JP2020519583A - （３ｒ，４ｓ）−３−アセトアミド−４−アリル−ｎ−（ｔｅｒｔ−ブチル）ピロリジン−３−カルボキサミドの製造方法 - Google Patents
（３ｒ，４ｓ）−３−アセトアミド−４−アリル−ｎ−（ｔｅｒｔ−ブチル）ピロリジン−３−カルボキサミドの製造方法 Download PDFInfo
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- JP2020519583A JP2020519583A JP2019561210A JP2019561210A JP2020519583A JP 2020519583 A JP2020519583 A JP 2020519583A JP 2019561210 A JP2019561210 A JP 2019561210A JP 2019561210 A JP2019561210 A JP 2019561210A JP 2020519583 A JP2020519583 A JP 2020519583A
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- amine compound
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- 238000000034 method Methods 0.000 title claims abstract description 46
- 230000008569 process Effects 0.000 title claims description 23
- IQHXABCGSFAKPN-UHFFFAOYSA-N pyrrolidine-3-carboxamide Chemical compound NC(=O)C1CCNC1 IQHXABCGSFAKPN-UHFFFAOYSA-N 0.000 title abstract description 20
- -1 amine compound Chemical class 0.000 claims description 162
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 107
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 99
- 125000000217 alkyl group Chemical group 0.000 claims description 83
- 239000000243 solution Substances 0.000 claims description 80
- 150000003839 salts Chemical class 0.000 claims description 78
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 36
- 150000001875 compounds Chemical class 0.000 claims description 35
- 125000000623 heterocyclic group Chemical group 0.000 claims description 33
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 32
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 23
- 125000001072 heteroaryl group Chemical group 0.000 claims description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 21
- 238000002425 crystallisation Methods 0.000 claims description 20
- 230000008025 crystallization Effects 0.000 claims description 20
- 239000011549 crystallization solution Substances 0.000 claims description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 18
- 239000002904 solvent Substances 0.000 claims description 18
- 125000005842 heteroatom Chemical group 0.000 claims description 16
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical group 0.000 claims description 15
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- 125000002252 acyl group Chemical group 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 125000004423 acyloxy group Chemical group 0.000 claims description 11
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 9
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 8
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 8
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 7
- 150000008052 alkyl sulfonates Chemical group 0.000 claims description 6
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 239000002243 precursor Substances 0.000 claims description 5
- 150000008055 alkyl aryl sulfonates Chemical group 0.000 claims description 4
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 4
- 238000006197 hydroboration reaction Methods 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 4
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 229940080328 Arginase inhibitor Drugs 0.000 claims description 3
- 238000001640 fractional crystallisation Methods 0.000 claims description 3
- 239000006228 supernatant Substances 0.000 claims description 3
- 125000003143 4-hydroxybenzyl group Chemical group [H]C([*])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 claims description 2
- 238000007112 amidation reaction Methods 0.000 claims description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 2
- 150000003335 secondary amines Chemical class 0.000 claims 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 abstract description 19
- 238000010956 selective crystallization Methods 0.000 abstract description 13
- 235000019439 ethyl acetate Nutrition 0.000 description 35
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
- 125000001424 substituent group Chemical group 0.000 description 26
- 125000003118 aryl group Chemical group 0.000 description 24
- 125000001183 hydrocarbyl group Chemical group 0.000 description 24
- 229910052739 hydrogen Inorganic materials 0.000 description 24
- 150000001412 amines Chemical class 0.000 description 22
- 238000004296 chiral HPLC Methods 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- 125000004429 atom Chemical group 0.000 description 19
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 229920006395 saturated elastomer Polymers 0.000 description 17
- 238000003786 synthesis reaction Methods 0.000 description 16
- 229910052799 carbon Inorganic materials 0.000 description 15
- 239000001257 hydrogen Substances 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 102000004452 Arginase Human genes 0.000 description 12
- 108700024123 Arginases Proteins 0.000 description 12
- 125000003342 alkenyl group Chemical group 0.000 description 12
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 description 11
- 125000000304 alkynyl group Chemical group 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- VCFKXWGKKDZMPO-LLVKDONJSA-N 2-[[(1r)-1-phenylethyl]carbamoyl]benzoic acid Chemical compound N([C@H](C)C=1C=CC=CC=1)C(=O)C1=CC=CC=C1C(O)=O VCFKXWGKKDZMPO-LLVKDONJSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 10
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 10
- 239000003112 inhibitor Substances 0.000 description 10
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 9
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
- 125000003545 alkoxy group Chemical group 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 238000001816 cooling Methods 0.000 description 9
- YUZORMGPDNJKHY-IRXDYDNUSA-N (2s,3s)-2,3-dibenzoyloxy-4-oxo-4-(propan-2-ylamino)butanoic acid Chemical compound O([C@H](C(=O)NC(C)C)[C@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 YUZORMGPDNJKHY-IRXDYDNUSA-N 0.000 description 8
- 239000002178 crystalline material Substances 0.000 description 8
- 238000006467 substitution reaction Methods 0.000 description 8
- LINPSOODYGSBAH-HOTGVXAUSA-N (2s,3s)-2,3-dibenzoyloxy-4-(dimethylamino)-4-oxobutanoic acid Chemical compound O([C@H](C(=O)N(C)C)[C@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 LINPSOODYGSBAH-HOTGVXAUSA-N 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- GUJPCNNCXFKSFY-UXHICEINSA-N C(C)(C)NC([C@H]([C@@H](C(C(=O)O)=O)OC(C1=CC=C(C=C1)C)=O)OC(C1=CC=C(C=C1)C)=O)=O Chemical compound C(C)(C)NC([C@H]([C@@H](C(C(=O)O)=O)OC(C1=CC=C(C=C1)C)=O)OC(C1=CC=C(C=C1)C)=O)=O GUJPCNNCXFKSFY-UXHICEINSA-N 0.000 description 7
- HERDIXDWRYMFKG-ROUUACIJSA-N C(C1=CC=CC=C1)(=O)O[C@H](C(=O)O)[C@@H](C(=O)N(CC)CC)OC(C1=CC=CC=C1)=O Chemical compound C(C1=CC=CC=C1)(=O)O[C@H](C(=O)O)[C@@H](C(=O)N(CC)CC)OC(C1=CC=CC=C1)=O HERDIXDWRYMFKG-ROUUACIJSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 125000004122 cyclic group Chemical group 0.000 description 7
- 125000000547 substituted alkyl group Chemical group 0.000 description 7
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- NQJVKRWCFTYRCZ-ROUUACIJSA-N C(C1=CC=CC=C1)(=O)O[C@H](C(=O)O)[C@@H](C(N1CCCC1)=O)OC(C1=CC=CC=C1)=O Chemical compound C(C1=CC=CC=C1)(=O)O[C@H](C(=O)O)[C@@H](C(N1CCCC1)=O)OC(C1=CC=CC=C1)=O NQJVKRWCFTYRCZ-ROUUACIJSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 6
- 125000002619 bicyclic group Chemical group 0.000 description 6
- 125000004093 cyano group Chemical group *C#N 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 239000011347 resin Substances 0.000 description 6
- 229920005989 resin Polymers 0.000 description 6
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 5
- AOJSSFUBPHWPLT-ZIAGYGMSSA-N C1=CC=C(C(=C1)[C@@H]2[C@H](C(=O)OC2=O)C3=CC=CC=C3C(=O)O)C(=O)O Chemical compound C1=CC=C(C(=C1)[C@@H]2[C@H](C(=O)OC2=O)C3=CC=CC=C3C(=O)O)C(=O)O AOJSSFUBPHWPLT-ZIAGYGMSSA-N 0.000 description 5
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 5
- 125000004414 alkyl thio group Chemical group 0.000 description 5
- 150000003857 carboxamides Chemical class 0.000 description 5
- 150000001735 carboxylic acids Chemical class 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 125000000392 cycloalkenyl group Chemical group 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- PAPNRQCYSFBWDI-UHFFFAOYSA-N 2,5-Dimethyl-1H-pyrrole Chemical compound CC1=CC=C(C)N1 PAPNRQCYSFBWDI-UHFFFAOYSA-N 0.000 description 4
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 4
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 125000003710 aryl alkyl group Chemical group 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 4
- 125000002837 carbocyclic group Chemical group 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 150000002118 epoxides Chemical class 0.000 description 4
- 150000002170 ethers Chemical class 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- 125000001153 fluoro group Chemical group F* 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 150000002894 organic compounds Chemical class 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- FKRCODPIKNYEAC-UHFFFAOYSA-N propionic acid ethyl ester Natural products CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 4
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 4
- 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 4
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 4
- 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 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 150000003862 amino acid derivatives Chemical class 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 3
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
- 125000004529 1,2,3-triazinyl group Chemical group N1=NN=C(C=C1)* 0.000 description 2
- 125000004530 1,2,4-triazinyl group Chemical group N1=NC(=NC=C1)* 0.000 description 2
- HNEGJTWNOOWEMH-UHFFFAOYSA-N 1-fluoropropane Chemical group [CH2]CCF HNEGJTWNOOWEMH-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- YONLFQNRGZXBBF-UHFFFAOYSA-N 2,3-dibenzoyloxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)OC(C(O)=O)C(C(=O)O)OC(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 239000002841 Lewis acid Substances 0.000 description 2
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 2
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
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- 125000001033 ether group Chemical group 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 125000004404 heteroalkyl group Chemical group 0.000 description 1
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- 125000004415 heterocyclylalkyl group Chemical group 0.000 description 1
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- 238000010348 incorporation Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- VCPPTNDHEILJHD-UHFFFAOYSA-N lithium;prop-1-ene Chemical compound [Li+].[CH2-]C=C VCPPTNDHEILJHD-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
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- 238000012986 modification Methods 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical compound C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 208000007056 sickle cell anemia Diseases 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 125000005017 substituted alkenyl group Chemical group 0.000 description 1
- 125000004426 substituted alkynyl group Chemical group 0.000 description 1
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- YEBDZDMYLQHGGZ-UHFFFAOYSA-N tert-butyl 2,5-dihydropyrrole-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC=CC1 YEBDZDMYLQHGGZ-UHFFFAOYSA-N 0.000 description 1
- NXZIGGBPLGAPTI-UHFFFAOYSA-N tert-butyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC2OC21 NXZIGGBPLGAPTI-UHFFFAOYSA-N 0.000 description 1
- NYBWUHOMYZZKOR-UHFFFAOYSA-N tes-adt Chemical class C1=C2C(C#C[Si](CC)(CC)CC)=C(C=C3C(SC=C3)=C3)C3=C(C#C[Si](CC)(CC)CC)C2=CC2=C1SC=C2 NYBWUHOMYZZKOR-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 125000004001 thioalkyl group Chemical group 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 210000004981 tumor-associated macrophage Anatomy 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/06—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B57/00—Separation of optically-active compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/22—Separation; Purification; Stabilisation; Use of additives
- C07C231/24—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/02—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C233/04—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C233/05—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/57—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/65—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C235/06—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C327/00—Thiocarboxylic acids
- C07C327/20—Esters of monothiocarboxylic acids
- C07C327/22—Esters of monothiocarboxylic acids having carbon atoms of esterified thiocarboxyl groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762505282P | 2017-05-12 | 2017-05-12 | |
| US62/505,282 | 2017-05-12 | ||
| PCT/US2018/032407 WO2018209290A1 (en) | 2017-05-12 | 2018-05-11 | Method of preparing (3r,4s)-3-acetamido-4-allyl-n-(tert-butyl)pyrrolidine-3-carboxamide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2020519583A true JP2020519583A (ja) | 2020-07-02 |
| JP2020519583A5 JP2020519583A5 (https=) | 2021-07-26 |
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| JP2019561210A Abandoned JP2020519583A (ja) | 2017-05-12 | 2018-05-11 | （３ｒ，４ｓ）−３−アセトアミド−４−アリル−ｎ−（ｔｅｒｔ−ブチル）ピロリジン−３−カルボキサミドの製造方法 |
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| Country | Link |
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| US (3) | US10494339B2 (https=) |
| EP (1) | EP3621954B1 (https=) |
| JP (1) | JP2020519583A (https=) |
| KR (1) | KR20200008578A (https=) |
| CN (1) | CN110709383A (https=) |
| AU (1) | AU2018265873A1 (https=) |
| BR (1) | BR112019023582A2 (https=) |
| CA (1) | CA3062851A1 (https=) |
| CL (1) | CL2019003212A1 (https=) |
| CO (1) | CO2019013923A2 (https=) |
| CR (1) | CR20190562A (https=) |
| EA (1) | EA201992695A1 (https=) |
| IL (2) | IL278757B (https=) |
| MA (1) | MA48626A (https=) |
| MX (1) | MX2019013533A (https=) |
| PE (1) | PE20200339A1 (https=) |
| PH (1) | PH12019502505A1 (https=) |
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| TW (1) | TW201900609A (https=) |
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| DK2632927T3 (en) | 2010-10-26 | 2016-04-11 | Mars Inc | Boronates AS ARGINSASEINHIBITORER |
| SMT202100573T1 (it) | 2016-12-22 | 2021-11-12 | Calithera Biosciences Inc | Composizioni e metodi per l'inibizione dell'attivita' dell'arginasi |
| WO2018209290A1 (en) * | 2017-05-12 | 2018-11-15 | Calithera Biosciences, Inc. | Method of preparing (3r,4s)-3-acetamido-4-allyl-n-(tert-butyl)pyrrolidine-3-carboxamide |
| EP3774843B1 (en) | 2018-03-29 | 2022-05-25 | Molecure SA | Dipeptide piperidine derivatives |
| CN110734456A (zh) * | 2019-11-06 | 2020-01-31 | 南京谷睿生物科技有限公司 | 一种化合物及其制备方法和医药上的应用 |
| US20220041630A1 (en) | 2020-07-17 | 2022-02-10 | Incyte Corporation | Processes for the preparation of arginase inhibitors and their synthetic intermediates |
| CN113866289A (zh) * | 2021-09-03 | 2021-12-31 | 上海凌凯医药科技有限公司 | 2,3-二苯甲酰氧基-4-二甲基氨基-4-氧代丁酸的手性分离检测方法 |
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| WO1999019295A1 (en) | 1997-10-10 | 1999-04-22 | Trustees Of The University Of Pennsylvania | Compositions and methods for inhibiting arginase activity |
| US20040063666A1 (en) | 1998-10-09 | 2004-04-01 | David Christianson | Compositions for inhibiting arginase activity |
| JP2004502948A (ja) | 2000-07-06 | 2004-01-29 | ファル ダイアグノスティクス | アルギニン化合物の検出のための方法及びキット |
| CA2431080A1 (en) | 2003-06-02 | 2004-12-02 | Catherine Adele O'brien | Enhancement of anticancer immunity through inhibition of arginase |
| WO2007005620A2 (en) | 2005-07-01 | 2007-01-11 | The Johns Hopkins University | Arginase ii: a target treatment of aging heart and heart failure |
| SI2389352T1 (sl) | 2009-01-26 | 2019-08-30 | The Trustees Of The University Of Pennsylvania, Center For Technology Transfer | Inhibitorji arginaze in postopki uporabe |
| CN103068830B (zh) | 2010-04-22 | 2016-06-29 | 马尔斯公司 | 精氨酸酶抑制剂及其治疗应用 |
| DK2632927T3 (en) | 2010-10-26 | 2016-04-11 | Mars Inc | Boronates AS ARGINSASEINHIBITORER |
| CA2824599C (en) | 2010-12-31 | 2020-03-10 | Astrazeneca Uk Limited | Arginase inhibitors and methods of use thereof |
| US9266908B2 (en) | 2011-10-19 | 2016-02-23 | Mars, Incorporated | Inhibitors of arginase and their therapeutic applications |
| RU2014120166A (ru) | 2011-10-20 | 2015-11-27 | ГЛЭКСОСМИТКЛАЙН ЭлЭлСи | Замещенные бициклические аза-гетероциклы и их аналоги в качестве модуляторов сиртуина |
| CA2870526C (en) | 2012-04-18 | 2020-05-05 | Mars, Incorporated | Ring constrained analogs as arginase inhibitors |
| JP6508785B2 (ja) | 2013-10-25 | 2019-05-08 | ファーマサイクリックス エルエルシー | ブルトンチロシンキナーゼ阻害剤および免疫療法を使用する処置 |
| CN105879030A (zh) | 2014-09-30 | 2016-08-24 | 复旦大学 | 治疗肿瘤的增效药物复合物及其制备方法 |
| CN107405404A (zh) | 2015-03-20 | 2017-11-28 | 塞米·欧尤·奥皮约 | 苏拉明和精氨酸酶抑制剂在恶性肿瘤中的用途 |
| KR20180021117A (ko) | 2015-06-23 | 2018-02-28 | 칼리테라 바이오사이언시즈, 인코포레이티드 | 아르기나제 활성 억제를 위한 조성물 및 방법 |
| WO2017075363A1 (en) * | 2015-10-30 | 2017-05-04 | Calithera Biosciences, Inc. | Compositions and methods for inhibiting arginase activity |
| WO2018209290A1 (en) * | 2017-05-12 | 2018-11-15 | Calithera Biosciences, Inc. | Method of preparing (3r,4s)-3-acetamido-4-allyl-n-(tert-butyl)pyrrolidine-3-carboxamide |
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2019
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| US11370754B2 (en) | 2022-06-28 |
| US20210155589A1 (en) | 2021-05-27 |
| PH12019502505A1 (en) | 2020-07-13 |
| IL278757B (en) | 2021-08-31 |
| EP3621954B1 (en) | 2022-03-09 |
| US20180362459A1 (en) | 2018-12-20 |
| ZA201908267B (en) | 2020-11-25 |
| TW201900609A (zh) | 2019-01-01 |
| WO2018209290A1 (en) | 2018-11-15 |
| EA201992695A1 (ru) | 2020-05-15 |
| EP3621954A1 (en) | 2020-03-18 |
| US20200087255A1 (en) | 2020-03-19 |
| US10906872B2 (en) | 2021-02-02 |
| CR20190562A (es) | 2020-03-04 |
| CL2019003212A1 (es) | 2020-02-21 |
| CN110709383A (zh) | 2020-01-17 |
| AU2018265873A1 (en) | 2019-11-28 |
| IL278757A (en) | 2021-01-31 |
| CA3062851A1 (en) | 2018-11-15 |
| SG10201912946TA (en) | 2020-02-27 |
| BR112019023582A2 (pt) | 2020-06-02 |
| PE20200339A1 (es) | 2020-02-14 |
| IL285299A (en) | 2021-09-30 |
| CO2019013923A2 (es) | 2020-04-01 |
| KR20200008578A (ko) | 2020-01-28 |
| US10494339B2 (en) | 2019-12-03 |
| MX2019013533A (es) | 2020-08-03 |
| MA48626A (fr) | 2020-03-18 |
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