Tag: M.W=500-550

Fukunishi, Yoshifumi published the artcilePrediction of Synthetic Accessibility Based on Commercially Available Compound Databases, COA of Formula: C21H17ClF4N4O4, the publication is Journal of Chemical Information and Modeling (2014), 54(12), 3259-3267, database is CAplus and MEDLINE.

A compound’s synthetic accessibility (SA) is an important aspect of drug design, since in some cases computer-designed compounds cannot be synthesized. There have been several reports on SA prediction, most of which have focused on the difficulties of synthetic reactions based on retro-synthesis analyses, reaction databases and the availability of starting materials. The authors developed a new method of predicting SA using com. available compound databases and mol. descriptors. SA was estimated from the probability of existence of substructures consisting of the compound in question, the number of symmetry atoms, the graph complexity, and the number of chiral centers of the compound The probabilities of the existence of given substructures were estimated based on a compound library. The predicted SA results reproduced the expert manual assessments with a Pearson correlation coefficient of 0.56. Since the authors method required a compound database and not a reaction database, it should be easy to customize the prediction for compound vendors. The correlation between the sales price of approved drugs and the SA values was also examined and weak. The price most likely depends on the total cost of development and other factors.

Journal of Chemical Information and Modeling published new progress about 1019206-88-2. 1019206-88-2 belongs to amides-buliding-blocks, auxiliary class Protein Tyrosine Kinase/RTK,VEGFR, name is 4-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)-3-fluorophenoxy)-N-methylpicolinamide hydrate, and the molecular formula is C21H17ClF4N4O4, COA of Formula: C21H17ClF4N4O4.

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

Tsuchiya, Ayako published the artcileIntracellularly transported adenosine induces apoptosis in MCF-7 human breast cancer cells by accumulating AMID in the nucleus, Formula: C27H29N5O5, the publication is Cancer Letters (New York, NY, United States) (2012), 321(1), 65-72, database is CAplus and MEDLINE.

Extracellular adenosine induced apoptosis of MCF-7 human breast cancer cells in a concentration (10 μM-10 mM)- and treatment time (24-72 h)-dependent manner, and the effect was inhibited by the adenosine transporter inhibitor dipyridamole, but not an inhibitor of adenosine kinase, an inhibitor of AMP-activated protein kinase, or inhibitors for A₁, A_2a, A_2b, and A₃ adenosine receptors. No significant activation of caspase-7, -8, or -9 was obtained with adenosine. Adenosine promoted translocation of apoptosis-inducing factor (AIF)-homologous mitochondrion-associated inducer of death (AMID) from the cytosol into the nucleus, although the total amount of AMID was not affected. Adenosine-induced MCF-7 cell death was abrogated by knocking-down AMID. The results of the present study indicate that intracellularly transported adenosine induces MCF-7 cell apoptosis by accumulating AMID in the nucleus in a caspase-independent manner.

Cancer Letters (New York, NY, United States) published new progress about 264622-53-9. 264622-53-9 belongs to amides-buliding-blocks, auxiliary class GPCR/G Protein,Adenosine Receptor, name is N-(4-Acetylphenyl)-2-(4-(2,6-dioxo-1,3-dipropyl-2,3,6,9-tetrahydro-1H-purin-8-yl)phenoxy)acetamide, and the molecular formula is C12H20O6, Formula: C27H29N5O5.

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

Kitabatake, Kazuki published the artcileInvolvement of CD73 and A2B receptor in radiation-induced DNA damage response and cell migration in human glioblastoma A172 cells, Computed Properties of 264622-53-9, the publication is Biological & Pharmaceutical Bulletin (2021), 44(2), 197-210, database is CAplus.

Glioblastoma is the most common malignant tumor of the central nervous system and is treated with a combination of surgery, radiation and chemotherapy. However, the tumor often acquires radiation resistance, which is characterized by an increased DNA damage response (DDR). Here, we show that CD73, which generates extracellular adenosine from ATP, and A2B receptor, which is activated by adenosine, are involved in the γ-radiation-induced DDR and the enhanced migration ability of human glioblastoma cell line A172. To investigate DDR, we evaluated ataxia telangiectasia mutated (ATM) activation and focus formation of histone H2A isoform γ (γH2AX) and p53-binding protein 1 (53BP1) in the nucleus of A172 cells after γ-irradiation Antagonists of A2B receptor and CD73, or knockdown with small interfering RNA (siRNA), suppressed γ-radiation-induced DDR and promoted γ-radiation-induced cell death, as well as suppressing γ-radiation-induced cell migration and actin remodeling. These results suggest that activation of A2B receptor by extracellular adenosine generated via CD73 promotes γ-radiation-induced DDR, leading to recovery from DNA damage, and also enhances cell migration and actin remodeling. The CD73-A2B receptor pathway may be a promising target for overcoming radiation resistance and the acquisition of malignant phenotypes during radiotherapy of glioblastoma.

Biological & Pharmaceutical Bulletin published new progress about 264622-53-9. 264622-53-9 belongs to amides-buliding-blocks, auxiliary class GPCR/G Protein,Adenosine Receptor, name is N-(4-Acetylphenyl)-2-(4-(2,6-dioxo-1,3-dipropyl-2,3,6,9-tetrahydro-1H-purin-8-yl)phenoxy)acetamide, and the molecular formula is C27H29N5O5, Computed Properties of 264622-53-9.

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

Kim, Yong-Chul published the artcileAnilide derivatives of an 8-phenylxanthine carboxylic congener are highly potent and selective antagonists at human A_2B adenosine receptors, Category: amides-buliding-blocks, the publication is Journal of Medicinal Chemistry (2000), 43(6), 1165-1172, database is CAplus and MEDLINE.

No highly selective antagonists of the A_2B adenosine receptor (AR) have been reported; however such antagonists have therapeutic potential as antiasthmatic agents. Here the synthesis of potent and selective A_2B receptor Antagonists is reported. The structure-activity relationships (SAR) of 8-phenyl-1,3-di-(n-propyl)xanthine derivatives in binding to recombinant human A_2B ARs in HEK-293 cells (HEK-A_2B) and at other AR subtypes were explored. Various amide derivatives of 8-[4-[[carboxymethyl]oxy]phenyl]-1,3-di(n-propyl)xanthine, I (R₁ = n-Pr, X = OCH₂, R₂ = OH) (II), were synthesized. A comparison of aryl, alkyl, and aralkyl amides demonstrated that simple anilides, particularly those substituted in the para-position with electron-withdrawing groups, such as nitro, cyano, and acetyl, bind selectively to human A_2B receptors in the range of 1-3 nM. The unsubstituted anilide I (R₁ = n-Pr, X = OCH₂, R₂ = NHPh) had a K_i value at A_2B receptors of 1.48 nM but was only moderately selective vs. human A₁/A_2A receptors and nonselective vs. rat A₁ receptors. Highly potent and selective A_2B antagonists were a p-aminoacetophenone derivative I (R₁ = n-Pr, X = OCH₂, R₂ = 4-MeOC₆H₄NH) (K_i value 1.39 nM) and a p-cyanoanilide I (R₁ = n-Pr, X = OCH₂, R₂ = NHC₆H₄CN-4) (III) (K_i value 1.97 nM). Compound III was 400-, 245-, and 123-fold selective for human A_2B receptors vs. human A₁/A_2A/A₃ receptors, resp., and 8.5- and 310-fold selective vs. rat A₁/A_2A receptors, resp. Substitution of the 1,3-di-Pr groups with 1,3-di-Et offered no disadvantage for selectivity, and high affinities at A_2B receptors were maintained. Substitution of the p-carboxymethyloxy group of II and its amides with acrylic acid decreased affinity at A_2B receptors while increasing affinity at A₁ receptors. 1,3-Di(cyclohexylmethyl) groups greatly reduced affinity at ARs, although the p-carboxymethyloxy derivative I (R₁ = cyclohexylmethyl, X = CH:CH, R₂ = OH) was moderately selective for A_2B receptors. Several selective A_2B antagonists inhibited NECA-stimulated calcium mobilization in HEK-A_2B cells.

Journal of Medicinal Chemistry published new progress about 264622-53-9. 264622-53-9 belongs to amides-buliding-blocks, auxiliary class GPCR/G Protein,Adenosine Receptor, name is N-(4-Acetylphenyl)-2-(4-(2,6-dioxo-1,3-dipropyl-2,3,6,9-tetrahydro-1H-purin-8-yl)phenoxy)acetamide, and the molecular formula is C27H29N5O5, Category: amides-buliding-blocks.

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

Rich, Rebecca L. published the artcileBiacore analysis with stabilized G-protein-coupled receptors, Recommanded Product: N-(4-Acetylphenyl)-2-(4-(2,6-dioxo-1,3-dipropyl-2,3,6,9-tetrahydro-1H-purin-8-yl)phenoxy)acetamide, the publication is Analytical Biochemistry (2011), 409(2), 267-272, database is CAplus and MEDLINE.

Using stabilized forms of β₁ adrenergic and A_2A adenosine G-protein-coupled receptors, we applied Biacore to monitor receptor activity and characterize binding constants of small-mol. antagonists spanning more than 20,000-fold in affinity. We also illustrate an improved method for tethering His-tagged receptors on NTA (carboxymethylated dextran preimmobilized with nitrilotriacetic acid) chips to yield stable, high-capacity, high-activity surfaces as well as a novel approach to regenerate receptor binding sites. Based on our success with this approach, we expect that the combination of stabilized receptors with biosensor technol. will become a common method for characterizing members of this receptor family.

Analytical Biochemistry published new progress about 264622-53-9. 264622-53-9 belongs to amides-buliding-blocks, auxiliary class GPCR/G Protein,Adenosine Receptor, name is N-(4-Acetylphenyl)-2-(4-(2,6-dioxo-1,3-dipropyl-2,3,6,9-tetrahydro-1H-purin-8-yl)phenoxy)acetamide, and the molecular formula is C27H29N5O5, Recommanded Product: N-(4-Acetylphenyl)-2-(4-(2,6-dioxo-1,3-dipropyl-2,3,6,9-tetrahydro-1H-purin-8-yl)phenoxy)acetamide.

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

Kiec-Kononowicz, K. published the artcileNew developments in A₁ and A₂ adenosine receptor antagonists, Application of N-(4-Acetylphenyl)-2-(4-(2,6-dioxo-1,3-dipropyl-2,3,6,9-tetrahydro-1H-purin-8-yl)phenoxy)acetamide, the publication is Pure and Applied Chemistry (2001), 73(9), 1411-1420, database is CAplus.

A review with references The aim of this article is to briefly present progress in the development of the potent adenosine receptor (AR) antagonists with high selectivity for either Al, A_2A or A_2B ARs. The structural requirements for each AR subtype were discussed as well as their potential therapeutic use. In the search for new AR antagonists. series of imidazo-, pyrimido-, and diazepino-purindione derivatives as well as oxazolo-, oxazino-, and oxazepino-purindiones were designed, synthesized, and preliminarily evaluated in pharmacol. studies. Oxygen-containing tricyclic derivatives were shown to be moderately potent AR antagonists exhibiting selectivity either for A₁ or A_2A ARs. Tricyclic purindiones with nitrogen in the third ring were generally more A₂A AR selective. The compounds tested in vivo according to the Antiepileptic Drug Development Program of the National Institutes of Health (USA) were generally active as anticonvulsants in chem. induced seizures.

Pure and Applied Chemistry published new progress about 264622-53-9. 264622-53-9 belongs to amides-buliding-blocks, auxiliary class GPCR/G Protein,Adenosine Receptor, name is N-(4-Acetylphenyl)-2-(4-(2,6-dioxo-1,3-dipropyl-2,3,6,9-tetrahydro-1H-purin-8-yl)phenoxy)acetamide, and the molecular formula is C27H29N5O5, Application of N-(4-Acetylphenyl)-2-(4-(2,6-dioxo-1,3-dipropyl-2,3,6,9-tetrahydro-1H-purin-8-yl)phenoxy)acetamide.

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

Coppi, Elisabetta published the artcileAdenosine A_2B receptors inhibit K⁺ currents and cell differentiation in cultured oligodendrocyte precursor cells and modulate sphingosine-1-phosphate signaling pathway, Related Products of amides-buliding-blocks, the publication is Biochemical Pharmacology (Amsterdam, Netherlands) (2020), 113956, database is CAplus and MEDLINE.

Oligodendrocytes are the only myelinating cells in the brain and differentiate from their progenitors (OPCs) throughout adult life. However, this process fails in demyelinating pathologies. Adenosine is emerging as an important player in OPC differentiation and we recently demonstrated that adenosine A_2A receptors inhibit cell maturation by reducing voltage-dependent K⁺ currents. No data are available to date about the A_2B receptor (A_2BR) subtype. The bioactive lipid mediator sphingosine-1-phosphate (S1P) and its receptors (S1P_1-5) are also crucial modulators of OPC development. An interaction between this pathway and the A_2BR is reported in peripheral cells. We studied the role of A_2BRs in modulating K⁺ currents and cell differentiation in OPC cultures and we investigated a possible interplay with S1P signaling. Our data indicate that the A_2BR agonist BAY60-6583 and its new analog P453 inhibit K⁺ currents in cultured OPC and the effect was prevented by the A_2BR antagonist MRS1706, by K⁺ channel blockers and was differently modulated by the S1P analog FTY720-P. An acute (10 min) exposure of OPCs to BAY60-6583 also increased the phosphorylated form of sphingosine kinase 1 (SphK1). A chronic (7 days) treatment with the same agonist decreased OPC differentiation whereas SphK1/2 inhibition exerted the opposite effect. Furthermore, A_2BR was overexpressed during OPC differentiation, an effect prevented by the pan SphK1/2 inhibitor VPC69047. Finally, A_2BR silenced cells showed increased cell maturation, decreased SphK1 expression and enhanced S1P lyase levels. We conclude that A_2BRs inhibit K⁺ currents and cell differentiation and pos. modulate S1P synthesis in cultured OPCs.

Biochemical Pharmacology (Amsterdam, Netherlands) published new progress about 264622-53-9. 264622-53-9 belongs to amides-buliding-blocks, auxiliary class GPCR/G Protein,Adenosine Receptor, name is N-(4-Acetylphenyl)-2-(4-(2,6-dioxo-1,3-dipropyl-2,3,6,9-tetrahydro-1H-purin-8-yl)phenoxy)acetamide, and the molecular formula is C27H29N5O5, Related Products of amides-buliding-blocks.

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

Coppi, Elisabetta published the artcileAdenosine A_2B receptors inhibit K⁺ currents and cell differentiation in cultured oligodendrocyte precursor cells and modulate sphingosine-1-phosphate signaling pathway, Related Products of amides-buliding-blocks, the publication is Biochemical Pharmacology (Amsterdam, Netherlands) (2020), 113956, database is CAplus and MEDLINE.

Oligodendrocytes are the only myelinating cells in the brain and differentiate from their progenitors (OPCs) throughout adult life. However, this process fails in demyelinating pathologies. Adenosine is emerging as an important player in OPC differentiation and we recently demonstrated that adenosine A_2A receptors inhibit cell maturation by reducing voltage-dependent K⁺ currents. No data are available to date about the A_2B receptor (A_2BR) subtype. The bioactive lipid mediator sphingosine-1-phosphate (S1P) and its receptors (S1P_1-5) are also crucial modulators of OPC development. An interaction between this pathway and the A_2BR is reported in peripheral cells. We studied the role of A_2BRs in modulating K⁺ currents and cell differentiation in OPC cultures and we investigated a possible interplay with S1P signaling. Our data indicate that the A_2BR agonist BAY60-6583 and its new analog P453 inhibit K⁺ currents in cultured OPC and the effect was prevented by the A_2BR antagonist MRS1706, by K⁺ channel blockers and was differently modulated by the S1P analog FTY720-P. An acute (10 min) exposure of OPCs to BAY60-6583 also increased the phosphorylated form of sphingosine kinase 1 (SphK1). A chronic (7 days) treatment with the same agonist decreased OPC differentiation whereas SphK1/2 inhibition exerted the opposite effect. Furthermore, A_2BR was overexpressed during OPC differentiation, an effect prevented by the pan SphK1/2 inhibitor VPC69047. Finally, A_2BR silenced cells showed increased cell maturation, decreased SphK1 expression and enhanced S1P lyase levels. We conclude that A_2BRs inhibit K⁺ currents and cell differentiation and pos. modulate S1P synthesis in cultured OPCs.

Biochemical Pharmacology (Amsterdam, Netherlands) published new progress about 264622-53-9. 264622-53-9 belongs to amides-buliding-blocks, auxiliary class GPCR/G Protein,Adenosine Receptor, name is N-(4-Acetylphenyl)-2-(4-(2,6-dioxo-1,3-dipropyl-2,3,6,9-tetrahydro-1H-purin-8-yl)phenoxy)acetamide, and the molecular formula is C27H29N5O5, Related Products of amides-buliding-blocks.

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