Month: November 2022

Liang, Honggang published the artcileSynthesis of Cyanamides from Cyanogen Bromide under Mild Conditions through N-Cyanation of Allylic Tertiary Amines, Computed Properties of 2451-91-4, the publication is Synlett (2017), 28(19), 2675-2679, database is CAplus.

Cyanamides were selectively formed through a one-step nucleophilic substitution reaction of allylic tertiary amines with cyanogen bromide. Because of the mild reaction conditions and good yields of the reaction, as well as the com. availability of the starting materials, this new method represented a valuable tool for the synthesis of cyanamides through an N-deallylation reaction and an N-cyanation reaction in one pot.

Synlett published new progress about 2451-91-4. 2451-91-4 belongs to amides-buliding-blocks, auxiliary class Nitrile,Amine,Benzene, name is N,N-Dibenzylcyanamide, and the molecular formula is C15H14N2, Computed Properties of 2451-91-4.

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

Priestley, E. Scott published the artcileDiscovery of Two Novel Antiplatelet Clinical Candidates (BMS-986120 and BMS-986141) That Antagonize Protease-Activated Receptor 4, Quality Control of 14294-10-1, the publication is Journal of Medicinal Chemistry (2022), 65(13), 8843-8854, database is CAplus and MEDLINE.

Herein, the optimization of a series of imidazothiadiazole PAR4 antagonists to a first-in-class clin. candidate, BMS-986120 I, and a backup clin. candidate, BMS-986141 II was described. Both compounds demonstrated excellent antithrombotic efficacy and minimal bleeding time prolongation in monkey models relative to the clin. important antiplatelet agent clopidogrel and provide a potential opportunity to improve the standard of care in the treatment of arterial thrombosis.

Journal of Medicinal Chemistry published new progress about 14294-10-1. 14294-10-1 belongs to amides-buliding-blocks, auxiliary class Morpholine,Thiourea,Amine,Amide, name is Morpholine-4-carbothioamide, and the molecular formula is C5H10N2OS, Quality Control of 14294-10-1.

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

Ghosal, Somnath published the artcileIn silico bioinformatics analysis for identification of differentially expressed genes and therapeutic drug molecules in Glucocorticoid-resistant Multiple myeloma, Quality Control of 169590-42-5, the publication is Medical Oncology (New York, NY, United States) (2022), 39(5), 53, database is CAplus and MEDLINE.

Multiple myeloma (MM), second most common hematol. malignancy, still remains irremediable because of acquisition of drug resistance. Glucocorticoid (GC) therapy, which is used as one of the key therapies against MM, is hindered by the incidence of GC resistance. The underlying mechanism of this acquired GC resistance in MM is not fully elucidated. Therefore, the present study was aimed to identify the differentially expressed genes (DEGs), associated micro RNAs (miRNAs), and transcription factors (TFs) from the microarray datasets of GC-resistant and GC-sensitive MM cell lines, obtained from Gene Expression Omnibus (GEO) database. DEGs were identified using GEO2R tool from two datasets and common DEGs were obtained by constructing Venn diagram. Then the Gene ontol. (GO) and pathway enrichment anal. were performed using DAVID database. Genetic alterations in DEGs were examined using COSMIC database. Protein-protein interaction (PPI) network of DEGs was constructed using STRING database and Cytoscape tool. Network of interaction of DEGs and miRNAs as well as TFs were obtained and constructed using mirDIP, TRRUST, and miRNet tools. Drug gene interaction was studied to identify potential drug mols. by DGIdb tool. Six common DEGs, CDKN1A, CDKN2A, NLRP11, BTK, CD52, and RELN, were found to be significantly upregulated in GC-resistant MM and selected for further anal. miRNA anal. detected hsa-mir-34a-5p that could interact with maximum target DEGs. Two TFs, Sp1 and Sp3, were found to regulate the expression of selected DEGs. The entire study may provide a new understanding about the GC resistance in MM.

Medical Oncology (New York, NY, United States) published new progress about 169590-42-5. 169590-42-5 belongs to amides-buliding-blocks, auxiliary class Sulfamide,Immunology/Inflammation,COX, name is 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C17H14F3N3O2S, Quality Control of 169590-42-5.

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

Geyer, Charles E. Jr. published the artcileDefinitive results of a phase III adjuvant trial comparing six cycles of FEC-100 to four cycles of AC in women with operable node-negative breast cancer: the NSABP B-36 trial (NRG Oncology), Product Details of C17H14F3N3O2S, the publication is Breast Cancer Research and Treatment (2022), 193(3), 555-564, database is CAplus and MEDLINE.

Results from adjuvant trials evaluating 6 cycles of epirubicin-based chemotherapy regimens suggested these programs may be more effective than 4 cycles of doxorubicin-based chemotherapy. NSABP B-36 was a phase III clin. trial originally designed as a 2 x 2 factorial study comparing 6 cycles of 5-FU, epirubicin, and cyclophosphamide (FEC-100) to 4 cycles of conventional doxorubicin and cyclophoshamide (AC) with celecoxib or placebo. Shortly after activation, concerns regarding increased cardiovascular risks among selective COX-2 inhibitors resulted in a decision to remove the celecoxib/placebo from the trial. Women with histol. node-neg. invasive breast cancer who had undergone primary surgery with a lumpectomy or total mastectomy were eligible. Primary endpoint was disease-free survival (DFS). Between May 2004 and July 2008, 2722 patients were enrolled. Administration of FEC-100 did not result in improvement in DFS compared to AC (HR 1.09; 95% CI 0.92-1.29, p value = 0.31). The effect of FEC-100 compared to AC on DFS was significantly different for receptor-pos. (HR 1.32, 95% CI 1.05-1.66) compared to receptor-neg. patients (HR 0.86, 95% CI 0.66-1.11) (treatment-by-receptor status interaction p value = 0.02). There was no statistically significant difference in the effect of treatment on overall survival (OS) with FEC-100 compared to AC (HR 1.06; 95% CI 0.84-1.35, p value = 0.61). Overall, Grade 3 and 4 adverse events were more frequent in the FEC-100 group. The results of B-36 do not support use of six-cycle anthracycline-based regimens in node-neg. breast cancer. Prolongation of anthracycline-based therapy with FEC-100 does not improve DFS or OS, relative to AC for 4 cycles, and was associated with expected increases in toxicity. A statistically significant interaction between treatment and hormone receptor status favoring AC in hormone-receptor-pos. breast cancers is consistent with the hypothesis that optimal duration of chemotherapy may be four cycles in these patients. Late cardiac events and deaths prior to recurrence or second cancer were infrequent on both arms, but slightly higher with FEC-100.

Breast Cancer Research and Treatment published new progress about 169590-42-5. 169590-42-5 belongs to amides-buliding-blocks, auxiliary class Sulfamide,Immunology/Inflammation,COX, name is 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C17H14F3N3O2S, Product Details of C17H14F3N3O2S.

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

Bhumireddy, Archana published the artcileDesign, synthesis, and biological evaluation of phenyl thiazole-based AR-V7 degraders, Safety of Morpholine-4-carbothioamide, the publication is Bioorganic & Medicinal Chemistry Letters (2022), 128448, database is CAplus and MEDLINE.

Multiple Splice variants of AR have been reported in the past few years. These splice variants are upregulated in most cases of CRPC resulting in poor prognosis. Most of these variants lack the ligand binding domain (LBD) but still bind to DNA resulting in constitutive activation of downstream targets. The AR-V7 splice variant has been characterized extensively and current clin. trials in CRPC are exploring the use of AR-V7 as a biomarker. New therapeutic mols. that selectively target AR-V7 are also being explored. However, there is a dearth of information available on the selectivity, phenotypic responses in AR-V7 dependent cell lines and pharmacokinetic properties of such mols. Using our proprietary computational algorithms and rational SAR optimization, we have developed a potent and selective AR-V7 degrader from a known AR DNA binding domain (DBD) binder. This mol. effectively degraded AR-V7 in a CRPC cell line and demonstrated good oral bioavailability in mouse PK studies. This tool compound can be used to evaluate the pharmacol. effects of AR-V7 degraders. Further exploration of SAR can be pursued to develop more optimized lead compounds

Bioorganic & Medicinal Chemistry Letters published new progress about 14294-10-1. 14294-10-1 belongs to amides-buliding-blocks, auxiliary class Morpholine,Thiourea,Amine,Amide, name is Morpholine-4-carbothioamide, and the molecular formula is C5H10N2OS, Safety of Morpholine-4-carbothioamide.

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

Li, Huifang published the artcileCorrection to Discovery of Small-Molecule Inhibitors Selectively Targeting the DNA-Binding Domain of the Human Androgen Receptor [Erratum to document cited in CA161:328452], Application of Morpholine-4-carbothioamide, the publication is Journal of Medicinal Chemistry (2017), 60(3), 1225, database is CAplus and MEDLINE.

In the original publication on page 6458, The abstract graphic shows the incorrect isomer; the correction is provided here. In the original publication on Page 6460, In line 22 of the right-hand column, the group should be “-OCH₃” instead of “-OCHH₃“; the correction is provided here. In the original publication, on page 6461,In lines 9 and 35 of the left-hand column, the compound should be “2,4-dibromoimidazole” instead of “4,5-dibromoimidazole”; the correction is provided here. In the original publication, on page 6462, in table 3, the structure for ring A in the compound is incorrect; the correction is provided here. In the original publication on Page 6463, Figure 3D is incorrect; the correction is provided here. In the original publication, ob Page 6464, In the right-hand column in the second line from the bottom, the compound should be “4-(4-(2,4-Dibromo-1Himidazol-1-yl)thiazol-2-yl)morpholine instead of “4-(4-(4,5-Dibromo-1H-imidazol-1-yl)thiazol-2-yl)morpholine”; the correction is provided here.

Journal of Medicinal Chemistry published new progress about 14294-10-1. 14294-10-1 belongs to amides-buliding-blocks, auxiliary class Morpholine,Thiourea,Amine,Amide, name is Morpholine-4-carbothioamide, and the molecular formula is C5H10N2OS, Application of Morpholine-4-carbothioamide.

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

Li, Huifang published the artcileDiscovery of Small-Molecule Inhibitors Selectively Targeting the DNA-Binding Domain of the Human Androgen Receptor, COA of Formula: C5H10N2OS, the publication is Journal of Medicinal Chemistry (2014), 57(15), 6458-6467, database is CAplus and MEDLINE.

The human androgen receptor (AR) is considered as a master regulator in the development and progression of prostate cancer (PCa). As resistance to clin. used anti-AR drugs remains a major challenge for the treatment of advanced PCa, there is a pressing need for new anti-AR therapeutic avenues. In this study, we identified a binding site on the DNA binding domain (DBD) of the receptor and utilized virtual screening to discover a set of micromolar hits for the target. Through further exploration of the most potent hit (1), a structural analog (6) was identified demonstrating 10-fold improved anti-AR potency. Further optimization resulted in a more potent synthetic analog (25) with anti-AR potency comparable to a newly FDA-approved drug Enzalutamide. Site-directed mutagenesis demonstrated that the developed inhibitors do interact with the intended target site. Importantly, the AR DBD inhibitors could effectively inhibit the growth of Enzalutamide-resistant cells as well as block the transcriptional activity of constitutively active AR splice variants, such as V7.

Journal of Medicinal Chemistry published new progress about 14294-10-1. 14294-10-1 belongs to amides-buliding-blocks, auxiliary class Morpholine,Thiourea,Amine,Amide, name is Morpholine-4-carbothioamide, and the molecular formula is C5H10N2OS, COA of Formula: C5H10N2OS.

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

Alexander, Rikki published the artcile4-(1,3-Thiazol-2-yl)morpholine derivatives as inhibitors of phosphoinositide 3-kinase, Quality Control of 14294-10-1, the publication is Bioorganic & Medicinal Chemistry Letters (2008), 18(15), 4316-4320, database is CAplus and MEDLINE.

4-(1,3-Thiazol-2-yl)morpholine derivatives have been identified as potent and selective inhibitors of phosphoinositide 3-kinase. The SAR data of selected examples are presented and the in vivo profiling of compound 18 (I) is shown to demonstrate the utility of this class of compounds in xenograft models of tumor growth.

Bioorganic & Medicinal Chemistry Letters published new progress about 14294-10-1. 14294-10-1 belongs to amides-buliding-blocks, auxiliary class Morpholine,Thiourea,Amine,Amide, name is Morpholine-4-carbothioamide, and the molecular formula is C5H10N2OS, Quality Control of 14294-10-1.

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

Abuelhassan, Suzan published the artcileSynthesis, characterization, and biological activities of some novel thienylpyrido[3′,2′:4,5]thieno[3,2-d]pyrimidines and related heterocycles, Formula: C2H4ClNO, the publication is Journal of Heterocyclic Chemistry (2021), 58(9), 1784-1801, database is CAplus.

3-Cyano-5-ethoxycarbonyl-6-methyl-4-(2′-thienyl)-pyridine-2(1H)-thione was synthesized and reacted with chloroacetonitrile or chloroacetamide to give I [R¹ = cyano, carbamoyl; R² = amino], resp. Cyclocondensation of I [R¹ = carbamoyl; R² = amino] with triethylorthoformate produced the corresponding pyridothienopyrimidineone II [R³ = hydroxy], which on heating with phosphorus oxychloride gave 4-chloropyrimidine derivative II [R³ =chloro]. Compound II [R³ = chloro] was used as key intermediate for synthesizing compounds II [R³ = sulfanyl, hydrazino, piperidyl, morpholino, (3-phenyl-1H-1,2,4-triazol-5-yl)sulfanyl] upon treatment with some nucleophilic reagents such as thiourea, hydrazine hydrate, piperidine, morpholine, or 5-phenyl-s-triazole-3(1H)-thione, resp. Reaction of pyridothienopyrimidinethione II [R³ = sulfanyl] with N-(4-tolyl)-2-chloroacetamide or Et bromoacetate afforded the corresponding S-substituted methylsulfanylpyrimidines II [R³ = [2-(4-methylanilino)-2-oxo-ethyl]sulfanyl, (2-ethoxy-2-oxo-ethyl)sulfanyl]. The condensation of I [R¹ = cyano; R² = amino] with triethylorthoformate gave azomethine derivative I [R¹ = cyano; R² = ethoxymethyleneamino], which was reacted with hydrazine hydrate to give compound III [R⁴ = amino]. Compounds II [R³ = hydrazino] and III [R⁴ = amino] were used as precursors for synthesizing other new thienylpyridothienopyrimidines as well as isomeric thienyl-s-triazolopyridothieno- pyrimidines. All synthesized compounds were characterized by elemental and spectral analyses such as IR, ¹H NMR, and ¹³C NMR. In addition, majority of synthesized compounds were tested for their antifungal activity against five strains of fungi. Moreover, compounds I [R¹ = carbamoyl; R² = amino], II [R³ = chloro, sulfanyl, (2-ethoxy-2-oxo-ethyl)sulfanyl], and III [R⁴ = 2-thienylmethyleneamino] were screened for their anticancer activity against HEPG-2 and MCF-7 cell lines.

Journal of Heterocyclic Chemistry published new progress about 79-07-2. 79-07-2 belongs to amides-buliding-blocks, auxiliary class Chloride,Amine,Aliphatic hydrocarbon chain,Amide,Inhibitor, name is 2-Chloroacetamide, and the molecular formula is C2H4ClNO, Formula: C2H4ClNO.

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

Cooper, Geoffrey K. published the artcileAn ortho-directing effect in the nucleophilic aromatic substitution reactions of primary and secondary 2,4-dichloro- and 2,3,4-trichlorobenzamides with ethanethiolate, Computed Properties of 2447-79-2, the publication is Synthetic Communications (1995), 25(6), 899-906, database is CAplus.

The reactions of the primary and secondary 2,4-dichlorobenzamides and 2,3,4-trichlorobenzamides with potassium ethanethiolate in DMF were shown to proceed with a remarkable degree of ortho-regioselectivity. This effect was found to be absent using related tertiary amides as substrates. For example, treatment of 2,3,4-trichlorobenzamide with potassium ethanethiolate in DMF gave 3,4-dichloro-2-(ethylthio)benzamide.

Synthetic Communications published new progress about 2447-79-2. 2447-79-2 belongs to amides-buliding-blocks, auxiliary class Chloride,Amine,Benzene,Amide, name is 2,4-Dichlorobenzamide, and the molecular formula is C7H5Cl2NO, Computed Properties of 2447-79-2.

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