JP6800872B2 - リシルオキシダーゼ様2阻害剤とその使用 - Google Patents
リシルオキシダーゼ様2阻害剤とその使用 Download PDFInfo
- Publication number
- JP6800872B2 JP6800872B2 JP2017545627A JP2017545627A JP6800872B2 JP 6800872 B2 JP6800872 B2 JP 6800872B2 JP 2017545627 A JP2017545627 A JP 2017545627A JP 2017545627 A JP2017545627 A JP 2017545627A JP 6800872 B2 JP6800872 B2 JP 6800872B2
- Authority
- JP
- Japan
- Prior art keywords
- substituted
- unsubstituted
- aminomethyl
- compound
- pyridine
- 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.)
- Expired - Fee Related
Links
- 229940119500 Lysyl oxidase-like 2 inhibitor Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 514
- -1 C 1- C 6 juteroalkyl Chemical group 0.000 claims description 236
- 150000003839 salts Chemical class 0.000 claims description 116
- 125000001072 heteroaryl group Chemical group 0.000 claims description 88
- 125000000623 heterocyclic group Chemical group 0.000 claims description 79
- 125000003118 aryl group Chemical group 0.000 claims description 73
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 66
- 125000002619 bicyclic group Chemical group 0.000 claims description 58
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 58
- 229910052739 hydrogen Inorganic materials 0.000 claims description 50
- 125000002950 monocyclic group Chemical group 0.000 claims description 49
- 206010016654 Fibrosis Diseases 0.000 claims description 47
- 241000124008 Mammalia Species 0.000 claims description 47
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 47
- 230000004761 fibrosis Effects 0.000 claims description 46
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 45
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 43
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 42
- 229910052805 deuterium Inorganic materials 0.000 claims description 40
- 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 claims description 39
- 238000011282 treatment Methods 0.000 claims description 35
- 229910052760 oxygen Inorganic materials 0.000 claims description 32
- 229910052799 carbon Inorganic materials 0.000 claims description 31
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 30
- 239000008194 pharmaceutical composition Substances 0.000 claims description 30
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 29
- 125000004434 sulfur atom Chemical group 0.000 claims description 29
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 28
- 125000006747 (C2-C10) heterocycloalkyl group Chemical group 0.000 claims description 26
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 23
- 229910052736 halogen Inorganic materials 0.000 claims description 22
- 150000002367 halogens Chemical class 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 21
- 229910052731 fluorine Inorganic materials 0.000 claims description 21
- 239000012453 solvate Substances 0.000 claims description 20
- 229910052801 chlorine Inorganic materials 0.000 claims description 19
- 125000004432 carbon atom Chemical group C* 0.000 claims description 17
- 125000003386 piperidinyl group Chemical group 0.000 claims description 17
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 17
- 125000004193 piperazinyl group Chemical group 0.000 claims description 15
- 229910052794 bromium Inorganic materials 0.000 claims description 14
- 239000003795 chemical substances by application Substances 0.000 claims description 14
- 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 13
- 125000002837 carbocyclic group Chemical group 0.000 claims description 13
- 150000001721 carbon Chemical group 0.000 claims description 13
- 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 12
- 125000002757 morpholinyl group Chemical group 0.000 claims description 11
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 11
- 125000002947 alkylene group Chemical group 0.000 claims description 10
- 125000004069 aziridinyl group Chemical group 0.000 claims description 10
- 239000005711 Benzoic acid Substances 0.000 claims description 9
- 235000010233 benzoic acid Nutrition 0.000 claims description 9
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 7
- 125000002393 azetidinyl group Chemical group 0.000 claims description 7
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 5
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 5
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 5
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims description 4
- GTRIVUDDNMZGDQ-UHFFFAOYSA-N 3-[4-(aminomethyl)pyridin-2-yl]-N-phenylbenzamide Chemical compound NCC1=CC(=NC=C1)C=1C=C(C(=O)NC2=CC=CC=C2)C=CC=1 GTRIVUDDNMZGDQ-UHFFFAOYSA-N 0.000 claims description 3
- DXQWWEUVIGNTOY-UHFFFAOYSA-N 4-[4-(aminomethyl)pyridin-2-yl]-N-benzylbenzamide Chemical compound NCC1=CC(=NC=C1)C1=CC=C(C(=O)NCC2=CC=CC=C2)C=C1 DXQWWEUVIGNTOY-UHFFFAOYSA-N 0.000 claims description 3
- LIUIDMWKNRWMIS-UHFFFAOYSA-N 3-[4-(aminomethyl)pyridin-2-yl]-N-benzylbenzamide Chemical compound NCC1=CC(=NC=C1)C=1C=C(C(=O)NCC2=CC=CC=C2)C=CC=1 LIUIDMWKNRWMIS-UHFFFAOYSA-N 0.000 claims description 2
- WKJSUDSRVONOIH-UHFFFAOYSA-N 3-[4-(aminomethyl)pyridin-2-yl]oxy-N-(2-phenylethyl)benzamide Chemical compound NCC1=CC(=NC=C1)OC=1C=C(C(=O)NCCC2=CC=CC=C2)C=CC=1 WKJSUDSRVONOIH-UHFFFAOYSA-N 0.000 claims description 2
- FQVUWJYJPDWXIX-UHFFFAOYSA-N 3-[4-(aminomethyl)pyridin-2-yl]oxy-N-benzylbenzamide Chemical compound NCC1=CC(=NC=C1)OC=1C=C(C(=O)NCC2=CC=CC=C2)C=CC=1 FQVUWJYJPDWXIX-UHFFFAOYSA-N 0.000 claims description 2
- KNHQKWFHWLBNHO-UHFFFAOYSA-N 3-[[4-(aminomethyl)pyridin-2-yl]oxymethyl]-N-phenylbenzamide Chemical compound NCC1=CC(=NC=C1)OCC=1C=C(C(=O)NC2=CC=CC=C2)C=CC=1 KNHQKWFHWLBNHO-UHFFFAOYSA-N 0.000 claims description 2
- CIBGXOAZCPUGAU-UHFFFAOYSA-N 4-[4-(aminomethyl)pyridin-2-yl]-N-phenylbenzamide Chemical compound NCC1=CC(=NC=C1)C1=CC=C(C(=O)NC2=CC=CC=C2)C=C1 CIBGXOAZCPUGAU-UHFFFAOYSA-N 0.000 claims description 2
- MAPGRQSVGRBDGP-UHFFFAOYSA-N [3-[4-(aminomethyl)pyridin-2-yl]oxyphenyl]-(3,4-dihydro-1H-isoquinolin-2-yl)methanone Chemical compound NCC1=CC(=NC=C1)OC=1C=C(C=CC=1)C(=O)N1CC2=CC=CC=C2CC1 MAPGRQSVGRBDGP-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000002527 bicyclic carbocyclic group Chemical group 0.000 claims 1
- 238000000034 method Methods 0.000 description 154
- 239000000203 mixture Substances 0.000 description 147
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 134
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 124
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 105
- 201000010099 disease Diseases 0.000 description 91
- 101001043352 Homo sapiens Lysyl oxidase homolog 2 Proteins 0.000 description 70
- 102100021948 Lysyl oxidase homolog 2 Human genes 0.000 description 64
- 235000019439 ethyl acetate Nutrition 0.000 description 62
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 59
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- 230000002829 reductive effect Effects 0.000 description 56
- 239000000243 solution Substances 0.000 description 49
- YWFWNGLGSZBXER-UHFFFAOYSA-N 2-(1-benzylindol-4-yl)oxypyridine-4-carbonitrile Chemical compound C(C1=CC=CC=C1)N1C=CC2=C(C=CC=C12)OC=1C=C(C#N)C=CN=1 YWFWNGLGSZBXER-UHFFFAOYSA-N 0.000 description 47
- 239000003814 drug Substances 0.000 description 45
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
- 229910001868 water Inorganic materials 0.000 description 37
- 125000000217 alkyl group Chemical group 0.000 description 35
- 239000000460 chlorine Substances 0.000 description 33
- 239000007787 solid Substances 0.000 description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 32
- 230000000694 effects Effects 0.000 description 31
- 125000004093 cyano group Chemical group *C#N 0.000 description 29
- 229940079593 drug Drugs 0.000 description 29
- 229940125782 compound 2 Drugs 0.000 description 28
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 27
- 239000011734 sodium Substances 0.000 description 26
- 239000000741 silica gel Substances 0.000 description 25
- 229910002027 silica gel Inorganic materials 0.000 description 25
- 239000002585 base Substances 0.000 description 24
- 229940002612 prodrug Drugs 0.000 description 24
- 239000000651 prodrug Substances 0.000 description 24
- 230000003176 fibrotic effect Effects 0.000 description 23
- 239000003112 inhibitor Substances 0.000 description 23
- 239000011541 reaction mixture Substances 0.000 description 23
- 238000000746 purification Methods 0.000 description 21
- 239000002904 solvent Substances 0.000 description 21
- QZOQTGJOEQVJKJ-UHFFFAOYSA-N CNC(OC1=CC(=NC=C1)C1=CC=C(C=C1)C(NCCOC)=O)=O Chemical compound CNC(OC1=CC(=NC=C1)C1=CC=C(C=C1)C(NCCOC)=O)=O QZOQTGJOEQVJKJ-UHFFFAOYSA-N 0.000 description 20
- 239000012044 organic layer Substances 0.000 description 20
- QXBAZVTVILOTGV-UHFFFAOYSA-N 2-[1-[(5-fluoropyridin-2-yl)methyl]indol-4-yl]oxypyridine-4-carbonitrile Chemical compound FC=1C=CC(=NC=1)CN1C=CC2=C(C=CC=C12)OC=1C=C(C#N)C=CN=1 QXBAZVTVILOTGV-UHFFFAOYSA-N 0.000 description 18
- 108010035532 Collagen Proteins 0.000 description 18
- 206010028980 Neoplasm Diseases 0.000 description 18
- 239000002253 acid Substances 0.000 description 18
- 238000009472 formulation Methods 0.000 description 18
- 102000008186 Collagen Human genes 0.000 description 17
- 229920001436 collagen Polymers 0.000 description 17
- 239000012267 brine Substances 0.000 description 16
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
- 229940124597 therapeutic agent Drugs 0.000 description 16
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
- 230000015572 biosynthetic process Effects 0.000 description 15
- 230000001225 therapeutic effect Effects 0.000 description 15
- 239000004480 active ingredient Substances 0.000 description 14
- 125000004429 atom Chemical group 0.000 description 14
- 208000035475 disorder Diseases 0.000 description 14
- 238000010828 elution Methods 0.000 description 14
- 238000002953 preparative HPLC Methods 0.000 description 14
- 208000024891 symptom Diseases 0.000 description 14
- 239000003643 water by type Substances 0.000 description 14
- GXCPUAUYERWURG-UHFFFAOYSA-N 2-[4-(4-cyanopyridin-2-yl)oxyindol-1-yl]acetic acid Chemical compound C(#N)C1=CC(=NC=C1)OC1=C2C=CN(C2=CC=C1)CC(=O)O GXCPUAUYERWURG-UHFFFAOYSA-N 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 13
- 241000699670 Mus sp. Species 0.000 description 13
- 150000001412 amines Chemical class 0.000 description 13
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 13
- 229960002591 hydroxyproline Drugs 0.000 description 13
- 238000010186 staining Methods 0.000 description 13
- 238000003786 synthesis reaction Methods 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 13
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 13
- 150000002148 esters Chemical class 0.000 description 12
- 239000012458 free base Substances 0.000 description 12
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 12
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- 210000004369 blood Anatomy 0.000 description 11
- 238000002347 injection Methods 0.000 description 11
- 239000007924 injection Substances 0.000 description 11
- 229910052763 palladium Inorganic materials 0.000 description 11
- 239000003826 tablet Substances 0.000 description 11
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 10
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 10
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 10
- 239000002775 capsule Substances 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 10
- 229940126214 compound 3 Drugs 0.000 description 10
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 10
- 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 10
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([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
- 239000000706 filtrate Substances 0.000 description 10
- 125000002883 imidazolyl group Chemical group 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- 239000000843 powder Substances 0.000 description 10
- 208000005069 pulmonary fibrosis Diseases 0.000 description 10
- 125000003373 pyrazinyl group Chemical group 0.000 description 10
- 125000003226 pyrazolyl group Chemical group 0.000 description 10
- 125000004076 pyridyl group Chemical group 0.000 description 10
- 125000000714 pyrimidinyl group Chemical group 0.000 description 10
- 125000000168 pyrrolyl group Chemical group 0.000 description 10
- 238000006722 reduction reaction Methods 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 10
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 10
- QRXBTPFMCTXCRD-UHFFFAOYSA-N 2-chloropyridine-4-carbonitrile Chemical compound ClC1=CC(C#N)=CC=N1 QRXBTPFMCTXCRD-UHFFFAOYSA-N 0.000 description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 9
- 125000004122 cyclic group Chemical group 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- 239000003960 organic solvent Substances 0.000 description 9
- 230000009467 reduction Effects 0.000 description 9
- XCILKXJLQBOLAB-UHFFFAOYSA-N 1-[4-(aminomethyl)pyridin-2-yl]-4-fluoropyrrolidin-3-ol Chemical compound NCC1=CC(=NC=C1)N1CC(C(C1)F)O XCILKXJLQBOLAB-UHFFFAOYSA-N 0.000 description 8
- 108010006654 Bleomycin Proteins 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 229960001561 bleomycin Drugs 0.000 description 8
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 8
- 201000011510 cancer Diseases 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- 125000004404 heteroalkyl group Chemical group 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 8
- 229940090044 injection Drugs 0.000 description 8
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 8
- GPHQHTOMRSGBNZ-UHFFFAOYSA-N pyridine-4-carbonitrile Chemical compound N#CC1=CC=NC=C1 GPHQHTOMRSGBNZ-UHFFFAOYSA-N 0.000 description 8
- VJGZHSIYZMBNBO-UHFFFAOYSA-N (2-pyridin-3-ylpyridin-4-yl)methanamine Chemical compound NCC1=CC=NC(C=2C=NC=CC=2)=C1 VJGZHSIYZMBNBO-UHFFFAOYSA-N 0.000 description 7
- LBHIXRZRIQKZKV-UHFFFAOYSA-N 4-(aminomethyl)-N,N-dimethyl-6-(3-phenoxyphenoxy)pyridin-2-amine hydrochloride Chemical compound Cl.CN(C)c1cc(CN)cc(Oc2cccc(Oc3ccccc3)c2)n1 LBHIXRZRIQKZKV-UHFFFAOYSA-N 0.000 description 7
- 102000004316 Oxidoreductases Human genes 0.000 description 7
- 108090000854 Oxidoreductases Proteins 0.000 description 7
- 230000008901 benefit Effects 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 208000019425 cirrhosis of liver Diseases 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 238000011534 incubation Methods 0.000 description 7
- 238000001990 intravenous administration Methods 0.000 description 7
- 239000002207 metabolite Substances 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 238000007920 subcutaneous administration Methods 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- DFPKSHHLTWTWBL-UHFFFAOYSA-N (2-phenoxypyridin-4-yl)methanamine hydrochloride Chemical compound Cl.NCc1ccnc(Oc2ccccc2)c1 DFPKSHHLTWTWBL-UHFFFAOYSA-N 0.000 description 6
- OOBXMSDWFPYZMZ-NTISSMGPSA-N (3S)-3-[4-(aminomethyl)pyridin-2-yl]oxy-N-phenylpiperidine-1-carboxamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NCc1ccnc(O[C@H]2CCCN(C2)C(=O)Nc2ccccc2)c1 OOBXMSDWFPYZMZ-NTISSMGPSA-N 0.000 description 6
- PKYCWFICOKSIHZ-UHFFFAOYSA-N 1-(3,7-dihydroxyphenoxazin-10-yl)ethanone Chemical compound OC1=CC=C2N(C(=O)C)C3=CC=C(O)C=C3OC2=C1 PKYCWFICOKSIHZ-UHFFFAOYSA-N 0.000 description 6
- QARJJLJKSORSKM-UHFFFAOYSA-N 2-(1H-indol-4-yloxy)pyridine-4-carbonitrile Chemical compound N1C=CC2=C(C=CC=C12)OC=1C=C(C#N)C=CN=1 QARJJLJKSORSKM-UHFFFAOYSA-N 0.000 description 6
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 6
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 6
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 6
- 108010067306 Fibronectins Proteins 0.000 description 6
- 102000016359 Fibronectins Human genes 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- QXAICJYOXBYPFW-UHFFFAOYSA-N N-[4-(aminomethyl)pyridin-2-yl]-2-fluoro-4-methylbenzamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.Cc1ccc(C(=O)Nc2cc(CN)ccn2)c(F)c1 QXAICJYOXBYPFW-UHFFFAOYSA-N 0.000 description 6
- JSAMLMMXPNCYLX-UHFFFAOYSA-N [2-(1-benzylindol-4-yl)oxypyridin-4-yl]methanamine hydrochloride Chemical compound Cl.NCc1ccnc(Oc2cccc3n(Cc4ccccc4)ccc23)c1 JSAMLMMXPNCYLX-UHFFFAOYSA-N 0.000 description 6
- YPJOXJAXUDZXAD-UHFFFAOYSA-N [2-(4-fluorophenyl)-6-(3-phenoxyphenoxy)pyridin-4-yl]methanamine 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NCc1cc(Oc2cccc(Oc3ccccc3)c2)nc(c1)-c1ccc(F)cc1 YPJOXJAXUDZXAD-UHFFFAOYSA-N 0.000 description 6
- SOABZDDRFRQNSO-UHFFFAOYSA-N [2-[1-(6-fluoro-1,3-benzothiazol-2-yl)indol-4-yl]oxypyridin-4-yl]methanamine hydrochloride Chemical compound Cl.NCc1ccnc(Oc2cccc3n(ccc23)-c2nc3ccc(F)cc3s2)c1 SOABZDDRFRQNSO-UHFFFAOYSA-N 0.000 description 6
- WEOQYRKXRABZGX-UHFFFAOYSA-N [2-[1-(6-methoxypyridin-3-yl)indol-4-yl]oxypyridin-4-yl]methanamine hydrochloride Chemical compound Cl.COc1ccc(cn1)-n1ccc2c(Oc3cc(CN)ccn3)cccc12 WEOQYRKXRABZGX-UHFFFAOYSA-N 0.000 description 6
- YWXAURCGPSYXOT-UHFFFAOYSA-N [2-[1-[2-(4-fluorophenyl)ethyl]indol-4-yl]oxypyridin-4-yl]methanamine hydrochloride Chemical compound Cl.NCc1ccnc(Oc2cccc3n(CCc4ccc(F)cc4)ccc23)c1 YWXAURCGPSYXOT-UHFFFAOYSA-N 0.000 description 6
- 230000002159 abnormal effect Effects 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 239000012298 atmosphere Substances 0.000 description 6
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 6
- 238000010586 diagram Methods 0.000 description 6
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 6
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 238000001802 infusion Methods 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 238000007912 intraperitoneal administration Methods 0.000 description 6
- 125000001786 isothiazolyl group Chemical group 0.000 description 6
- 125000000842 isoxazolyl group Chemical group 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 210000004185 liver Anatomy 0.000 description 6
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 6
- 125000001715 oxadiazolyl group Chemical group 0.000 description 6
- 125000002971 oxazolyl group Chemical group 0.000 description 6
- 230000002265 prevention Effects 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 6
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 6
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 6
- 125000003831 tetrazolyl group Chemical group 0.000 description 6
- 125000001113 thiadiazolyl group Chemical group 0.000 description 6
- 125000000335 thiazolyl group Chemical group 0.000 description 6
- 125000004306 triazinyl group Chemical group 0.000 description 6
- 125000001425 triazolyl group Chemical group 0.000 description 6
- XWILGJHIQSAUAX-UHFFFAOYSA-N 1-[4-(aminomethyl)pyridin-2-yl]-3-(trifluoromethyl)pyrrolidin-3-ol Chemical compound NCC1=CC(=NC=C1)N1CC(CC1)(O)C(F)(F)F XWILGJHIQSAUAX-UHFFFAOYSA-N 0.000 description 5
- 150000005749 2-halopyridines Chemical class 0.000 description 5
- 239000007821 HATU Substances 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- HDHDSEZROIGIML-NTISSMGPSA-N [(3S)-3-[4-(aminomethyl)pyridin-2-yl]oxypiperidin-1-yl]-phenylmethanone 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NCc1ccnc(O[C@H]2CCCN(C2)C(=O)c2ccccc2)c1 HDHDSEZROIGIML-NTISSMGPSA-N 0.000 description 5
- PTLXEYOPKPMFKC-UHFFFAOYSA-N [2-(3-phenoxyphenoxy)pyridin-4-yl]methanamine Chemical compound O(C1=CC=CC=C1)C=1C=C(OC2=NC=CC(=C2)CN)C=CC=1 PTLXEYOPKPMFKC-UHFFFAOYSA-N 0.000 description 5
- VRDUACHQJUIGQJ-UHFFFAOYSA-N [2-(4-fluorophenyl)pyridin-4-yl]methanamine Chemical compound NCC1=CC=NC(C=2C=CC(F)=CC=2)=C1 VRDUACHQJUIGQJ-UHFFFAOYSA-N 0.000 description 5
- 238000009825 accumulation Methods 0.000 description 5
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 5
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 5
- 125000002576 diazepinyl group Chemical group N1N=C(C=CC=C1)* 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 230000007705 epithelial mesenchymal transition Effects 0.000 description 5
- 210000002950 fibroblast Anatomy 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 102000045293 human LOXL2 Human genes 0.000 description 5
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 5
- 210000003734 kidney Anatomy 0.000 description 5
- 210000004072 lung Anatomy 0.000 description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- 125000003566 oxetanyl group Chemical group 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 230000000069 prophylactic effect Effects 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 5
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 5
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 5
- 201000002793 renal fibrosis Diseases 0.000 description 5
- 210000003491 skin Anatomy 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 125000005308 thiazepinyl group Chemical group S1N=C(C=CC=C1)* 0.000 description 5
- 125000001583 thiepanyl group Chemical group 0.000 description 5
- 125000002053 thietanyl group Chemical group 0.000 description 5
- 238000011269 treatment regimen Methods 0.000 description 5
- KZKRRZFCAYOXQE-UHFFFAOYSA-N 1$l^{2}-azinane Chemical group C1CC[N]CC1 KZKRRZFCAYOXQE-UHFFFAOYSA-N 0.000 description 4
- IBLMYGXJKQIGSN-UHFFFAOYSA-N 1-(bromomethyl)-2,4-difluorobenzene Chemical compound FC1=CC=C(CBr)C(F)=C1 IBLMYGXJKQIGSN-UHFFFAOYSA-N 0.000 description 4
- UDKYFLNRPYBRIO-UHFFFAOYSA-N 2-[4-[4-(aminomethyl)pyridin-2-yl]oxyindol-1-yl]-N,N-dimethylacetamide hydrochloride Chemical compound Cl.CN(C)C(=O)Cn1ccc2c(Oc3cc(CN)ccn3)cccc12 UDKYFLNRPYBRIO-UHFFFAOYSA-N 0.000 description 4
- FBGBTUWITWYDAA-UHFFFAOYSA-N 2-[4-[4-(aminomethyl)pyridin-2-yl]oxyindol-1-yl]-N-methyl-N-phenylacetamide hydrochloride Chemical compound Cl.CN(C(=O)Cn1ccc2c(Oc3cc(CN)ccn3)cccc12)c1ccccc1 FBGBTUWITWYDAA-UHFFFAOYSA-N 0.000 description 4
- QDJSEILRWZMZFQ-UHFFFAOYSA-N 3-(trifluoromethyl)pyrrolidin-3-ol;hydrochloride Chemical compound Cl.FC(F)(F)C1(O)CCNC1 QDJSEILRWZMZFQ-UHFFFAOYSA-N 0.000 description 4
- HDIJSYDKXMDELD-UHFFFAOYSA-N 3-[4-(aminomethyl)pyridin-2-yl]-N-benzylbenzamide hydrochloride Chemical compound Cl.NCc1ccnc(c1)-c1cccc(c1)C(=O)NCc1ccccc1 HDIJSYDKXMDELD-UHFFFAOYSA-N 0.000 description 4
- IIJOUPDJYSTSBW-UHFFFAOYSA-N 3-[4-(aminomethyl)pyridin-2-yl]oxy-N-(3-methoxyphenyl)benzamide Chemical compound NCC1=CC(=NC=C1)OC=1C=C(C(=O)NC2=CC(=CC=C2)OC)C=CC=1 IIJOUPDJYSTSBW-UHFFFAOYSA-N 0.000 description 4
- XGRLLLJVGNTYSK-UHFFFAOYSA-N 3-[4-(aminomethyl)pyridin-2-yl]oxy-N-tridecylbenzamide Chemical compound NCC1=CC(=NC=C1)OC=1C=C(C(=O)NCCCCCCCCCCCCC)C=CC=1 XGRLLLJVGNTYSK-UHFFFAOYSA-N 0.000 description 4
- MXYKPLWFQYKQAQ-UHFFFAOYSA-N 3-[4-(aminomethyl)pyridin-2-yl]oxybenzoic acid Chemical compound NCC1=CC(=NC=C1)OC=1C=C(C(=O)O)C=CC=1 MXYKPLWFQYKQAQ-UHFFFAOYSA-N 0.000 description 4
- WKBFSPDTDFWNSC-UHFFFAOYSA-N 4-(aminomethyl)-N-(2-methoxyethyl)-6-(3-phenoxyphenoxy)pyridin-2-amine Chemical compound NCC1=CC(=NC(=C1)OC1=CC(=CC=C1)OC1=CC=CC=C1)NCCOC WKBFSPDTDFWNSC-UHFFFAOYSA-N 0.000 description 4
- MWDJHBRCBQFLAW-UHFFFAOYSA-N 4-(aminomethyl)-N-benzylpyridine-2-carboxamide Chemical compound NCC1=CC(=NC=C1)C(=O)NCC1=CC=CC=C1 MWDJHBRCBQFLAW-UHFFFAOYSA-N 0.000 description 4
- YZQJLVOSOFHLJC-UHFFFAOYSA-N 4-[4-(aminomethyl)pyridin-2-yl]-N-phenylbenzamide hydrochloride Chemical compound Cl.NCc1ccnc(c1)-c1ccc(cc1)C(=O)Nc1ccccc1 YZQJLVOSOFHLJC-UHFFFAOYSA-N 0.000 description 4
- GWVQHPSORNQPKO-UHFFFAOYSA-N 4-[4-(aminomethyl)pyridin-2-yl]benzoic acid 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NCc1ccnc(c1)-c1ccc(cc1)C(O)=O GWVQHPSORNQPKO-UHFFFAOYSA-N 0.000 description 4
- QGKIMIBJSGNJRD-UHFFFAOYSA-N 4-[4-(aminomethyl)pyridin-2-yl]oxybenzoic acid Chemical compound NCC1=CC(=NC=C1)OC1=CC=C(C(=O)O)C=C1 QGKIMIBJSGNJRD-UHFFFAOYSA-N 0.000 description 4
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 4
- YNCJGPOTUFPVTB-UHFFFAOYSA-N 5-(chloromethyl)-2-methoxypyridine Chemical compound COC1=CC=C(CCl)C=N1 YNCJGPOTUFPVTB-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- CKWMMPKRTDERCF-UHFFFAOYSA-N N-[4-(aminomethyl)pyridin-2-yl]-2-(3,4-dichlorophenyl)acetamide Chemical compound NCC1=CC(=NC=C1)NC(CC1=CC(=C(C=C1)Cl)Cl)=O CKWMMPKRTDERCF-UHFFFAOYSA-N 0.000 description 4
- 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 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- NRVGZBBDWOURNR-UHFFFAOYSA-N [2-(1H-indol-4-yloxy)pyridin-4-yl]methanamine 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NCc1ccnc(Oc2cccc3[nH]ccc23)c1 NRVGZBBDWOURNR-UHFFFAOYSA-N 0.000 description 4
- XNQBNJUHOPGLTN-UHFFFAOYSA-N [2-[1-(1-methylpyrazol-4-yl)indol-4-yl]oxypyridin-4-yl]methanamine hydrochloride Chemical compound Cl.Cn1cc(cn1)-n1ccc2c(Oc3cc(CN)ccn3)cccc12 XNQBNJUHOPGLTN-UHFFFAOYSA-N 0.000 description 4
- ZGHCSKZYLSYUGI-UHFFFAOYSA-N [2-[1-(4-fluorophenyl)indol-4-yl]oxypyridin-4-yl]methanamine hydrochloride Chemical compound Cl.NCc1ccnc(Oc2cccc3n(ccc23)-c2ccc(F)cc2)c1 ZGHCSKZYLSYUGI-UHFFFAOYSA-N 0.000 description 4
- ZDKLXXMOTCKVBD-UHFFFAOYSA-N [2-[1-(quinolin-2-ylmethyl)indol-4-yl]oxypyridin-4-yl]methanamine hydrochloride Chemical compound Cl.NCc1ccnc(Oc2cccc3n(Cc4ccc5ccccc5n4)ccc23)c1 ZDKLXXMOTCKVBD-UHFFFAOYSA-N 0.000 description 4
- UPJHJCSHLZOBLX-UHFFFAOYSA-N [2-[1-[(6-methoxypyridin-3-yl)methyl]-2-methylindol-4-yl]oxypyridin-4-yl]methanamine 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.COc1ccc(Cn2c(C)cc3c(Oc4cc(CN)ccn4)cccc23)cn1 UPJHJCSHLZOBLX-UHFFFAOYSA-N 0.000 description 4
- HTTQQNBAPYKFPK-UHFFFAOYSA-N [2-[1-[(6-methoxypyridin-3-yl)methyl]-3-methylindol-4-yl]oxypyridin-4-yl]methanamine 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.COc1ccc(Cn2cc(C)c3c(Oc4cc(CN)ccn4)cccc23)cn1 HTTQQNBAPYKFPK-UHFFFAOYSA-N 0.000 description 4
- QMDSQAHRXDPTCU-UHFFFAOYSA-N [2-[3-bromo-1-[2-(4-fluorophenyl)ethyl]indol-4-yl]oxypyridin-4-yl]methanamine hydrochloride Chemical compound Cl.NCc1ccnc(Oc2cccc3n(CCc4ccc(F)cc4)cc(Br)c23)c1 QMDSQAHRXDPTCU-UHFFFAOYSA-N 0.000 description 4
- BTQVAWOPTVAMCX-UHFFFAOYSA-N [2-[[1-(6-fluoro-1,3-benzothiazol-2-yl)-2,3-dihydroindol-4-yl]oxy]pyridin-4-yl]methanamine hydrochloride Chemical compound Cl.NCc1ccnc(Oc2cccc3N(CCc23)c2nc3ccc(F)cc3s2)c1 BTQVAWOPTVAMCX-UHFFFAOYSA-N 0.000 description 4
- ABRVLXLNVJHDRQ-UHFFFAOYSA-N [2-pyridin-3-yl-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound FC(C1=CC(=CC(=N1)C=1C=NC=CC=1)CN)(F)F ABRVLXLNVJHDRQ-UHFFFAOYSA-N 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000003638 chemical reducing agent Substances 0.000 description 4
- VDQQXEISLMTGAB-UHFFFAOYSA-N chloramine T Chemical compound [Na+].CC1=CC=C(S(=O)(=O)[N-]Cl)C=C1 VDQQXEISLMTGAB-UHFFFAOYSA-N 0.000 description 4
- 239000012320 chlorinating reagent Substances 0.000 description 4
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 4
- 238000011284 combination treatment Methods 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 230000002708 enhancing effect Effects 0.000 description 4
- 210000002744 extracellular matrix Anatomy 0.000 description 4
- 125000002541 furyl group Chemical group 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- 238000010562 histological examination Methods 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 230000004060 metabolic process Effects 0.000 description 4
- 239000002480 mineral oil Substances 0.000 description 4
- 235000010446 mineral oil Nutrition 0.000 description 4
- 125000001620 monocyclic carbocycle group Chemical group 0.000 description 4
- 125000003551 oxepanyl group Chemical group 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- 230000007115 recruitment Effects 0.000 description 4
- 239000003381 stabilizer Substances 0.000 description 4
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 4
- 239000011593 sulfur Substances 0.000 description 4
- 239000000375 suspending agent Substances 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 125000002873 tetrahydrofuranonyl group Chemical group 0.000 description 4
- 230000000699 topical effect Effects 0.000 description 4
- 230000003442 weekly effect Effects 0.000 description 4
- ORBSSWJRHPFEBR-UHFFFAOYSA-N (2-fluoropyridin-3-yl)methanamine Chemical compound NCC1=CC=CN=C1F ORBSSWJRHPFEBR-UHFFFAOYSA-N 0.000 description 3
- PJFOUMAUWJEBRT-UHFFFAOYSA-N (2-phenoxypyridin-4-yl)methanamine Chemical compound NCC1=CC=NC(OC=2C=CC=CC=2)=C1 PJFOUMAUWJEBRT-UHFFFAOYSA-N 0.000 description 3
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 3
- OKDGRDCXVWSXDC-UHFFFAOYSA-N 2-chloropyridine Chemical compound ClC1=CC=CC=N1 OKDGRDCXVWSXDC-UHFFFAOYSA-N 0.000 description 3
- ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 3
- FVQKGQNSCKJPIJ-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-[2-(2-oxo-1,3-oxazolidin-3-yl)ethyl]benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NCCN2C(OCC2)=O)C=CC=1 FVQKGQNSCKJPIJ-UHFFFAOYSA-N 0.000 description 3
- QLVFXWKFILAMRV-UHFFFAOYSA-N 3-[4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]pyridin-2-yl]benzoic acid Chemical compound C(C)(C)(C)OC(=O)NCC1=CC(=NC=C1)C=1C=C(C(=O)O)C=CC=1 QLVFXWKFILAMRV-UHFFFAOYSA-N 0.000 description 3
- UUEWDWQJEYMAQA-UHFFFAOYSA-N 3-[4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]pyridin-2-yl]oxybenzoic acid Chemical compound C(C)(C)(C)OC(=O)NCC1=CC(=NC=C1)OC=1C=C(C(=O)O)C=CC=1 UUEWDWQJEYMAQA-UHFFFAOYSA-N 0.000 description 3
- KRBDRWBWJAFVCL-UHFFFAOYSA-N 3-[[4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]pyridin-2-yl]oxymethyl]benzoic acid Chemical compound C(C)(C)(C)OC(=O)NCC1=CC(=NC=C1)OCC=1C=C(C(=O)O)C=CC=1 KRBDRWBWJAFVCL-UHFFFAOYSA-N 0.000 description 3
- AVUJHYKQCMXSGM-UHFFFAOYSA-N 4-(aminomethyl)-N,N-dimethyl-6-(3-phenoxyphenoxy)pyridin-2-amine Chemical compound NCC1=CC(=NC(=C1)OC1=CC(=CC=C1)OC1=CC=CC=C1)N(C)C AVUJHYKQCMXSGM-UHFFFAOYSA-N 0.000 description 3
- 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
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- 241000792859 Enema Species 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 3
- 206010027476 Metastases Diseases 0.000 description 3
- 150000001204 N-oxides Chemical class 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 206010034665 Peritoneal fibrosis Diseases 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- YIQKLZYTHXTDDT-UHFFFAOYSA-H Sirius red F3B Chemical compound C1=CC(=CC=C1N=NC2=CC(=C(C=C2)N=NC3=C(C=C4C=C(C=CC4=C3[O-])NC(=O)NC5=CC6=CC(=C(C(=C6C=C5)[O-])N=NC7=C(C=C(C=C7)N=NC8=CC=C(C=C8)S(=O)(=O)[O-])S(=O)(=O)[O-])S(=O)(=O)O)S(=O)(=O)O)S(=O)(=O)[O-])S(=O)(=O)[O-].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+] YIQKLZYTHXTDDT-UHFFFAOYSA-H 0.000 description 3
- 206010050207 Skin fibrosis Diseases 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical group [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 238000006069 Suzuki reaction reaction Methods 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- LETQLOMLPJORPB-UHFFFAOYSA-N [2-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound NCC1=CC=NC(C(F)(F)F)=C1 LETQLOMLPJORPB-UHFFFAOYSA-N 0.000 description 3
- YLEYXQJHVSWUPE-UHFFFAOYSA-N [2-[1-[(2,4-difluorophenyl)methyl]-2-methylindol-4-yl]oxypyridin-4-yl]methanamine Chemical compound FC1=C(CN2C(=CC3=C(C=CC=C23)OC2=NC=CC(=C2)CN)C)C=CC(=C1)F YLEYXQJHVSWUPE-UHFFFAOYSA-N 0.000 description 3
- WPRCLEBGYAUMRK-UHFFFAOYSA-N [2-[1-[(2,4-difluorophenyl)methyl]-3-methylindazol-4-yl]oxypyridin-4-yl]methanamine Chemical compound FC1=C(CN2N=C(C3=C(C=CC=C23)OC2=NC=CC(=C2)CN)C)C=CC(=C1)F WPRCLEBGYAUMRK-UHFFFAOYSA-N 0.000 description 3
- YTFMTTFTWAWXCI-UHFFFAOYSA-N [2-[1-[(2,4-difluorophenyl)methyl]-3-methylindol-4-yl]oxypyridin-4-yl]methanamine Chemical compound FC1=C(CN2C=C(C3=C(C=CC=C23)OC2=NC=CC(=C2)CN)C)C=CC(=C1)F YTFMTTFTWAWXCI-UHFFFAOYSA-N 0.000 description 3
- NLKOONDADISCBS-UHFFFAOYSA-N [2-[1-[(6-methoxypyridin-3-yl)methyl]indol-5-yl]oxypyridin-4-yl]methanamine Chemical compound COC1=CC=C(C=N1)CN1C=CC2=CC(=CC=C12)OC1=NC=CC(=C1)CN NLKOONDADISCBS-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 125000000304 alkynyl group Chemical group 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 239000012131 assay buffer Substances 0.000 description 3
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 3
- JXHYCCGOZUGBFD-UHFFFAOYSA-N benzoic acid;hydrochloride Chemical compound Cl.OC(=O)C1=CC=CC=C1 JXHYCCGOZUGBFD-UHFFFAOYSA-N 0.000 description 3
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 125000001246 bromo group Chemical group Br* 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 238000004296 chiral HPLC Methods 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 229940125904 compound 1 Drugs 0.000 description 3
- 229940125898 compound 5 Drugs 0.000 description 3
- 238000004132 cross linking Methods 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000002270 dispersing agent Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 229940095399 enema Drugs 0.000 description 3
- 239000007920 enema Substances 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 125000003709 fluoroalkyl group Chemical group 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000008595 infiltration Effects 0.000 description 3
- 238000001764 infiltration Methods 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
- 229960002725 isoflurane Drugs 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 230000009401 metastasis Effects 0.000 description 3
- 238000003801 milling Methods 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical group [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 230000002685 pulmonary effect Effects 0.000 description 3
- 238000007388 punch biopsy Methods 0.000 description 3
- TXQWFIVRZNOPCK-UHFFFAOYSA-N pyridin-4-ylmethanamine Chemical compound NCC1=CC=NC=C1 TXQWFIVRZNOPCK-UHFFFAOYSA-N 0.000 description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 238000007390 skin biopsy Methods 0.000 description 3
- 125000003003 spiro group Chemical group 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000012258 stirred mixture Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000011200 topical administration Methods 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- GGHCWJWUOSNCSK-UHFFFAOYSA-N (2-chloropyridin-4-yl)methanamine Chemical compound NCC1=CC=NC(Cl)=C1 GGHCWJWUOSNCSK-UHFFFAOYSA-N 0.000 description 2
- ULGNIWUOIJPCIG-UHFFFAOYSA-N (2-cyclohexyloxypyridin-4-yl)methanamine Chemical compound NCC1=CC=NC(OC2CCCCC2)=C1 ULGNIWUOIJPCIG-UHFFFAOYSA-N 0.000 description 2
- LPEUVSAZSYDINS-UHFFFAOYSA-N (2-fluoropyridin-4-yl)methanamine Chemical compound NCC1=CC=NC(F)=C1 LPEUVSAZSYDINS-UHFFFAOYSA-N 0.000 description 2
- DQTSFNDKOUQLGP-UHFFFAOYSA-N (2-imidazol-1-ylpyridin-4-yl)methanamine Chemical compound NCC1=CC=NC(N2C=NC=C2)=C1 DQTSFNDKOUQLGP-UHFFFAOYSA-N 0.000 description 2
- AFQIEAJIXXIVCX-UHFFFAOYSA-N (2-phenylmethoxypyridin-4-yl)methanamine Chemical compound NCC1=CC=NC(OCC=2C=CC=CC=2)=C1 AFQIEAJIXXIVCX-UHFFFAOYSA-N 0.000 description 2
- VJLYHTOSFSGXGH-CQSZACIVSA-N (2R)-1-[3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxybenzoyl]pyrrolidine-2-carboxylic acid Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)N2[C@H](CCC2)C(=O)O)C=CC=1 VJLYHTOSFSGXGH-CQSZACIVSA-N 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 2
- YPJQSIDUEOBFTE-UHFFFAOYSA-N (3-fluoropyridin-4-yl)methanamine Chemical compound NCC1=CC=NC=C1F YPJQSIDUEOBFTE-UHFFFAOYSA-N 0.000 description 2
- ZXAQFYZQHPGMMN-BZSJEYESSA-N (3R)-3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-phenylcyclohexane-1-carboxamide Chemical compound C1C[C@H](CC(C1)C(=O)NC2=CC=CC=C2)OC3=CC(=CC(=N3)C(F)(F)F)CN ZXAQFYZQHPGMMN-BZSJEYESSA-N 0.000 description 2
- ZWHOTPNCEFWATE-CQSZACIVSA-N (3R)-3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-phenylpyrrolidine-1-carboxamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)O[C@H]1CN(CC1)C(=O)NC1=CC=CC=C1 ZWHOTPNCEFWATE-CQSZACIVSA-N 0.000 description 2
- ZWHOTPNCEFWATE-AWEZNQCLSA-N (3S)-3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-phenylpyrrolidine-1-carboxamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)O[C@@H]1CN(CC1)C(=O)NC1=CC=CC=C1 ZWHOTPNCEFWATE-AWEZNQCLSA-N 0.000 description 2
- SNAKUPLQASYKTC-AWEZNQCLSA-N (3S)-3-[[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxymethyl]-N-phenylpiperidine-1-carboxamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC[C@@H]1CN(CCC1)C(=O)NC1=CC=CC=C1 SNAKUPLQASYKTC-AWEZNQCLSA-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
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 2
- YHIOCGXGAXHMDQ-UHFFFAOYSA-N 2-(chloromethyl)-5-fluoropyridine Chemical compound FC1=CC=C(CCl)N=C1 YHIOCGXGAXHMDQ-UHFFFAOYSA-N 0.000 description 2
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 2
- DGPBVJWCIDNDPN-UHFFFAOYSA-N 2-(dimethylamino)benzaldehyde Chemical compound CN(C)C1=CC=CC=C1C=O DGPBVJWCIDNDPN-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 2
- KSUCDCXZFNCXGV-PPHPATTJSA-N 2-[(3s)-piperidin-3-yl]oxypyridine-4-carbonitrile;hydrochloride Chemical compound Cl.N#CC1=CC=NC(O[C@@H]2CNCCC2)=C1 KSUCDCXZFNCXGV-PPHPATTJSA-N 0.000 description 2
- BVKRPQCDGACLPX-UHFFFAOYSA-N 2-[4-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxyindol-1-yl]-N-methyl-N-phenylacetamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC1=C2C=CN(C2=CC=C1)CC(=O)N(C1=CC=CC=C1)C BVKRPQCDGACLPX-UHFFFAOYSA-N 0.000 description 2
- IWKBPPQZIJBLHA-UHFFFAOYSA-N 2-chloro-6-(3-phenoxyphenoxy)pyridine-4-carbonitrile Chemical compound ClC=1C=C(C#N)C=C(N=1)OC1=CC(=CC=C1)OC1=CC=CC=C1 IWKBPPQZIJBLHA-UHFFFAOYSA-N 0.000 description 2
- XBVSGEGNQZAQPM-UHFFFAOYSA-N 2-methyl-1h-indol-4-ol Chemical compound C1=CC=C2NC(C)=CC2=C1O XBVSGEGNQZAQPM-UHFFFAOYSA-N 0.000 description 2
- WSNKEJIFARPOSQ-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-(1-benzothiophen-2-ylmethyl)benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NCC2=CC3=C(S2)C=CC=C3)C=CC=1 WSNKEJIFARPOSQ-UHFFFAOYSA-N 0.000 description 2
- CJYDQTAWSHWBIT-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-(2-hydroxy-2-methylpropyl)benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NCC(C)(C)O)C=CC=1 CJYDQTAWSHWBIT-UHFFFAOYSA-N 0.000 description 2
- MROVZCRMXJZHCN-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-(2-hydroxyethyl)benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NCCO)C=CC=1 MROVZCRMXJZHCN-UHFFFAOYSA-N 0.000 description 2
- SHBHYINHXNTBRP-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-(2-methylsulfonylethyl)benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NCCS(=O)(=O)C)C=CC=1 SHBHYINHXNTBRP-UHFFFAOYSA-N 0.000 description 2
- LIDBMZYKSAXTQG-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-(2-sulfamoylethyl)benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NCCS(N)(=O)=O)C=CC=1 LIDBMZYKSAXTQG-UHFFFAOYSA-N 0.000 description 2
- VTNULXUEOJMRKZ-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-(2H-tetrazol-5-ylmethyl)benzamide Chemical compound N=1NN=NC=1CNC(C1=CC(=CC=C1)OC1=NC(=CC(=C1)CN)C(F)(F)F)=O VTNULXUEOJMRKZ-UHFFFAOYSA-N 0.000 description 2
- SONNQRNOTIAJDS-GFCCVEGCSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-[(2R)-2,3-dihydroxypropyl]benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NC[C@H](CO)O)C=CC=1 SONNQRNOTIAJDS-GFCCVEGCSA-N 0.000 description 2
- GDSLUYKCPYECNN-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-[(4-fluorophenyl)methyl]benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NCC2=CC=C(C=C2)F)C=CC=1 GDSLUYKCPYECNN-UHFFFAOYSA-N 0.000 description 2
- ISXSUKUXUPLGTD-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-[(5-oxopyrrolidin-2-yl)methyl]benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NCC2NC(CC2)=O)C=CC=1 ISXSUKUXUPLGTD-UHFFFAOYSA-N 0.000 description 2
- FJPUKTJEFOXMJX-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-[1-(hydroxymethyl)cyclopropyl]benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NC2(CC2)CO)C=CC=1 FJPUKTJEFOXMJX-UHFFFAOYSA-N 0.000 description 2
- ZMCQQCBOZIGNRV-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-[2-(1,2,4-triazol-1-yl)ethyl]benzamide Chemical compound NCC1=CC(OC2=CC=CC(=C2)C(=O)NCCN2C=NC=N2)=NC(=C1)C(F)(F)F ZMCQQCBOZIGNRV-UHFFFAOYSA-N 0.000 description 2
- ZUNFPBNHELLPPP-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-[2-(dimethylamino)ethyl]benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NCCN(C)C)C=CC=1 ZUNFPBNHELLPPP-UHFFFAOYSA-N 0.000 description 2
- AJZDHLHTTJRNQJ-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-[2-(tetrazol-1-yl)ethyl]benzamide Chemical compound N1(N=NN=C1)CCNC(C1=CC(=CC=C1)OC1=NC(=CC(=C1)CN)C(F)(F)F)=O AJZDHLHTTJRNQJ-UHFFFAOYSA-N 0.000 description 2
- MZSAMHOCTRNOIZ-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-phenylaniline Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(NC2=CC=CC=C2)C=CC=1 MZSAMHOCTRNOIZ-UHFFFAOYSA-N 0.000 description 2
- HAEQAUJYNHQVHV-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-phenylbenzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NC2=CC=CC=C2)C=CC=1 HAEQAUJYNHQVHV-UHFFFAOYSA-N 0.000 description 2
- RYRARARYUZMODI-UHFFFAOYSA-N 3-methyl-1h-indol-4-ol Chemical compound C1=CC(O)=C2C(C)=CNC2=C1 RYRARARYUZMODI-UHFFFAOYSA-N 0.000 description 2
- HBUCPZGYBSEEHF-UHFFFAOYSA-N 3-phenoxyphenol Chemical compound OC1=CC=CC(OC=2C=CC=CC=2)=C1 HBUCPZGYBSEEHF-UHFFFAOYSA-N 0.000 description 2
- QEIVWSRXBYOTAZ-UHFFFAOYSA-N 4-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-phenylpiperidine-1-carboxamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC1CCN(CC1)C(=O)NC1=CC=CC=C1 QEIVWSRXBYOTAZ-UHFFFAOYSA-N 0.000 description 2
- PVUHBMXOIZKNHK-UHFFFAOYSA-N 4-[4-(aminomethyl)pyridin-2-yl]oxy-N-benzylbenzamide Chemical compound NCC1=CC(=NC=C1)OC1=CC=C(C(=O)NCC2=CC=CC=C2)C=C1 PVUHBMXOIZKNHK-UHFFFAOYSA-N 0.000 description 2
- HOWFLZVASJDZRZ-UHFFFAOYSA-N 4-[[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxymethyl]-N-phenylpiperidine-1-carboxamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OCC1CCN(CC1)C(=O)NC1=CC=CC=C1 HOWFLZVASJDZRZ-UHFFFAOYSA-N 0.000 description 2
- LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 2
- NLMQHXUGJIAKTH-UHFFFAOYSA-N 4-hydroxyindole Chemical compound OC1=CC=CC2=C1C=CN2 NLMQHXUGJIAKTH-UHFFFAOYSA-N 0.000 description 2
- UTTJAIFHRUAFED-UHFFFAOYSA-N 5-hydroxy-3,4-dihydro-2(1h)-quinolinone Chemical compound N1C(=O)CCC2=C1C=CC=C2O UTTJAIFHRUAFED-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-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
- NRLQBVLOUUPAMI-UHFFFAOYSA-N 8-[3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxybenzoyl]-1-oxa-3,8-diazaspiro[4.5]decan-2-one Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)N2CCC3(CNC(O3)=O)CC2)C=CC=1 NRLQBVLOUUPAMI-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- 102000007469 Actins Human genes 0.000 description 2
- 108010085238 Actins Proteins 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-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
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 101150065749 Churc1 gene Proteins 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 102000016942 Elastin Human genes 0.000 description 2
- 108010014258 Elastin Proteins 0.000 description 2
- 102000016621 Focal Adhesion Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108010067715 Focal Adhesion Protein-Tyrosine Kinases Proteins 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 101001043321 Homo sapiens Lysyl oxidase homolog 1 Proteins 0.000 description 2
- 101001043354 Homo sapiens Lysyl oxidase homolog 3 Proteins 0.000 description 2
- 101001043351 Homo sapiens Lysyl oxidase homolog 4 Proteins 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 102100021958 Lysyl oxidase homolog 1 Human genes 0.000 description 2
- 102100021949 Lysyl oxidase homolog 3 Human genes 0.000 description 2
- 102100021968 Lysyl oxidase homolog 4 Human genes 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 102100038239 Protein Churchill Human genes 0.000 description 2
- 108010003894 Protein-Lysine 6-Oxidase Proteins 0.000 description 2
- 102100026858 Protein-lysine 6-oxidase Human genes 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 206010039710 Scleroderma Diseases 0.000 description 2
- 206010040867 Skin hypertrophy Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- RVIFLPFRMQLWBE-UHFFFAOYSA-N [2-(4-ethylpiperazin-1-yl)pyridin-4-yl]methanamine Chemical compound C1CN(CC)CCN1C1=CC(CN)=CC=N1 RVIFLPFRMQLWBE-UHFFFAOYSA-N 0.000 description 2
- FFFAEFIVCXMBKE-UHFFFAOYSA-N [2-(4-fluorophenoxy)pyridin-4-yl]methanamine Chemical compound NCC1=CC=NC(OC=2C=CC(F)=CC=2)=C1 FFFAEFIVCXMBKE-UHFFFAOYSA-N 0.000 description 2
- AJQSGEUUHKBUSX-UHFFFAOYSA-N [2-[2-(trifluoromethyl)phenoxy]pyridin-4-yl]methanamine Chemical compound NCC1=CC=NC(OC=2C(=CC=CC=2)C(F)(F)F)=C1 AJQSGEUUHKBUSX-UHFFFAOYSA-N 0.000 description 2
- SAHIZENKTPRYSN-UHFFFAOYSA-N [2-[3-(phenoxymethyl)phenoxy]-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound O(C1=CC=CC=C1)CC=1C=C(OC2=NC(=CC(=C2)CN)C(F)(F)F)C=CC=1 SAHIZENKTPRYSN-UHFFFAOYSA-N 0.000 description 2
- YQYBUJYBXOVWQW-UHFFFAOYSA-N [3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxyphenyl]-(3,4-dihydro-1H-isoquinolin-2-yl)methanone Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C=CC=1)C(=O)N1CC2=CC=CC=C2CC1 YQYBUJYBXOVWQW-UHFFFAOYSA-N 0.000 description 2
- JOSCNYCOYXTLTN-GFCCVEGCSA-N [3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxyphenyl]-[(3R)-3-(hydroxymethyl)pyrrolidin-1-yl]methanone Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C=CC=1)C(=O)N1C[C@@H](CC1)CO JOSCNYCOYXTLTN-GFCCVEGCSA-N 0.000 description 2
- BYWBCSRCPLBDFU-CYBMUJFWSA-N [3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxyphenyl]-[(3R)-3-aminopyrrolidin-1-yl]methanone Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C=CC=1)C(=O)N1C[C@@H](CC1)N BYWBCSRCPLBDFU-CYBMUJFWSA-N 0.000 description 2
- LJHFUFVRZNYVMK-CYBMUJFWSA-N [3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxyphenyl]-[(3R)-3-hydroxypyrrolidin-1-yl]methanone Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C=CC=1)C(=O)N1C[C@@H](CC1)O LJHFUFVRZNYVMK-CYBMUJFWSA-N 0.000 description 2
- LJHFUFVRZNYVMK-ZDUSSCGKSA-N [3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxyphenyl]-[(3S)-3-hydroxypyrrolidin-1-yl]methanone Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C=CC=1)C(=O)N1C[C@H](CC1)O LJHFUFVRZNYVMK-ZDUSSCGKSA-N 0.000 description 2
- JWSIZPAOIFLWKM-UHFFFAOYSA-N [3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxyphenyl]-[3-(dimethylamino)-4-hydroxypyrrolidin-1-yl]methanone Chemical compound CN(C)C1CN(CC1O)C(=O)c1cccc(Oc2cc(CN)cc(n2)C(F)(F)F)c1 JWSIZPAOIFLWKM-UHFFFAOYSA-N 0.000 description 2
- KDSYNTPPPISIJB-UHFFFAOYSA-N [3-[[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxymethyl]phenyl]-(3-fluoro-4-hydroxypyrrolidin-1-yl)methanone Chemical compound NCc1cc(OCc2cccc(c2)C(=O)N2CC(O)C(F)C2)nc(c1)C(F)(F)F KDSYNTPPPISIJB-UHFFFAOYSA-N 0.000 description 2
- 238000005903 acid hydrolysis reaction Methods 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000005907 alkyl ester group Chemical group 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 229940040609 bleomycin injection Drugs 0.000 description 2
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 125000002843 carboxylic acid group Chemical group 0.000 description 2
- 230000020411 cell activation Effects 0.000 description 2
- 230000021164 cell adhesion Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 239000007891 compressed tablet Substances 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 239000002285 corn oil Substances 0.000 description 2
- 235000005687 corn oil Nutrition 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000001064 degrader Substances 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 230000002183 duodenal effect Effects 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 210000005069 ears Anatomy 0.000 description 2
- 229920002549 elastin Polymers 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 239000010685 fatty oil Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 238000007489 histopathology method Methods 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 230000001146 hypoxic effect Effects 0.000 description 2
- 238000002991 immunohistochemical analysis Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 238000006241 metabolic reaction Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- YKUCHDXIBAQWSF-UHFFFAOYSA-N methyl 3-hydroxybenzoate Chemical compound COC(=O)C1=CC=CC(O)=C1 YKUCHDXIBAQWSF-UHFFFAOYSA-N 0.000 description 2
- LZXXNPOYQCLXRS-UHFFFAOYSA-N methyl 4-aminobenzoate Chemical compound COC(=O)C1=CC=C(N)C=C1 LZXXNPOYQCLXRS-UHFFFAOYSA-N 0.000 description 2
- MZDGXTXYHXDWIM-UHFFFAOYSA-N methyl benzoate;hydrochloride Chemical compound Cl.COC(=O)C1=CC=CC=C1 MZDGXTXYHXDWIM-UHFFFAOYSA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 239000005022 packaging material Substances 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 2
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 2
- 150000003014 phosphoric acid esters Chemical class 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 210000003240 portal vein Anatomy 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 229940043274 prophylactic drug Drugs 0.000 description 2
- 239000012658 prophylactic medication Substances 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical compound OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 230000000707 stereoselective effect Effects 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 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 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000011285 therapeutic regimen Methods 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- 229940042129 topical gel Drugs 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- ZMCBYSBVJIMENC-UHFFFAOYSA-N tricaine Chemical compound CCOC(=O)C1=CC=CC(N)=C1 ZMCBYSBVJIMENC-UHFFFAOYSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- QDZZDVQGBKTLHV-UHFFFAOYSA-N (2,4-difluorophenyl)methanamine Chemical compound NCC1=CC=C(F)C=C1F QDZZDVQGBKTLHV-UHFFFAOYSA-N 0.000 description 1
- BBJLHJAXTVGITH-INIZCTEOSA-N (3S)-3-(4-cyanopyridin-2-yl)oxy-N-phenylpiperidine-1-carboxamide Chemical compound C(#N)C1=CC(=NC=C1)O[C@@H]1CN(CCC1)C(=O)NC1=CC=CC=C1 BBJLHJAXTVGITH-INIZCTEOSA-N 0.000 description 1
- JQTHHDBNODNFIU-INIZCTEOSA-N (3S)-3-[4-(aminomethyl)pyridin-2-yl]oxy-N-phenylpiperidine-1-carboxamide Chemical compound NCC1=CC(=NC=C1)O[C@@H]1CN(CCC1)C(=O)NC1=CC=CC=C1 JQTHHDBNODNFIU-INIZCTEOSA-N 0.000 description 1
- ZZJHCOUWDLIGPH-VKKIDBQXSA-N (3r,4r)-4-fluoropyrrolidin-3-ol;hydrochloride Chemical compound Cl.O[C@@H]1CNC[C@H]1F ZZJHCOUWDLIGPH-VKKIDBQXSA-N 0.000 description 1
- XRNVSPDQTPVECU-UHFFFAOYSA-N (4-bromophenyl)methanamine Chemical compound NCC1=CC=C(Br)C=C1 XRNVSPDQTPVECU-UHFFFAOYSA-N 0.000 description 1
- ZLNFACCFYUFTLD-UHFFFAOYSA-N (4-ethoxycarbonylphenyl)boronic acid Chemical compound CCOC(=O)C1=CC=C(B(O)O)C=C1 ZLNFACCFYUFTLD-UHFFFAOYSA-N 0.000 description 1
- BKLMFAZXPZQITJ-UHFFFAOYSA-N (5-fluoropyridin-2-yl)methanol Chemical compound OCC1=CC=C(F)C=N1 BKLMFAZXPZQITJ-UHFFFAOYSA-N 0.000 description 1
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- IJXJGQCXFSSHNL-QMMMGPOBSA-N (R)-(-)-2-Phenylglycinol Chemical compound OC[C@H](N)C1=CC=CC=C1 IJXJGQCXFSSHNL-QMMMGPOBSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
- JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- FLRUNCJXOVYWDH-UHFFFAOYSA-N 1-(2-bromoethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CCBr)C=C1 FLRUNCJXOVYWDH-UHFFFAOYSA-N 0.000 description 1
- UTDGDGFOENJMAA-UHFFFAOYSA-N 1-(4-methoxy-1h-indol-3-yl)-n,n-dimethylmethanamine Chemical compound COC1=CC=CC2=C1C(CN(C)C)=CN2 UTDGDGFOENJMAA-UHFFFAOYSA-N 0.000 description 1
- WKYFWFHTABURGB-UHFFFAOYSA-N 1-benzothiophen-2-ylmethanamine Chemical compound C1=CC=C2SC(CN)=CC2=C1 WKYFWFHTABURGB-UHFFFAOYSA-N 0.000 description 1
- XNHLSAAJAXEJLT-UHFFFAOYSA-N 1-benzyl-4-phenylmethoxyindole Chemical compound C=1C=CC=CC=1COC(C=1C=C2)=CC=CC=1N2CC1=CC=CC=C1 XNHLSAAJAXEJLT-UHFFFAOYSA-N 0.000 description 1
- PYDYILSIDWNPMK-UHFFFAOYSA-N 1-benzylindol-4-ol Chemical compound C1=CC=2C(O)=CC=CC=2N1CC1=CC=CC=C1 PYDYILSIDWNPMK-UHFFFAOYSA-N 0.000 description 1
- AITNMTXHTIIIBB-UHFFFAOYSA-N 1-bromo-4-fluorobenzene Chemical compound FC1=CC=C(Br)C=C1 AITNMTXHTIIIBB-UHFFFAOYSA-N 0.000 description 1
- RCMLKQSZCSYLLS-UHFFFAOYSA-N 1-hydroxy-2,3-dihydroindole Chemical compound C1=CC=C2N(O)CCC2=C1 RCMLKQSZCSYLLS-UHFFFAOYSA-N 0.000 description 1
- SJJCQDRGABAVBB-UHFFFAOYSA-N 1-hydroxy-2-naphthoic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CC=C21 SJJCQDRGABAVBB-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- UJIBOGAQJRDRES-UHFFFAOYSA-N 1h-pyridin-2-one Chemical compound OC1=CC=CC=N1.O=C1C=CC=CN1 UJIBOGAQJRDRES-UHFFFAOYSA-N 0.000 description 1
- CEPCPXLLFXPZGW-UHFFFAOYSA-N 2,4-difluoroaniline Chemical compound NC1=CC=C(F)C=C1F CEPCPXLLFXPZGW-UHFFFAOYSA-N 0.000 description 1
- FILKGCRCWDMBKA-UHFFFAOYSA-N 2,6-dichloropyridine Chemical compound ClC1=CC=CC(Cl)=N1 FILKGCRCWDMBKA-UHFFFAOYSA-N 0.000 description 1
- BTUKLHWINORBTN-UHFFFAOYSA-N 2,6-dichloropyridine-4-carbonitrile Chemical compound ClC1=CC(C#N)=CC(Cl)=N1 BTUKLHWINORBTN-UHFFFAOYSA-N 0.000 description 1
- QQSGIDQMMHPNNX-UHFFFAOYSA-N 2-(1-benzoylindol-4-yl)oxypyridine-4-carbonitrile Chemical compound C(C1=CC=CC=C1)(=O)N1C=CC2=C(C=CC=C12)OC=1C=C(C#N)C=CN=1 QQSGIDQMMHPNNX-UHFFFAOYSA-N 0.000 description 1
- ZOUPGSMSNQLUNW-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(Cl)C(Cl)=C1 ZOUPGSMSNQLUNW-UHFFFAOYSA-N 0.000 description 1
- KFQNIXASIZAACV-UHFFFAOYSA-N 2-(4-fluorophenyl)-6-(3-phenoxyphenoxy)pyridine-4-carbonitrile Chemical compound FC1=CC=C(C=C1)C=1C=C(C#N)C=C(N=1)OC1=CC(=CC=C1)OC1=CC=CC=C1 KFQNIXASIZAACV-UHFFFAOYSA-N 0.000 description 1
- NNAYPIDFVQLEDK-UHFFFAOYSA-N 2-(bromomethyl)quinoline Chemical compound C1=CC=CC2=NC(CBr)=CC=C21 NNAYPIDFVQLEDK-UHFFFAOYSA-N 0.000 description 1
- GZJGVYZBAWLWBO-UHFFFAOYSA-N 2-(dimethylamino)-6-(3-phenoxyphenoxy)pyridine-4-carbonitrile Chemical compound CN(C=1C=C(C#N)C=C(N=1)OC1=CC(=CC=C1)OC1=CC=CC=C1)C GZJGVYZBAWLWBO-UHFFFAOYSA-N 0.000 description 1
- NDRWWJGDQIHRLE-INIZCTEOSA-N 2-[(3S)-1-benzoylpiperidin-3-yl]oxypyridine-4-carbonitrile Chemical compound C(C1=CC=CC=C1)(=O)N1C[C@H](CCC1)OC=1C=C(C#N)C=CN=1 NDRWWJGDQIHRLE-INIZCTEOSA-N 0.000 description 1
- QAKRYUTXZGRMMF-UHFFFAOYSA-N 2-[1-(6-fluoro-1,3-benzothiazol-2-yl)indol-4-yl]oxypyridine-4-carbonitrile Chemical compound FC1=CC2=C(N=C(S2)N2C=CC3=C(C=CC=C23)OC=2C=C(C#N)C=CN=2)C=C1 QAKRYUTXZGRMMF-UHFFFAOYSA-N 0.000 description 1
- WYHONWXLHCEHLA-UHFFFAOYSA-N 2-[1-(6-methoxypyridin-3-yl)indol-4-yl]oxypyridine-4-carbonitrile Chemical compound COC1=CC=C(C=N1)N1C=CC2=C(C=CC=C12)OC=1C=C(C#N)C=CN=1 WYHONWXLHCEHLA-UHFFFAOYSA-N 0.000 description 1
- JUCLYSCZKFDOJP-UHFFFAOYSA-N 2-[4-[4-(aminomethyl)pyridin-2-yl]oxyindol-1-yl]-N,N-dimethylacetamide Chemical compound NCC1=CC(=NC=C1)OC1=C2C=CN(C2=CC=C1)CC(=O)N(C)C JUCLYSCZKFDOJP-UHFFFAOYSA-N 0.000 description 1
- BMRXODHPBMWLNX-UHFFFAOYSA-N 2-[4-[4-(aminomethyl)pyridin-2-yl]oxyindol-1-yl]-N-methyl-N-phenylacetamide Chemical compound NCC1=CC(=NC=C1)OC1=C2C=CN(C2=CC=C1)CC(=O)N(C1=CC=CC=C1)C BMRXODHPBMWLNX-UHFFFAOYSA-N 0.000 description 1
- GEEAYLFEIFJFGP-UHFFFAOYSA-N 2-aminopyridine-4-carbonitrile Chemical compound NC1=CC(C#N)=CC=N1 GEEAYLFEIFJFGP-UHFFFAOYSA-N 0.000 description 1
- GVRIASYEWWYYBU-UHFFFAOYSA-N 2-bromo-1-(3,4-dihydro-2h-quinolin-1-yl)ethanone Chemical compound C1=CC=C2N(C(=O)CBr)CCCC2=C1 GVRIASYEWWYYBU-UHFFFAOYSA-N 0.000 description 1
- GWJIPNKXIAJCPA-UHFFFAOYSA-N 2-bromo-1-piperidin-1-ylethanone Chemical compound BrCC(=O)N1CCCCC1 GWJIPNKXIAJCPA-UHFFFAOYSA-N 0.000 description 1
- MJLVLHNXEOQASX-UHFFFAOYSA-N 2-bromo-3,3-dimethylbutanoic acid Chemical compound CC(C)(C)C(Br)C(O)=O MJLVLHNXEOQASX-UHFFFAOYSA-N 0.000 description 1
- QPIOVNJLOVNTMW-UHFFFAOYSA-N 2-bromo-n,n-dimethylacetamide Chemical compound CN(C)C(=O)CBr QPIOVNJLOVNTMW-UHFFFAOYSA-N 0.000 description 1
- YLDILLQKQASWBA-UHFFFAOYSA-N 2-bromo-n-methyl-n-phenylacetamide Chemical compound BrCC(=O)N(C)C1=CC=CC=C1 YLDILLQKQASWBA-UHFFFAOYSA-N 0.000 description 1
- ISIIQFDYFMPPOA-UHFFFAOYSA-N 2-chloro-6-fluoro-1,3-benzothiazole Chemical compound FC1=CC=C2N=C(Cl)SC2=C1 ISIIQFDYFMPPOA-UHFFFAOYSA-N 0.000 description 1
- FNRMMDCDHWCQTH-UHFFFAOYSA-N 2-chloropyridine;3-chloropyridine;4-chloropyridine Chemical compound ClC1=CC=NC=C1.ClC1=CC=CN=C1.ClC1=CC=CC=N1 FNRMMDCDHWCQTH-UHFFFAOYSA-N 0.000 description 1
- ALFWHEYHCZRVLO-UHFFFAOYSA-N 2-fluoro-4-methylbenzoic acid Chemical compound CC1=CC=C(C(O)=O)C(F)=C1 ALFWHEYHCZRVLO-UHFFFAOYSA-N 0.000 description 1
- 102100027324 2-hydroxyacyl-CoA lyase 1 Human genes 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
- CRIVCEBEXJZQRH-UHFFFAOYSA-N 2-phenoxypyridine-4-carbonitrile Chemical compound N#CC1=CC=NC(OC=2C=CC=CC=2)=C1 CRIVCEBEXJZQRH-UHFFFAOYSA-N 0.000 description 1
- WXYQZMFCIXKNFT-UHFFFAOYSA-N 2-pyridin-3-ylpyridine-4-carbonitrile Chemical compound N#CC1=CC=NC(C=2C=NC=CC=2)=C1 WXYQZMFCIXKNFT-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- 125000001698 2H-pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- KHSACZVQYSVGDJ-UHFFFAOYSA-N 2h-indole Chemical compound C1=CC=CC2=NCC=C21 KHSACZVQYSVGDJ-UHFFFAOYSA-N 0.000 description 1
- KSNKQSPJFRQSEI-UHFFFAOYSA-N 3,3,3-trifluoropropanoic acid Chemical compound OC(=O)CC(F)(F)F KSNKQSPJFRQSEI-UHFFFAOYSA-N 0.000 description 1
- VIUDTWATMPPKEL-UHFFFAOYSA-N 3-(trifluoromethyl)aniline Chemical compound NC1=CC=CC(C(F)(F)F)=C1 VIUDTWATMPPKEL-UHFFFAOYSA-N 0.000 description 1
- SCISXSIATSHKKJ-UHFFFAOYSA-N 3-(trifluoromethyl)piperidin-3-ol Chemical compound FC(F)(F)C1(O)CCCNC1 SCISXSIATSHKKJ-UHFFFAOYSA-N 0.000 description 1
- CSSUQIZMQWWUOW-UHFFFAOYSA-N 3-[4-(aminomethyl)pyridin-2-yl]-N-(2-methoxyethyl)benzamide hydrochloride Chemical compound Cl.COCCNC(=O)c1cccc(c1)-c1cc(CN)ccn1 CSSUQIZMQWWUOW-UHFFFAOYSA-N 0.000 description 1
- FJYDBKYVCJLPTH-UHFFFAOYSA-N 3-[4-(aminomethyl)pyridin-2-yl]-N-(5-chloro-2-methylphenyl)benzamide Chemical compound NCC1=CC(=NC=C1)C=1C=C(C(=O)NC2=C(C=CC(=C2)Cl)C)C=CC=1 FJYDBKYVCJLPTH-UHFFFAOYSA-N 0.000 description 1
- HZOSNBJSMRCDMY-UHFFFAOYSA-N 3-[4-(aminomethyl)pyridin-2-yl]oxy-N-(1-benzothiophen-2-ylmethyl)benzamide Chemical compound NCC1=CC(=NC=C1)OC=1C=C(C(=O)NCC2=CC3=C(S2)C=CC=C3)C=CC=1 HZOSNBJSMRCDMY-UHFFFAOYSA-N 0.000 description 1
- IUMJMWGBIFYVAC-UHFFFAOYSA-N 3-[4-(aminomethyl)pyridin-2-yl]oxy-N-(2-methoxyethyl)benzamide Chemical compound NCC1=CC(=NC=C1)OC=1C=C(C(=O)NCCOC)C=CC=1 IUMJMWGBIFYVAC-UHFFFAOYSA-N 0.000 description 1
- BFTRSRQMNCXYRT-UHFFFAOYSA-N 3-[4-(aminomethyl)pyridin-2-yl]oxy-N-(4-bromophenyl)benzamide Chemical compound NCC1=CC(=NC=C1)OC=1C=C(C(=O)NC2=CC=C(C=C2)Br)C=CC=1 BFTRSRQMNCXYRT-UHFFFAOYSA-N 0.000 description 1
- BHKAZBAZIKMOGM-UHFFFAOYSA-N 3-[4-(aminomethyl)pyridin-2-yl]oxy-N-[(2,4-difluorophenyl)methyl]benzamide Chemical compound NCC1=CC(=NC=C1)OC=1C=C(C(=O)NCC2=C(C=C(C=C2)F)F)C=CC=1 BHKAZBAZIKMOGM-UHFFFAOYSA-N 0.000 description 1
- HEURIQPAZZQVGE-UHFFFAOYSA-N 3-[4-(aminomethyl)pyridin-2-yl]oxy-N-[(3-fluoro-4-imidazol-1-ylphenyl)methyl]benzamide Chemical compound NCC1=CC(=NC=C1)OC=1C=C(C(=O)NCC2=CC(=C(C=C2)N2C=NC=C2)F)C=CC=1 HEURIQPAZZQVGE-UHFFFAOYSA-N 0.000 description 1
- ZRUBRPSILIFDQG-UHFFFAOYSA-N 3-[4-(aminomethyl)pyridin-2-yl]oxy-N-[4-(trifluoromethyl)phenyl]benzamide Chemical compound NCC1=CC(=NC=C1)OC=1C=C(C(=O)NC2=CC=C(C=C2)C(F)(F)F)C=CC=1 ZRUBRPSILIFDQG-UHFFFAOYSA-N 0.000 description 1
- HGMGTTVDCACMDN-UHFFFAOYSA-N 3-[4-(aminomethyl)pyridin-2-yl]oxy-N-[[4-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound NCC1=CC(=NC=C1)OC=1C=C(C(=O)NCC2=CC=C(C=C2)C(F)(F)F)C=CC=1 HGMGTTVDCACMDN-UHFFFAOYSA-N 0.000 description 1
- IPYSFFBSHQXWBX-UHFFFAOYSA-N 3-[4-(aminomethyl)pyridin-2-yl]oxy-N-[[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]methyl]benzamide Chemical compound CCN1CCN(CC2=CC=C(CNC(=O)C3=CC(OC4=CC(CN)=CC=N4)=CC=C3)C=C2)CC1 IPYSFFBSHQXWBX-UHFFFAOYSA-N 0.000 description 1
- NUXWUXXXTZFTHA-UHFFFAOYSA-N 3-[4-(aminomethyl)pyridin-2-yl]oxy-N-benzylbenzamide hydrochloride Chemical compound Cl.NCc1ccnc(Oc2cccc(c2)C(=O)NCc2ccccc2)c1 NUXWUXXXTZFTHA-UHFFFAOYSA-N 0.000 description 1
- XRJBHVFXDQUQJP-UHFFFAOYSA-N 3-[4-(aminomethyl)pyridin-2-yl]oxy-N-phenylbenzamide hydrochloride Chemical compound Cl.NCc1ccnc(Oc2cccc(c2)C(=O)Nc2ccccc2)c1 XRJBHVFXDQUQJP-UHFFFAOYSA-N 0.000 description 1
- QCALSSCEUZVSHZ-UHFFFAOYSA-N 3-[[4-(aminomethyl)pyridin-2-yl]oxymethyl]-N-phenylbenzamide hydrochloride Chemical compound Cl.NCc1ccnc(OCc2cccc(c2)C(=O)Nc2ccccc2)c1 QCALSSCEUZVSHZ-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 description 1
- IORFQVZJHMWVSO-UHFFFAOYSA-N 3-methyl-2H-indazol-4-ol Chemical compound C1=CC(O)=C2C(C)=NNC2=C1 IORFQVZJHMWVSO-UHFFFAOYSA-N 0.000 description 1
- KIJQPTRIOXCOEG-UHFFFAOYSA-N 3-methyl-n-(4-phenylbutan-2-yl)butanamide Chemical compound CC(C)CC(=O)NC(C)CCC1=CC=CC=C1 KIJQPTRIOXCOEG-UHFFFAOYSA-N 0.000 description 1
- GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 description 1
- GRTTUFZTCCBQNQ-UHFFFAOYSA-N 4-[4-(aminomethyl)pyridin-2-yl]benzoic acid Chemical compound NCC1=CC(=NC=C1)C1=CC=C(C(=O)O)C=C1 GRTTUFZTCCBQNQ-UHFFFAOYSA-N 0.000 description 1
- MMVQJHXOWFTQPV-UHFFFAOYSA-N 4-[4-(aminomethyl)pyridin-2-yl]oxy-N-phenylbenzamide Chemical compound NCC1=CC(=NC=C1)OC1=CC=C(C(=O)NC2=CC=CC=C2)C=C1 MMVQJHXOWFTQPV-UHFFFAOYSA-N 0.000 description 1
- AHRCCEDCOGUFIG-UHFFFAOYSA-N 4-[4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]pyridin-2-yl]benzoic acid Chemical compound C(C)(C)(C)OC(=O)NCC1=CC(=NC=C1)C1=CC=C(C(=O)O)C=C1 AHRCCEDCOGUFIG-UHFFFAOYSA-N 0.000 description 1
- GVUFIQXODRDSEQ-UHFFFAOYSA-N 4-[4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]pyridin-2-yl]oxybenzoic acid Chemical compound C(C)(C)(C)OC(=O)NCC1=CC(=NC=C1)OC1=CC=C(C(=O)O)C=C1 GVUFIQXODRDSEQ-UHFFFAOYSA-N 0.000 description 1
- BSNYTBOSHJFWQM-UHFFFAOYSA-N 4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]pyridine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)NCC1=CC=NC(C(O)=O)=C1 BSNYTBOSHJFWQM-UHFFFAOYSA-N 0.000 description 1
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
- IXJSDKIJPVSPKF-UHFFFAOYSA-N 4-bromo-1-methylpyrazole Chemical compound CN1C=C(Br)C=N1 IXJSDKIJPVSPKF-UHFFFAOYSA-N 0.000 description 1
- WDFQBORIUYODSI-UHFFFAOYSA-N 4-bromoaniline Chemical compound NC1=CC=C(Br)C=C1 WDFQBORIUYODSI-UHFFFAOYSA-N 0.000 description 1
- RPHHYRNGCJYQSP-UHFFFAOYSA-N 4-bromopyridine-2-carboxylic acid Chemical class OC(=O)C1=CC(Br)=CC=N1 RPHHYRNGCJYQSP-UHFFFAOYSA-N 0.000 description 1
- KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 1
- LJFVSIDBFJPKLD-UHFFFAOYSA-N 4-phenylmethoxy-1h-indole Chemical compound C=1C=CC=2NC=CC=2C=1OCC1=CC=CC=C1 LJFVSIDBFJPKLD-UHFFFAOYSA-N 0.000 description 1
- ODGIMMLDVSWADK-UHFFFAOYSA-N 4-trifluoromethylaniline Chemical compound NC1=CC=C(C(F)(F)F)C=C1 ODGIMMLDVSWADK-UHFFFAOYSA-N 0.000 description 1
- 125000001826 4H-pyranyl group Chemical group O1C(=CCC=C1)* 0.000 description 1
- KSZYJEJPFGNGQA-UHFFFAOYSA-N 5-(bromomethyl)-2-(trifluoromethyl)-1,3-thiazole Chemical compound FC(F)(F)C1=NC=C(CBr)S1 KSZYJEJPFGNGQA-UHFFFAOYSA-N 0.000 description 1
- WRZOMWDJOLIVQP-UHFFFAOYSA-N 5-Chloro-ortho-toluidine Chemical compound CC1=CC=C(Cl)C=C1N WRZOMWDJOLIVQP-UHFFFAOYSA-N 0.000 description 1
- HSUWUUARKYGBBO-UHFFFAOYSA-N 5-[4-(aminomethyl)pyridin-2-yl]oxy-1-[(2,4-difluorophenyl)methyl]-3,4-dihydroquinolin-2-one hydrochloride Chemical compound Cl.NCc1ccnc(Oc2cccc3N(Cc4ccc(F)cc4F)C(=O)CCc23)c1 HSUWUUARKYGBBO-UHFFFAOYSA-N 0.000 description 1
- XADICJHFELMBGX-UHFFFAOYSA-N 5-bromo-2-methoxypyridine Chemical compound COC1=CC=C(Br)C=N1 XADICJHFELMBGX-UHFFFAOYSA-N 0.000 description 1
- LMIQERWZRIFWNZ-UHFFFAOYSA-N 5-hydroxyindole Chemical compound OC1=CC=C2NC=CC2=C1 LMIQERWZRIFWNZ-UHFFFAOYSA-N 0.000 description 1
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
- WQESCKJRCSIUGY-UHFFFAOYSA-N 6-chloro-1h-indol-4-amine Chemical compound NC1=CC(Cl)=CC2=C1C=CN2 WQESCKJRCSIUGY-UHFFFAOYSA-N 0.000 description 1
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 1
- 101710151806 72 kDa type IV collagenase Proteins 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 206010001580 Albuminuria Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 240000003291 Armoracia rusticana Species 0.000 description 1
- 235000011330 Armoracia rusticana Nutrition 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
- 102100031168 CCN family member 2 Human genes 0.000 description 1
- 102000000905 Cadherin Human genes 0.000 description 1
- 108050007957 Cadherin Proteins 0.000 description 1
- 101100294102 Caenorhabditis elegans nhr-2 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 108010078791 Carrier Proteins Proteins 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
- 108010077544 Chromatin Proteins 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-UWTATZPHSA-N D-aspartic acid Chemical compound OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 1
- YVECGMZCTULTIS-HSUXUTPPSA-N D-galactal Chemical compound OC[C@H]1OC=C[C@@H](O)[C@H]1O YVECGMZCTULTIS-HSUXUTPPSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 229920002307 Dextran Polymers 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
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- ZJWNUCQCXTZVCT-UHFFFAOYSA-N FC=1C=C(C=CC1N1C=NC=C1)NC Chemical compound FC=1C=C(C=CC1N1C=NC=C1)NC ZJWNUCQCXTZVCT-UHFFFAOYSA-N 0.000 description 1
- ADJMWWXZPXFHEB-RKDXNWHRSA-N F[C@@H]1CN(C[C@H]1O)C=1C=C(C#N)C=CN=1 Chemical compound F[C@@H]1CN(C[C@H]1O)C=1C=C(C#N)C=CN=1 ADJMWWXZPXFHEB-RKDXNWHRSA-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
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 102000016354 Glucuronosyltransferase Human genes 0.000 description 1
- 108010092364 Glucuronosyltransferase Proteins 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 206010019695 Hepatic neoplasm Diseases 0.000 description 1
- 208000002972 Hepatolenticular Degeneration Diseases 0.000 description 1
- 108010033040 Histones Proteins 0.000 description 1
- 101001009252 Homo sapiens 2-hydroxyacyl-CoA lyase 1 Proteins 0.000 description 1
- 101000777550 Homo sapiens CCN family member 2 Proteins 0.000 description 1
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
- 101000621309 Homo sapiens Wilms tumor protein Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- LCWXJXMHJVIJFK-UHFFFAOYSA-N Hydroxylysine Natural products NCC(O)CC(N)CC(O)=O LCWXJXMHJVIJFK-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 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 description 1
- 102100032825 Integrin alpha-8 Human genes 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 208000005016 Intestinal Neoplasms Diseases 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 101150043981 LOXL2 gene Proteins 0.000 description 1
- 206010023856 Laryngeal squamous cell carcinoma Diseases 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 102100027998 Macrophage metalloelastase Human genes 0.000 description 1
- 101710187853 Macrophage metalloelastase Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 1
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 238000006751 Mitsunobu reaction Methods 0.000 description 1
- GPFXDYCSWXCHOR-UHFFFAOYSA-N N-(4-cyanopyridin-2-yl)-2-fluoro-4-methylbenzamide Chemical compound C(#N)C1=CC(=NC=C1)NC(C1=C(C=C(C=C1)C)F)=O GPFXDYCSWXCHOR-UHFFFAOYSA-N 0.000 description 1
- GJUROINTDORGPH-UHFFFAOYSA-N N-[4-(aminomethyl)pyridin-2-yl]-2-fluoro-4-methylbenzamide Chemical compound NCC1=CC(=NC=C1)NC(C1=C(C=C(C=C1)C)F)=O GJUROINTDORGPH-UHFFFAOYSA-N 0.000 description 1
- 238000007126 N-alkylation reaction Methods 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 206010029098 Neoplasm skin Diseases 0.000 description 1
- 101000578290 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) Nitrogen metabolite repression protein nmr Proteins 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 238000010934 O-alkylation reaction Methods 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 206010053159 Organ failure Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 108010087367 P-glycoprotein 2 Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 101150003085 Pdcl gene Proteins 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 1
- ODHCTXKNWHHXJC-GSVOUGTGSA-N Pyroglutamic acid Natural products OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 238000000297 Sandmeyer reaction Methods 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 208000036844 Squamous cell carcinoma of the larynx Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 102100028848 Stromelysin-2 Human genes 0.000 description 1
- 101710108792 Stromelysin-2 Proteins 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 208000002847 Surgical Wound Diseases 0.000 description 1
- 102000000591 Tight Junction Proteins Human genes 0.000 description 1
- 108010002321 Tight Junction Proteins Proteins 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- XCCTYIAWTASOJW-XVFCMESISA-N Uridine-5'-Diphosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 XCCTYIAWTASOJW-XVFCMESISA-N 0.000 description 1
- 102100022748 Wilms tumor protein Human genes 0.000 description 1
- 208000018839 Wilson disease Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- YXHUARUUINLMOH-UHFFFAOYSA-N [2-(1-benzylindol-4-yl)oxypyridin-4-yl]methanamine Chemical compound C(C1=CC=CC=C1)N1C=CC2=C(C=CC=C12)OC1=NC=CC(=C1)CN YXHUARUUINLMOH-UHFFFAOYSA-N 0.000 description 1
- ZMTRPJUAINHTPB-UHFFFAOYSA-N [2-(1H-indol-4-yloxy)pyridin-4-yl]methanamine Chemical compound N1C=CC2=C(C=CC=C12)OC1=NC=CC(=C1)CN ZMTRPJUAINHTPB-UHFFFAOYSA-N 0.000 description 1
- ZEEBGORNQSEQBE-UHFFFAOYSA-N [2-(3-phenylphenoxy)-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound C1(=CC(=CC=C1)OC1=NC(=CC(=C1)CN)C(F)(F)F)C1=CC=CC=C1 ZEEBGORNQSEQBE-UHFFFAOYSA-N 0.000 description 1
- UMBYAXDQQPIBEI-UHFFFAOYSA-N [2-(4-fluorophenyl)-6-(3-phenoxyphenoxy)pyridin-4-yl]methanamine Chemical compound FC1=CC=C(C=C1)C1=NC(=CC(=C1)CN)OC1=CC(=CC=C1)OC1=CC=CC=C1 UMBYAXDQQPIBEI-UHFFFAOYSA-N 0.000 description 1
- GXFIJNNOECYQOJ-UHFFFAOYSA-N [2-[1-(1-methylpyrazol-4-yl)indol-4-yl]oxy-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound CN1N=CC(=C1)N1C=CC2=C(C=CC=C12)OC1=NC(=CC(=C1)CN)C(F)(F)F GXFIJNNOECYQOJ-UHFFFAOYSA-N 0.000 description 1
- XNRPIWBMJFMHEK-UHFFFAOYSA-N [2-[1-(1-methylpyrazol-4-yl)indol-4-yl]oxypyridin-4-yl]methanamine Chemical compound CN1N=CC(=C1)N1C=CC2=C(C=CC=C12)OC1=NC=CC(=C1)CN XNRPIWBMJFMHEK-UHFFFAOYSA-N 0.000 description 1
- LKDDCRRCULDRBU-UHFFFAOYSA-N [2-[1-(4-fluorophenyl)indol-4-yl]oxypyridin-4-yl]methanamine Chemical compound FC1=CC=C(C=C1)N1C=CC2=C(C=CC=C12)OC1=NC=CC(=C1)CN LKDDCRRCULDRBU-UHFFFAOYSA-N 0.000 description 1
- YGNIIMKOTGQNME-UHFFFAOYSA-N [2-[1-(6-fluoro-1,3-benzothiazol-2-yl)indol-4-yl]oxypyridin-4-yl]methanamine Chemical compound FC1=CC2=C(N=C(S2)N2C=CC3=C(C=CC=C23)OC2=NC=CC(=C2)CN)C=C1 YGNIIMKOTGQNME-UHFFFAOYSA-N 0.000 description 1
- XHBMWTZYCXGEIJ-UHFFFAOYSA-N [2-[1-(6-methoxypyridin-3-yl)indol-4-yl]oxypyridin-4-yl]methanamine Chemical compound COC1=CC=C(C=N1)N1C=CC2=C(C=CC=C12)OC1=NC=CC(=C1)CN XHBMWTZYCXGEIJ-UHFFFAOYSA-N 0.000 description 1
- VKFVCHUIDJATKY-UHFFFAOYSA-N [2-[1-(quinolin-2-ylmethyl)indol-4-yl]oxypyridin-4-yl]methanamine Chemical compound N1=C(C=CC2=CC=CC=C12)CN1C=CC2=C(C=CC=C12)OC1=NC=CC(=C1)CN VKFVCHUIDJATKY-UHFFFAOYSA-N 0.000 description 1
- MLYKXVHKBSBRKJ-UHFFFAOYSA-N [2-[1-[(2,4-difluorophenyl)methyl]-2-methylindol-4-yl]oxypyridin-4-yl]methanamine 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.Cc1cc2c(Oc3cc(CN)ccn3)cccc2n1Cc1ccc(F)cc1F MLYKXVHKBSBRKJ-UHFFFAOYSA-N 0.000 description 1
- PHMFJEXYUMBWFJ-UHFFFAOYSA-N [2-[1-[(2,4-difluorophenyl)methyl]-3-methylindazol-4-yl]oxypyridin-4-yl]methanamine 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.Cc1nn(Cc2ccc(F)cc2F)c2cccc(Oc3cc(CN)ccn3)c12 PHMFJEXYUMBWFJ-UHFFFAOYSA-N 0.000 description 1
- YAAULZNHHUUZCZ-UHFFFAOYSA-N [2-[1-[(2,4-difluorophenyl)methyl]-3-methylindol-4-yl]oxypyridin-4-yl]methanamine 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.Cc1cn(Cc2ccc(F)cc2F)c2cccc(Oc3cc(CN)ccn3)c12 YAAULZNHHUUZCZ-UHFFFAOYSA-N 0.000 description 1
- LPZKEZSGLXHDIE-UHFFFAOYSA-N [2-[1-[(6-methoxypyridin-3-yl)methyl]-2-methylindol-4-yl]oxypyridin-4-yl]methanamine Chemical compound COC1=CC=C(C=N1)CN1C(=CC2=C(C=CC=C12)OC1=NC=CC(=C1)CN)C LPZKEZSGLXHDIE-UHFFFAOYSA-N 0.000 description 1
- CKOHXIVUCOIOFO-UHFFFAOYSA-N [2-[1-[(6-methoxypyridin-3-yl)methyl]-3-methylindol-4-yl]oxypyridin-4-yl]methanamine Chemical compound COC1=CC=C(C=N1)CN1C=C(C2=C(C=CC=C12)OC1=NC=CC(=C1)CN)C CKOHXIVUCOIOFO-UHFFFAOYSA-N 0.000 description 1
- VPJPPFDSDCLVDG-UHFFFAOYSA-N [2-[1-[(6-methoxypyridin-3-yl)methyl]indol-5-yl]oxypyridin-4-yl]methanamine 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.COc1ccc(Cn2ccc3cc(Oc4cc(CN)ccn4)ccc23)cn1 VPJPPFDSDCLVDG-UHFFFAOYSA-N 0.000 description 1
- CLQUVBGAMRTAEN-UHFFFAOYSA-N [2-[1-[[2-(trifluoromethyl)-1,3-thiazol-5-yl]methyl]indol-4-yl]oxypyridin-4-yl]methanamine hydrochloride Chemical compound Cl.NCc1ccnc(Oc2cccc3n(Cc4cnc(s4)C(F)(F)F)ccc23)c1 CLQUVBGAMRTAEN-UHFFFAOYSA-N 0.000 description 1
- REAYFGLASQTHKB-UHFFFAOYSA-N [2-[3-(1H-pyrazol-4-yl)phenoxy]-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound N1N=CC(=C1)C=1C=C(OC2=NC(=CC(=C2)CN)C(F)(F)F)C=CC=1 REAYFGLASQTHKB-UHFFFAOYSA-N 0.000 description 1
- GKGHSIYMNBGRJE-UHFFFAOYSA-N [2-[3-bromo-1-[2-(4-fluorophenyl)ethyl]indol-4-yl]oxypyridin-4-yl]methanamine Chemical compound BrC1=CN(C2=CC=CC(=C12)OC1=NC=CC(=C1)CN)CCC1=CC=C(C=C1)F GKGHSIYMNBGRJE-UHFFFAOYSA-N 0.000 description 1
- IOWVFWHDGIWANZ-UHFFFAOYSA-N [2-[[1-(6-fluoro-1,3-benzothiazol-2-yl)-2,3-dihydroindol-4-yl]oxy]pyridin-4-yl]methanamine Chemical compound FC1=CC2=C(N=C(S2)N2CCC3=C(C=CC=C23)OC2=NC=CC(=C2)CN)C=C1 IOWVFWHDGIWANZ-UHFFFAOYSA-N 0.000 description 1
- YKKPYMXANSSQCA-UHFFFAOYSA-N [3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxyphenyl]-(3-pyrazol-1-ylazetidin-1-yl)methanone Chemical compound N1(N=CC=C1)C1CN(C1)C(=O)C1=CC(=CC=C1)OC1=NC(=CC(=C1)CN)C(F)(F)F YKKPYMXANSSQCA-UHFFFAOYSA-N 0.000 description 1
- PRDBLLIPPDOICK-UHFFFAOYSA-N [4-(trifluoromethyl)phenyl]methanamine Chemical compound NCC1=CC=C(C(F)(F)F)C=C1 PRDBLLIPPDOICK-UHFFFAOYSA-N 0.000 description 1
- SAUDSDDZIRPWMO-UHFFFAOYSA-N [4-[(4-ethylpiperazin-1-yl)methyl]phenyl]methanamine Chemical compound C1CN(CC)CCN1CC1=CC=C(CN)C=C1 SAUDSDDZIRPWMO-UHFFFAOYSA-N 0.000 description 1
- PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 125000005041 acyloxyalkyl group Chemical group 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 238000012382 advanced drug delivery Methods 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000005205 alkoxycarbonyloxyalkyl group Chemical group 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 125000005360 alkyl sulfoxide group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 229960004909 aminosalicylic acid Drugs 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 150000007860 aryl ester derivatives Chemical class 0.000 description 1
- 125000005362 aryl sulfone group Chemical group 0.000 description 1
- 125000005361 aryl sulfoxide group Chemical group 0.000 description 1
- 125000005110 aryl thio group Chemical group 0.000 description 1
- 125000000732 arylene group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 239000010425 asbestos Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- MVXVYAKCVDQRLW-UHFFFAOYSA-N azain Natural products C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 description 1
- 239000000022 bacteriostatic agent Substances 0.000 description 1
- UDSRUCAJZSIRHZ-UHFFFAOYSA-N benzamide dihydrochloride Chemical compound Cl.Cl.NC(=O)C1=CC=CC=C1.NC(=O)C1=CC=CC=C1 UDSRUCAJZSIRHZ-UHFFFAOYSA-N 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- YINMBLWEHNCLFF-UHFFFAOYSA-N benzenesulfonic acid;benzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OS(=O)(=O)C1=CC=CC=C1 YINMBLWEHNCLFF-UHFFFAOYSA-N 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 238000012742 biochemical analysis Methods 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 150000003842 bromide salts Chemical class 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- RLDQYSHDFVSAPL-UHFFFAOYSA-L calcium;dithiocyanate Chemical compound [Ca+2].[S-]C#N.[S-]C#N RLDQYSHDFVSAPL-UHFFFAOYSA-L 0.000 description 1
- 230000009702 cancer cell proliferation Effects 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 229960004424 carbon dioxide Drugs 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000009087 cell motility Effects 0.000 description 1
- 230000009134 cell regulation Effects 0.000 description 1
- 230000010307 cell transformation Effects 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 150000003841 chloride salts Chemical class 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 229940126523 co-drug Drugs 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000000625 cyclamic acid and its Na and Ca salt Substances 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
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 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
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000009615 deamination Effects 0.000 description 1
- 238000006481 deamination reaction Methods 0.000 description 1
- HABLENUWIZGESP-UHFFFAOYSA-N decanoic acid Chemical class CCCCCCCCCC(O)=O.CCCCCCCCCC(O)=O HABLENUWIZGESP-UHFFFAOYSA-N 0.000 description 1
- NXMUXTAGFPJGTQ-UHFFFAOYSA-N decanoic acid;octanoic acid Chemical compound CCCCCCCC(O)=O.CCCCCCCCCC(O)=O NXMUXTAGFPJGTQ-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 239000008380 degradant Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
- BAVYZALUXZFZLV-MICDWDOJSA-N deuteriomethanamine Chemical compound [2H]CN BAVYZALUXZFZLV-MICDWDOJSA-N 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 229940042935 dichlorodifluoromethane Drugs 0.000 description 1
- USPLDBATMHXKKD-UHFFFAOYSA-N dichloromethane;pentane Chemical compound ClCCl.CCCCC USPLDBATMHXKKD-UHFFFAOYSA-N 0.000 description 1
- 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 125000005057 dihydrothienyl group Chemical group S1C(CC=C1)* 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- 238000007907 direct compression Methods 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 125000005883 dithianyl group Chemical group 0.000 description 1
- 125000005411 dithiolanyl group Chemical group S1SC(CC1)* 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 239000003221 ear drop Substances 0.000 description 1
- 229940047652 ear drops Drugs 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 208000023965 endometrium neoplasm Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
- QJZOIPFECDFUMS-UHFFFAOYSA-N ethane-1,2-disulfonic acid;ethanesulfonic acid Chemical compound CCS(O)(=O)=O.OS(=O)(=O)CCS(O)(=O)=O QJZOIPFECDFUMS-UHFFFAOYSA-N 0.000 description 1
- JOCFOKUHJNIUHP-UHFFFAOYSA-N ethyl 4-(4-cyanopyridin-2-yl)benzoate Chemical compound C(#N)C1=CC(=NC=C1)C1=CC=C(C(=O)OCC)C=C1 JOCFOKUHJNIUHP-UHFFFAOYSA-N 0.000 description 1
- NBHKSWMUAABERS-UHFFFAOYSA-N ethyl 4-[4-(aminomethyl)pyridin-2-yl]benzoate Chemical compound NCC1=CC(=NC=C1)C1=CC=C(C(=O)OCC)C=C1 NBHKSWMUAABERS-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 102000034240 fibrous proteins Human genes 0.000 description 1
- 108091005899 fibrous proteins Proteins 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000004428 fluoroalkoxy group Chemical group 0.000 description 1
- 210000001650 focal adhesion Anatomy 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- NKHAVTQWNUWKEO-UHFFFAOYSA-N fumaric acid monomethyl ester Natural products COC(=O)C=CC(O)=O NKHAVTQWNUWKEO-UHFFFAOYSA-N 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 210000000585 glomerular basement membrane Anatomy 0.000 description 1
- 206010061989 glomerulosclerosis Diseases 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 description 1
- 208000024348 heart neoplasm Diseases 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 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 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- QJHBJHUKURJDLG-UHFFFAOYSA-N hydroxy-L-lysine Natural products NCCCCC(NO)C(O)=O QJHBJHUKURJDLG-UHFFFAOYSA-N 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 229960003943 hypromellose Drugs 0.000 description 1
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 description 1
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 1
- 125000000336 imidazol-5-yl group Chemical group [H]N1C([H])=NC([H])=C1[*] 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 229940060367 inert ingredients Drugs 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 108010024081 integrin alpha8 Proteins 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000006525 intracellular process Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 229940125425 inverse agonist Drugs 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 239000004922 lacquer Substances 0.000 description 1
- 229940099563 lactobionic acid Drugs 0.000 description 1
- 108010088360 laminin alpha5 Proteins 0.000 description 1
- 238000002350 laparotomy Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- FUJCRWPEOMXPAD-UHFFFAOYSA-N lithium oxide Chemical compound [Li+].[Li+].[O-2] FUJCRWPEOMXPAD-UHFFFAOYSA-N 0.000 description 1
- 229910001947 lithium oxide Inorganic materials 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 230000004199 lung function Effects 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- NCBZRJODKRCREW-UHFFFAOYSA-N m-anisidine Chemical compound COC1=CC=CC(N)=C1 NCBZRJODKRCREW-UHFFFAOYSA-N 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 238000007885 magnetic separation Methods 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- OWBKDJSKHXGOJY-UHFFFAOYSA-N methyl 3-(aminomethyl)benzoate Chemical compound COC(=O)C1=CC=CC(CN)=C1 OWBKDJSKHXGOJY-UHFFFAOYSA-N 0.000 description 1
- FGOQWQMPNSYDBL-UHFFFAOYSA-N methyl 3-(hydroxymethyl)benzoate Chemical compound COC(=O)C1=CC=CC(CO)=C1 FGOQWQMPNSYDBL-UHFFFAOYSA-N 0.000 description 1
- 229940120152 methyl 3-hydroxybenzoate Drugs 0.000 description 1
- AQBJGAUQEJFPKZ-UHFFFAOYSA-N methyl 4-(aminomethyl)benzoate Chemical compound COC(=O)C1=CC=C(CN)C=C1 AQBJGAUQEJFPKZ-UHFFFAOYSA-N 0.000 description 1
- GIZCKBSSWNIUMZ-UHFFFAOYSA-N methyl 4-(aminomethyl)benzoate;hydrochloride Chemical compound Cl.COC(=O)C1=CC=C(CN)C=C1 GIZCKBSSWNIUMZ-UHFFFAOYSA-N 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 125000005699 methyleneoxy group Chemical group [H]C([H])([*:1])O[*:2] 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 231100000324 minimal toxicity Toxicity 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000007932 molded tablet Substances 0.000 description 1
- NKHAVTQWNUWKEO-NSCUHMNNSA-N monomethyl fumarate Chemical compound COC(=O)\C=C\C(O)=O NKHAVTQWNUWKEO-NSCUHMNNSA-N 0.000 description 1
- 229940005650 monomethyl fumarate Drugs 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 206010028537 myelofibrosis Diseases 0.000 description 1
- KVKFRMCSXWQSNT-UHFFFAOYSA-N n,n'-dimethylethane-1,2-diamine Chemical compound CNCCNC KVKFRMCSXWQSNT-UHFFFAOYSA-N 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 208000025402 neoplasm of esophagus Diseases 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 208000010655 oral cavity squamous cell carcinoma Diseases 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000007833 oxidative deamination reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-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
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 125000005575 polycyclic aromatic hydrocarbon group Chemical group 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 208000023958 prostate neoplasm Diseases 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- HQIBSDCOMQYSPF-UHFFFAOYSA-N pyrazin-2-ylmethanamine Chemical compound NCC1=CN=CC=N1 HQIBSDCOMQYSPF-UHFFFAOYSA-N 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 1
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical group 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
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 210000002254 renal artery Anatomy 0.000 description 1
- 230000008085 renal dysfunction Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229910052895 riebeckite Inorganic materials 0.000 description 1
- 239000005060 rubber Substances 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003459 sulfonic acid esters Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- KTEGNWDORFBCHD-ZDUSSCGKSA-N tert-butyl (3s)-3-(4-cyanopyridin-2-yl)oxypiperidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC[C@@H]1OC1=CC(C#N)=CC=N1 KTEGNWDORFBCHD-ZDUSSCGKSA-N 0.000 description 1
- UIJXHKXIOCDSEB-QMMMGPOBSA-N tert-butyl (3s)-3-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@H](O)C1 UIJXHKXIOCDSEB-QMMMGPOBSA-N 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- AYEKOFBPNLCAJY-UHFFFAOYSA-O thiamine pyrophosphate Chemical group CC1=C(CCOP(O)(=O)OP(O)(O)=O)SC=[N+]1CC1=CN=C(C)N=C1N AYEKOFBPNLCAJY-UHFFFAOYSA-O 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 210000001578 tight junction Anatomy 0.000 description 1
- 238000003354 tissue distribution assay Methods 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000004627 transmission electron microscopy Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- ABVVEAHYODGCLZ-UHFFFAOYSA-N tridecan-1-amine Chemical compound CCCCCCCCCCCCCN ABVVEAHYODGCLZ-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 208000025421 tumor of uterus Diseases 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 239000006200 vaporizer Substances 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/56—Amides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
- C07D213/53—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/55—Acids; Esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
- C07D213/643—2-Phenoxypyridines; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562129531P | 2015-03-06 | 2015-03-06 | |
| US62/129,531 | 2015-03-06 | ||
| PCT/US2016/020731 WO2016144702A1 (en) | 2015-03-06 | 2016-03-03 | Lysyl oxidase-like 2 inhibitors and uses thereof |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2018510852A JP2018510852A (ja) | 2018-04-19 |
| JP2018510852A5 JP2018510852A5 (enExample) | 2020-07-16 |
| JP6800872B2 true JP6800872B2 (ja) | 2020-12-16 |
Family
ID=56878985
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017545627A Expired - Fee Related JP6800872B2 (ja) | 2015-03-06 | 2016-03-03 | リシルオキシダーゼ様2阻害剤とその使用 |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US10766860B2 (enExample) |
| EP (1) | EP3265445B1 (enExample) |
| JP (1) | JP6800872B2 (enExample) |
| CN (1) | CN107624110B (enExample) |
| ES (1) | ES2872553T3 (enExample) |
| WO (1) | WO2016144702A1 (enExample) |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107624110B (zh) | 2015-03-06 | 2021-01-26 | 法玛克亚公司 | 赖氨酰氧化酶样2抑制剂及其用途 |
| EA034891B1 (ru) | 2015-03-06 | 2020-04-02 | Фармакеа, Инк. | Фторированные ингибиторы лизилоксидазоподобного фермента-2 и их применение |
| AU2017218889A1 (en) | 2016-02-09 | 2018-08-30 | Pharmakea, Inc. | Quinolinone lysyl oxidase-like 2 inhibitors and uses thereof |
| GB201602934D0 (en) | 2016-02-19 | 2016-04-06 | Cancer Res Inst Royal | Compounds |
| EP3509594B1 (en) | 2016-09-07 | 2025-02-26 | Pharmakea, Inc. | A lysyl oxidase-like 2 inhibitor for use in treating myelofibrosis |
| CA3036064A1 (en) | 2016-09-07 | 2018-03-15 | Pharmakea, Inc. | Crystalline forms of a lysyl oxidase-like 2 inhibitor and methods of making |
| WO2018049214A1 (en) | 2016-09-09 | 2018-03-15 | Incyte Corporation | Pyrazolopyridine derivatives as hpk1 modulators and uses thereof for the treatment of cancer |
| US10280164B2 (en) | 2016-09-09 | 2019-05-07 | Incyte Corporation | Pyrazolopyridone compounds and uses thereof |
| WO2018049152A1 (en) | 2016-09-09 | 2018-03-15 | Incyte Corporation | Pyrazolopyrimidine derivatives as hpk1 modulators and uses thereof for the treatment of cancer |
| EP3510032B1 (en) | 2016-09-09 | 2022-07-06 | Incyte Corporation | Pyrazolopyridine derivatives as hpk1 modulators and uses thereof for the treatment of cancer |
| WO2018152220A1 (en) | 2017-02-15 | 2018-08-23 | Incyte Corporation | Pyrazolopyridine compounds and uses thereof |
| WO2019051199A1 (en) | 2017-09-08 | 2019-03-14 | Incyte Corporation | 6-CYANO-INDAZOLE COMPOUNDS AS HEMATOPOIETIC PROGENITOR KINASE 1 (HPK1) MODULATORS |
| KR20200133747A (ko) | 2018-02-20 | 2020-11-30 | 인사이트 코포레이션 | 암을 치료하기 위한 hpk1 억제제로서의 n-(페닐)-2-(페닐)피리미딘-4-카복스아미드 유도체 및 관련 화합물 |
| US10745388B2 (en) | 2018-02-20 | 2020-08-18 | Incyte Corporation | Indazole compounds and uses thereof |
| WO2019164847A1 (en) | 2018-02-20 | 2019-08-29 | Incyte Corporation | Indazole compounds and uses thereof |
| TWI827583B (zh) | 2018-03-08 | 2024-01-01 | 美商英塞特公司 | 作為PI3K-γ抑制劑之胺基吡嗪二醇化合物 |
| US11299473B2 (en) | 2018-04-13 | 2022-04-12 | Incyte Corporation | Benzimidazole and indole compounds and uses thereof |
| JP7350061B2 (ja) * | 2018-05-11 | 2023-10-02 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッド | フューリンインヒビター |
| GB201809295D0 (en) | 2018-06-06 | 2018-07-25 | Institute Of Cancer Res Royal Cancer Hospital | Lox inhibitors |
| WO2020010003A1 (en) | 2018-07-02 | 2020-01-09 | Incyte Corporation | AMINOPYRAZINE DERIVATIVES AS PI3K-γ INHIBITORS |
| JP7414803B2 (ja) | 2018-08-03 | 2024-01-16 | ファーマクシス リミテッド | リシルオキシダーゼのハロアリルアミンスルホン誘導体阻害剤およびそれらの使用 |
| US10899755B2 (en) | 2018-08-08 | 2021-01-26 | Incyte Corporation | Benzothiazole compounds and uses thereof |
| EP3856348B1 (en) | 2018-09-25 | 2024-01-03 | Incyte Corporation | Pyrazolo[4,3-d]pyrimidine compounds as alk2 and/or fgfr modulators |
| GB201818750D0 (en) | 2018-11-16 | 2019-01-02 | Institute Of Cancer Res Royal Cancer Hospital | Lox inhibitors |
| AU2019387370A1 (en) | 2018-11-30 | 2021-06-10 | Nuvation Bio Inc. | Pyrrole and pyrazole compounds and methods of use thereof |
| US11430112B2 (en) * | 2019-05-24 | 2022-08-30 | PharmaNest LLC | Systems and methods for quantitative phenotyping of fibrosis |
| AU2020311940A1 (en) | 2019-07-11 | 2022-02-03 | ESCAPE Bio, Inc. | Indazoles and azaindazoles as LRRK2 inhibitors |
| JP2022543155A (ja) | 2019-08-06 | 2022-10-07 | インサイト・コーポレイション | Hpk1阻害剤の固体形態 |
| US20220273593A1 (en) * | 2019-09-19 | 2022-09-01 | Johann Wolfgang Goethe-Universität Frankfurt am Main | Compounds and compositions for treating kidney disease |
| US20230310445A1 (en) * | 2020-04-21 | 2023-10-05 | Anovia Biosciences, Inc. | Lox enzyme inhibiting methods and compositions |
| US12233056B2 (en) | 2022-04-06 | 2025-02-25 | Syntara Limited | Lysyl oxidase inhibitors for treating myeloid malignancies |
| GB202209624D0 (en) | 2022-06-30 | 2022-08-17 | Institute Of Cancer Res Royal Cancer Hospital | Prodrugs |
| GB202209622D0 (en) | 2022-06-30 | 2022-08-17 | Institute Of Cancer Res Royal Cancer Hospital | Compounds |
Family Cites Families (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1057009A (en) | 1912-11-07 | 1913-03-25 | Lewis T Rhoades | Spark-producing mechanism for internal-combustion engines. |
| IE56702B1 (en) | 1982-12-01 | 1991-11-06 | Usv Pharma Corp | Antiinflammatory antiallergic compounds |
| US5021456A (en) | 1988-02-25 | 1991-06-04 | Merrell Dow Pharmaceuticals Inc. | Inhibitors of lysyl oxidase |
| US5250532A (en) | 1991-04-11 | 1993-10-05 | Dowelanco | 3,4,N-trisubstituted-4,5-dihydro-1H-pyrazole-1-carboxamides and their use as insecticides |
| US5563143A (en) | 1994-09-21 | 1996-10-08 | Pfizer Inc. | Catechol diether compounds as inhibitors of TNF release |
| US5691364A (en) * | 1995-03-10 | 1997-11-25 | Berlex Laboratories, Inc. | Benzamidine derivatives and their use as anti-coagulants |
| US7125880B1 (en) | 1995-06-06 | 2006-10-24 | Pfizer Inc. | Corticotropin releasing factor antagonists |
| US6956047B1 (en) | 1995-06-06 | 2005-10-18 | Pfizer Inc. | Corticotropin releasing factor antagonists |
| US6632823B1 (en) | 1997-12-22 | 2003-10-14 | Merck & Co., Inc. | Substituted pyridine compounds useful as modulators of acetylcholine receptors |
| HUP0204272A3 (en) | 2000-01-18 | 2005-03-29 | Pfizer Prod Inc | Corticotropin releasing factor antagonists, pharmaceutical compositions containing them and their use |
| US6878714B2 (en) | 2001-01-12 | 2005-04-12 | Amgen Inc. | Substituted alkylamine derivatives and methods of use |
| US7105682B2 (en) | 2001-01-12 | 2006-09-12 | Amgen Inc. | Substituted amine derivatives and methods of use |
| US20020147198A1 (en) | 2001-01-12 | 2002-10-10 | Guoqing Chen | Substituted arylamine derivatives and methods of use |
| US20030134836A1 (en) | 2001-01-12 | 2003-07-17 | Amgen Inc. | Substituted arylamine derivatives and methods of use |
| US6995162B2 (en) | 2001-01-12 | 2006-02-07 | Amgen Inc. | Substituted alkylamine derivatives and methods of use |
| US7102009B2 (en) | 2001-01-12 | 2006-09-05 | Amgen Inc. | Substituted amine derivatives and methods of use |
| AUPR688101A0 (en) * | 2001-08-08 | 2001-08-30 | Luminis Pty Limited | Protein domains and their ligands |
| TWI319387B (en) | 2002-04-05 | 2010-01-11 | Astrazeneca Ab | Benzamide derivatives |
| US7307088B2 (en) | 2002-07-09 | 2007-12-11 | Amgen Inc. | Substituted anthranilic amide derivatives and methods of use |
| FI20030030A0 (fi) | 2003-01-09 | 2003-01-09 | Orion Corp | Uusia yhdisteitä |
| JP2007519705A (ja) | 2004-01-29 | 2007-07-19 | ファイザー・プロダクツ・インク | Cns障害を治療するための非定型抗精神病薬とアミノメチルピリジルオキシメチル/ベンゾイソオキサゾールアザビシクロ誘導体の組合せ |
| US7381750B2 (en) | 2004-03-12 | 2008-06-03 | Eli Lilly And Company | Amino-phenoxymethyl-benzamide opioid receptor antagonists |
| CA2557794A1 (en) | 2004-03-15 | 2005-10-06 | Eli Lilly And Company | Opioid receptor antagonists |
| RU2006142305A (ru) | 2004-04-30 | 2008-06-10 | Такеда Фармасьютикал Компани Лимитед (Jp) | Гетероциклическое амидное соединение и его применение в качестве ингибитора ммр-3 |
| US7507748B2 (en) | 2004-07-22 | 2009-03-24 | Amgen Inc. | Substituted aryl-amine derivatives and methods of use |
| CA2580034A1 (en) | 2004-09-10 | 2006-03-16 | Pfizer Products Inc. | Methods of treating mood disorders using benzisoxazole containing diazabicyclic compounds |
| EP1791540A2 (en) | 2004-09-10 | 2007-06-06 | Pfizer Products Incorporated | Methods of treating cognitive disorders using pyridyloxymethyl and benzisoxazole azabicyclic derivatives |
| EP1807417A2 (en) | 2004-11-04 | 2007-07-18 | Neurogen Corporation | Pyrazolylmethyl heteroaryl derivatives |
| DE102004056226A1 (de) | 2004-11-22 | 2006-05-24 | Burchardt, Elmar Reinhold, Dr.Dr. | Neuartige Inhibitoren der Lysyloxidase |
| ATE440091T1 (de) | 2005-01-31 | 2009-09-15 | Merck & Co Inc | Antidiabetische bicyclische verbindungen |
| GB0614579D0 (en) | 2006-07-21 | 2006-08-30 | Black James Foundation | Pyrimidine derivatives |
| EP2121703A4 (en) | 2006-08-18 | 2011-12-28 | Astrazeneca Ab | THIENOPYRIMIDIN-4-ON- AND THIENOPYRIDAZIN-7-ONDERIVATES AS MCH-RL ANTAGONISTS |
| IL184627A0 (en) | 2007-07-15 | 2008-12-29 | Technion Res & Dev Foundation | Agents for diagnosing and modulating metastasis and fibrosis as well as inflammation in a mammalian tissue |
| CN101842114A (zh) | 2007-08-02 | 2010-09-22 | 阿雷斯托生物科学股份有限公司 | 治疗和诊断纤维化、肿瘤侵入、血管生成和转移的方法和组合物 |
| BR112012001987A2 (pt) | 2009-07-28 | 2015-09-01 | Anacor Pharmaceuticals Inc | Composto, combinação, formulação farmacêutica, uso de um composto, uma combinação ou um sal farmaceuticamente aceitável dos mesmos, e, métodos para tratar uma infecção bacteriana, para matar ou inibir o crescimento de uma bactéria, e para inibir uma beta-lactamase. |
| EP2534145A4 (en) | 2010-02-08 | 2013-09-11 | Kinagen Inc | THERAPEUTIC METHODS AND COMPOSITIONS INVOLVING THE INHIBITION OF ALLOSTERIC KINASE |
| CN103002742B (zh) | 2010-03-05 | 2016-07-13 | 卡尔约药物治疗公司 | 核转运调节剂及其应用 |
| WO2011150201A2 (en) * | 2010-05-27 | 2011-12-01 | Ambit Biosciences Corporation | Azolyl amide compounds and methods of use thereof |
| EP2441755A1 (en) * | 2010-09-30 | 2012-04-18 | Almirall, S.A. | Pyridine- and isoquinoline-derivatives as Syk and JAK kinase inhibitors |
| KR20140019300A (ko) | 2010-11-19 | 2014-02-14 | 인사이트 코포레이션 | Jak 억제제로서 사이클로부틸 치환된 피롤로피리딘 및 피롤로피리미딘 유도체 |
| TW201313721A (zh) | 2011-08-18 | 2013-04-01 | Incyte Corp | 作為jak抑制劑之環己基氮雜環丁烷衍生物 |
| KR20140077963A (ko) | 2011-10-20 | 2014-06-24 | 글락소스미스클라인 엘엘씨 | 시르투인 조절제로서의 치환된 비시클릭 아자-헤테로사이클 및 유사체 |
| JP6175673B2 (ja) | 2012-04-25 | 2017-08-09 | ラクオリア創薬株式会社 | Ttx−s遮断薬としてのアミド誘導体 |
| MX2015005448A (es) | 2012-10-30 | 2015-11-06 | Gilead Sciences Inc | Metodos de terapia y diagnostico relacionados con lisil oxidasa-tipo 2 (loxl2). |
| WO2014098098A1 (ja) | 2012-12-18 | 2014-06-26 | 味の素株式会社 | 複素環アミド誘導体及びそれを含有する医薬 |
| DE112015001269T5 (de) | 2014-08-05 | 2017-06-08 | The University Of British Columbia | Modulatoren von Caspase-6 |
| EP3256463B1 (en) | 2015-02-15 | 2019-10-09 | F. Hoffmann-La Roche AG | 1-(het)arylsulfonyl-(pyrrolidine or piperidine)-2-carboxamide derivatives and their use as trpa1 antagonists |
| CN107624110B (zh) | 2015-03-06 | 2021-01-26 | 法玛克亚公司 | 赖氨酰氧化酶样2抑制剂及其用途 |
| EA034891B1 (ru) | 2015-03-06 | 2020-04-02 | Фармакеа, Инк. | Фторированные ингибиторы лизилоксидазоподобного фермента-2 и их применение |
| US20180186755A1 (en) * | 2015-07-01 | 2018-07-05 | Pharmakea, Inc. | Lysyl oxidase-like 2 inhibitors and uses thereof |
| AU2017218889A1 (en) * | 2016-02-09 | 2018-08-30 | Pharmakea, Inc. | Quinolinone lysyl oxidase-like 2 inhibitors and uses thereof |
| EP3509594B1 (en) * | 2016-09-07 | 2025-02-26 | Pharmakea, Inc. | A lysyl oxidase-like 2 inhibitor for use in treating myelofibrosis |
| CA3036064A1 (en) * | 2016-09-07 | 2018-03-15 | Pharmakea, Inc. | Crystalline forms of a lysyl oxidase-like 2 inhibitor and methods of making |
-
2016
- 2016-03-03 CN CN201680026238.9A patent/CN107624110B/zh not_active Expired - Fee Related
- 2016-03-03 US US15/555,785 patent/US10766860B2/en not_active Expired - Fee Related
- 2016-03-03 WO PCT/US2016/020731 patent/WO2016144702A1/en not_active Ceased
- 2016-03-03 JP JP2017545627A patent/JP6800872B2/ja not_active Expired - Fee Related
- 2016-03-03 EP EP16762185.3A patent/EP3265445B1/en active Active
- 2016-03-03 ES ES16762185T patent/ES2872553T3/es active Active
-
2020
- 2020-07-17 US US16/932,617 patent/US11358936B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN107624110A (zh) | 2018-01-23 |
| EP3265445A1 (en) | 2018-01-10 |
| ES2872553T3 (es) | 2021-11-02 |
| US10766860B2 (en) | 2020-09-08 |
| JP2018510852A (ja) | 2018-04-19 |
| US11358936B2 (en) | 2022-06-14 |
| EP3265445A4 (en) | 2018-07-25 |
| WO2016144702A1 (en) | 2016-09-15 |
| US20180057458A1 (en) | 2018-03-01 |
| US20210171465A1 (en) | 2021-06-10 |
| EP3265445B1 (en) | 2021-05-05 |
| CN107624110B (zh) | 2021-01-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6800872B2 (ja) | リシルオキシダーゼ様2阻害剤とその使用 | |
| KR102594441B1 (ko) | 플루오르화된 리실 옥시다아제-유사 2 억제제 및 이의 용도 | |
| CN110372671B (zh) | 自分泌运动因子抑制剂化合物 | |
| US11058676B2 (en) | Quinolinone lysyl oxidase-like 2 inhibitors and uses thereof | |
| JP2018519292A (ja) | リシルオキシダーゼ様2阻害剤およびその使用 | |
| HK40012668B (en) | Autotaxin inhibitor compounds |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20171012 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190221 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20190221 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20191128 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200107 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20200331 |
|
| A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20200605 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20201028 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20201125 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6800872 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| LAPS | Cancellation because of no payment of annual fees |