IL307317A - תרכובת דימר רעילה של dna וצימוד שלה - Google Patents

Info

Publication number

IL307317A

IL307317A IL307317A IL30731723A IL307317A IL 307317 A IL307317 A IL 307317A IL 307317 A IL307317 A IL 307317A IL 30731723 A IL30731723 A IL 30731723A IL 307317 A IL307317 A IL 307317A

Authority

IL

Israel

Prior art keywords

compound

antibody

group

mmol

reaction

Prior art date

2021-04-01

Links

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• 150000001875 compounds Chemical class 0.000 title claims description 435
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• 230000002588 toxic effect Effects 0.000 title description 8
• 239000000539 dimer Substances 0.000 title description 6
• -1 hydroxy, amino Chemical group 0.000 claims description 99
• 125000000217 alkyl group Chemical group 0.000 claims description 67
• 239000003814 drug Substances 0.000 claims description 62
• 229940079593 drug Drugs 0.000 claims description 61
• 150000003839 salts Chemical class 0.000 claims description 46
• 125000001118 alkylidene group Chemical group 0.000 claims description 44
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 35
• 239000012453 solvate Substances 0.000 claims description 33
• 239000003446 ligand Substances 0.000 claims description 31
• 206010028980 Neoplasm Diseases 0.000 claims description 30
• 229910052739 hydrogen Inorganic materials 0.000 claims description 28
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 25
• 125000004432 carbon atom Chemical group C* 0.000 claims description 24
• 125000005647 linker group Chemical group 0.000 claims description 23
• 229910052736 halogen Inorganic materials 0.000 claims description 22
• 229910052757 nitrogen Inorganic materials 0.000 claims description 22
• 150000001413 amino acids Chemical class 0.000 claims description 21
• 125000003118 aryl group Chemical group 0.000 claims description 21
• 150000002367 halogens Chemical class 0.000 claims description 21
• 235000001014 amino acid Nutrition 0.000 claims description 19
• 229910052805 deuterium Inorganic materials 0.000 claims description 19
• 229910052799 carbon Inorganic materials 0.000 claims description 18
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 17
• 125000001072 heteroaryl group Chemical group 0.000 claims description 17
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 16
• 125000000623 heterocyclic group Chemical group 0.000 claims description 13
• 108090000765 processed proteins & peptides Chemical group 0.000 claims description 13
• 229910052717 sulfur Inorganic materials 0.000 claims description 13
• 125000003342 alkenyl group Chemical group 0.000 claims description 11
• 125000003545 alkoxy group Chemical group 0.000 claims description 11
• 125000000304 alkynyl group Chemical group 0.000 claims description 11
• 150000001975 deuterium Chemical group 0.000 claims description 11
• 125000005345 deuteroalkyl group Chemical group 0.000 claims description 11
• 125000001424 substituent group Chemical group 0.000 claims description 11
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• 108090000623 proteins and genes Proteins 0.000 claims description 9
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 8
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 8
• 230000027455 binding Effects 0.000 claims description 8
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
• 125000006165 cyclic alkyl group Chemical group 0.000 claims description 8
• 125000001188 haloalkyl group Chemical group 0.000 claims description 8
• 125000001183 hydrocarbyl group Chemical group 0.000 claims description 8
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
• 239000000126 substance Substances 0.000 claims description 7
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 7
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 6
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 6
• LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 claims description 6
• 230000002378 acidificating effect Effects 0.000 claims description 6
• 125000002947 alkylene group Chemical group 0.000 claims description 6
• 239000012634 fragment Substances 0.000 claims description 6
• 125000000524 functional group Chemical group 0.000 claims description 6
• 125000005842 heteroatom Chemical group 0.000 claims description 6
• 239000001257 hydrogen Substances 0.000 claims description 6
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• 125000005843 halogen group Chemical group 0.000 claims description 5
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• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
• 230000001225 therapeutic effect Effects 0.000 claims description 5
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
• 206010009944 Colon cancer Diseases 0.000 claims description 4
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 4
• 125000002070 alkenylidene group Chemical group 0.000 claims description 4
• 125000000539 amino acid group Chemical group 0.000 claims description 4
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
• VNEOHNUYPRAJMX-UHFFFAOYSA-N 3-[[2-[[2-amino-3-(1h-indol-3-yl)propanoyl]amino]-4-methylpentanoyl]amino]-4-[[1-(butoxycarbonylamino)-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoic acid Chemical compound C=1NC2=CC=CC=C2C=1CC(N)C(=O)NC(CC(C)C)C(=O)NC(CC(O)=O)C(=O)NC(C(=O)NC(=O)OCCCC)CC1=CC=CC=C1 VNEOHNUYPRAJMX-UHFFFAOYSA-N 0.000 claims description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 3
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 3
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims description 3
• 101000606465 Homo sapiens Inactive tyrosine-protein kinase 7 Proteins 0.000 claims description 3
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
• 102100039813 Inactive tyrosine-protein kinase 7 Human genes 0.000 claims description 3
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 3
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 3
• 241001529936 Murinae Species 0.000 claims description 3
• 229910002651 NO3 Inorganic materials 0.000 claims description 3
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 3
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 3
• 108091006576 SLC34A2 Proteins 0.000 claims description 3
• 102100038437 Sodium-dependent phosphate transport protein 2B Human genes 0.000 claims description 3
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 3
• 229940072107 ascorbate Drugs 0.000 claims description 3
• 235000010323 ascorbic acid Nutrition 0.000 claims description 3
• 239000011668 ascorbic acid Substances 0.000 claims description 3
• 229940077388 benzenesulfonate Drugs 0.000 claims description 3
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims description 3
• 239000011575 calcium Substances 0.000 claims description 3
• 229910052791 calcium Inorganic materials 0.000 claims description 3
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 claims description 3
• 229940044170 formate Drugs 0.000 claims description 3
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• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 claims description 3
• 159000000003 magnesium salts Chemical class 0.000 claims description 3
• 229920001481 poly(stearyl methacrylate) Polymers 0.000 claims description 3
• 239000011591 potassium Substances 0.000 claims description 3
• 229910052700 potassium Inorganic materials 0.000 claims description 3
• YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 claims description 3
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• 239000011734 sodium Substances 0.000 claims description 3
• 229910052708 sodium Inorganic materials 0.000 claims description 3
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 3
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• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
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