Day: November 2, 2022

On April 26, 2012, Connolly, Peter J.; Bian, Haiyan; Li, Xun; Liu, Li; Macielag, Mark J.; McDonnell, Mark E. published a patent.Application of 1251006-64-0 The title of the patent was Azetidinylpiperidine derivatives as monoacylglycerol lipase inhibitors and their preparation and use for the treatment of inflammatory pain. And the patent contained the following:

The invention relates to azetidinylpiperidine of formula I, which are monoacylglycerol lipase (MGL) inhibitors and which are useful in the treatment of inflammatory pain. Compounds of formula I wherein Y and Z are independently (un)substituted C6-10 aryl, (un)substituted thiazolyl, (un)substituted isothiazolyl, etc.; R is H and OH; with provisions; and enantiomers, diastereoisomers and pharmaceutically acceptable salts thereof, are claimed. Example compound II was prepared by a multistep procedure (procedure given). All the invention compounds were evaluated for their MGL inhibitory activity. From the assay, it was determined that compound II exhibited an IC50 value of 0.006 μM. The experimental process involved the reaction of tert-Butyl 3-(piperidin-4-yl)azetidine-1-carboxylate(cas: 1251006-64-0).Application of 1251006-64-0

The Article related to azetidinyl piperidine preparation monoacylglycerol lipase inhibitor treatment inflammatory pain, Heterocyclic Compounds (One Hetero Atom): Pyridines and other aspects.Application of 1251006-64-0

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

Ronson, Thomas O.; Renders, Evelien; Van Steijvoort, Ben F.; Wang, Xubin; Wybon, Clarence C. D.; Prokopcova, Hana; Meerpoel, Lieven; Maes, Bert U. W. published an article in 2019, the title of the article was Ruthenium-Catalyzed Reductive Arylation of N-(2-Pyridinyl)amides with Isopropanol and Arylboronate Esters.Quality Control of 4-(4-Chlorophenyl)piperidin-4-ol And the article contains the following content:

A new three-component reductive arylation of amides with stable reactants (iPrOH and arylboronate esters), making use of a 2-pyridinyl (Py) directing group, is described. The N-Py-amide substrates are readily prepared from carboxylic acids and PyNH2, and the resulting N-Py-1-arylalkanamine reaction products are easily transformed into the corresponding chlorides by substitution of the HN-Py group with HCl. The 1-aryl-1-chloroalkane products allow substitution and cross-coupling reactions. Therefore, a general protocol for the transformation of carboxylic acids into a variety of functionalities is obtained. The Py-NH2 byproduct can be recycled. The experimental process involved the reaction of 4-(4-Chlorophenyl)piperidin-4-ol(cas: 39512-49-7).Quality Control of 4-(4-Chlorophenyl)piperidin-4-ol

The Article related to multicomponent reductive arylation amide arylboronate ester pyridinyl directing group, amides, amines, arylation, multicomponent reactions, ruthenium, Heterocyclic Compounds (One Hetero Atom): Pyridines and other aspects.Quality Control of 4-(4-Chlorophenyl)piperidin-4-ol

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 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 31, 2014, Shimakami, Natsumi; Yabutani, Tomoki; Takayanagi, Toshio published an article.Name: 4-(4-Chlorophenyl)piperidin-4-ol The title of the article was Analysis of acid dissociation of photo-degradable haloperidol through the measurement of electrophoretic mobility by capillary zone electrophoresis. And the article contained the following:

The acid dissociation constants (Ka) of Haloperidol and its degraded product were determined by capillary zone electrophoresis (CZE). Haloperidol is degraded by UV-light irradiation, and 4-(p-chlorophenyl)-4-hydroxypiperidine (CPHP) is generated from Haloperidol. When the irradiated solution was analyzed by CZE, residual Haloperidol and two degraded products were detected. The acid dissociation constant of Haloperidol was determined through the electrophoretic mobility of the residual Haloperidol, and the pKa value determined was similar to that measured under no degradation conditions, as well as literature values. It was also confirmed that one of the degraded products was assigned to CPHP based on the migration time, the electrophoretic mobility, and its acid dissociation constant analyzed. It was demonstrated in this study that the acid dissociation constants are accurately determined by using CZE, even under degraded conditions of the analyte. The experimental process involved the reaction of 4-(4-Chlorophenyl)piperidin-4-ol(cas: 39512-49-7).Name: 4-(4-Chlorophenyl)piperidin-4-ol

The Article related to haloperidol photodegradation acid dissociation constant capillary zone electrophoresis, Pharmaceutical Analysis: Synthetic Organic Compounds and other aspects.Name: 4-(4-Chlorophenyl)piperidin-4-ol

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Gitto, Rosaria; De Luca, Laura; Mancuso, Francesca; Del Prete, Sonia; Vullo, Daniela; Supuran, Claudiu T.; Capasso, Clemente published an article in 2019, the title of the article was Seeking new approach for therapeutic treatment of cholera disease via inhibition of bacterial carbonic anhydrases: experimental and theoretical studies for sixteen benzenesulfonamide derivatives.Recommanded Product: 4-(4-Chlorophenyl)piperidin-4-ol And the article contains the following content:

A series of sixteen benzenesulfonamide derivatives has been synthesized and tested as inhibitors of Vibrio cholerae carbonic anhydrase (CA) enzymes, belonging to α-CA, β-CA, and γ-CA classes (VchCAα, VchCAβ, and VchCAγ). The determined Ki values were compared to those of selected human CA isoforms (hCA I and hCA II). Structure-affinity relationship anal. highlighted that all tested compounds proved to be active inhibitors of VchCAα at nanomolar concentration The VchCAβ activity was lower to respect inhibitory efficacy toward VchCAα, whereas, these benzenesulfonamide derivatives failed to inhibit VchCAγ. Interestingly, compound combined the best activity toward VchCAα and VchCAβ. In order to obtain a model for binding mode of our inhibitors toward bacterial CAs, we carried out docking simulations by using the available crystal structures of VchCAβ. The experimental process involved the reaction of 4-(4-Chlorophenyl)piperidin-4-ol(cas: 39512-49-7).Recommanded Product: 4-(4-Chlorophenyl)piperidin-4-ol

The Article related to benzene sulfonamide derivative preparation carbonic anhydrase inhibitor cholera, carbonic anhydrase inhibitors (cais), benzenesulfonamides, molecular docking, Pharmacology: Effects Of Antimicrobials and Parasiticides and other aspects.Recommanded Product: 4-(4-Chlorophenyl)piperidin-4-ol

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Guo, Yi-An; Lee, Wonchul; Krische, Michael J. published an article in 2017, the title of the article was Enantioselective Synthesis of Oxetanes Bearing All-Carbon Quaternary Stereocenters via Iridium-Catalyzed C-C Bond-Forming Transfer Hydrogenation.Related Products of 39512-49-7 And the article contains the following content:

Oxetanes bearing all-carbon quaternary stereocenters are readily prepared through the iridium-catalyzed anti-diastereo- and enantioselective C-C coupling of primary alcs. and isoprene oxide. Based on this methodol., an oxetane containing analog of haloperidol was prepared A related azetidine formation is also described. The experimental process involved the reaction of 4-(4-Chlorophenyl)piperidin-4-ol(cas: 39512-49-7).Related Products of 39512-49-7

The Article related to enantioselective synthesis oxetane, iridium catalyst coupling primary alc isoprene oxide, enantioselectivity, iridium, oxetane, quaternary center, transfer hydrogenation, Heterocyclic Compounds (One Hetero Atom): 4-Membered Rings and other aspects.Related Products of 39512-49-7

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