Tag: 300-400

On June 30, 2016, Bradner, James; Buckley, Dennis; Winter, Georg published a patent.Application of 1216805-11-6 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 methods for the targeted degradation of endogenous proteins through the use of the 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. 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).Application of 1216805-11-6

The Article related to targeted protein degradation bifunctional mol preparation, Heterocyclic Compounds (One Hetero Atom): Pyridines and other aspects.Application of 1216805-11-6

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 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 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 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 June 23, 2016, Bradner, James; Buckley, Dennis; Winter, Georg published a patent.Computed Properties of 1216805-11-6 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 I [wherein: M = (R1)m; Y is a bond, (CH2)1-6, (CH2)0-6-O, (CH2)0-6-C(:O)NR2′, (CH2)0-6-NR2’C(:O), (CH2)0-6-NH or (CH2)0-6-NR2; X is C(:O) or C(R3)2;]. [Each R1 is independently halogen, OH, C1-6-alkyl or C1-6-alkoxy; R2 is C1-6-alkyl, C(:O)-C1-6-alkyl or C(:O)-C3-6-cycloalkyl; R2′ is H or C1-6-alkyl; each R3 is independently H or C1-3-alkyl; each R3′ is independently C1-3-alkyl;]. [Each R4is independently H or C1-3-alkyl and at least one R4 is C1-3-alkyl; or two R4, together with the carbon atom to which they are attached, form a C3-6-carbocycle or a 4-, 5- or 6-membered heterocycle comprising 1 or 2 heteroatoms selected from N and O;]. [R5 is H, deuterium, C1-3-alkyl, F or Cl; ; m is 0, 1, 2 or 3; n is 0, 1 or 2; the Linker is a group that covalently binds to the Targeting Ligand and Y; and, the Targeting Ligand binds to a targeted protein selected from EGFR, FLT3, KSR1, Raf, SMARCA2 and Ras] and II [ X1-X2 is C(R3):N or C(R3)2-C(R3)2;], or an enantiomer, diastereomer, stereoisomer, or a pharmaceutically acceptable salt thereof, which act as protein degradation inducing moieties. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of the 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. The present application also provides methods for making compounds of the application and intermediates thereof. Thus, dBET1 [DB-2-190-2 (III)] was prepared from JQ1 (IV) via acid hydrolysis with HCO2H and amidation with N-(4-aminobutyl)-2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamide trifluoroacetate (V·CF3CO2H) in DMF containing HATU and DIPEA. The bioactivity of III was determined [IC50 = 20 nM vs. BRD4; 85% loss of BRD4 in a human AML cell line MV4-11 an 100 nM; potent downregulation of total BRD4 in human cancer cell line SUM149 breast cancer cells (EC50 = 430 nM); showed comparable response in cell lines SUM159 and MOLM13]. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).Computed Properties of 1216805-11-6

The Article related to steroid bifunctional derivative preparation induction targeted protein degradation, proliferative disorder treatment steroid bifunctional derivative, Heterocyclic Compounds (One Hetero Atom): Pyridines and other aspects.Computed Properties of 1216805-11-6

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 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 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 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