQHTXDP-UHFFFAOYSA-N 0.000 description 2
- XKQPKSBAPXVCOK-UHFFFAOYSA-N 2-methylsulfonyl-3,4-dihydro-1h-isoquinolin-7-amine Chemical compound C1=C(N)C=C2CN(S(=O)(=O)C)CCC2=C1 XKQPKSBAPXVCOK-UHFFFAOYSA-N 0.000 description 2
- LIRXDOMEVZTKCF-UHFFFAOYSA-N 2-methylsulfonyl-7-nitro-3,4-dihydro-1h-isoquinoline Chemical compound C1=C([N+]([O-])=O)C=C2CN(S(=O)(=O)C)CCC2=C1 LIRXDOMEVZTKCF-UHFFFAOYSA-N 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical compound O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 2
- OZLBNELUODRSQZ-UHFFFAOYSA-N 5,6,7,8-tetrahydro-1h-1,7-naphthyridin-2-one Chemical compound C1CNCC2=C1C=CC(=O)N2 OZLBNELUODRSQZ-UHFFFAOYSA-N 0.000 description 2
- OIVLITBTBDPEFK-UHFFFAOYSA-N 5,6-dihydrouracil Chemical compound O=C1CCNC(=O)N1 OIVLITBTBDPEFK-UHFFFAOYSA-N 0.000 description 2
- ZCIYSRNFJKEFIQ-UHFFFAOYSA-N 7-chloro-4,4-difluoroisoquinoline-1,3-dione Chemical compound ClC1=CC=C2C(F)(F)C(=O)NC(=O)C2=C1 ZCIYSRNFJKEFIQ-UHFFFAOYSA-N 0.000 description 2
- OWYCULFQZJTLSU-UHFFFAOYSA-N 7-nitro-2-propan-2-yl-3,4-dihydro-1h-isoquinoline Chemical compound C1=C([N+]([O-])=O)C=C2CN(C(C)C)CCC2=C1 OWYCULFQZJTLSU-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- XMGSHZHMTZONJW-UHFFFAOYSA-N C1=CC(=O)NC2=C1CCN(C)C2 Chemical compound C1=CC(=O)NC2=C1CCN(C)C2 XMGSHZHMTZONJW-UHFFFAOYSA-N 0.000 description 2
- ODRKHSWISFBTOF-UHFFFAOYSA-N CC1=NCC(C2=CC=CC=C12)(C)C Chemical compound CC1=NCC(C2=CC=CC=C12)(C)C ODRKHSWISFBTOF-UHFFFAOYSA-N 0.000 description 2
- CMFMTDCTQADGLM-UHFFFAOYSA-N CCOC(=O)C(F)(F)C1=CC=C(Cl)C=C1C#N Chemical compound CCOC(=O)C(F)(F)C1=CC=C(Cl)C=C1C#N CMFMTDCTQADGLM-UHFFFAOYSA-N 0.000 description 2
- 108010034798 CDC2 Protein Kinase Proteins 0.000 description 2
- HHUBSUAVEKAPCO-UHFFFAOYSA-N CN1CCC2=CC=C(N)N=C2C1 Chemical compound CN1CCC2=CC=C(N)N=C2C1 HHUBSUAVEKAPCO-UHFFFAOYSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 241000887125 Chaptalia nutans Species 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- AGJFFPYEVQIRIS-UHFFFAOYSA-N Cl.O=C1N(C(=O)c2ccccc12)c1ccc2CNCCc2c1 Chemical compound Cl.O=C1N(C(=O)c2ccccc12)c1ccc2CNCCc2c1 AGJFFPYEVQIRIS-UHFFFAOYSA-N 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 230000005778 DNA damage Effects 0.000 description 2
- 231100000277 DNA damage Toxicity 0.000 description 2
- 230000033616 DNA repair Effects 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
- 239000005977 Ethylene Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- VFAAWBJUAISRRC-UHFFFAOYSA-N N-(7-methyl-6,8-dihydro-5H-1,7-naphthyridin-2-yl)-1,1-diphenylmethanimine Chemical compound CN1CCC2=CC=C(N=C(C3=CC=CC=C3)C3=CC=CC=C3)N=C2C1 VFAAWBJUAISRRC-UHFFFAOYSA-N 0.000 description 2
- YKWUFULGRIUJJB-UHFFFAOYSA-N NC1=CC2=C(CCN(C2)C2COC2)C=C1 Chemical compound NC1=CC2=C(CCN(C2)C2COC2)C=C1 YKWUFULGRIUJJB-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- JBHULJPQQSMPQT-UHFFFAOYSA-N O1CC(C1)N1CC2=CC=C(C=C2CC1)N Chemical compound O1CC(C1)N1CC2=CC=C(C=C2CC1)N JBHULJPQQSMPQT-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 241000720974 Protium Species 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- QZWOEROZCQZFDA-UHFFFAOYSA-N [N+](=O)([O-])C1=CC=C2CCN(CC2=C1)C1COC1 Chemical compound [N+](=O)([O-])C1=CC=C2CCN(CC2=C1)C1COC1 QZWOEROZCQZFDA-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- CUFNKYGDVFVPHO-UHFFFAOYSA-N azulene Chemical compound C1=CC=CC2=CC=CC2=C1 CUFNKYGDVFVPHO-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000005605 benzo group Chemical group 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000012820 cell cycle checkpoint Effects 0.000 description 2
- 230000023359 cell cycle switching, meiotic to mitotic cell cycle Effects 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 238000001516 cell proliferation assay Methods 0.000 description 2
- 239000002738 chelating agent Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
- 229960004316 cisplatin Drugs 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- WDVGNXKCFBOKDF-UHFFFAOYSA-N dicyclohexyl-[3,6-dimethoxy-2-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane Chemical compound COC1=CC=C(OC)C(C=2C(=CC(=CC=2C(C)C)C(C)C)C(C)C)=C1P(C1CCCCC1)C1CCCCC1 WDVGNXKCFBOKDF-UHFFFAOYSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 125000004475 heteroaralkyl group Chemical group 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 2
- 239000010977 jade Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 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 2
- 238000004020 luminiscence type Methods 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- VHJXKDAKXQLJMF-UHFFFAOYSA-N methyl 1-(2-cyanophenyl)cyclopropane-1-carboxylate Chemical compound C=1C=CC=C(C#N)C=1C1(C(=O)OC)CC1 VHJXKDAKXQLJMF-UHFFFAOYSA-N 0.000 description 2
- MBLNSABLVSWAKD-UHFFFAOYSA-N methyl 2-(2-cyanophenyl)acetate Chemical compound COC(=O)CC1=CC=CC=C1C#N MBLNSABLVSWAKD-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 230000011278 mitosis Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- JKOVMSLZOOFBCS-UHFFFAOYSA-N n-(2-methyl-2-phenylpropyl)acetamide Chemical compound CC(=O)NCC(C)(C)C1=CC=CC=C1 JKOVMSLZOOFBCS-UHFFFAOYSA-N 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 2
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 2
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 2
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 2
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 229960004889 salicylic acid Drugs 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 235000011150 stannous chloride Nutrition 0.000 description 2
- 239000001119 stannous chloride Substances 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 125000004646 sulfenyl group Chemical group S(*)* 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 2
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 2
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- VMEDBFRQSKKEEQ-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinolin-7-amine Chemical compound C1CNCC2=CC(N)=CC=C21 VMEDBFRQSKKEEQ-UHFFFAOYSA-N 0.000 description 1
- UGUHFDPGDQDVGX-UHFFFAOYSA-N 1,2,3-thiadiazole Chemical compound C1=CSN=N1 UGUHFDPGDQDVGX-UHFFFAOYSA-N 0.000 description 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 1
- YGTAZGSLCXNBQL-UHFFFAOYSA-N 1,2,4-thiadiazole Chemical compound C=1N=CSN=1 YGTAZGSLCXNBQL-UHFFFAOYSA-N 0.000 description 1
- KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 1
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
- CIISBYKBBMFLEZ-UHFFFAOYSA-N 1,2-oxazolidine Chemical compound C1CNOC1 CIISBYKBBMFLEZ-UHFFFAOYSA-N 0.000 description 1
- LKLLNYWECKEQIB-UHFFFAOYSA-N 1,3,5-triazinane Chemical compound C1NCNCN1 LKLLNYWECKEQIB-UHFFFAOYSA-N 0.000 description 1
- BGJSXRVXTHVRSN-UHFFFAOYSA-N 1,3,5-trioxane Chemical compound C1OCOCO1 BGJSXRVXTHVRSN-UHFFFAOYSA-N 0.000 description 1
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- SILNNFMWIMZVEQ-UHFFFAOYSA-N 1,3-dihydrobenzimidazol-2-one Chemical compound C1=CC=C2NC(O)=NC2=C1 SILNNFMWIMZVEQ-UHFFFAOYSA-N 0.000 description 1
- ZPPXWZDJDIOJFP-UHFFFAOYSA-N 1,3-dihydroisoindole-2-carboxylic acid Chemical compound C1=CC=C2CN(C(=O)O)CC2=C1 ZPPXWZDJDIOJFP-UHFFFAOYSA-N 0.000 description 1
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 1
- IMLSAISZLJGWPP-UHFFFAOYSA-N 1,3-dithiolane Chemical compound C1CSCS1 IMLSAISZLJGWPP-UHFFFAOYSA-N 0.000 description 1
- IVJFXSLMUSQZMC-UHFFFAOYSA-N 1,3-dithiole Chemical compound C1SC=CS1 IVJFXSLMUSQZMC-UHFFFAOYSA-N 0.000 description 1
- QVFHFKPGBODJJB-UHFFFAOYSA-N 1,3-oxathiane Chemical compound C1COCSC1 QVFHFKPGBODJJB-UHFFFAOYSA-N 0.000 description 1
- WJJSZTJGFCFNKI-UHFFFAOYSA-N 1,3-oxathiolane Chemical compound C1CSCO1 WJJSZTJGFCFNKI-UHFFFAOYSA-N 0.000 description 1
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
- XWVFMJLNNGXNSG-UHFFFAOYSA-N 1-(7-amino-3,4-dihydro-1h-isoquinolin-2-yl)ethanone Chemical compound C1=C(N)C=C2CN(C(=O)C)CCC2=C1 XWVFMJLNNGXNSG-UHFFFAOYSA-N 0.000 description 1
- VFROHYRVZBVJAL-UHFFFAOYSA-N 1-(7-aminospiro[1,3-dihydroisoquinoline-4,1'-cyclopropane]-2-yl)ethanone Chemical compound CC(=O)N1Cc2cc(N)ccc2C2(CC2)C1 VFROHYRVZBVJAL-UHFFFAOYSA-N 0.000 description 1
- XRJLQSGHVNNKIO-QGZVFWFLSA-N 1-[6-(2-hydroxypropan-2-yl)pyridin-2-yl]-2-prop-2-enyl-6-[[(1R)-1,4,4-trimethyl-2,3-dihydro-1H-isoquinolin-7-yl]amino]pyrazolo[3,4-d]pyrimidin-3-one Chemical compound C1(C(O)(C)C)=CC=CC(N2C3=NC(NC4=CC=C5C([C@H](NCC5(C)C)C)=C4)=NC=C3C(=O)N2CC=C)=N1 XRJLQSGHVNNKIO-QGZVFWFLSA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
- CUCJJMLDIUSNPU-UHFFFAOYSA-N 1-oxidopiperidin-1-ium Chemical compound [O-][NH+]1CCCCC1 CUCJJMLDIUSNPU-UHFFFAOYSA-N 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- IWAGGDFROAISJT-UHFFFAOYSA-N 1h-isoquinoline-2-carboxylic acid Chemical compound C1=CC=C2C=CN(C(=O)O)CC2=C1 IWAGGDFROAISJT-UHFFFAOYSA-N 0.000 description 1
- UDSAJFSYJMHNFI-UHFFFAOYSA-N 2,6-diazaspiro[3.3]heptane Chemical compound C1NCC11CNC1 UDSAJFSYJMHNFI-UHFFFAOYSA-N 0.000 description 1
- IUHXGZHKSYYDIL-UHFFFAOYSA-N 2-(2-iodophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1I IUHXGZHKSYYDIL-UHFFFAOYSA-N 0.000 description 1
- JECYNCQXXKQDJN-UHFFFAOYSA-N 2-(2-methylhexan-2-yloxymethyl)oxirane Chemical compound CCCCC(C)(C)OCC1CO1 JECYNCQXXKQDJN-UHFFFAOYSA-N 0.000 description 1
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 1
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
- IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 1
- SPGSUUUJJUUXPJ-UHFFFAOYSA-N 2-[2-[tert-butyl(dimethyl)silyl]oxyethyl]-3,4-dihydro-1H-isoquinolin-6-amine Chemical compound CC(C)(C)[Si](C)(C)OCCN1CCC2=C(C1)C=CC(N)=C2 SPGSUUUJJUUXPJ-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
- QPEJAHMNOVMSOZ-UHFFFAOYSA-N 2-azaspiro[3.3]heptane Chemical compound C1CCC21CNC2 QPEJAHMNOVMSOZ-UHFFFAOYSA-N 0.000 description 1
- PSNDWZOXFDKLLH-UHFFFAOYSA-N 2-azaspiro[3.4]octane Chemical compound C1NCC11CCCC1 PSNDWZOXFDKLLH-UHFFFAOYSA-N 0.000 description 1
- CTSHRMBLMKPDAG-UHFFFAOYSA-N 2-bromo-5-chlorobenzonitrile Chemical compound ClC1=CC=C(Br)C(C#N)=C1 CTSHRMBLMKPDAG-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- HXQGLHSLMHBNCR-UHFFFAOYSA-N 2-ethyl-3,4-dihydro-1h-isoquinolin-7-amine Chemical compound C1=C(N)C=C2CN(CC)CCC2=C1 HXQGLHSLMHBNCR-UHFFFAOYSA-N 0.000 description 1
- VFCWGXGWQPTGNQ-UHFFFAOYSA-N 2-ethyl-3,4-dihydro-1h-isoquinoline Chemical compound C1=CC=C2CN(CC)CCC2=C1 VFCWGXGWQPTGNQ-UHFFFAOYSA-N 0.000 description 1
- QAJAXOPOSLBUDC-UHFFFAOYSA-N 2-methyl-1,3-dihydroisoindol-5-amine Chemical compound C1=C(N)C=C2CN(C)CC2=C1 QAJAXOPOSLBUDC-UHFFFAOYSA-N 0.000 description 1
- 125000006020 2-methyl-1-propenyl group Chemical group 0.000 description 1
- CWSGTPMVOJFVIF-UHFFFAOYSA-N 2-methyl-2-phenylpropan-1-amine Chemical compound NCC(C)(C)C1=CC=CC=C1 CWSGTPMVOJFVIF-UHFFFAOYSA-N 0.000 description 1
- WKFXXCRBUQGXHM-UHFFFAOYSA-N 2-methyl-7-nitrospiro[1,3-dihydroisoquinoline-4,1'-cyclopropane] Chemical compound C1N(C)CC2=CC([N+]([O-])=O)=CC=C2C21CC2 WKFXXCRBUQGXHM-UHFFFAOYSA-N 0.000 description 1
- SJZKTTYDLPTPPR-UHFFFAOYSA-N 2-n,2-n-dimethyl-2,3-dihydro-1h-indene-2,5-diamine Chemical compound C1=C(N)C=C2CC(N(C)C)CC2=C1 SJZKTTYDLPTPPR-UHFFFAOYSA-N 0.000 description 1
- HPJALMWOZYIZGE-UHFFFAOYSA-N 2-oxa-6-azaspiro[3.3]heptane Chemical compound C1NCC11COC1 HPJALMWOZYIZGE-UHFFFAOYSA-N 0.000 description 1
- SUSDYISRJSLTST-UHFFFAOYSA-N 2-oxaspiro[3.3]heptane Chemical compound C1CCC21COC2 SUSDYISRJSLTST-UHFFFAOYSA-N 0.000 description 1
- NTMUDPWGPGZGQW-UHFFFAOYSA-N 2-oxaspiro[3.4]octane Chemical compound C1OCC11CCCC1 NTMUDPWGPGZGQW-UHFFFAOYSA-N 0.000 description 1
- KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 description 1
- MGEZLOOETLTLSI-UHFFFAOYSA-N 2-propan-2-yl-3,4-dihydro-1h-isoquinolin-7-amine Chemical compound C1=C(N)C=C2CN(C(C)C)CCC2=C1 MGEZLOOETLTLSI-UHFFFAOYSA-N 0.000 description 1
- FOAUHWOFIUVODV-UHFFFAOYSA-N 2-propan-2-ylspiro[1,3-dihydroisoquinoline-4,1'-cyclopropane]-7-amine Chemical compound C1N(C(C)C)CC2=CC(N)=CC=C2C21CC2 FOAUHWOFIUVODV-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- RVBUGGBMJDPOST-UHFFFAOYSA-N 2-thiobarbituric acid Chemical compound O=C1CC(=O)NC(=S)N1 RVBUGGBMJDPOST-UHFFFAOYSA-N 0.000 description 1
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 description 1
- ICDBZRYXNCPKRM-UHFFFAOYSA-N 3,4-dihydroisoquinolin-7-amine Chemical compound C1CN=CC2=CC(N)=CC=C21 ICDBZRYXNCPKRM-UHFFFAOYSA-N 0.000 description 1
- ZJRSKTXMSIVNAU-UHFFFAOYSA-N 3-amino-4-iodopyridine Chemical compound NC1=CN=CC=C1I ZJRSKTXMSIVNAU-UHFFFAOYSA-N 0.000 description 1
- ROADCYAOHVSOLQ-UHFFFAOYSA-N 3-oxetanone Chemical compound O=C1COC1 ROADCYAOHVSOLQ-UHFFFAOYSA-N 0.000 description 1
- WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 description 1
- CNPURSDMOWDNOQ-UHFFFAOYSA-N 4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound COC1=NC(N)=NC2=C1C=CN2 CNPURSDMOWDNOQ-UHFFFAOYSA-N 0.000 description 1
- MRUWJENAYHTDQG-UHFFFAOYSA-N 4H-pyran Chemical compound C1C=COC=C1 MRUWJENAYHTDQG-UHFFFAOYSA-N 0.000 description 1
- UCZQXJKDCHCTAI-UHFFFAOYSA-N 4h-1,3-dioxine Chemical compound C1OCC=CO1 UCZQXJKDCHCTAI-UHFFFAOYSA-N 0.000 description 1
- VSEBFWRYDORZJI-UHFFFAOYSA-N 5-nitro-1,3-dihydroinden-2-one Chemical compound [O-][N+](=O)C1=CC=C2CC(=O)CC2=C1 VSEBFWRYDORZJI-UHFFFAOYSA-N 0.000 description 1
- AYLQLJZSJWZVGJ-UHFFFAOYSA-N 6-methyl-7,8-dihydro-5h-1,6-naphthyridin-2-amine Chemical compound NC1=CC=C2CN(C)CCC2=N1 AYLQLJZSJWZVGJ-UHFFFAOYSA-N 0.000 description 1
- YWVJXRLEURDFAJ-UHFFFAOYSA-N 6-methyl-7,8-dihydro-5h-1,6-naphthyridin-3-amine Chemical compound C1=C(N)C=C2CN(C)CCC2=N1 YWVJXRLEURDFAJ-UHFFFAOYSA-N 0.000 description 1
- VNUQVKZHEBCTNT-UHFFFAOYSA-N 7-amino-3,4-dihydro-2h-isoquinolin-1-one Chemical compound C1CNC(=O)C2=CC(N)=CC=C21 VNUQVKZHEBCTNT-UHFFFAOYSA-N 0.000 description 1
- XMJQDQBUALBXKH-UHFFFAOYSA-N 7-aminospiro[1,3-dihydroisoquinoline-4,1'-cyclopropane]-2-carboxylic acid Chemical compound C=1C(N)=CC=C2C=1CN(C(O)=O)CC21CC1 XMJQDQBUALBXKH-UHFFFAOYSA-N 0.000 description 1
- IAXZYZLBSPZMGH-UHFFFAOYSA-N 7-benzyl-1,5,6,8-tetrahydro-1,7-naphthyridin-2-one Chemical compound C1C=2NC(=O)C=CC=2CCN1CC1=CC=CC=C1 IAXZYZLBSPZMGH-UHFFFAOYSA-N 0.000 description 1
- CNXWOMHHSOZWIA-UHFFFAOYSA-N 7-nitro-2-propan-2-ylspiro[1,3-dihydroisoquinoline-4,1'-cyclopropane] Chemical compound C(C)(C)N1CC2=CC(=CC=C2C2(C1)CC2)[N+](=O)[O-] CNXWOMHHSOZWIA-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 239000012099 Alexa Fluor family Substances 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 125000000041 C6-C10 aryl group Chemical group 0.000 description 1
- 125000005915 C6-C14 aryl group Chemical group 0.000 description 1
- WOBLPQMIMKNCIR-UHFFFAOYSA-N CC(C)(O)C1=CC=CC(=N1)N1N(CC=C)C(=O)C2=C1N=C(NC1=CC=C3C(CNCC3(C)C)=C1)N=C2 Chemical compound CC(C)(O)C1=CC=CC(=N1)N1N(CC=C)C(=O)C2=C1N=C(NC1=CC=C3C(CNCC3(C)C)=C1)N=C2 WOBLPQMIMKNCIR-UHFFFAOYSA-N 0.000 description 1
- JZNQZUXXRGOTBT-UHFFFAOYSA-N CC(C)(O)C1=CC=CC(=N1)N1N(CC=C)C(=O)C2=C1N=C(NC1=CC=C3CCNCC3=C1)N=C2 Chemical compound CC(C)(O)C1=CC=CC(=N1)N1N(CC=C)C(=O)C2=C1N=C(NC1=CC=C3CCNCC3=C1)N=C2 JZNQZUXXRGOTBT-UHFFFAOYSA-N 0.000 description 1
- REGNBRLNVNNABP-UHFFFAOYSA-N CC(C)(O)C1=CC=CC(=N1)N1N(CC=C)C(=O)C2=C1N=C(NC1=CC=C3CNCCC3=C1)N=C2 Chemical compound CC(C)(O)C1=CC=CC(=N1)N1N(CC=C)C(=O)C2=C1N=C(NC1=CC=C3CNCCC3=C1)N=C2 REGNBRLNVNNABP-UHFFFAOYSA-N 0.000 description 1
- XRLVZQOAYKJPKT-UHFFFAOYSA-N CC(C)(O)c1cccc(n1)-n1n(CC=C)c(=O)c2cnc(Nc3ccc4CN(CCc4c3)C3COC3)nc12 Chemical compound CC(C)(O)c1cccc(n1)-n1n(CC=C)c(=O)c2cnc(Nc3ccc4CN(CCc4c3)C3COC3)nc12 XRLVZQOAYKJPKT-UHFFFAOYSA-N 0.000 description 1
- USRRDSNROPAIAN-UHFFFAOYSA-N CC1N(CC(C)(C)C2=C1C=C(N)C=C2)C(=O)OC(C)(C)C Chemical compound CC1N(CC(C)(C)C2=C1C=C(N)C=C2)C(=O)OC(C)(C)C USRRDSNROPAIAN-UHFFFAOYSA-N 0.000 description 1
- RBJMZCQXBGXAAQ-UHFFFAOYSA-N CC1N(CC(C)(C)c2ccc(cc12)[N+]([O-])=O)C(=O)OC(C)(C)C Chemical compound CC1N(CC(C)(C)c2ccc(cc12)[N+]([O-])=O)C(=O)OC(C)(C)C RBJMZCQXBGXAAQ-UHFFFAOYSA-N 0.000 description 1
- YCSMRTDYKWCSFC-UHFFFAOYSA-N CC1NCC(C)(C)c2ccc(cc12)[N+]([O-])=O Chemical compound CC1NCC(C)(C)c2ccc(cc12)[N+]([O-])=O YCSMRTDYKWCSFC-UHFFFAOYSA-N 0.000 description 1
- SWVJBZZZZVUFGL-UHFFFAOYSA-N CN(C)C1Cc2ccc(Nc3ncc4c(n3)n(-c3cccc(n3)C(C)(C)O)n(CC=C)c4=O)cc2C1 Chemical compound CN(C)C1Cc2ccc(Nc3ncc4c(n3)n(-c3cccc(n3)C(C)(C)O)n(CC=C)c4=O)cc2C1 SWVJBZZZZVUFGL-UHFFFAOYSA-N 0.000 description 1
- JKZNAPFFSTYVBO-UHFFFAOYSA-N CN1CC2=C(C=CC(Cl)=C2)C(F)(F)C1 Chemical compound CN1CC2=C(C=CC(Cl)=C2)C(F)(F)C1 JKZNAPFFSTYVBO-UHFFFAOYSA-N 0.000 description 1
- DDEWQOWVNDYQSR-UHFFFAOYSA-N CN1CC2=CC(NC3=NC4=C(C=N3)C(=O)N(CC=C)N4C3=NC(=CC=C3)C(C)(C)O)=CC=C2C(C)(C)C1 Chemical compound CN1CC2=CC(NC3=NC4=C(C=N3)C(=O)N(CC=C)N4C3=NC(=CC=C3)C(C)(C)O)=CC=C2C(C)(C)C1 DDEWQOWVNDYQSR-UHFFFAOYSA-N 0.000 description 1
- HRASECDAYBQKKB-UHFFFAOYSA-N CN1CCc2ccc(Nc3ncc4c(n3)n(-c3cccc(n3)C(C)(C)O)n(CC=C)c4=O)nc2C1 Chemical compound CN1CCc2ccc(Nc3ncc4c(n3)n(-c3cccc(n3)C(C)(C)O)n(CC=C)c4=O)nc2C1 HRASECDAYBQKKB-UHFFFAOYSA-N 0.000 description 1
- AIIQGACKJFCVPT-UHFFFAOYSA-N CN1CCc2nc(Nc3ncc4c(n3)n(-c3cccc(n3)C(C)(C)O)n(CC=C)c4=O)ccc2C1 Chemical compound CN1CCc2nc(Nc3ncc4c(n3)n(-c3cccc(n3)C(C)(C)O)n(CC=C)c4=O)ccc2C1 AIIQGACKJFCVPT-UHFFFAOYSA-N 0.000 description 1
- HMBWORYDEKEWDM-UHFFFAOYSA-N CN1CCc2ncc(Nc3ncc4c(n3)n(-c3cccc(n3)C(C)(C)O)n(CC=C)c4=O)cc2C1 Chemical compound CN1CCc2ncc(Nc3ncc4c(n3)n(-c3cccc(n3)C(C)(C)O)n(CC=C)c4=O)cc2C1 HMBWORYDEKEWDM-UHFFFAOYSA-N 0.000 description 1
- XRJLQSGHVNNKIO-KRWDZBQOSA-N C[C@@H]1NCC(C)(C)c2ccc(Nc3ncc4c(n3)n(-c3cccc(n3)C(C)(C)O)n(CC=C)c4=O)cc12 Chemical compound C[C@@H]1NCC(C)(C)c2ccc(Nc3ncc4c(n3)n(-c3cccc(n3)C(C)(C)O)n(CC=C)c4=O)cc12 XRJLQSGHVNNKIO-KRWDZBQOSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 241000938605 Crocodylia Species 0.000 description 1
- 241000238424 Crustacea Species 0.000 description 1
- 239000012623 DNA damaging agent Substances 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
- 206010012735 Diarrhoea Diseases 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 230000037057 G1 phase arrest Effects 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 238000010268 HPLC based assay Methods 0.000 description 1
- 241001272567 Hominoidea Species 0.000 description 1
- 101000868333 Homo sapiens Cyclin-dependent kinase 1 Proteins 0.000 description 1
- 101000909198 Homo sapiens DNA polymerase delta catalytic subunit Proteins 0.000 description 1
- 101000777293 Homo sapiens Serine/threonine-protein kinase Chk1 Proteins 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 229910010082 LiAlH Inorganic materials 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 102100031081 Serine/threonine-protein kinase Chk1 Human genes 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 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
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
- 239000012964 benzotriazole Substances 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 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
- 238000004166 bioassay Methods 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-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
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000006369 cell cycle progression Effects 0.000 description 1
- 108091092356 cellular DNA Proteins 0.000 description 1
- 229910052729 chemical element Inorganic materials 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 229940124301 concurrent medication Drugs 0.000 description 1
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 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 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000005508 decahydronaphthalenyl group Chemical group 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- SNQXJPARXFUULZ-UHFFFAOYSA-N dioxolane Chemical compound C1COOC1 SNQXJPARXFUULZ-UHFFFAOYSA-N 0.000 description 1
- SXZIXHOMFPUIRK-UHFFFAOYSA-N diphenylmethanimine Chemical compound C=1C=CC=CC=1C(=N)C1=CC=CC=C1 SXZIXHOMFPUIRK-UHFFFAOYSA-N 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000008029 eradication Effects 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- IRSJDVYTJUCXRV-UHFFFAOYSA-N ethyl 2-bromo-2,2-difluoroacetate Chemical compound CCOC(=O)C(F)(F)Br IRSJDVYTJUCXRV-UHFFFAOYSA-N 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 239000010200 folin Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 150000002244 furazanes Chemical class 0.000 description 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N glycerol 1-phosphate Chemical compound OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 1
- 229940091173 hydantoin Drugs 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000005461 lubrication Methods 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- YNHWTTUTWBNFGQ-UHFFFAOYSA-N methyl 2-(2-iodophenyl)acetate Chemical compound COC(=O)CC1=CC=CC=C1I YNHWTTUTWBNFGQ-UHFFFAOYSA-N 0.000 description 1
- BXXLTVBTDZXPTN-UHFFFAOYSA-N methyl 2-iodobenzoate Chemical compound COC(=O)C1=CC=CC=C1I BXXLTVBTDZXPTN-UHFFFAOYSA-N 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 125000006682 monohaloalkyl group Chemical group 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- OGBUEPQWMSSWCR-UHFFFAOYSA-N n,n-dimethyl-5-nitro-2,3-dihydro-1h-inden-2-amine Chemical compound C1=C([N+]([O-])=O)C=C2CC(N(C)C)CC2=C1 OGBUEPQWMSSWCR-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000001326 naphthylalkyl group Chemical group 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 208000004235 neutropenia Diseases 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 125000005593 norbornanyl group Chemical group 0.000 description 1
- 230000004768 organ dysfunction Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
- JTHRRMFZHSDGNJ-UHFFFAOYSA-N piperazine-2,3-dione Chemical compound O=C1NCCNC1=O JTHRRMFZHSDGNJ-UHFFFAOYSA-N 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 125000006684 polyhaloalkyl group Polymers 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000004323 potassium nitrate Substances 0.000 description 1
- 235000010333 potassium nitrate Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000012041 precatalyst Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
- DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 241000894007 species Species 0.000 description 1
- LKOZZVJLXRDMHK-UHFFFAOYSA-N spiro[1,2-dihydroisoquinoline-4,1'-cyclopropane]-3-one Chemical compound O=C1NCC2=CC=CC=C2C11CC1 LKOZZVJLXRDMHK-UHFFFAOYSA-N 0.000 description 1
- LBJQKYPPYSCCBH-UHFFFAOYSA-N spiro[3.3]heptane Chemical group C1CCC21CCC2 LBJQKYPPYSCCBH-UHFFFAOYSA-N 0.000 description 1
- CTDQAGUNKPRERK-UHFFFAOYSA-N spirodecane Chemical compound C1CCCC21CCCCC2 CTDQAGUNKPRERK-UHFFFAOYSA-N 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- WJFWIRWHYIDBAQ-UHFFFAOYSA-N tert-butyl 5-amino-1,3-dihydroisoindole-2-carboxylate Chemical compound C1=C(N)C=C2CN(C(=O)OC(C)(C)C)CC2=C1 WJFWIRWHYIDBAQ-UHFFFAOYSA-N 0.000 description 1
- MUWKVARUMOGZBW-UHFFFAOYSA-N tert-butyl 7-nitro-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound C1=C([N+]([O-])=O)C=C2CN(C(=O)OC(C)(C)C)CCC2=C1 MUWKVARUMOGZBW-UHFFFAOYSA-N 0.000 description 1
- HKWQZZQLVYRRGT-UHFFFAOYSA-N tert-butyl-dimethyl-[2-(7-nitro-3,4-dihydro-1h-isoquinolin-2-yl)ethoxy]silane Chemical compound C1=C([N+]([O-])=O)C=C2CN(CCO[Si](C)(C)C(C)(C)C)CCC2=C1 HKWQZZQLVYRRGT-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000004952 trihaloalkoxy group Chemical group 0.000 description 1
- 125000004385 trihaloalkyl group Chemical group 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 238000000836 variable-temperature nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762539734P | 2017-08-01 | 2017-08-01 | |
| US62/539,734 | 2017-08-01 | ||
| PCT/US2018/044580 WO2019028008A1 (en) | 2017-08-01 | 2018-07-31 | 1,2-DIHYDRO-3H-PYRAZOLO [3,4-D] PYRIMIDIN-3-ONE ANALOGUES |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20200034781A true KR20200034781A (ko) | 2020-03-31 |
Family
ID=65233095
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020207005636A Ceased KR20200034781A (ko) | 2017-08-01 | 2018-07-31 | 1,2-다이하이드로-3H-피라졸로[3,4-d]피리미딘-3-온 유사체 |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US11124518B2 (enExample) |
| EP (1) | EP3661918B1 (enExample) |
| JP (1) | JP7203816B2 (enExample) |
| KR (1) | KR20200034781A (enExample) |
| CN (1) | CN111094253B (enExample) |
| AR (1) | AR112774A1 (enExample) |
| AU (1) | AU2018312448B2 (enExample) |
| BR (1) | BR112020002104A2 (enExample) |
| CA (1) | CA3071405A1 (enExample) |
| ES (1) | ES2980537T3 (enExample) |
| IL (1) | IL272262A (enExample) |
| MX (1) | MX2020001235A (enExample) |
| RU (1) | RU2020105058A (enExample) |
| SG (1) | SG11202000789WA (enExample) |
| TW (1) | TW201910335A (enExample) |
| WO (1) | WO2019028008A1 (enExample) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2018347307A1 (en) | 2017-10-09 | 2020-04-23 | Nuvation Bio Inc. | Heterocyclic compounds and uses thereof |
| EP3694861A4 (en) * | 2017-10-09 | 2021-05-19 | Nuvation Bio Inc. | HETEROCYCLIC COMPOUNDS AND USES THEREOF |
| CA3088997A1 (en) * | 2018-02-28 | 2019-09-06 | The Regents Of The University Of Colorado, A Body Corporate | Wee1 kinase inhibitors and methods of treating cancer using the same |
| RS66798B1 (sr) * | 2018-03-09 | 2025-06-30 | Recurium Ip Holdings Llc | Supstituisani 1,2-dihidro-3h-pirazolo[3,4-d]pirimidin-3-oni |
| CN110872296B (zh) * | 2018-08-31 | 2023-05-23 | 上海弘翊生物科技有限公司 | 一种二氢异吲哚-1H-吡唑并[3,4-d]嘧啶酮化合物、其制备方法和应用 |
| EP3952876A4 (en) * | 2019-04-09 | 2023-04-19 | Nuvation Bio Inc. | HETEROCYCLIC COMPOUNDS AND THEIR USES |
| WO2020210380A1 (en) * | 2019-04-09 | 2020-10-15 | Nuvation Bio Inc. | Heterocyclic compounds and uses thereof |
| CN113939296A (zh) * | 2019-04-09 | 2022-01-14 | 诺维逊生物股份有限公司 | 杂环化合物及其用途 |
| WO2020210320A1 (en) * | 2019-04-11 | 2020-10-15 | Recurium Ip Holdings, Llc | Substituted l,2-dihydro-3h-pyrazolo[3,4-d]pyrimidin-3-ones |
| KR20220042127A (ko) | 2019-06-28 | 2022-04-04 | 상하이 파마슈티컬스 홀딩 컴퍼니 리미티드 | 피라졸로피리미딘 화합물, 그의 제조 방법 및 그의 응용 |
| CN112142748B (zh) * | 2019-06-28 | 2023-07-04 | 上海医药集团股份有限公司 | 一种吡唑酮并嘧啶类化合物、其制备方法及应用 |
| CN112442049A (zh) * | 2019-09-03 | 2021-03-05 | 微境生物医药科技(上海)有限公司 | 作为Wee1抑制剂的嘧啶衍生物 |
| KR20220103748A (ko) | 2019-11-15 | 2022-07-22 | 리커리엄 아이피 홀딩스, 엘엘씨 | 3차 알코올의 키랄 합성 |
| EP4069235A4 (en) * | 2019-12-20 | 2024-01-10 | Recurium IP Holdings, LLC | ASSOCIATIONS |
| NZ793883A (en) * | 2020-05-15 | 2025-11-28 | Recurium Ip Holdings Llc | Mono- and combination therapies |
| WO2021254389A1 (zh) * | 2020-06-17 | 2021-12-23 | 微境生物医药科技(上海)有限公司 | 作为Wee-1抑制剂的吡唑并[3，4-d]嘧啶-3-酮衍生物 |
| CN114805357B (zh) * | 2021-01-21 | 2023-12-19 | 四川大学 | 一种靶向setdb1-ttd的小分子抑制剂及其制药用途 |
| KR20240004539A (ko) * | 2021-04-30 | 2024-01-11 | 위겐 바이오메더슨 테크널러지 (상하이) 컴퍼니 리미티드 | Wee-1 억제제로서의 축합 고리 화합물, 그를 위한 제조 방법 및 그의 용도 |
| CN117751122A (zh) * | 2021-08-11 | 2024-03-22 | 微境生物医药科技(上海)有限公司 | 作为Wee-1抑制剂的1,2-二氢-3H-吡唑[3,4-d]嘧啶-3-酮化合物 |
| CN117940430B (zh) * | 2021-09-22 | 2025-10-31 | 微境生物医药科技(上海)有限公司 | 作为Wee-1抑制剂的1,2-二氢-3H-吡唑[3,4-d]嘧啶-3-酮化合物 |
| WO2023166080A1 (en) | 2022-03-01 | 2023-09-07 | Step Pharma S.A.S. | Combination treatments comprising a ctps1 inhibitor and a wee1 inhibitor |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2594425A1 (en) * | 2005-01-14 | 2006-07-20 | Janssen Pharmaceutica N.V. | 5-membered annelated heterocyclic pyrimidines as kinase inhibitors |
| AR060635A1 (es) * | 2006-04-27 | 2008-07-02 | Banyu Pharma Co Ltd | Derivados de 1,2-dihidro-3h-pirazolo[3,4-d]pirimidin-3-ona, composiciones farmaceuticas que los comprenden y su uso en el tratamiento del cancer |
| WO2009054332A1 (ja) * | 2007-10-23 | 2009-04-30 | Banyu Pharmaceutical Co., Ltd. | ピリドン置換ジヒドロピラゾロピリミジノン誘導体 |
| RS58956B1 (sr) * | 2012-09-10 | 2019-08-30 | Principia Biopharma Inc | Jedinjenja pirazolopirimidina kao inhibitori kinaze |
| GB201612092D0 (en) * | 2016-07-12 | 2016-08-24 | Almac Discovery Ltd | Pharmaceutical compounds |
-
2018
- 2018-07-31 TW TW107126578A patent/TW201910335A/zh unknown
- 2018-07-31 KR KR1020207005636A patent/KR20200034781A/ko not_active Ceased
- 2018-07-31 BR BR112020002104-0A patent/BR112020002104A2/pt not_active Application Discontinuation
- 2018-07-31 JP JP2020505356A patent/JP7203816B2/ja active Active
- 2018-07-31 ES ES18842344T patent/ES2980537T3/es active Active
- 2018-07-31 AU AU2018312448A patent/AU2018312448B2/en not_active Ceased
- 2018-07-31 CA CA3071405A patent/CA3071405A1/en active Pending
- 2018-07-31 RU RU2020105058A patent/RU2020105058A/ru unknown
- 2018-07-31 US US16/635,348 patent/US11124518B2/en active Active
- 2018-07-31 WO PCT/US2018/044580 patent/WO2019028008A1/en not_active Ceased
- 2018-07-31 CN CN201880059242.4A patent/CN111094253B/zh active Active
- 2018-07-31 MX MX2020001235A patent/MX2020001235A/es unknown
- 2018-07-31 EP EP18842344.6A patent/EP3661918B1/en active Active
- 2018-07-31 SG SG11202000789WA patent/SG11202000789WA/en unknown
- 2018-08-01 AR ARP180102185A patent/AR112774A1/es not_active Application Discontinuation
-
2020
- 2020-01-26 IL IL272262A patent/IL272262A/en unknown
-
2021
- 2021-06-15 US US17/304,154 patent/US20210317124A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP3661918B1 (en) | 2024-05-08 |
| WO2019028008A1 (en) | 2019-02-07 |
| RU2020105058A3 (enExample) | 2021-11-17 |
| JP7203816B2 (ja) | 2023-01-13 |
| RU2020105058A (ru) | 2021-09-02 |
| AU2018312448B2 (en) | 2022-09-15 |
| AU2018312448A1 (en) | 2020-02-13 |
| ES2980537T3 (es) | 2024-10-01 |
| IL272262A (en) | 2020-03-31 |
| CA3071405A1 (en) | 2019-02-07 |
| TW201910335A (zh) | 2019-03-16 |
| MX2020001235A (es) | 2020-07-20 |
| AR112774A1 (es) | 2019-12-11 |
| EP3661918A1 (en) | 2020-06-10 |
| CN111094253A (zh) | 2020-05-01 |
| US20210317124A1 (en) | 2021-10-14 |
| EP3661918C0 (en) | 2024-05-08 |
| CN111094253B (zh) | 2023-08-29 |
| US11124518B2 (en) | 2021-09-21 |
| SG11202000789WA (en) | 2020-02-27 |
| US20200157112A1 (en) | 2020-05-21 |
| BR112020002104A2 (pt) | 2020-08-04 |
| EP3661918A4 (en) | 2021-05-12 |
| JP2020529993A (ja) | 2020-10-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7203816B2 (ja) | １，２－ジヒドロ－３Ｈ－ピラゾロ［３，４－ｄ］ピリミジン－３－オン類似体 | |
| JP7726563B2 (ja) | 置換１，２－ジヒドロ－３Ｈ－ピラゾロ［３，４－ｄ］ピリミジン－３－オン | |
| KR20220133874A (ko) | 매크로사이클릭 화합물 | |
| RU2847224C2 (ru) | Замещенные 1,2-дигидро-3н-пиразоло[3,4-d]пиримидин-3-оны | |
| RU2812726C2 (ru) | Замещенные 1,2-дигидро-3н-пиразоло[3,4-d]пиримидин-3-оны | |
| HK40043303A (en) | Substituted 1,2-dihydro-3h-pyrazolo[3,4-d]pyrimidin-3-ones | |
| HK40043303B (en) | Substituted 1,2-dihydro-3h-pyrazolo[3,4-d]pyrimidin-3-ones |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20200226 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20210716 Comment text: Request for Examination of Application |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20230718 Patent event code: PE09021S01D |
|
| E601 | Decision to refuse application | ||
| PE0601 | Decision on rejection of patent |
Patent event date: 20231006 Comment text: Decision to Refuse Application Patent event code: PE06012S01D Patent event date: 20230718 Comment text: Notification of reason for refusal Patent event code: PE06011S01I |