JP2018510904A5 - - Google Patents

Download PDF

Info

Publication number: JP2018510904A5
Authority: JP; Japan
Prior art keywords: group; substituted; pharmaceutical composition; composition according; heterocycle
Prior art date: 2016-02-11
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.): Granted

Application number

JP2017560888A

Other languages

English (en)

Japanese (ja)

Other versions

JP2018510904A (ja

JP6887389B2 (ja

Filing date

2016-02-11

Publication date

2019-03-22

2016-02-11 Application filed filed Critical

2016-02-11 Priority claimed from PCT/US2016/017504 external-priority patent/WO2016130774A1/en

2018-04-19 Publication of JP2018510904A publication Critical patent/JP2018510904A/ja

2019-03-22 Publication of JP2018510904A5 publication Critical patent/JP2018510904A5/ja

2021-06-16 Application granted granted Critical

2021-06-16 Publication of JP6887389B2 publication Critical patent/JP6887389B2/ja

Status Active legal-status Critical Current

2036-02-11 Anticipated expiration legal-status Critical

Links

150000001875 compounds Chemical class 0.000 claims description 15
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
208000015439 Lysosomal storage disease Diseases 0.000 claims description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
208000024720 Fabry Disease Diseases 0.000 claims description 2
208000010055 Globoid Cell Leukodystrophy Diseases 0.000 claims description 2
208000028226 Krabbe disease Diseases 0.000 claims description 2
208000026589 Wolman disease Diseases 0.000 claims description 2
125000005843 halogen group Chemical group 0.000 claims 12
239000008194 pharmaceutical composition Substances 0.000 claims 12
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 10
-1 dimethylaminopropoxy group Chemical group 0.000 claims 7
125000000623 heterocyclic group Chemical group 0.000 claims 6
125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 5
UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims 4
LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 claims 4
125000003277 amino group Chemical group 0.000 claims 4
125000002883 imidazolyl group Chemical group 0.000 claims 4
229910052757 nitrogen Inorganic materials 0.000 claims 4
125000004433 nitrogen atom Chemical group N* 0.000 claims 4
125000001424 substituent group Chemical group 0.000 claims 4
125000006823 (C1-C6) acyl group Chemical group 0.000 claims 3
125000004093 cyano group Chemical group *C#N 0.000 claims 3
125000001183 hydrocarbyl group Chemical group 0.000 claims 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
MZBVNYACSSGXID-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-1-benzazepine Chemical group N1CCCCC2=CC=CC=C21 MZBVNYACSSGXID-UHFFFAOYSA-N 0.000 claims 2
208000032007 Glycogen storage disease due to acid maltase deficiency Diseases 0.000 claims 2
206010053185 Glycogen storage disease type II Diseases 0.000 claims 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 2
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims 2
125000003545 alkoxy group Chemical group 0.000 claims 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
208000035475 disorder Diseases 0.000 claims 2
201000004502 glycogen storage disease II Diseases 0.000 claims 2
125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims 2
GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 claims 2
125000002950 monocyclic group Chemical group 0.000 claims 2
208000025919 mucopolysaccharidosis type 7 Diseases 0.000 claims 2
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 2
208000001948 Farber Lipogranulomatosis Diseases 0.000 claims 1
208000033149 Farber disease Diseases 0.000 claims 1
208000015872 Gaucher disease Diseases 0.000 claims 1
102100033448 Lysosomal alpha-glucosidase Human genes 0.000 claims 1
208000002678 Mucopolysaccharidoses Diseases 0.000 claims 1
206010056893 Mucopolysaccharidosis VII Diseases 0.000 claims 1
201000001828 Sly syndrome Diseases 0.000 claims 1
208000010346 Sphingolipidoses Diseases 0.000 claims 1
201000001307 Sphingolipidosis Diseases 0.000 claims 1
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims 1
125000003118 aryl group Chemical group 0.000 claims 1
XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 claims 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
229910052731 fluorine Inorganic materials 0.000 claims 1
125000001153 fluoro group Chemical group F* 0.000 claims 1
125000001072 heteroaryl group Chemical group 0.000 claims 1
150000002460 imidazoles Chemical class 0.000 claims 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
125000002911 monocyclic heterocycle group Chemical group 0.000 claims 1
206010028093 mucopolysaccharidosis Diseases 0.000 claims 1
201000007633 neuronal ceroid lipofuscinosis 2 Diseases 0.000 claims 1
125000000719 pyrrolidinyl group Chemical group 0.000 claims 1
125000000168 pyrrolyl group Chemical group 0.000 claims 1
210000004027 cell Anatomy 0.000 description 13
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 8
239000000523 sample Substances 0.000 description 7
239000000203 mixture Substances 0.000 description 5
PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 4
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
108060001084 Luciferase Proteins 0.000 description 4
239000005089 Luciferase Substances 0.000 description 4
102000028677 Rab9 Human genes 0.000 description 4
108050007276 Rab9 Proteins 0.000 description 4
238000006243 chemical reaction Methods 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
235000019439 ethyl acetate Nutrition 0.000 description 4
239000012044 organic layer Substances 0.000 description 4
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
238000003556 assay Methods 0.000 description 3
230000014759 maintenance of location Effects 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
239000003053 toxin Substances 0.000 description 3
231100000765 toxin Toxicity 0.000 description 3
108700012359 toxins Proteins 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
241000588724 Escherichia coli Species 0.000 description 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 2
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
238000001514 detection method Methods 0.000 description 2
230000000694 effects Effects 0.000 description 2
150000002632 lipids Chemical class 0.000 description 2
210000003712 lysosome Anatomy 0.000 description 2
230000001868 lysosomic effect Effects 0.000 description 2
239000002609 medium Substances 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
239000000243 solution Substances 0.000 description 2
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
239000000725 suspension Substances 0.000 description 2
DSSUHBJSDMHACJ-UHFFFAOYSA-N 2-methoxy-5-nitrobenzenesulfonyl chloride Chemical compound COC1=CC=C([N+]([O-])=O)C=C1S(Cl)(=O)=O DSSUHBJSDMHACJ-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
ZKUZSTXNVMIDCY-UHFFFAOYSA-N 4-methylpyridine-3-carboxylic acid Chemical compound CC1=CC=NC=C1C(O)=O ZKUZSTXNVMIDCY-UHFFFAOYSA-N 0.000 description 1
WNUKMPUZMALMLG-UHFFFAOYSA-N 5-amino-n-(4-bromophenyl)-2-methoxybenzenesulfonamide Chemical compound COC1=CC=C(N)C=C1S(=O)(=O)NC1=CC=C(Br)C=C1 WNUKMPUZMALMLG-UHFFFAOYSA-N 0.000 description 1
108010011170 Ala-Trp-Arg-His-Pro-Gln-Phe-Gly-Gly Proteins 0.000 description 1
102100026277 Alpha-galactosidase A Human genes 0.000 description 1
102220486220 Alpha-galactosidase A_N34S_mutation Human genes 0.000 description 1
208000031277 Amaurotic familial idiocy Diseases 0.000 description 1
108090000331 Firefly luciferases Proteins 0.000 description 1
101000933374 Gallus gallus Brain-specific homeobox/POU domain protein 3 Proteins 0.000 description 1
101000600434 Homo sapiens Putative uncharacterized protein encoded by MIR7-3HG Proteins 0.000 description 1
ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
229930182816 L-glutamine Natural products 0.000 description 1
102100026001 Lysosomal acid lipase/cholesteryl ester hydrolase Human genes 0.000 description 1
TTZOQOXARXTTRK-UHFFFAOYSA-N N-[3-[(4-bromophenyl)sulfamoyl]-4-methoxyphenyl]-4-methylpyridine-3-carboxamide Chemical compound COC1=C(C=C(NC(=O)C2=C(C)C=CN=C2)C=C1)S(=O)(=O)NC1=CC=C(Br)C=C1 TTZOQOXARXTTRK-UHFFFAOYSA-N 0.000 description 1
208000002537 Neuronal Ceroid-Lipofuscinoses Diseases 0.000 description 1
BNUHAJGCKIQFGE-UHFFFAOYSA-N Nitroanisol Chemical compound COC1=CC=C([N+]([O-])=O)C=C1 BNUHAJGCKIQFGE-UHFFFAOYSA-N 0.000 description 1
229930182555 Penicillin Natural products 0.000 description 1
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
102100037401 Putative uncharacterized protein encoded by MIR7-3HG Human genes 0.000 description 1
239000012980 RPMI-1640 medium Substances 0.000 description 1
108700008625 Reporter Genes Proteins 0.000 description 1
108010017898 Shiga Toxins Proteins 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
108010055297 Sterol Esterase Proteins 0.000 description 1
108010090804 Streptavidin Proteins 0.000 description 1
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical class [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
238000009825 accumulation Methods 0.000 description 1
239000002253 acid Substances 0.000 description 1
230000004913 activation Effects 0.000 description 1
108010030291 alpha-Galactosidase Proteins 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
239000012267 brine Substances 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
235000012000 cholesterol Nutrition 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
238000001816 cooling Methods 0.000 description 1
210000001163 endosome Anatomy 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
230000005284 excitation Effects 0.000 description 1
LEZNRPFLOGYEIO-QSEDPUOVSA-N ganglioside GT1b Chemical compound O[C@@H]1[C@@H](O)[C@H](OC[C@H](NC(=O)CCCCCCCCCCCCCCCCC)[C@H](O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@]2(O[C@H]([C@H](NC(C)=O)[C@@H](O)C2)[C@H](O)[C@@H](CO)O[C@]2(O[C@H]([C@H](NC(C)=O)[C@@H](O)C2)[C@H](O)[C@H](O)CO)C(O)=O)C(O)=O)[C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O[C@]4(O[C@H]([C@H](NC(C)=O)[C@@H](O)C4)[C@H](O)[C@H](O)CO)C(O)=O)[C@@H](O)[C@@H](CO)O3)O)[C@@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](CO)O1 LEZNRPFLOGYEIO-QSEDPUOVSA-N 0.000 description 1
239000000499 gel Substances 0.000 description 1
238000011534 incubation Methods 0.000 description 1
208000017476 juvenile neuronal ceroid lipofuscinosis Diseases 0.000 description 1
239000010410 layer Substances 0.000 description 1
235000019626 lipase activity Nutrition 0.000 description 1
238000003468 luciferase reporter gene assay Methods 0.000 description 1
238000004020 luminiscence type Methods 0.000 description 1
230000002132 lysosomal effect Effects 0.000 description 1
239000002184 metal Substances 0.000 description 1
230000035772 mutation Effects 0.000 description 1
201000007607 neuronal ceroid lipofuscinosis 3 Diseases 0.000 description 1
229940049954 penicillin Drugs 0.000 description 1
238000010647 peptide synthesis reaction Methods 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
235000019833 protease Nutrition 0.000 description 1
238000000746 purification Methods 0.000 description 1
238000011002 quantification Methods 0.000 description 1
238000010791 quenching Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
238000002390 rotary evaporation Methods 0.000 description 1
238000012216 screening Methods 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000002904 solvent Substances 0.000 description 1
238000010186 staining Methods 0.000 description 1
229960005322 streptomycin Drugs 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
108010044241 tetanus toxin fragment C Proteins 0.000 description 1
GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 1
FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000000844 transformation Methods 0.000 description 1

JP2017560888A 2015-02-11 2016-02-11 ニーマン・ピック病および他のリソソーム蓄積障害のためのｎｐｃ１のベンゼンスルホンアミド上方制御剤 Active JP6887389B2 (ja)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US201562114840P	2015-02-11	2015-02-11
US62/114,840		2015-02-11
PCT/US2016/017504 WO2016130774A1 (en)	2015-02-11	2016-02-11	Benzenesulfonamide upregulators of npc1 for neimann-pick disease and other lysosomal storage disorders

Publications (3)

Publication Number	Publication Date
JP2018510904A JP2018510904A (ja)	2018-04-19
JP2018510904A5 true JP2018510904A5 (2)	2019-03-22
JP6887389B2 JP6887389B2 (ja)	2021-06-16

Family

ID=56614815

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP2017560888A Active JP6887389B2 (ja)	2015-02-11	2016-02-11	ニーマン・ピック病および他のリソソーム蓄積障害のためのｎｐｃ１のベンゼンスルホンアミド上方制御剤

Country Status (8)

Country	Link
US (1)	US10239830B2 (2)
EP (1)	EP3256116B1 (2)
JP (1)	JP6887389B2 (2)
CN (1)	CN107949380B (2)
AU (1)	AU2016219231B2 (2)
CA (1)	CA2976449C (2)
IL (2)	IL253896B (2)
WO (1)	WO2016130774A1 (2)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN111289749B (zh) *	2018-12-10	2023-04-14	北京蛋白质组研究中心	C型1类尼曼-匹克蛋白检测物在制备筛查肝细胞癌产品中的应用
WO2021150695A1 (en) *	2020-01-22	2021-07-29	Icahn School Of Medicine At Mount Sinai	Constrained n-substituted tetrahydrobenzoazepine sulfonamides as anticancer and neuroprotective agents
WO2022159566A1 (en)	2021-01-21	2022-07-28	Icahn School Of Medicine At Mount Sinai	Benzenesulfonamide agonists of trap1 for treating organ fibrosis

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ATE322900T1 (de) *	1996-07-15	2006-04-15	Macrozyme Dnm B V	Deoxynojirimycin derivate und ihre verwendung als glukosesylceramidase-inhibitoren
ATE299499T1 (de) *	1998-11-09	2005-07-15	Black James Foundation	Gastrin und cholecystokinin rezeptor ligande
WO2004035545A2 (en) *	2002-10-18	2004-04-29	E.I. Du Pont De Nemours And Company	Azolecarboxamide herbicides
LT2502911T (lt)	2004-06-24	2017-09-11	Vertex Pharmaceuticals Incorporated	Atp surišančios kasetės transporterių moduliatoriai
US8354427B2 (en)	2004-06-24	2013-01-15	Vertex Pharmaceutical Incorporated	Modulators of ATP-binding cassette transporters
EP2004596A2 (en)	2006-04-11	2008-12-24	Vertex Pharmaceuticals Incorporated	Compositions useful as inhibitors of voltage-gated sodium channels
WO2013192165A2 (en)	2012-06-20	2013-12-27	University Of Kansas	Compounds and methods for activating the apoptotic arm of the unfolded protein response
CN107865968B (zh) *	2012-08-03	2021-03-05	美国政府(由卫生和人类服务部的部长所代表)	用于治疗溶酶体贮积症的环糊精
US20140128352A1 (en) *	2012-09-20	2014-05-08	Buck Institute For Research On Aging	Compounds and methods for modulating mitochondrial metabolism and reactive oxygen species production
EP2823816A1 (en) *	2013-07-09	2015-01-14	Tragex Pharma	Inhibitors of Neuropilin and use thereof for the treatment of Neuropilin-related diseases

2016
- 2016-02-11 CN CN201680020467.XA patent/CN107949380B/zh active Active
- 2016-02-11 JP JP2017560888A patent/JP6887389B2/ja active Active
- 2016-02-11 WO PCT/US2016/017504 patent/WO2016130774A1/en not_active Ceased
- 2016-02-11 US US15/549,743 patent/US10239830B2/en active Active
- 2016-02-11 CA CA2976449A patent/CA2976449C/en active Active
- 2016-02-11 AU AU2016219231A patent/AU2016219231B2/en active Active
- 2016-02-11 EP EP16749864.1A patent/EP3256116B1/en active Active
2017
- 2017-08-08 IL IL253896A patent/IL253896B/en active IP Right Grant
2019
- 2019-08-21 IL IL26881119A patent/IL268811A/en unknown

Publication	Publication Date	Title
KR100538359B1 (ko)	2005-12-22	α,β-불포화 하이드록사믹 액시드 유도체와 이 화합물의히스톤 디아세틸라제 억제제로서의 용도
CA2349227C (en)	2008-02-05	Substituted 2-phenylbenzimidazoles, the production thereof and their use
Huber et al.	2009	1, 1′-Disubstituted ferrocenes as molecular hinges in mono-and bivalent dopamine receptor ligands
PL212494B1 (pl)	2012-10-31	Nowe zwiazki chemiczne, kompozycje zawierajace nowe zwiazki chemiczne i zastosowanie nowych zwiazków chemicznych
CN103333156B (zh)	2015-03-11	一种2-取代芳乙烯基-n-甲基化喹啉衍生物的制备及其在抗阿尔兹海默症药物中的应用
Dehbi et al.	2014	Synthesis and optimization of an original V-shaped collection of 4-7-disubstituted Pyrido [3, 2-d] pyrimidines as CDK5 and DYRK1A inhibitors
Thalhammer et al.	2011	Inhibition of the histone demethylase JMJD2E by 3-substituted pyridine 2, 4-dicarboxylates
CN105524061A (zh)	2016-04-27	多靶点抗肿瘤活性的吴茱萸碱衍生物及其制备与应用
US20210101891A1 (en)	2021-04-08	Histone acetyltransferase (hat) inhibitor and use thereof
JP2018510904A5 (2)	2019-03-22
Laha et al.	2019	Palladium-catalysed regioselective N-arylation of anthranilamides: a tandem route for dibenzodiazepinone synthesis
CN103508960A (zh)	2014-01-15	苯并杂环衍生物
Xu et al.	2016	Design, synthesis, and evaluation of potent Wnt signaling inhibitors featuring a fused 3-ring system
CN114957250B (zh)	2023-05-09	N-(9H-吡啶[2,3-b]吲哚-4-基)芳基甲酰胺类衍生物及其制备方法与应用
CN111592530A (zh)	2020-08-28	含醛肟的他克林衍生物类选择性丁酰胆碱酯酶抑制剂及其制备方法和应用
Liu et al.	2012	Synthesis and cytotoxic evaluation of some new phthalazinylpiperazine derivatives
CN105924385A (zh)	2016-09-07	一种具有抗肿瘤活性的二芳基硫脲化合物及其制备方法和应用
CN106946896B (zh)	2019-05-21	呋喃并[2,3-d]嘧啶-4-胺衍生物
Singh et al.	2020	6‐(Hetero) arylindolizino [1, 2‐c] quinolines as highly fluorescent chemical space: Synthesis and photophysical properties
CN119661474A (zh)	2025-03-21	一类羟肟酸类的双靶点化合物衍生物及其应用
CN110590640B (zh)	2020-12-15	一种靛玉红衍生物及其作为cdk/hdac双靶标抑制剂的应用
CN114835640B (zh)	2024-02-13	成纤维细胞生长因子受体抑制剂、制备方法及应用
JP5881460B2 (ja)	2016-03-09	新規アミド化合物及びその用途
Wang et al.	2020	Synthesis and biological evaluation of 2-quinolineacrylamides
CN110590664A (zh)	2019-12-20	一种荧光探针的制备方法及该荧光探针的应用