Day: November 21, 2022

Owens, Timothy D. published the artcileDiscovery of Reversible Covalent Bruton′s Tyrosine Kinase Inhibitors PRN473 and PRN1008 (Rilzabrutinib), Quality Control of 1971920-73-6, the publication is Journal of Medicinal Chemistry (2022), 65(7), 5300-5316, database is CAplus and MEDLINE.

Bruton′s tyrosine kinase (BTK), a Tec family tyrosine kinase, is critical in immune pathways as an essential intracellular signaling element, participating in both adaptive and immune responses. Currently approved BTK inhibitors are irreversible covalent inhibitors and limited to oncol. indications. Herein, we describe the design of covalent reversible BTK inhibitors and the discoveries of PRN473 (11) and rilzabrutinib (PRN1008, 12). These compounds have exhibited potent and durable inhibition of BTK, in vivo efficacy in rodent arthritis models, and clin. efficacy in canine pemphigus foliaceus. Compound 11 has completed phase 1 trials as a topical agent, and 12 is in phase 3 trials for pemphigus vulgaris and immune thrombocytopenia.

Journal of Medicinal Chemistry published new progress about 1971920-73-6. 1971920-73-6 belongs to piperidines, auxiliary class Other Aliphatic Heterocyclic,Piperidine,Alkenyl,Amine,Benzene,Ether,Inhibitor,Inhibitor, name is (R)-1-(1-Acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one, and the molecular formula is C26H25N5O3, Quality Control of 1971920-73-6.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Ball, Matthew published the artcileDevelopment of a Manufacturing Route to Avibactam, a β-Lactamase Inhibitor, Quality Control of 1416134-49-0, the publication is Organic Process Research & Development (2016), 20(10), 1799-1805, database is CAplus.

Process development work to provide an efficient, robust, and cost-effective manufacturing route to avibactam, a β-lactamase inhibitor is presented herewith. Aspects of this optimization work include the counterintuitive introduction of a protecting group to effect a difficult urea formation and the use of controlled feed hydrogenation conditions to facilitate an elegant one pot debenzylation and sulfation reaction. Overall, the com. process delivers avibactam in much improved yield with significant reduction in the environmental footprint.

Organic Process Research & Development published new progress about 1416134-49-0. 1416134-49-0 belongs to piperidines, auxiliary class Piperidine,Chiral,Amine,Benzene,Amide, name is (2S,5R)-5-((Benzyloxy)amino)piperidine-2-carboxamide, and the molecular formula is C13H19N3O2, Quality Control of 1416134-49-0.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Heald, Robert published the artcileNoncovalent Mutant Selective Epidermal Growth Factor Receptor Inhibitors: A Lead Optimization Case Study, Category: piperidines, the publication is Journal of Medicinal Chemistry (2015), 58(22), 8877-8895, database is CAplus and MEDLINE.

Because of their increased activity against activating mutants, first-generation epidermal growth factor receptor (EGFR) kinase inhibitors have had remarkable success in treating non-small-cell lung cancer (NSCLC) patients, but acquired resistance, through a secondary mutation of the gatekeeper residue, means that clin. responses only last for 8-14 mo. Addressing this unmet medical need requires agents that can target both of the most common double mutants: T790M/L858R (TMLR) and T790M/del(746-750) (TMdel). Herein we describe how a noncovalent double mutant selective lead compound was optimized using a strategy focused on the structure-guided increase in potency without added lipophilicity or reduction of three-dimensional character. Following successive rounds of design and synthesis it was discovered that cis-fluoro substitution on 4-hydroxy- and 4-methoxypiperidinyl groups provided synergistic, substantial, and specific potency gain through direct interaction with the enzyme and/or effects on the proximal ligand oxygen atom. Further development of the fluorohydroxypiperidine series resulted in the identification of a pair of diastereomers that showed 50-fold enzyme and cell based selectivity for T790M mutants over wild-type EGFR (wtEGFR) in vitro and pathway knock-down in an in vivo xenograft model.

Journal of Medicinal Chemistry published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C6H12N2O, Category: piperidines.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Marchand-Brynaert, Jacqueline published the artcileDesign and Synthesis of Functionalized Oxaziridines as Topological Analogs of Penicillins, Product Details of C19H21N, the publication is Israel Journal of Chemistry (2013), 29(2-3), 247-255, database is CAplus.

Oxaziridines were examined as potential alkylating inhibitors of bacterial serine D,D-peptidases. Structures were designed to mimic known β-lactam antibiotics taking into account stereoelectronic requirements for a nucleophilic attack on a three-membered ring. Novel oxaziridines equipped with functionalized side chains were prepared They showed poor antibacterial activities in vitro, perhaps as a result of their low chem. stability.

Israel Journal of Chemistry published new progress about 35661-58-6. 35661-58-6 belongs to piperidines, auxiliary class Piperidine,Benzene, name is 1-((9H-Fluoren-9-yl)methyl)piperidine, and the molecular formula is C19H21N, Product Details of C19H21N.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Marchand-Brynaert, Jacqueline published the artcileDesign and synthesis of functionalized oxaziridines as topological analogs of penicillins, SDS of cas: 35661-58-6, the publication is Israel Journal of Chemistry (1989), 29(2-3), 247-55, database is CAplus.

Oxaziridines were examined as potential alkylating inhibitors of bacterial serine D,D-peptidases. Structures were designed to mimic known β-lactam antibiotics taking into account stereoelectronic requirements for a nucleophilic attack on a 3-membered ring. Novel oxaziridines, e.g., I (R = CO₂CMe₃, fluorenylmethyloxycarbonyl, COCH₂Ph, COCH₂OPh; R¹ = Me, allyl, SiPh₂CMe₃), with functionalized side chains were prepared They showed poor antibacterial activity in vitro, perhaps, as a result of their low chem. stability.

Israel Journal of Chemistry published new progress about 35661-58-6. 35661-58-6 belongs to piperidines, auxiliary class Piperidine,Benzene, name is 1-((9H-Fluoren-9-yl)methyl)piperidine, and the molecular formula is C19H21N, SDS of cas: 35661-58-6.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Luxenburger, Andreas published the artcileDiscovery of AL-GDa62 as a Potential Synthetic Lethal Lead for the Treatment of Gastric Cancer, Related Products of piperidines, the publication is Journal of Medicinal Chemistry (2021), 64(24), 18114-18142, database is CAplus and MEDLINE.

Diffuse gastric cancer and lobular breast cancer are aggressive malignancies that are frequently associated with inactivating mutations in the tumor suppressor gene CDH1. Synthetic lethal (SL) vulnerabilities arising from CDH1 dysfunction represent attractive targets for drug development. Recently, SLEC-11 (1) emerged as a SL lead in E-cadherin-deficient cells. Here, we describe our efforts to optimize 1. Overall, 63 analogs were synthesized and tested for their SL activity toward isogenic mammary epithelial CDH1-deficient cells (MCF10A-CDH1^-/-). Among the 26 compounds with greater cytotoxicity, AL-GDa62 (3)(I) was four-times more potent and more selective than 1 with an EC₅₀ ratio of 1.6. Furthermore, 3 preferentially induced apoptosis in CDH1^-/- cells, and Cdh1^-/- mammary and gastric organoids were significantly more sensitive to 3 at low micromolar concentrations Thermal proteome profiling of treated MCF10A-CDH1^-/- cell protein lysates revealed that 3 specifically inhibits TCOF1, ARPC5, and UBC9. In vitro, 3 inhibited SUMOylation at low micromolar concentrations

Journal of Medicinal Chemistry published new progress about 14613-37-7. 14613-37-7 belongs to piperidines, auxiliary class Piperidine,Amine, name is (1-Methylpiperidin-3-yl)methanamine, and the molecular formula is C7H16N2, Related Products of piperidines.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Lachkar, David published the artcile2-(Selenocyanatomethyl)-2-propenol – A convenient synthon for ligation via the deselenative allylic rearrangement of allyl selenosulfides: preparation, functional group compatibility, and application, Related Products of piperidines, the publication is Canadian Journal of Chemistry (2012), 90(11), 944-953, database is CAplus.

The preparation and reactions of 2-(selenocyanatomethyl)-2-propenol are described and reveal the compatibility of the allylic selenocyanate group with a range of mild oxidizing and Lewis acidic conditions. 2-(Selenocyanatomethyl)-2-propenol and its derivatives are employed in the functionalization of simple and amino acid derived thiols in methanolicsoln. at room temperature to give 2-(hydroxymethyl)allyl sulfides in good to excellent yield.

Canadian Journal of Chemistry published new progress about 4972-31-0. 4972-31-0 belongs to piperidines, auxiliary class Piperidine,Benzene, name is 1-(Phenylsulfinyl)piperidine, and the molecular formula is C11H15NOS, Related Products of piperidines.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Tilley, Leon J. published the artcileA revised preparation of (4-acetamido-2,2,6,6-tetramethylpiperidin-1-yl)oxyl and 4-acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium tetrafluoroborate: reagents for stoichiometric oxidations of alcohols, Quality Control of 219543-09-6, the publication is Synthesis (2013), 45(3), 326-329, database is CAplus.

Revised preparations of (4-acetamido-2,2,6,6-tetramethylpiperidin-1-yl)oxyl and the corresponding oxoammonium salt, 4-acetamido-2,2,6,6-tetramethyl-1-oxoammonium tetrafluoroborate, are presented together with some of the important properties of these two oxidizing reagents.

Synthesis published new progress about 219543-09-6. 219543-09-6 belongs to piperidines, auxiliary class Piperidine,Fluoride,Salt,Amine,Amide, name is 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate, and the molecular formula is C8H16O2, Quality Control of 219543-09-6.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Pradhan, Priya P. published the artcileEne-like addition of an oxoammonium cation to alkenes: highly selective route to allylic alkoxyamines, SDS of cas: 219543-09-6, the publication is Organic Letters (2006), 8(24), 5485-5487, database is CAplus and MEDLINE.

The addition of oxoammonium cation of 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate in an ene-like fashion to trisubstituted alkenes afforded allylic alkoxyamines, e.g., I, in high yields.

Organic Letters published new progress about 219543-09-6. 219543-09-6 belongs to piperidines, auxiliary class Piperidine,Fluoride,Salt,Amine,Amide, name is 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate, and the molecular formula is C11H21BF4N2O2, SDS of cas: 219543-09-6.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Pradhan, Priya P. published the artcileOxidative Cleavage of Benzylic and Related Ethers, Using an Oxoammonium Salt, Synthetic Route of 219543-09-6, the publication is Journal of Organic Chemistry (2009), 74(24), 9524-9527, database is CAplus and MEDLINE.

Benzylic ethers and related ArCH₂OR substrates are oxidatively cleaved by 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (I) in wet CH₃CN at room temperature to give the corresponding aromatic aldehyde and alc. in high yield. Primary or secondary alc. products are further oxidized by I to give carboxylic acids and ketones, resp. The oxidation likely involves a formal hydride abstraction from the benzylic carbon as evidenced by slow reaction of substrates bearing electron-withdrawing substituents.

Journal of Organic Chemistry published new progress about 219543-09-6. 219543-09-6 belongs to piperidines, auxiliary class Piperidine,Fluoride,Salt,Amine,Amide, name is 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate, and the molecular formula is C11H21BF4N2O2, Synthetic Route of 219543-09-6.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem