Tag: 300-400

On April 23, 2009, Gottschling, Dirk; Dahmann, Georg; Doods, Henri; Heimann, Annekatrin; Mueller, Stephan Georg; Rudolf, Klaus; Schaenzle, Gerhard; Stenkamp, Dirk published a patent.Safety of Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate The title of the patent was Preparation of 4-aminopyrimidines as CGRP antagonists. And the patent contained the following:

Title compounds I [R1 = spirocylic heterocycles with provisos; R2 = H, alkyl, etc.; R3 = aryl, heteroaryl, etc.; U = N, N-oxide, etc.; V = N, N-oxide, etc.; X = N, N-oxide, etc.; Y = N, C-R7; R7 = H, halo, alkyl] and their pharmaceutically acceptable salts and formulations were prepared For example, N-arylation of a piperidine II and chloropyrimidine III afforded claimedaminopyrimidine IV in 55% yield. In CGRP inhibition assays, 2-examples of compounds I exhibited Ki values of 6 and 27 nM. The experimental process involved the reaction of Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate(cas: 883984-95-0).Safety of Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate

The Article related to aminopyrimidine preparation cgrp antagonist, Heterocyclic Compounds (More Than One Hetero Atom): Pyrimidines and Quinazolines and other aspects.Safety of Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On April 5, 2012, Inoue, Yasunao; Konishi, Yasuko published a patent.HPLC of Formula: 883984-95-0 The title of the patent was Preparation of polycyclic spiro-piperidine derivatives as M1 and M4 agonists. And the patent contained the following:

Disclosed are compounds I [R1 = (un)substituted alkyl; R2-R4 = H, halo, (un)substituted alkyl, etc.; R5 = H, (un)substituted alkyl, (un)substituted cycloalkyl, etc.; R6, R7 = H or (un)substituted alkyl; R6 and R7, together with the carbon atom to which they are attached, may combine to form C:O group with a proviso that when Y is oxygen, R6 and R7, together with the carbon atom to which they are attached, may combine to form C:O group; m, n = 1-3; A = single bond or CH2; X = NH, oxygen or sulfur atom; Y = CR8R9 or oxygen atom; R8, R9 = H or alkyl; or pharmaceutically acceptable salts thereof], useful for the treatment of Alzheimer disease and schizophrenia. For example, compound II was prepared via reaction of N-tert-butoxycarbonylpiperidone with tri-Et phosphonoacetate followed by treatment with DBU, amidation with 2-amino-3-bromopyridine, Pd(OAc)2-catalyzed cyclization, dealkoxycarbonylation using HCl, and reaction with Et 4-formylpiperidine-1-carboxylate/NaBH(OAc)3. Compound II exhibited agonistic activities of 89%, 66%, 21%, and 138% (at 1 μM) for M1, M2, M3, and M4, resp. The experimental process involved the reaction of Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate(cas: 883984-95-0).HPLC of Formula: 883984-95-0

The Article related to polycyclic spiro piperidine preparation m1 m4 agonist, alzheimer disease schizophrenia treatment polycyclic spiro piperidine, Heterocyclic Compounds (More Than One Hetero Atom): Oxazines (Including Morpholine) and other aspects.HPLC of Formula: 883984-95-0

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 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

On April 20, 2006, Burgey, Christopher S.; Deng, James Z.; Potteiger, Craig; Williams, Theresa M. published a patent.Recommanded Product: Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate The title of the patent was Preparation of oxohomopiperidinyl oxospiropiperidinepyrrolopyridinecarboxamides and related compounds as calcitonin gene-related peptide (CGRP) receptor antagonists.. And the patent contained the following:

Title compounds [I; A = bond, C(R2)2, O, SOm, NR2; B = [C(R2)2]n; R1, R2 = H, (substituted) alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl; pairs of R2 may form rings; R3 = H, F, cyano, (substituted) alkyl, CO2R4; R4 = H, (substituted) alkyl, fluoroalkyl, cycloalkyl, aryl, heteroaryl, PhCH2; X = C, S; Y = O, (R4)2, NCN, NHSO2Me, NCONH2; or Y = O2 when X = S; J = bond, C(R6)2, O, NR6; V = bond, C(R6)2, O, SOm, NR6, NR6NR6, etc.; Q = CR7a, C(R7A)2, CO, SOm, N, NR7a; T = CR7b, C(R7b)2, CO, SOm, N, NR7b; R6 = H, halo, OR4, CO2R4, alkyl, cycloalkyl, (substituted) aryl, heteroaryl, heterocyclyl, etc.; R7a, R7b = R2; R7aR7b = atoms to form cycloalkyl, aryl, heterocyclyl, heteroaryl rings; m = 0-2; n = 0, 1], were prepared for treatment of headache (no data). Thus, (3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepan-2-one (preparation given) and 4-nitrophenyl chloroformate in THF at 0° were treated with Et3N; after 60 min. spiro[piperidine-4,3′-pyrrolo[2,3-b]pyridin]-2′(1’H)-one dihydrochloride (preparation given) and Et3N in CHCl3 were added followed by warming to room temperature to give title compound (II). The experimental process involved the reaction of Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate(cas: 883984-95-0).Recommanded Product: Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate

The Article related to oxoazepanyl oxospiropiperidinepyrrolopyridinecarboxamide preparation cgrp receptor antagonist, headache treatment oxohomopiperidinyl spiropiperidinepyrrolopyridinecarboxamide preparation and other aspects.Recommanded Product: Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On January 14, 2021, Tong, Youzhi; Lai, Luhua published a patent.SDS of cas: 1216805-11-6 The title of the patent was C-myc protein inhibitor, and preparation method therefor and use thereof. And the patent contained the following:

Provided are a c-Myc protein inhibitor, and a preparation method therefor and use thereof. The c-Myc protein inhibitor selectively inhibits c-Myc protein. Therefore, the inhibitor can be used for prevention and treatment of diseases related to c-Myc protein disorders, such as cancers, cardiovascular and cerebrovascular diseases, diseases related to virus infection. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).SDS of cas: 1216805-11-6

The Article related to amino acid boronic acid boronate derivative preparation, myc protein inhibitor amino acid boronic acid boronate derivative, antitumor activity amino acid boronic acid boronate derivative and other aspects.SDS of cas: 1216805-11-6

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On September 21, 2018, Mowrey, Dale R.; Reif, James J.; Milkiewicz, Karen L.; Allwein, Shawn P. published an article.Related Products of 883984-95-0 The title of the article was Development of a Novel Process for the Kilogram-Scale Synthesis of Spiro[1H-pyrido[2,3-d][1,3]oxazine-4,4′-piperidine]-2-one. And the article contained the following:

The dihydrochloride of spiro[1H-pyrido[2,3-d][1,3]oxazine-4,4′-piperidine]-2-one I·2 HCl was prepared on kilogram scale by base-mediated Boc protection of 3-bromo-2-pyridinamine, metalation with i-PrMgCl and spirocyclization with 1-Boc-4-piperidinone, and Boc deprotection with aqueous HCl in isopropanol. A two-batch kilo lab campaign generated I·2 HCl in >99% HPLC area purity and in 77% overall yield. The experimental process involved the reaction of Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate(cas: 883984-95-0).Related Products of 883984-95-0

The Article related to spiropyridooxazinepiperidinone kilogram scale preparation, butoxycarbonylation bromopyridinamine metalation spirocyclization butoxycarbonylpiperidone neutralization kilogram scale and other aspects.Related Products of 883984-95-0

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

On September 21, 2006, Paone, Daniel V.; Nguyen, Diem N.; Shaw, Anthony W.; Burgey, Christopher S.; Tucker, Thomas J.; Graham, Samuel L. published a patent.Name: Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate The title of the patent was Preparation of oxoimidazopyridylpiperidinylcarbonylaminopyridones and related compounds as calcitonin gene-related peptide (CGRP) receptor antagonists. And the patent contained the following:

Title compounds [I; Z = Q1, Q2; A = N, CR2; B = O, S; R1, R2, R7a, R7b = H, (substituted) alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl; R1R2, R2R2 = atoms to form rings; R3 = H, F, cyano, CO2R4, (substituted) alkyl; W = O, NR4, C(R4)2; X = C, S; Y = O, (R4)2, NCN, NCONH2, O2; J = bond, C(R6)2, O, NR6; V = bond, C(R6)2, O, S, SO, SO2, NR6, etc.; GL = N, NC(R6)2, C:CR6, CN, CR6, etc.; Q = CR7a, C(R7a)2, CO, S, SO, SO2, N, NR7a; T = CR7b, C(R7b)2, CO, S, SO, SO2, N, NR7b; with provisos], were prepared for treatment of headache, migraine, and cluster headache. Thus, N-(5-bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-yl)-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide (preparation given), phenylboronic acid, diisopropylamine, Pd(OAc)2, and 3,3′,3”-phosphinidynetris(benzenesulfonic acid) trisodium salt were heated in DMF/H2O at 80° for 18 h to give N-(1-methyl-2-oxo-5-phenyl-1,2-dihydropyridin-3-yl)-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide as the trifluoroacetate. I generally antagonized CGRP receptors with Ki or IC50 values of ≤50 μM. The experimental process involved the reaction of Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate(cas: 883984-95-0).Name: Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate

The Article related to oxoimidazopyridylpiperidinylcarbonylaminopyridone preparation calcitonin gene related peptide antagonist, cgrp antagonist pyridone oxoimidazopyridyl piperidinyl carbamoyl preparation, piperidinecarboxamide oxopyridyl oxoimidazopyridyl preparation headache migraine treatment and other aspects.Name: Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On January 12, 2017, Bradner, James; Buckley, Dennis; Winter, Georg published a patent.Safety of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid The title of the patent was Preparation of bifunctional molecules for inducing targeted protein degradation. And the patent contained the following:

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).Safety of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid

The Article related to bifunctional compound preparation targeted protein degradation inducer cereblon binding, e3 ubiquitin ligase binding bifunctional compound preparation proliferative disorder, bromodomain brd4 protein degradation inducer bifunctional compound preparation and other aspects.Safety of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem