AU2017226005A1 - Inhibitors of WDR5 protein-protein binding - Google Patents
Inhibitors of WDR5 protein-protein binding Download PDFInfo
- Publication number
- AU2017226005A1 AU2017226005A1 AU2017226005A AU2017226005A AU2017226005A1 AU 2017226005 A1 AU2017226005 A1 AU 2017226005A1 AU 2017226005 A AU2017226005 A AU 2017226005A AU 2017226005 A AU2017226005 A AU 2017226005A AU 2017226005 A1 AU2017226005 A1 AU 2017226005A1
- Authority
- AU
- Australia
- Prior art keywords
- phenyl
- 6alkyl
- carboxamide
- trifluoromethyl
- fluoro
- 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.)
- Abandoned
Links
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- LNJCTKSOCLAUCL-MRXNPFEDSA-N C[C@H](CN(C1)c(c(NC(C(C(C(F)(F)F)=C2)=CNC2=O)=O)c2)ccc2-c(cc(nc2)OCC3CC3)c2F)NC1=C Chemical compound C[C@H](CN(C1)c(c(NC(C(C(C(F)(F)F)=C2)=CNC2=O)=O)c2)ccc2-c(cc(nc2)OCC3CC3)c2F)NC1=C LNJCTKSOCLAUCL-MRXNPFEDSA-N 0.000 description 1
- JOMNTHCQHJPVAZ-RXMQYKEDSA-N C[C@H]1NCCNC1 Chemical compound C[C@H]1NCCNC1 JOMNTHCQHJPVAZ-RXMQYKEDSA-N 0.000 description 1
- 0 C[C@](C1)NCCN1c(c(NC(c(c(*)c1)cnc1OCCS)=O)c1)ccc1[Sn] Chemical compound C[C@](C1)NCCN1c(c(NC(c(c(*)c1)cnc1OCCS)=O)c1)ccc1[Sn] 0.000 description 1
- YLMJVOFBEFVCIF-UHFFFAOYSA-N Cc(c(C(F)(F)F)cc(F)c1)c1F Chemical compound Cc(c(C(F)(F)F)cc(F)c1)c1F YLMJVOFBEFVCIF-UHFFFAOYSA-N 0.000 description 1
- DCDDOKJPLXZXPC-UHFFFAOYSA-N Cc(cc(cc1C)C(Nc2cc(-c3c(C)nc(C)cc3)ccc2N2CCNCC2)=O)c1F Chemical compound Cc(cc(cc1C)C(Nc2cc(-c3c(C)nc(C)cc3)ccc2N2CCNCC2)=O)c1F DCDDOKJPLXZXPC-UHFFFAOYSA-N 0.000 description 1
- XXLNKGOPDHIOCS-UHFFFAOYSA-N Cc(cc1)c(C(F)(F)F)cc1F Chemical compound Cc(cc1)c(C(F)(F)F)cc1F XXLNKGOPDHIOCS-UHFFFAOYSA-N 0.000 description 1
- WRFHKNNJGVHNFX-UHFFFAOYSA-N Cc(cc1F)c(C(F)(F)F)cc1F Chemical compound Cc(cc1F)c(C(F)(F)F)cc1F WRFHKNNJGVHNFX-UHFFFAOYSA-N 0.000 description 1
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- BOVKVTDVQGJRCJ-UHFFFAOYSA-N Cc1cc(C(Nc2cc(-c(cc(CN3CCOCC3)cc3)c3F)ccc2N2CCN(C)CC2)=O)cc(C(F)(F)F)c1F Chemical compound Cc1cc(C(Nc2cc(-c(cc(CN3CCOCC3)cc3)c3F)ccc2N2CCN(C)CC2)=O)cc(C(F)(F)F)c1F BOVKVTDVQGJRCJ-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
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- 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
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- 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
- C07D213/82—Amides; Imides in position 3
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/08—Radicals containing only hydrogen and carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles 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 in position 2
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D237/14—Oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D237/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- 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
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- C07D—HETEROCYCLIC COMPOUNDS
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- 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
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
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- C—CHEMISTRY; METALLURGY
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/08—Bridged systems
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| DK3423451T3 (da) | 2016-03-01 | 2022-11-28 | Propellon Therapeutics Inc | Inhibitorer af wdr5-protein-proteinbinding |
| CA3041840A1 (en) | 2016-10-28 | 2018-05-03 | Icahn School Of Medicine At Mount Sinai | Compositions and methods for treating ezh2-mediated cancer |
| EP3551185A4 (en) | 2016-12-08 | 2021-07-14 | Icahn School of Medicine at Mount Sinai | COMPOSITIONS AND METHODS OF TREATMENT OF CDK4 / 6 MEDIATED CANCER |
| MX2020002399A (es) * | 2017-09-06 | 2020-07-22 | Propellon Therapeutics Inc | Inhibidores del enlace proteína-proteína de wdr5. |
| US10501466B2 (en) | 2017-09-19 | 2019-12-10 | Vanderbilt University | WDR5 inhibitors and modulators |
| US11472799B2 (en) | 2018-03-06 | 2022-10-18 | Icahn School Of Medicine At Mount Sinai | Serine threonine kinase (AKT) degradation / disruption compounds and methods of use |
| CN108715585A (zh) * | 2018-04-23 | 2018-10-30 | 中国药科大学 | 苯基联三氮唑类mll1-wdr5蛋白-蛋白相互作用抑制剂 |
| US10844044B2 (en) | 2018-06-14 | 2020-11-24 | Vanderbilt University | WDR5 inhibitors and modulators |
| CA3104298A1 (en) | 2018-06-21 | 2019-12-26 | Icahn School Of Medicine At Mount Sinai | Wd40 repeat domain protein 5 (wdr5) degradation / disruption compounds and methods of use |
| US10807959B2 (en) | 2018-08-16 | 2020-10-20 | Vanderbilt University | WDR5-MLL1 inhibitors and modulators |
| CN109734674B (zh) | 2019-02-26 | 2022-08-26 | 中国药科大学 | 苯胺类wdr5蛋白-蛋白相互作用抑制剂及其制法和用途 |
| CN114423463B (zh) | 2019-05-06 | 2025-09-26 | 西奈山伊坎医学院 | 作为hpk1的降解剂的异双功能化合物 |
| US12103924B2 (en) | 2020-06-01 | 2024-10-01 | Icahn School Of Medicine At Mount Sinai | Mitogen-activated protein kinase kinase (MEK) degradation compounds and methods of use |
| US20230286948A1 (en) * | 2022-03-14 | 2023-09-14 | Huyabio International, Llc | Haloalkylpyridyl triazole mll1-wdr5 protein-protein interaction inhibitor |
| WO2024002379A1 (zh) * | 2022-07-01 | 2024-01-04 | 甘李药业股份有限公司 | 一种用作wdr5抑制剂的化合物或其可药用盐及其应用 |
| CN117486791A (zh) * | 2023-10-18 | 2024-02-02 | 南通敏言生物医药科技有限公司 | 一种5-甲氧基-4-(三氟甲基)吡啶-2-甲酸甲酯的合成方法 |
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| CN103189067A (zh) | 2010-06-16 | 2013-07-03 | 密执安大学评议会 | Wdr5与其结合配偶体的相互作用的抑制及治疗方法 |
| CN201802360U (zh) | 2010-06-29 | 2011-04-20 | 中国石油化工股份有限公司胜利油田分公司采油工艺研究院 | 曲柄无游梁抽油机 |
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| CN105585565B (zh) | 2014-10-23 | 2019-10-01 | 中国医学科学院药物研究所 | 含2-苯胺基-4-噻唑基吡啶衍生物及其制法和药物组合物与用途 |
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| CN116375797A (zh) | 2016-03-01 | 2023-07-04 | 伊玛提克斯生物技术有限公司 | 用于膀胱癌和其他癌症免疫治疗的肽、肽组合物和细胞类药物 |
| DK3423451T3 (da) | 2016-03-01 | 2022-11-28 | Propellon Therapeutics Inc | Inhibitorer af wdr5-protein-proteinbinding |
| JP2019522049A (ja) | 2016-06-20 | 2019-08-08 | ノバルティス アーゲー | トリアゾロピリジン化合物及びその使用 |
| US10160763B2 (en) | 2016-09-13 | 2018-12-25 | Vanderbilt University | WDR5 inhibitors and modulators |
| MX2020002399A (es) | 2017-09-06 | 2020-07-22 | Propellon Therapeutics Inc | Inhibidores del enlace proteína-proteína de wdr5. |
| US10501466B2 (en) | 2017-09-19 | 2019-12-10 | Vanderbilt University | WDR5 inhibitors and modulators |
| WO2020086857A1 (en) | 2018-10-24 | 2020-04-30 | Vanderbilt University | Wdr5 inhibitors and modulators |
| WO2021026672A1 (en) | 2019-08-09 | 2021-02-18 | Novartis Ag | Heterocyclic wdr5 inhibitors as anti-cancer compounds |
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| US11174250B2 (en) | 2021-11-16 |
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| US20190119264A1 (en) | 2019-04-25 |
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