Category: 1197171-76-8

Pike, Kurt G. published the artcileOptimization of potent and selective dual mTORC1 and mTORC2 inhibitors: The discovery of AZD8055 and AZD2014, Computed Properties of 1197171-76-8, the publication is Bioorganic & Medicinal Chemistry Letters (2013), 23(5), 1212-1216, database is CAplus and MEDLINE.

The optimization of a potent and highly selective series of dual mTORC1 and mTORC2 inhibitors is described. An initial focus on improving cellular potency while maintaining or improving other key parameters, such as aqueous solubility and margins over hERG IC₅₀, led to the discovery of the clin. candidate AZD8055. Further optimization, particularly aimed at reducing the rate of metabolism in human hepatocyte incubations, resulted in the discovery of the clin. candidate AZD2014.

Bioorganic & Medicinal Chemistry Letters published new progress about 1197171-76-8. 1197171-76-8 belongs to amides-buliding-blocks, auxiliary class Boronic acid and ester,Amine,Benzene,Amide,Boronate Esters,Boronic Acids,Boronic acid and ester,, name is N-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, and the molecular formula is C14H20BNO3, Computed Properties of 1197171-76-8.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Hu, Shengquan published the artcileDesign, synthesis and biological evaluation of 4-aryl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one derivatives as a PI3Kα inhibitor, Quality Control of 1197171-76-8, the publication is Biological & Pharmaceutical Bulletin (2019), 42(6), 1013-1018, database is CAplus and MEDLINE.

A series of 4-aryl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one derivatives I [R = Ph, 6-amino-3-pyridyl, 2-amino-1,3-benzoxazol-5-yl, etc.] were designed as a phosphoinositide 3-kinase α (PI3Kα) inhibitor by scaffold hopping. The target compounds I were synthesized from di-Et malonate and Et chloroacetate by nucleophilic substitution, ring-closure, chlorination and Suzuki reaction, etc. The biol. activities of compounds I were evaluated with cytotoxic activity in vitro on Uppsala 87 Malignant Glioma (U87MG) and prostate cancer-3 (PC-3) by cell counting kit-8 (CCK-8). The results showed that compound I [R = 6-amino-3-pyridyl] displayed higher inhibition than pos. control PI-103, and high PI3Kα inhibitory activity with IC₅₀ of 113 ± 9nM in same order of magnitude as BEZ235. In addition, the LogK_ow values and mol. docking studies were performed to further investigate drug-like properties of target compounds I and interactions between compound I [R = 6-amino-3-pyridyl] and PI3Kα.

Biological & Pharmaceutical Bulletin published new progress about 1197171-76-8. 1197171-76-8 belongs to amides-buliding-blocks, auxiliary class Boronic acid and ester,Amine,Benzene,Amide,Boronate Esters,Boronic Acids,Boronic acid and ester,, name is N-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, and the molecular formula is C14H20BNO3, Quality Control of 1197171-76-8.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Wang, Ruifeng published the artcileDesign, synthesis, biological evaluation and molecular docking study of novel thieno[3,2-d]pyrimidine derivatives as potent FAK inhibitors, Formula: C14H20BNO3, the publication is European Journal of Medicinal Chemistry (2020), 112024, database is CAplus and MEDLINE.

A series of 2,7-disubstituted thieno[3,2-d]pyrimidine derivatives I [R¹ = 2-methoxy, 3-acetyl, 3-methylsulfonyl, etc.], II [R² = methylcarbamoyl, piperidine-3-carbonylamino, diethoxyphosphorylmethyl, etc.], III [R³ = H, Me, ethoxy, etc.; R⁴ = H, fluoro, methyl; R⁵ = H, fluoro] and IV [R⁶ = pyrrolidin-3-yl, tetrahydro-2H-pyran-4-yl, piperidin-3-ylmethyl, etc.] were synthesized and evaluated as novel focal adhesion kinase (FAK) inhibitors. The novel 2,7-disubstituted thieno[3,2-d]pyrimidine scaffold was designed as a new kinase inhibitor platform that mimics the bioactive conformation of the well-known diaminopyrimidine motif. Most of the compounds potently suppressed the enzymic activities of FAK and potently inhibited the proliferation of U-87MG, A-549 and MDA-MB-231 cancer cell lines. Among these derivatives, the optimized compound III [R³ = R⁵ = H, R⁴ = fluoro] potently inhibited the enzyme (IC₅₀ = 28.2 nM) and displayed stronger potency than TAE-226 in U-87MG, A-549 and MDA-MB-231 cells, with IC₅₀ values of 0.16, 0.27, and 0.19μM, resp. Compound III [R³ = R⁵ = H, R⁴ = fluoro] also exhibited relatively less cytotoxicity (IC₅₀ = 3.32μM) toward a normal human cell line, HK2. According to the flow cytometry results, compound III [R³ = R⁵ = H, R⁴ = fluoro] induced the apoptosis of MDA-MB-231 cells in a dose-dependent manner and effectively arrested MDA-MB-231 cells in G0/G1 phase. Further investigations revealed that compound III [R³ = R⁵ = H, R⁴ = fluoro] potently suppressed the migration of MDA-MB-231 cells. Collectively, these data support the further development of compound III [R³ = R⁵ = H, R⁴ = fluoro] as a lead compound for FAK-targeted anticancer drug discovery.

European Journal of Medicinal Chemistry published new progress about 1197171-76-8. 1197171-76-8 belongs to amides-buliding-blocks, auxiliary class Boronic acid and ester,Amine,Benzene,Amide,Boronate Esters,Boronic Acids,Boronic acid and ester,, name is N-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, and the molecular formula is C10H15ClO3S, Formula: C14H20BNO3.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Liu, Yinyin published the artcileDesign and synthesis of alkyl substituted pyridino[2,3-D]pyrimidine compounds as PI3Kα/mTOR dual inhibitors with improved pharmacokinetic properties and potent in vivo antitumor activity, SDS of cas: 1197171-76-8, the publication is Bioorganic & Medicinal Chemistry (2018), 26(14), 3992-4000, database is CAplus and MEDLINE.

Using pyridino[2,3-D]pyrimidine as the core, total 13 pyridino[2,3-D]pyrimidine derivatives with different alkyl substituents at C2 site have been designed and synthesized to search for novel PI3Kα/mTOR dual inhibitors. Most of the target compounds showed potent mTOR inhibition activity with IC₅₀ values ranging from single to double digit nanomole. Five target compounds exhibited pronounced PI3Kα inhibition activity. In vitro cellular assay indicated that most of the target compounds showed excellent antiproliferative activity, especially I whose potency against SKOV3 was 8-fold higher than the pos. control AZD8055. In vitro metabolic stability study found that I had a comparable stability to that of AZD8055. More importantly, I showed better antitumor activity and pharmacokinetic properties in vivo as compared with AZD8055.

Bioorganic & Medicinal Chemistry published new progress about 1197171-76-8. 1197171-76-8 belongs to amides-buliding-blocks, auxiliary class Boronic acid and ester,Amine,Benzene,Amide,Boronate Esters,Boronic Acids,Boronic acid and ester,, name is N-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, and the molecular formula is C14H20BNO3, SDS of cas: 1197171-76-8.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Wang, Xiao-Meng published the artcileSynthesis and antitumor activities evaluation of m-(4-morpholinoquinazolin-2-yl)benzamides in vitro and in vivo, Application of N-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, the publication is European Journal of Medicinal Chemistry (2015), 382-395, database is CAplus and MEDLINE.

In the present study, a series of m-(4-morpholinoquinazolin-2-yl)benzamides were designed, synthesized, and characterized. The antiproliferative activities of the synthesized compounds were evaluated against two human cell lines (HCT-116 and MCF-7). Compounds with IC₅₀ values below 4 μM were further evaluated against U-87 MG and A549 cell lines. Among these evaluated compounds, compound I displayed a remarkable antiproliferative effect in vitro. The hoechst staining assay showed that compound I caused morphol. changes. The cell cycle and apoptosis assay further indicated that compound I can arrest HCT-116 cells in G2/M and G0/G1 phase and induce apoptosis. PI3K enzyme assays indicated that compounds I and II selectively inhibit PI3Kα. A Western bolt assay further suggested that compound I can block the PI3K/Akt/mTOR pathway. Moreover, compound I inhibited tumor growth on a mice S180 homograft model. These findings directly identify m-(4-morpholinoquinazolin-2-yl)benzamide derivatives as novel anticancer agents.

European Journal of Medicinal Chemistry published new progress about 1197171-76-8. 1197171-76-8 belongs to amides-buliding-blocks, auxiliary class Boronic acid and ester,Amine,Benzene,Amide,Boronate Esters,Boronic Acids,Boronic acid and ester,, name is N-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, and the molecular formula is C18H28B2O4, Application of N-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Cusumano, Corinne K. published the artcileTreatment and prevention of urinary tract infection with orally active FimH inhibitors, Recommanded Product: N-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, the publication is Science Translational Medicine (2011), 3(109), ra115, 10 pp., database is CAplus and MEDLINE.

Chronic and recurrent urinary tract infections pose a serious medical problem because there are few effective treatment options. Patients with chronic urinary tract infections are commonly treated with long-term prophylactic antibiotics that promote the development of antibiotic-resistant forms of uropathogenic Escherichia coli (UPEC), further complicating treatment. We developed small-mol. weight compounds termed mannosides that specifically inhibit the FimH type 1 pilus lectin of UPEC, which mediates bacterial colonization, invasion, and formation of recalcitrant intracellular bacterial communities in the bladder epithelium. Here, we optimized these compounds for oral bioavailability and demonstrated their fast-acting efficacy in treating chronic urinary tract infections in a preclin. murine model. These compounds also prevented infection in vivo when given prophylactically and strongly potentiated the activity of the current standard of care therapy, trimethoprim-sulfamethoxazole, against clin. resistant PBC-1 UPEC bacteria. These compounds have therapeutic efficacy after oral administration for the treatment of established urinary tract infections in vivo. Their unique mechanism of action-targeting the pilus tip adhesin FimH-circumvents the conventional requirement for drug penetration of the outer membrane, minimizing the potential for the development of resistance. The small-mol. weight compounds described herein promise to provide substantial benefit to women suffering from chronic and recurrent urinary tract infections.

Science Translational Medicine published new progress about 1197171-76-8. 1197171-76-8 belongs to amides-buliding-blocks, auxiliary class Boronic acid and ester,Amine,Benzene,Amide,Boronate Esters,Boronic Acids,Boronic acid and ester,, name is N-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, and the molecular formula is C14H20BNO3, Recommanded Product: N-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Han, Zhenfu published the artcileLead Optimization Studies on FimH Antagonists: Discovery of Potent and Orally Bioavailable Ortho-Substituted Biphenyl Mannosides, Computed Properties of 1197171-76-8, the publication is Journal of Medicinal Chemistry (2012), 55(8), 3945-3959, database is CAplus and MEDLINE.

Herein, we describe the X-ray structure-based design and optimization of biaryl mannoside FimH inhibitors. Diverse modifications to the biaryl ring to improve druglike phys. and pharmacokinetic properties of mannosides were assessed for FimH binding affinity based on their effects on hemagglutination and biofilm formation along with direct FimH binding assays. Substitution on the mannoside Ph ring ortho to the glycosidic bond results in large potency enhancements several-fold higher than those of corresponding unsubstituted matched pairs and can be rationalized from increased hydrophobic interactions with the FimH hydrophobic ridge (Ile13) or “tyrosine gate” (Tyr137 and Tyr48) also lined by Ile52. The lead mannosides have increased metabolic stability and oral bioavailability as determined from in vitro PAMPA predictive model of cellular permeability and in vivo pharmacokinetic studies in mice, thereby representing advanced preclin. candidates with promising potential as novel therapeutics for the clin. treatment and prevention of recurring urinary tract infections.

Journal of Medicinal Chemistry published new progress about 1197171-76-8. 1197171-76-8 belongs to amides-buliding-blocks, auxiliary class Boronic acid and ester,Amine,Benzene,Amide,Boronate Esters,Boronic Acids,Boronic acid and ester,, name is N-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, and the molecular formula is C14H20BNO3, Computed Properties of 1197171-76-8.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Vantourout, Julien C. published the artcileChan-Evans-Lam Amination of Boronic Acid Pinacol (BPin) Esters: Overcoming the Aryl Amine Problem, Category: amides-buliding-blocks, the publication is Journal of Organic Chemistry (2016), 81(9), 3942-3950, database is CAplus and MEDLINE.

The Chan-Evans-Lam reaction is a valuable C-N bond forming process. However, aryl boronic acid pinacol (BPin) ester reagents can be difficult coupling partners that often deliver low yields, in particular in reactions with aryl amines. Herein, we report effective reaction conditions for the Chan-Evans-Lam amination of aryl BPin with alkyl and aryl amines. A mixed MeCN/EtOH solvent system was found to enable effective C-N bond formation using aryl amines while EtOH is not required for the coupling of alkyl amines.

Journal of Organic Chemistry published new progress about 1197171-76-8. 1197171-76-8 belongs to amides-buliding-blocks, auxiliary class Boronic acid and ester,Amine,Benzene,Amide,Boronate Esters,Boronic Acids,Boronic acid and ester,, name is N-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, and the molecular formula is C15H21BO2, Category: amides-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Bisht, Ranjana published the artcileAmide Effects in C-H Activation: Noncovalent Interactions with L-Shaped Ligand for meta Borylation of Aromatic Amides, COA of Formula: C14H20BNO3, the publication is Angewandte Chemie, International Edition (2018), 57(48), 15762-15766, database is CAplus and MEDLINE.

Borylated aromatic amides 3-pinBC₆H_4-nX_nCONR₂ (6a–t; X = halo, CN, Ph, benzo, MeO) were prepared by meta C-H activation/borylation of amides X_nC₆H_5-nCONR₂ with B₂pin₂, catalyzed by [Ir₂(cod)₂(μ-OMe)₂]/L¹ with up to 99% regioselectivity. A new concept for the meta-selective iridium-catalyzed borylation of aromatic amides is described. It has been demonstrated that while esters gave para-borylated products, amides lead to meta borylations. For achieving high meta selectivity, an L-shaped bifunctional ligand I (L¹) has been employed and engages in an O…K noncovalent interaction with the oxygen atom of the moderately distorted amide carbonyl group. This interaction provides exceptional control for providing up to 99% selective formation of meta-borylated products.

Angewandte Chemie, International Edition published new progress about 1197171-76-8. 1197171-76-8 belongs to amides-buliding-blocks, auxiliary class Boronic acid and ester,Amine,Benzene,Amide,Boronate Esters,Boronic Acids,Boronic acid and ester,, name is N-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, and the molecular formula is C14H20BNO3, COA of Formula: C14H20BNO3.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Partridge, Benjamin M. published the artcileSterically controlled iodination of arenes via iridium-catalyzed C-H borylation, Safety of N-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, the publication is Organic Letters (2013), 15(1), 140-143, database is CAplus and MEDLINE.

A mild method to prepare aryl and heteroaryl iodides by sequential C-H borylation and iodination is reported. The regioselectivity of this process is controlled by steric effects on the C-H borylation step and is complementary to existing methods to form aryl iodides. The iodination of boronic esters has potential for the synthesis of radiolabeled aryl iodides, as demonstrated by the concise synthesis of a potential tracer for SPECT imaging.

Organic Letters published new progress about 1197171-76-8. 1197171-76-8 belongs to amides-buliding-blocks, auxiliary class Boronic acid and ester,Amine,Benzene,Amide,Boronate Esters,Boronic Acids,Boronic acid and ester,, name is N-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, and the molecular formula is C14H20BNO3, Safety of N-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics