Category: 1216805-11-6

On May 31, 2018, Gray, Nathanael S.; Dobrovolsky, Dennis; Huang, Hai-Tsang published a patent.COA of Formula: C14H10N2O6 The title of the patent was Degradation of Bruton’s tyrosine kinase (BTK) by conjugation of BTK inhibitors with E3 ligase ligand and methods of use. And the patent contained the following:

The present invention provides bifunctional compounds Targeting Ligand-Linker-Degron [I; the Targeting Ligand (TL) is capable of binding to one or more protein kinases (TL = II [B = (un)substituted Ph or 5-6 membered heteroaryl containing 1-2 heteroatoms selected from N, S; when Y1 is absent, B is bonded to a carbon atom or Y4 in III; Y1 = absent or C(O), wherein Y1 is bonded to a carbon atom or Y4 in III; Y2 = O or NR10a; Y3 = C(O)NR10b or NR10bC(O); Y4 = NR51 or, when Y1 is bonded to Y4 or when Y1 is absent and B is bonded to Y4, Y4 = N (wherein R51 = H, alkyl, haloalkyl, etc.); each R5 = alkyl, haloalkyl, alkoxy, etc.; R6 = H, alkyl, haloalkyl; each R7 = alkyl, haloalkyl, alkoxy, etc.; each R8 = alkyl, haloalkyl, alkoxy, etc.; R9 = alkyl, haloalkyl, alkoxy, etc.; R10a and R10b = H, alkyl or haloalkyl; o1, o2 or o3 = 0-3], etc.); the Linker is a group that covalently binds to the Targeting Ligand and the Degron; and the Degron is capable of binding to a ubiquitin ligase] or enantiomers, diastereomers, or stereoisomers thereof, or pharmaceutically acceptable salts, hydrates, solvates, or prodrugs thereof, which act as protein degradation inducing moieties for Bruton’s tyrosine kinase (BTK). Compound IV was prepared in a multi-step synthesis, starting from tert-Bu piperazine-1-carboxylate and 4-nitrobenzoic acid. The present application also relates to methods for the targeted degradation of BTK through the use of the bifunctional compounds I that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to BTK which can be utilized in the treatment of disorders modulated by BTK. Exemplified compound IV was tested and showed BTK degradation in the cell assay. Pharmaceutical composition comprising compound I was disclosed. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).COA of Formula: C14H10N2O6

The Article related to bifunctional compound preparation protein btk degradation inducer ubiquitin ligase, antitumor bifunctional compound preparation bruton’s tyrosine kinase btk inhibitor, Heterocyclic Compounds (One Hetero Atom): Pyridines and other aspects.COA of Formula: C14H10N2O6

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On May 31, 2018, Bradner, James; Buckley, Dennis; Ishoey, Mette; Winter, Georg published a patent.Name: 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid The title of the patent was Degradation of protein kinases by conjugation of protein kinase inhibitors with E3 ligase ligand and methods of use. And the patent contained the following:

The present invention provides bifunctional compounds Targeting Ligand-Linker-Degron [I; the Targeting Ligand (TL) is capable of binding to one or more protein kinases (TL = II [X1 = NR5 or O; each R1 and each R4 = (independently) alkyl, haloalkyl, alkoxy, etc.; R2 and R3 = (independently) H, alkyl, or haloalkyl; R5 = H, alkyl, haloalkyl, or C(O)alkyl; n1 = 0-3; n2 = 0-2], III [A = (un)substituted aryl or 5-6 membered heteroaryl comprising 1-3 heteroatoms selected from N, S, and O; X2 = O, S, or NR10; X3 = N or CR11; each R6 = (independently) alkyl, haloalkyl, alkoxy, etc.; R7 = H, alkyl, or haloalkyl; each R8 and each R9 = (independently) alkyl, haloalkyl, alkoxy, etc.; R10 = H or alkyl; R11 = alkyl, haloalkyl, alkoxy, etc.; q1 = 0-4; q2 = 0-3], etc.); the Linker is a group that covalently binds to the Targeting Ligand and the Degron; and the Degron is capable of binding to a ubiquitin ligase] or enantiomers, diastereomers, or stereoisomers thereof, or pharmaceutically acceptable salts, hydrates, solvates, or prodrugs thereof, which act as protein degradation inducing moieties for protein kinases. Fifteen compounds I [TL = II] were prepared Thus, amidating N-(4-aminobutyl)-2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamide with Sunitinib acid afforded 36% IV. The present application also relates to methods for the targeted degradation of one or more protein kinases through the use of the bifunctional compounds I that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to one or more protein kinases which can be utilized in the treatment of disorders modulated by protein kinases. Exemplified compounds I were tested in the dose-ranging viability assays (data given for representative compounds I). Pharmaceutical composition comprising compound I was disclosed. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).Name: 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid

The Article related to bifunctional compound preparation protein degradation inducer ubiquitin ligase binding, antitumor bifunctional compound preparation e3 ubiquitin ligase binding moiety, Heterocyclic Compounds (One Hetero Atom): Pyridines and other aspects.Name: 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On August 16, 2018, Bradner, James; Roberts, Justin; Behman, Nabet; Winter, Georg; Phillips, Andrews J.; Heffernan, Timothy P.; Buckley, Dennis published a patent.Application In Synthesis of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid The title of the patent was Regulating CAR-cells against inflammatory side effects by targeted CAR protein degradation through the use of ubiquitin ligase binding heterobifunctional compounds. And the patent contained the following:

Provided are compositions and methods for regulating chimeric antigen receptor (CAR) immune effector cell, for example T-cell, to modulate immunotherapy associated adverse inflammatory responses, for example, cytokine release syndrome and tumor lysis syndrome. This is done through the incorporation into CAR of a heterobifunctional compound-targeted protein or protein domain (dTAG) which allows for reversible control of the CAR expression and in turn the immune effector cell response while sparing the immune effector cell itself. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).Application In Synthesis of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid

The Article related to dtag chimeric antigen receptor targeting protein degradation adverse inflammation, ubiquitin ligase binding heterobifunctional compound dtag car immune cell, Immunochemistry: Adjuvants, Antigens, Haptens, and Vaccines and other aspects.Application In Synthesis of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On February 9, 2017, Bradner, James; Roberts, Justin; Nabet, Behnam; Winter, Georg; Phillips, Andrew J.; Heffernan, Timothy P.; Buckley, Dennis published a patent.Safety of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid The title of the patent was Using heterobifunctional compounds for targeted CAR protein degradation to attenuate adoptive immunotherapy associated adverse inflammation. And the patent contained the following:

Provided are compositions and methods for regulating chimeric antigen receptor immune effector cell, for example chimeric antigen receptor-expressing T-cell (CAR-T), therapy to modulate associated adverse inflammatory responses, for example, cytokine release syndrome and tumor lysis syndrome, using targeted protein degradation The chimeric antigen receptor (CAR) construct incorporate a heterobifunctional compound targeted protein or heterobifunctional compound tag, referred to as a dTAG, that allows for reversible targeted CAR protein degradation upon binding to a heterobifunctional compound Provided are heterobifunctional compounds that bind to a ubiquitin ligase through its ubiquitin ligase binding moiety and also bind to the CAR that contains the dTAG through a dTAG Targeting Ligand in vivo. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).Safety of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid

The Article related to targeted car protein degradation adoptive immunotherapy adverse inflammation attenuation, heterobifunctional compound car protein degradation t cell therapy cancer, Immunochemistry: Adjuvants, Antigens, Haptens, and Vaccines and other aspects.Safety of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On August 1, 2019, Crews, Craig M.; Burslem, George; Cromm, Philipp M.; Jaime-Figueroa, Saul; Toure, Momar published a patent.Category: piperidines The title of the patent was Preparation of imide-based compounds as modulators of proteolysis and methods of use. And the patent contained the following:

The description relates to imide-based compounds of formula I, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacol. activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type. Compounds of formula I wherein L is a chem. linker: PTM is a protein target moiety that binds to at target protein or polypeptide; CLM is a cereblon E3 ubiquitin ligase binding moiety; and salts, solvates, polymorphs, and deuterated forms thereof, are claimed. Example compound II was prepared by a multistep procedure (procedure given). The invention compounds were evaluated for their protein degradation activity (data given). The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).Category: piperidines

The Article related to imide preparation protein degradation proteolysis modulator, Heterocyclic Compounds (More Than One Hetero Atom): Diazepines and other aspects.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On February 9, 2017, Bradner, James; Buckley, Dennis; Winter, Georg published a patent.Formula: C14H10N2O6 The title of the patent was Methods to induce targeted protein degradation through bifunctional molecules. And the patent contained the following:

The present application provides bifunctional compounds which act as protein degradation inducing moieties. The present application also relates to nucleic acids, polypeptides, cells, and methods for highly regulated, targeted degradation of proteins through the use of the bifunctional compounds A polynucleotide comprising a first nucleotide sequence encoding a first polypeptide to which a Targeting Ligand of formula I (wherein ring containing T1-T5 is (a) T1, T2, T4 = N; T3, T5 = C, or (b) T1 = N, T2 = O; T3-T5 = C; A1 is S and C=C; A2 is NH and derivatives and O; each R1 is independently C1-3 alkyl, (CH2)0-3CN, (CH2)0-3OH, etc.; R2 is H, C1-6 alkyl, (CH2)0-3heterocyclyl, etc.; R3 is independently C1-3 alkyl, (CH2)0-3CN, (CH2)0-3OH, etc.; R4 is C1-3 alkyl) is capable of binding, and a second nucleotide sequence encoding a second polypeptide, wherein the first polypeptide and the second polypeptide are linked together with a peptide bond to form a fused polypeptide, is claimed. Example compound II was prepared by acylation of N-(4-aminobutyl)-2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamide trifluoroacetate with (S)-2-(4-(4-cyanophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetic acid. Exemplified compounds I demonstrated to have potent biol. activities, e.g., binding to the protein target, mediating protein degradation, etc. (data given). The title bifunctional compounds Degron-Linker-Targeting Ligand [Degron = I (ring A = II, III; Y = a bond, O, NH, etc.; X = C(O), C(R3); X1-X2 = C(R3):N or C(R3)2C(R3)2; R1 = halo, NO2, NH2, etc.; R3 = H, alkyl optionally substituted with aryl or 5-10 membered heteroaryl; each R31 = (independently) alkyl; R4 = (independently) H or alkyl; or two R4, together with the carbon atom to which they are attached, form C(O), carbocycle, or 4-6 membered heterocycle comprising 1-2 heteroatoms selected from N and O; R5 = H, alkyl, F or Cl; n = 0-2; m = 0-3; t = 0-1); Linker = IV (p1 = 0-12; p2 = 0-12; p3 = 0-6; each W = (independently) absent, CH2, O, S, NH or NR5; Z = absent, CH2, O, NH or NR5; each R5 = (independently) alkyl; Q = absent, C(O)NH, C(O)O, etc.); Targeting Ligand = V (ring containing T1-T5 = (a) T1, T2, T4 = N; T3, T5 = C, or (b) T1 = N, T2 = O; T3-T5 = C; A1 = S or C:C; A2 = NR15 or O; nn1 = 0-2; each R11 = (independently) alkyl, (CH2)0-3CN, (CH2)0-3halogen, etc.; R12 = H, alkyl, (CH2)0-3heterocyclyl, etc.; nn2 = 0-3; each R13 = alkyl, (CH2)0-3CN, (CH2)0-3halogen, etc.; R14 = alkyl; R15 = H or alkyl); with the proviso] which act as protein degradation inducing moieties, were prepared E.g., a multi-step synthesis of VI, starting from JQ1 (VII), was described. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of the title bifunctional compounds that link a cereblon-binding moiety to a ligand that is capable of binding to the targeted protein which can be utilized in the treatment of proliferative disorders. Exemplified compounds I demonstrated to have potent biol. activities, e.g., binding to the protein target (e.g. BRD4), mediating protein degradation, etc. (data given). The present application also provides methods for making compounds of the application and intermediates thereof. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).Formula: C14H10N2O6

The Article related to bifunctional compound preparation targeted protein degradation inducer, Heterocyclic Compounds (More Than One Hetero Atom): Diazepines and other aspects.Formula: C14H10N2O6

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On June 24, 2022, Xu, Junyu; Li, Youbin; Zheng, Danyang; Wang, Xuesong; Wang, Yan; Tan, Yinfeng; Wang, Yong; Yang, Chenqi; Zhang, Yuchen; Guo, Tong published a patent.Related Products of 1216805-11-6 The title of the patent was Preparation method of N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)formamide derivative, and application thereof in preparation of drugs for treating and/or preventing hyperproliferative diseases. And the patent contained the following:

The title N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)formamide derivative is obtained by covalently linking T or Q and T with N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)formamide fragment, and has structural formulas as shown in claim 1, wherein Q is linking group, and is linear or branched alkylene chain composed of 1-10 CH2 or CH, and the linear or branched alkylene chain is linked with T via -NH-; and T is any one of fragments having structural formulas as shown in claim 1. The derivative has a specific structural formula as shown in claim 2, and is 2-(2,6-dioxopiperidin-3-yl)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)-1,3-dioxoisoindoline-5-carboxamide. The derivative can effectively inhibit activity of human chronic myeloid leukemia cells and human gastrointestinal stromal tumor cells, and can be used in the preparation of drugs for treatment and/or prevention of hyperproliferative diseases, in particular for treatment of chronic myeloid leukemia and gastrointestinal stromal tumor. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).Related Products of 1216805-11-6

The Article related to formamide pyrimidinylaminophenyl preparation hyperproliferative disease, Heterocyclic Compounds (More Than One Hetero Atom): Pyrimidines and Quinazolines and other aspects.Related Products of 1216805-11-6

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On August 26, 2021, Palmer, Wylie Solang; Wu, Jeffrey; Zipfel, Sheila; Ozboya, Kerem; Weiss, Dahlia published a patent.Quality Control of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid The title of the patent was Preparation of bifunctional degraders of interleukin-1 receptor-associated kinases and therapeutic use thereof. And the patent contained the following:

The present disclosure provides bifunctional compounds I [R1 = (un)substituted C1-10 alkyl, C3-10 cycloalkyl, or 3-12 membered heterocyclyl; L = L1L2L3L4L5, each L1-L5 being independently: (a) (un)substituted C3-12 cycloalkyl, (b) (un)substituted C6-12 aryl, (c) (un)substituted 3-12 membered heterocyclyl, etc.; LHM = a ligase harness moiety] or pharmaceutically acceptable salts as IRAK4 degraders via ubiquitin proteasome pathway, and method for treating diseases modulated by IRAK4. E.g., a multi-step synthesis of II, starting from Me 4,6-dichloropyridine-3-carboxylate and tetrahydropyran-4-amine hydrochloride, was described. IRAK4 degradation of exemplified compounds I were measured in multiple runs using HTRF assay and HiBit assay (data given). Pharmaceutical composition comprising I was disclosed. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).Quality Control of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid

The Article related to interleukin1 receptor associated kinase irak4 bifunctional degrader pyrrolopyridazinecarbonitrile preparation, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.Quality Control of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Liu, Kai; Zhang, Datong; Chojnacki, Jeremy; Du, Yuhong; Fu, Haian; Grant, Steven; Zhang, Shijun published an article in 2013, the title of the article was Design and biological characterization of hybrid compounds of curcumin and thalidomide for multiple myeloma.Application In Synthesis of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid And the article contains the following content:

In our efforts to develop effective treatment agents for human multiple myeloma (MM), a series of hybrid mols. based on the structures of thalidomide (I) and curcumin (II) were designed, synthesized, and biol. characterized in human multiple myeloma MM1S, RPMI8226, U266 cells, and human lung cancer A549 cells. The biol. results showed that two hybrid compounds, III and IV, exhibited significantly improved lethal effects towards all three human MM cell models compared to I or II alone, as well as the combination of I and II. Furthermore, mechanistic studies in U266 cells demonstrated that III and IV can induce the production of reactive oxygen species (ROS) and cause G1/S arrest, thus leading to apoptosis and cell death. Addnl., they exhibited inhibitory effects on NFκB activation in A549 cells. Collectively, the results obtained from these hybrid compounds strongly encourage their further optimization as new leads to develop effective treatment agents for human MM. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).Application In Synthesis of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid

The Article related to curcumin thalidomide hybrid preparation multiple myeloma treatment, Biomolecules and Their Synthetic Analogs: Others, Including Purines, Pyrimidine Nucleic Acid Bases, Flavins, Lignans and other aspects.Application In Synthesis of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On September 1, 2020, Donoghue, Craig; Cubillos-Rojas, Monica; Gutierrez-Prat, Nuria; Sanchez-Zarzalejo, Carolina; Verdaguer, Xavier; Riera, Antoni; Nebreda, Angel R. published an article.Application of 1216805-11-6 The title of the article was Optimal linker length for small molecule PROTACs that selectively target p38α and p38β for degradation. And the article contained the following:

We report the design of hetero-bifunctional small mols. that selectively target p38α and p38β for degradation These proteolysis targeted chimeras (PROTACs) are based on an ATP competitive inhibitor of p38α and p38β, which is linked to thalidomide analogs to recruit the Cereblon E3 ubiquitin ligase complex. Compound synthesis was facilitated by the use of a copper catalyzed “click” reaction. We show that optimization of the linker length and composition is crucial for the degradation-inducing activity of these PROTACs. We provide evidence that these chem. compounds can induce degradation of p38α and p38β but no other related kinases at nanomolar concentrations in several mammalian cell lines. Accordingly, the PROTACs inhibit stress and cytokine-induced p38α signaling. Our compounds contribute to understanding the development of PROTACs, and provide a useful tool to investigate functions of the p38 MAPK pathway and its involvement in diseases. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).Application of 1216805-11-6

The Article related to preparation protacs targeting p38 alpha beta proteolysis, azide-alkyne click reaction, cereblon, protac linker optimization, protein degradation, thalidomide derivative, p38 mapk and other aspects.Application of 1216805-11-6

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem