KR20240005777A - Hras 및 nras에 대해서 선택적인 kras 저해 작용을 갖는 환상 화합물 - Google Patents
Hras 및 nras에 대해서 선택적인 kras 저해 작용을 갖는 환상 화합물 Download PDFInfo
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- KR20240005777A KR20240005777A KR1020237040757A KR20237040757A KR20240005777A KR 20240005777 A KR20240005777 A KR 20240005777A KR 1020237040757 A KR1020237040757 A KR 1020237040757A KR 20237040757 A KR20237040757 A KR 20237040757A KR 20240005777 A KR20240005777 A KR 20240005777A
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- alkyl
- hydrogen
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- membered
- substituted
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- 150000001923 cyclic compounds Chemical class 0.000 title claims abstract description 203
- 102100030708 GTPase KRas Human genes 0.000 title claims description 78
- 230000002401 inhibitory effect Effects 0.000 title claims description 52
- 102100039788 GTPase NRas Human genes 0.000 title claims description 36
- 101000744505 Homo sapiens GTPase NRas Proteins 0.000 title claims description 36
- 102100029974 GTPase HRas Human genes 0.000 title claims description 35
- 101000584633 Homo sapiens GTPase HRas Proteins 0.000 title claims description 35
- 150000001875 compounds Chemical class 0.000 claims abstract description 124
- 125000000539 amino acid group Chemical group 0.000 claims abstract description 95
- 102000015636 Oligopeptides Human genes 0.000 claims abstract description 83
- 108010038807 Oligopeptides Chemical class 0.000 claims abstract description 82
- -1 SF 5 Chemical group 0.000 claims description 533
- 229910052739 hydrogen Inorganic materials 0.000 claims description 331
- 239000001257 hydrogen Substances 0.000 claims description 331
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 283
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 271
- 150000003839 salts Chemical class 0.000 claims description 240
- 239000012453 solvate Substances 0.000 claims description 237
- 125000000623 heterocyclic group Chemical group 0.000 claims description 235
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 199
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 192
- 229910052757 nitrogen Inorganic materials 0.000 claims description 188
- 229910052736 halogen Inorganic materials 0.000 claims description 178
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 152
- 229910052799 carbon Inorganic materials 0.000 claims description 148
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 142
- 150000002367 halogens Chemical class 0.000 claims description 140
- 150000001721 carbon Chemical group 0.000 claims description 129
- 125000002723 alicyclic group Chemical group 0.000 claims description 93
- 125000000217 alkyl group Chemical group 0.000 claims description 88
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 83
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 77
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 67
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 66
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 64
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 62
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 54
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 51
- 125000005843 halogen group Chemical group 0.000 claims description 42
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 37
- 125000003118 aryl group Chemical group 0.000 claims description 36
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 36
- 230000036961 partial effect Effects 0.000 claims description 35
- 125000004429 atom Chemical group 0.000 claims description 34
- 125000006239 protecting group Chemical group 0.000 claims description 34
- 125000003342 alkenyl group Chemical group 0.000 claims description 31
- 238000000034 method Methods 0.000 claims description 30
- 125000004432 carbon atom Chemical group C* 0.000 claims description 27
- 125000005842 heteroatom Chemical group 0.000 claims description 25
- 125000004450 alkenylene group Chemical group 0.000 claims description 24
- 125000002947 alkylene group Chemical group 0.000 claims description 23
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 23
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 22
- 125000000732 arylene group Chemical group 0.000 claims description 22
- 125000004419 alkynylene group Chemical group 0.000 claims description 21
- 239000011347 resin Substances 0.000 claims description 21
- 229920005989 resin Polymers 0.000 claims description 21
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 20
- 125000004104 aryloxy group Chemical group 0.000 claims description 19
- 229910052717 sulfur Inorganic materials 0.000 claims description 19
- 125000006832 (C1-C10) alkylene group Chemical group 0.000 claims description 18
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 18
- 229910052760 oxygen Inorganic materials 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 238000010532 solid phase synthesis reaction Methods 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
- 125000003277 amino group Chemical group 0.000 claims description 13
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 claims description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 6
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 4
- 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 4
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 3
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 claims description 3
- 125000002837 carbocyclic group Chemical group 0.000 claims description 3
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 3
- 150000004678 hydrides Chemical class 0.000 claims description 3
- 125000004043 oxo group Chemical group O=* 0.000 claims description 3
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 claims description 3
- 229920003002 synthetic resin Polymers 0.000 claims description 3
- 239000000057 synthetic resin Substances 0.000 claims description 3
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 3
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 3
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 2
- 125000003320 C2-C6 alkenyloxy group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 35
- 150000001413 amino acids Chemical class 0.000 abstract description 33
- 108010069514 Cyclic Peptides Proteins 0.000 abstract description 7
- 102000001189 Cyclic Peptides Human genes 0.000 abstract description 7
- 125000004122 cyclic group Chemical class 0.000 abstract description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 390
- 125000003003 spiro group Chemical group 0.000 description 208
- 101000584612 Homo sapiens GTPase KRas Proteins 0.000 description 92
- 125000001424 substituent group Chemical group 0.000 description 45
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 45
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 40
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 35
- 229940024606 amino acid Drugs 0.000 description 34
- 235000001014 amino acid Nutrition 0.000 description 33
- 102000016914 ras Proteins Human genes 0.000 description 28
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 27
- 206010028980 Neoplasm Diseases 0.000 description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- 230000027455 binding Effects 0.000 description 26
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 26
- 201000011510 cancer Diseases 0.000 description 22
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 22
- 230000003993 interaction Effects 0.000 description 22
- 125000000304 alkynyl group Chemical group 0.000 description 21
- 125000001072 heteroaryl group Chemical group 0.000 description 21
- SCIFESDRCALIIM-VIFPVBQESA-N N-methyl-L-phenylalanine Chemical compound C[NH2+][C@H](C([O-])=O)CC1=CC=CC=C1 SCIFESDRCALIIM-VIFPVBQESA-N 0.000 description 20
- 235000018102 proteins Nutrition 0.000 description 20
- 108090000623 proteins and genes Proteins 0.000 description 20
- 102000004169 proteins and genes Human genes 0.000 description 20
- 125000002393 azetidinyl group Chemical group 0.000 description 19
- 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 19
- 102000049555 human KRAS Human genes 0.000 description 19
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 18
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 17
- QWCKQJZIFLGMSD-UHFFFAOYSA-N alpha-aminobutyric acid Chemical compound CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 description 17
- 238000004519 manufacturing process Methods 0.000 description 16
- 125000003386 piperidinyl group Chemical group 0.000 description 16
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 15
- 102000004196 processed proteins & peptides Human genes 0.000 description 15
- 241001102832 Meseres Species 0.000 description 14
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 14
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 14
- 239000003814 drug Substances 0.000 description 14
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 14
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 13
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 13
- 241000282414 Homo sapiens Species 0.000 description 12
- 229910052731 fluorine Inorganic materials 0.000 description 12
- 125000004193 piperazinyl group Chemical group 0.000 description 12
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 11
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 10
- 241000252506 Characiformes Species 0.000 description 10
- 125000001309 chloro group Chemical group Cl* 0.000 description 10
- 229910052698 phosphorus Inorganic materials 0.000 description 10
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 10
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 9
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 9
- 239000011737 fluorine Substances 0.000 description 9
- 239000011574 phosphorus Substances 0.000 description 9
- 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 description 8
- QGWNDRXFNXRZMB-UUOKFMHZSA-N GDP Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O QGWNDRXFNXRZMB-UUOKFMHZSA-N 0.000 description 8
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 8
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- QGWNDRXFNXRZMB-UHFFFAOYSA-N guanidine diphosphate Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O QGWNDRXFNXRZMB-UHFFFAOYSA-N 0.000 description 8
- 201000005202 lung cancer Diseases 0.000 description 8
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- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 8
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- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 7
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 7
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- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 7
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- RYYVLZVUVIJVGH-UHFFFAOYSA-N trimethylxanthine Natural products CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 7
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 6
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- 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 description 6
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- 125000006281 4-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)C([H])([H])* 0.000 description 4
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 4
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- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
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- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 3
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- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 3
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000005942 tetrahydropyridyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- RLTPJVKHGBFGQA-UHFFFAOYSA-N thiadiazolidine Chemical group C1CSNN1 RLTPJVKHGBFGQA-UHFFFAOYSA-N 0.000 description 1
- 125000005304 thiadiazolidinyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000005300 thiocarboxy group Chemical group C(=S)(O)* 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 125000005208 trialkylammonium group Chemical group 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000004950 trifluoroalkyl group Chemical group 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000012982 x-ray structure analysis Methods 0.000 description 1
Images
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/64—Cyclic peptides containing only normal peptide links
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/06—Tripeptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/50—Cyclic peptides containing at least one abnormal peptide link
- C07K7/54—Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| JP2021079012 | 2021-05-07 | ||
| JPJP-P-2021-079012 | 2021-05-07 | ||
| PCT/JP2022/019544 WO2022234853A1 (ja) | 2021-05-07 | 2022-05-06 | Ｈｒａｓおよびｎｒａｓに対して選択的なｋｒａｓ阻害作用を有する環状化合物 |
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| PE (1) | PE20250071A1 (https=) |
| TW (1) | TW202309063A (https=) |
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| TW202446781A (zh) | 2011-12-28 | 2024-12-01 | 日商中外製藥股份有限公司 | 胜肽化合物之製造方法 |
| EP4166664A1 (en) | 2015-03-13 | 2023-04-19 | Chugai Seiyaku Kabushiki Kaisha | Modified aminoacyl-trna synthetase and use thereof |
| JP7187323B2 (ja) | 2017-01-31 | 2022-12-12 | 中外製薬株式会社 | 無細胞翻訳系におけるペプチドの合成方法 |
| KR20250007021A (ko) | 2017-06-09 | 2025-01-13 | 추가이 세이야쿠 가부시키가이샤 | N-치환 아미노산을 포함하는 펩타이드의 합성 방법 |
| EP3878836B1 (en) | 2018-11-07 | 2025-07-23 | Chugai Seiyaku Kabushiki Kaisha | O-substituted serine derivative production method |
| EP4056580A4 (en) | 2019-11-07 | 2023-12-06 | Chugai Seiyaku Kabushiki Kaisha | METHOD FOR PRODUCING A PEPTIDE COMPOUND COMPRISING A STERICALLY HINDERED AMINO ACID |
| BR112022007535A2 (pt) | 2019-11-07 | 2022-07-12 | Chugai Pharmaceutical Co Ltd | Composto peptídico cíclico tendo ação inibitória de kras |
| US12312379B2 (en) | 2021-05-07 | 2025-05-27 | Chugai Seiyaku Kabushiki Kaisha | Methods for producing cyclic compounds comprising N-substituted amino acid residues |
| JP7823181B2 (ja) * | 2022-05-06 | 2026-03-03 | 中外製薬株式会社 | Ｈｒａｓおよびｎｒａｓに対して選択的なｋｒａｓ阻害作用を有する環状化合物 |
| CN115385867A (zh) * | 2022-09-19 | 2022-11-25 | 安徽普利药业有限公司 | 一种氨基酸及其类似物的成环反应与开环方法 |
| TW202430537A (zh) * | 2022-10-20 | 2024-08-01 | 日商中外製藥股份有限公司 | 環狀胜肽的結晶的製造方法 |
| EP4603105A1 (en) * | 2022-11-09 | 2025-08-20 | Chugai Seiyaku Kabushiki Kaisha | Pharmaceutical composition containing cyclic compound having selective kras inhibitory effect against hras and nras |
| CN120659773A (zh) * | 2022-11-09 | 2025-09-16 | 锐新医药公司 | 化合物、复合物以及其制备方法和用途 |
| WO2024101386A1 (ja) * | 2022-11-09 | 2024-05-16 | 中外製薬株式会社 | Ｈｒａｓおよびｎｒａｓに対して選択的なｋｒａｓ阻害作用を有する環状化合物 |
| WO2024195801A1 (ja) | 2023-03-20 | 2024-09-26 | 中外製薬株式会社 | 環状ペプチドの共結晶の製造方法 |
| TW202506168A (zh) | 2023-04-19 | 2025-02-16 | 日商中外製藥股份有限公司 | 包含環狀胜肽化合物及界面活性劑之組合物 |
| CN120936619A (zh) | 2023-04-20 | 2025-11-11 | 中外制药株式会社 | 用于生产环肽化合物的方法 |
| CN116655766B (zh) * | 2023-04-23 | 2023-12-12 | 山东第一医科大学(山东省医学科学院) | 一种订书肽及其制备方法和应用 |
| US20250049810A1 (en) | 2023-08-07 | 2025-02-13 | Revolution Medicines, Inc. | Methods of treating a ras protein-related disease or disorder |
| AU2024360465A1 (en) | 2023-10-12 | 2026-04-09 | Revolution Medicines, Inc. | Macrocyclic ras inhibitors |
| WO2025162428A1 (en) * | 2024-01-29 | 2025-08-07 | Syneron Technology Co. Ltd. | Cyclic peptide compounds and compositions as ras inhibitors |
| WO2025171296A1 (en) | 2024-02-09 | 2025-08-14 | Revolution Medicines, Inc. | Ras inhibitors |
| CN118324664B (zh) * | 2024-03-14 | 2026-04-07 | 四川鸿日医药科技有限公司 | 一种丝氨酸衍生物的制备方法 |
| TW202547461A (zh) | 2024-05-17 | 2025-12-16 | 美商銳新醫藥公司 | Ｒａｓ抑制劑 |
| WO2025255438A1 (en) | 2024-06-07 | 2025-12-11 | Revolution Medicines, Inc. | Methods of treating a ras protein-related disease or disorder |
| WO2025265060A1 (en) | 2024-06-21 | 2025-12-26 | Revolution Medicines, Inc. | Therapeutic compositions and methods for managing treatment-related effects |
| WO2026004834A1 (ja) * | 2024-06-25 | 2026-01-02 | 中外製薬株式会社 | 固体分散体、及びそれを含む組成物 |
| WO2026006747A1 (en) | 2024-06-28 | 2026-01-02 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2026009920A1 (ja) * | 2024-07-03 | 2026-01-08 | 中外製薬株式会社 | 環状ペプチドの精製法及び製造法 |
| WO2026015796A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Methods of treating a ras related disease or disorder |
| WO2026015790A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Methods of treating a ras related disease or disorder |
| WO2026015801A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Methods of treating a ras related disease or disorder |
| WO2026015825A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Use of ras inhibitor for treating pancreatic cancer |
| WO2026050446A1 (en) | 2024-08-29 | 2026-03-05 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2026072904A2 (en) | 2024-09-26 | 2026-04-02 | Revolution Medicines, Inc. | Compositions and methods for treating lung cancer |
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| WO2012122059A1 (en) | 2011-03-04 | 2012-09-13 | New York University | Hydrogen bond surrogate macrocycles as modulators of ras |
| WO2013100132A1 (ja) | 2011-12-28 | 2013-07-04 | 中外製薬株式会社 | ペプチド化合物の環化方法 |
| WO2017181061A1 (en) | 2016-04-15 | 2017-10-19 | Ra Pharmaceuticals, Inc. | Ras binding peptides and methods of use |
| WO2018225864A1 (ja) | 2017-06-09 | 2018-12-13 | 中外製薬株式会社 | 膜透過性の高い環状ペプチド化合物、及びこれを含むライブラリ |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015179438A1 (en) * | 2014-05-20 | 2015-11-26 | Ohio State Innovation Foundation | Small molecule rac or rho inhibitors |
| KR20250007021A (ko) * | 2017-06-09 | 2025-01-13 | 추가이 세이야쿠 가부시키가이샤 | N-치환 아미노산을 포함하는 펩타이드의 합성 방법 |
| WO2020122182A1 (ja) * | 2018-12-12 | 2020-06-18 | 中外製薬株式会社 | 分子内水素結合可能な官能基を有するアミノ酸とそれらのアミノ酸を含むペプチド化合物、およびそれらの製造方法 |
| BR112022007535A2 (pt) * | 2019-11-07 | 2022-07-12 | Chugai Pharmaceutical Co Ltd | Composto peptídico cíclico tendo ação inibitória de kras |
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| WO2012122059A1 (en) | 2011-03-04 | 2012-09-13 | New York University | Hydrogen bond surrogate macrocycles as modulators of ras |
| WO2013100132A1 (ja) | 2011-12-28 | 2013-07-04 | 中外製薬株式会社 | ペプチド化合物の環化方法 |
| WO2017181061A1 (en) | 2016-04-15 | 2017-10-19 | Ra Pharmaceuticals, Inc. | Ras binding peptides and methods of use |
| WO2018225864A1 (ja) | 2017-06-09 | 2018-12-13 | 中外製薬株式会社 | 膜透過性の高い環状ペプチド化合物、及びこれを含むライブラリ |
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Also Published As
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| CL2023003137A1 (es) | 2024-06-14 |
| IL307605A (en) | 2023-12-01 |
| PE20250071A1 (es) | 2025-01-13 |
| CR20230572A (es) | 2024-01-25 |
| CA3218182A1 (en) | 2022-11-10 |
| MX2023013139A (es) | 2023-11-28 |
| AR125796A1 (es) | 2023-08-16 |
| TW202309063A (zh) | 2023-03-01 |
| JPWO2022234853A1 (https=) | 2022-11-10 |
| CN117279933A (zh) | 2023-12-22 |
| US20240158446A1 (en) | 2024-05-16 |
| EP4309741A1 (en) | 2024-01-24 |
| WO2022234853A1 (ja) | 2022-11-10 |
| EP4309741A4 (en) | 2025-05-14 |
| BR112023022755A2 (pt) | 2024-01-02 |
| CO2023014807A2 (es) | 2023-11-20 |
| AU2022268781A1 (en) | 2023-12-21 |
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