Month: February 2023

Syntheses and properties of 2,3-dibromo- and 2,3-dichloro-1,8-naphthyridines was written by Czuba, Wladyslaw;Wozniak, Marian. And the article was included in Roczniki Chemii in 1973.Safety of 2-Bromo-3-chloro-1,8-naphthyridine This article mentions the following:

Naphthyridinol I with KClO3 in concentrated HCl at 50° yielded 73% II, which heated at 125° with POBr3 gave 80% III. Similarly, II refluxed with POCl3 gave 98% IV. III and p-MeC6H4SO2-NHNH2 refluxed 24 hr in CHCl3 yielded 82% V.HBr; a similar reaction attempted with IV failed. V.HBr refluxed with aqueous Na2CO3 gave 28% VI. Analogs of II, IV, V, and VI with Br in place of Cl were prepared similarly. In the experiment, the researchers used many compounds, for example, 2-Bromo-3-chloro-1,8-naphthyridine (cas: 52626-32-1Safety of 2-Bromo-3-chloro-1,8-naphthyridine).

2-Bromo-3-chloro-1,8-naphthyridine (cas: 52626-32-1) belongs to naphthyridine derivatives. Six naphthyridine isomers are white solids with a surprisingly wide span of melting points: 1,6-Naphthyridine’s is the lowest at <40 ºC; 2,6-naphthyridine’s is the highest at 114–115 ºC. Halogen atoms attached to the naphthyridine moiety can be easily replaced by other nucleophiles such as alkoxides and amines.Safety of 2-Bromo-3-chloro-1,8-naphthyridine

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Casein Kinase II exacerbates rheumatoid arthritis via promoting Th1 and Th17 cell inflammatory responses was written by Ye, Hua;Fu, Dongdong;Fang, Xiangyu;Xie, Yang;Zheng, Xi;Fan, Wenqiang;Hu, Fanlei;Li, Zhanguo. And the article was included in Expert Opinion on Therapeutic Targets in 2021.SDS of cas: 1009820-21-6 This article mentions the following:

ObjectivesStudies have demonstrated that CK2 is engaged in CD4⁺ T cell proliferation and activation. We investigated the potential involvement of CK2 in the pathogenesis of rheumatoid arthritis (RA). Peripheral blood and synovial fluid mononuclear cells (PBMC and SFMC) of RA patients, as well as splenocytes of collagen-induced arthritis (CIA) mice were treated with different doses of CK2 inhibitor CX4945 in vitro. Then, the Th1, Th2, Th17, and Treg cell responses were analyzed. In addition, CIA mice were administrated with CX4945 via oral gavage. Accordingly, the arthritis scores, bone destruction, tissue damage, and the CD4⁺ T cell subsets were assessed. The expression of CK2 was upregulated in CD4⁺ T cells under RA circumstance. In vitro CX4945 treatment significantly inhibited the Th1 and Th17 cell responses, while promoted the Th2 cell responses in RA patient PBMC, SFMC and CIA mouse splenocytes, dampening IFN-γ and IL-17A production Moreover, administration of CX4945 ameliorated the severity of arthritis in CIA mice, along with decreased Th1 and Th17 cells. However, CX4945 seemed to have minimal effect on RA Treg cells. CK2 serves as an important regulator of the Th1 and Th17 cell axes in RA, thus contributing to the disease aggravation. In the experiment, the researchers used many compounds, for example, 5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid (cas: 1009820-21-6SDS of cas: 1009820-21-6).

5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid (cas: 1009820-21-6) belongs to naphthyridine derivatives. The naphthyridine ring system, being very π-deficient, is highly vulnerable towards nucleophilic attack, and consequently there has been extensive investigation of reactions involving nitrogen nucleophiles. Imidazonaphthyridines have been prepared through a ‘one-pot’ three-component ‘domino’ reaction between the keto-ester, acrolein, and ethylenediamine in presence of 4 Å molecular sieves. The corresponding thiazolonaphthyridine is obtained from a similar reaction using 2-aminoethanethiol and Dowex basic anion-exchange resin.SDS of cas: 1009820-21-6

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

ROCK2-Specific Inhibitor KD025 Suppresses Adipocyte Differentiation by Inhibiting Casein Kinase 2 was written by Tran, Nhu Nguyen Quynh;Chun, Kwang-Hoon. And the article was included in Molecules in 2021.Application In Synthesis of 5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid This article mentions the following:

KD025, a ROCK2 isoform-specific inhibitor, has an anti-adipogenic activity which is not mediated by ROCK2 inhibition. To identify the target, we searched binding targets of KD025 by using the KINOMEscanTM screening platform, and we identified casein kinase 2 (CK2) as a novel target. KD025 showed comparable binding affinity to CK2α (Kd = 128 nM). By contrast, CK2 inhibitor CX-4945 and ROCK inhibitor fasudil did not show such cross-reactivity. In addition, KD025 effectively inhibited CK2 at a nanomolar concentration (IC₅₀ = 50 nM). We examined if the inhibitory effect of KD025 on adipocyte differentiation is through the inhibition of CK2. Both CX-4945 and KD025 suppressed the generation of lipid droplets and the expression of proadipogenic genes Pparg and Cebpa in 3T3-L1 cells during adipocyte differentiation. Fasudil exerted no significant effect on the quantity of lipid droplets, but another ROCK inhibitor Y-27632 increased the expression of Pparg and Cebpa. Both CX-4945 and KD025 acted specifically in the middle stage (days 1-3) but were ineffective when treated at days 0-1 or the late stages, indicating that CX-4945 and KD025 may regulate the same target, CK2. The mRNA and protein levels of CK2α and CK2β generally decreased in 3T3-L1 cells at day 2 but recovered thereafter. Other well-known CK2 inhibitors DMAT and quinalizarin inhibited effectively the differentiation of 3T3-L1 cells. Taken together, the results of this study confirmed that KD025 inhibits ROCK2 and CK2, and that the inhibitory effect on adipocyte differentiation is through the inhibition of CK2. In the experiment, the researchers used many compounds, for example, 5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid (cas: 1009820-21-6Application In Synthesis of 5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid).

5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid (cas: 1009820-21-6) belongs to naphthyridine derivatives. The naphthyridines and their derivatives exhibit various types of biological activity, and the organic chemistry has been frequently reviewed. Imidazonaphthyridines have been prepared through a ‘one-pot’ three-component ‘domino’ reaction between the keto-ester, acrolein, and ethylenediamine in presence of 4 Å molecular sieves. The corresponding thiazolonaphthyridine is obtained from a similar reaction using 2-aminoethanethiol and Dowex basic anion-exchange resin.Application In Synthesis of 5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

An eco-sustainable green approach for the synthesis of 2,6-naphthyridines under microwave irradiation was written by Srivastava, K. P.;Singh, Indu;Kumari, Anupma. And the article was included in Pharma Chemica in 2014.Application In Synthesis of 2,6-Naphthyridine This article mentions the following:

A microwave-promoted new easy, efficient, clean and environmentally benign method for the synthesis of 2,6-naphthyridine and its derivatives from 4-cyano-3-pyridylacetonitrile has been developed. The desired products were isolated in excellent yields and high purity under eco-friendly conditions. In the experiment, the researchers used many compounds, for example, 2,6-Naphthyridine (cas: 253-50-9Application In Synthesis of 2,6-Naphthyridine).

2,6-Naphthyridine (cas: 253-50-9) belongs to naphthyridine derivatives. The naphthyridine ring system, being very π-deficient, is highly vulnerable towards nucleophilic attack, and consequently there has been extensive investigation of reactions involving nitrogen nucleophiles. Imidazonaphthyridines have been prepared through a ‘one-pot’ three-component ‘domino’ reaction between the keto-ester, acrolein, and ethylenediamine in presence of 4 Å molecular sieves.Application In Synthesis of 2,6-Naphthyridine

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Phosphorescence of aromatic molecules was written by Knuts, Soeren;Agren, Hans;Minaev, Boris F.. And the article was included in Journal of Molecular Structure: THEOCHEM in 1994.Application of 253-50-9 This article mentions the following:

Quadratic response theory for singlet and triplet operators (O. Vahtras et al., 1992) was recently applied to series of small mols. as well as to several aromatic compounds A comparative anal. of the results of such calculations on the phosphorescence effect in benzene, naphthalene and various azabenzenes and azanaphthalenes is presented. The information gained from such calculations concerns polarization directions, oscillator strengths, radiative lifetimes and excitation energies for the triplet states. These quantities either refer to values averaged over the triplet states or to the specific triplet state spin sublevels. The vibronically induced phosphorescence problem, with specific reference to benzene phosphorescence which is forbidden both by spin and orbital symmetry and only allowed through the coupling of nuclear and electronic motions is also discussed. Results are compared with vapor phase data concerning total radiative lifetimes, and with data from phosphorescence microwave double resonance measurements of matrix isolated samples concerning the spin sublevel rates. In the experiment, the researchers used many compounds, for example, 2,6-Naphthyridine (cas: 253-50-9Application of 253-50-9).

2,6-Naphthyridine (cas: 253-50-9) belongs to naphthyridine derivatives. Six naphthyridine isomers are white solids with a surprisingly wide span of melting points: 1,6-Naphthyridine’s is the lowest at <40 ºC; 2,6-naphthyridine’s is the highest at 114–115 ºC. Very few metal complexes of naphthyridines other than 1,8-naphthyridine have been described.Application of 253-50-9

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Emerging JWA-targeted Pt(IV) prodrugs conjugated with CX-4945 to overcome chemo-immune-resistance was written by Chen, Feihong;Pei, Sinan;Wang, Xing;Zhu, Qian;Gou, Shaohua. And the article was included in Biochemical and Biophysical Research Communications in 2020.Application of 1009820-21-6 This article mentions the following:

Two Pt(IV) prodrugs, Cx-platin-Cl and Cx-DN604-Cl, derived from the conjugation of cisplatin or DN604 with a CK2 inhibitor CX-4945, were constructed to suppress DNA damage repair-related elements. During in vitro biol. studies, the Pt(IV) prodrugs had excellent cytotoxicity superior to cisplatin and DN604 to reverse drug resistance. Further mechanistic investigations revealed that the powerful anticancer activity of Cx-platin-Cl and Cx-DN604-Cl arisen from its suppression of JWA-XRCC1-mediated single-strand breaks repair. The emerging Pt(IV) prodrugs inhibited the growth of the xenografted tumors of C57BL6 and nude mice apart from JWA^-/- mice. Between them, Cx-platin-Cl augmented the infiltration and proliferation of T_eff cells, alleviated the recruitment of T_reg cells. The results provided compelling preclin. support that Cx-platin-Cl and Cx-DN604-Cl could reverse chemo-immune resistance via decaying JWA-XRCC1-mediated SSBR and immunosuppression, improving the development of emerging Pt(IV) candidate as a potential immunotherapeutic agent for cancer resistant prevention. In the experiment, the researchers used many compounds, for example, 5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid (cas: 1009820-21-6Application of 1009820-21-6).

5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid (cas: 1009820-21-6) belongs to naphthyridine derivatives. Six naphthyridine isomers are white solids with a surprisingly wide span of melting points: 1,6-Naphthyridine’s is the lowest at <40 ºC; 2,6-naphthyridine’s is the highest at 114–115 ºC. Halogen atoms attached to the naphthyridine moiety can be easily replaced by other nucleophiles such as alkoxides and amines.Application of 1009820-21-6

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Paramagnetic resonance of phosphorescent diazanaphthalenes. II. Crystal packing of 1,7- and 1,3-diazanaphthalenes in durene was written by McCool, Brian J.;Markey, B. R.;Bramley, Richard. And the article was included in Molecular Physics in 1984.Category: naphthyridine This article mentions the following:

The EPR spectra of the lowest triplet state of each of 1,3- and 1,7-diazanaphthalene in solid solution in durene single crystals at 97 K reveal deviations from perfect guest substitution. Crystal packing calculations using atom-atom potentials and allowing for host lattice relaxation confirm that guest rotations about the normal axis are to be expected and could be several tens of degrees away from perfect substitution. Guest center of mass positions can be up to 1 Å away from the inversion center of durene. The calculated potential curves with respect to this rotation show shallow potential min. corresponding to metastable sites. The broad, shallow features of the potential wells suggest that measurements at liquid N temperatures may well differ from those recorded at liquid He temperatures In the experiment, the researchers used many compounds, for example, 2,6-Naphthyridine (cas: 253-50-9Category: naphthyridine).

2,6-Naphthyridine (cas: 253-50-9) belongs to naphthyridine derivatives. Functionalized naphthyridines and their benzo/heterofused analogs are present in numerous marine products and reported to possess wide-ranging activities such as antiproliferative, antiaggressive, and HIV-1 integrase inhibition in addition to their use as anti-HCV agents. Imidazonaphthyridines have been prepared through a ‘one-pot’ three-component ‘domino’ reaction between the keto-ester, acrolein, and ethylenediamine in presence of 4 Å molecular sieves.Category: naphthyridine

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Combined Casein Kinase II inhibition and epigenetic modulation in acute B-lymphoblastic leukemia. was written by Richter, Anna;Roolf, Catrin;Hamed, Mohamed;Gladbach, Yvonne Saara;Sender, Sina;Konkolefski, Christoph;Knübel, Gudrun;Sekora, Anett;Fuellen, Georg;Vollmar, Brigitte;Murua Escobar, Hugo;Junghanss, Christian. And the article was included in BMC cancer in 2019.Name: 5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid This article mentions the following:

BACKGROUND: The tumor suppressor protein phosphatase and tensin homolog (PTEN) is a key regulator of the PI3K/AKT pathway which is frequently altered in a variety of tumors including a subset of acute B-lymphoblastic leukemias (B-ALL). While PTEN mutations and deletions are rare in B-ALL, promoter hypermethylation and posttranslational modifications are the main pathways of PTEN inactivation. Casein Kinase II (CK2) is often upregulated in B-ALL and phosphorylates both PTEN and DNA methyltransferase 3A, resulting in increased PI3K/AKT signaling and offering a potential mechanism for further regulation of tumor-related pathways. METHODS: Here, we evaluated the effects of CK2 inhibitor CX-4945 alone and in combination with hypomethylating agent decitabine on B-ALL proliferation and PI3K/AKT pathway activation. We further investigated if CX-4945 intensified decitabine-induced hypomethylation and identified aberrantly methylated biological processes after CK2 inhibition. In vivo tumor cell proliferation in cell line and patient derived xenografts was assessed by longitudinal full body bioluminescence imaging and peripheral blood flow cytometry of NSG mice. RESULTS: CX-4945 incubation resulted in CK2 inhibition and PI3K pathway downregulation thereby inducing apoptosis and anti-proliferative effects. CX-4945 further affected methylation patterns of tumor-related transcription factors and regulators of cellular metabolism. No overlap with decitabine-affected genes or processes was detected. Decitabine alone revealed only modest anti-proliferative effects on B-ALL cell lines, however, if combined with CX-4945 a synergistic inhibition was observed. In vivo assessment of CX-4945 in B-ALL cell line xenografts resulted in delayed proliferation of B-ALL cells. Combination with DEC further decelerated B-ALL expansion significantly and decreased infiltration in bone marrow and spleen. Effects in patient-derived xenografts all harboring a t(4;11) translocation were heterogeneous. CONCLUSIONS: We herein demonstrate the anti-leukemic potential of CX-4945 in synergy with decitabine in vitro as well as in vivo identifying CK2 as a potentially targetable kinase in B-ALL. In the experiment, the researchers used many compounds, for example, 5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid (cas: 1009820-21-6Name: 5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid).

5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid (cas: 1009820-21-6) belongs to naphthyridine derivatives. Six naphthyridine isomers exist, based on the positions of the nitrogen atoms; they can be in the 1,5, 1,6, 1,7, 1,8, 2,6, or 2,7 positions. 1,6-Naphthyridine and some of its derivatives have been reported to have medicinal, electronic, and catalytic properties. But none of these investigations has yet resulted in any practical applications. Very few metal complexes of naphthyridines other than 1,8-naphthyridine have been described.Name: 5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Bioanalytical method for vinpocetine and apovincamine acid from human plasma by LC-MS/MS was written by Dongare, B. B.;Kashid, B. B.;Ghanvat, A. A.. And the article was included in Journal of Applicable Chemistry (Lumami, India) in 2018.HPLC of Formula: 42971-09-5 This article mentions the following:

A sensitive and reproducible liquid chromatog.-electro spray ionization-tandem mass spectrometry (LC-MS/MS) method was developed for the quantification of vinpocetine (VP) and its active metabolite apovincamine acid (AVA) in human plasma, with racem Pr vinpocetine(VP-IS) and racem Pr apovincamine acid (AVA-IS) as an internal standard (IS). The analyte was extracted with Solid Phase Extraction using ion exchange cartridges and analyzed on a Zorbax SB-CN (250 mm × 4.6 mm, 5μm) column. The mobile phase was composed of methanol 10 mM ammonium acetate with 0.1% Formic Acid (70:30). Vinpocetine, apovincamine acid and IS racem Pr vinpocetine, racem Pr apovincamine acid were ionized by pos. ion pneumatically assisted electro spray and detected in the multi-reaction monitoring (MRM) mode using LC-MS/MS (API 5500 QTrap)→ productions of m/z 351.4→280.1, m/z 323.2→279.2, m/z 365.3→294.1 and m/z 337.1→293.2 resp. The specificity, matrix effect, recovery, sensitivity, linearity, accuracy, precision, and stabilities were all validated over the concentration range of 0.5-250.0 ng mL-1 for both vinpocetine and apovincamine acid. The method developed was successfully and demonstrated for evaluation of pharmacokinetic profile of vinpocetine and apovincamine acid in human plasma. In the experiment, the researchers used many compounds, for example, (41S,13aS)-Ethyl 13a-ethyl-2,3,41,5,6,13a-hexahydro-1H-indolo[3,2,1-de]pyrido[3,2,1-ij][1,5]naphthyridine-12-carboxylate (cas: 42971-09-5HPLC of Formula: 42971-09-5).

(41S,13aS)-Ethyl 13a-ethyl-2,3,41,5,6,13a-hexahydro-1H-indolo[3,2,1-de]pyrido[3,2,1-ij][1,5]naphthyridine-12-carboxylate (cas: 42971-09-5) belongs to naphthyridine derivatives. The naphthyridines have 10 delocalized π-electrons located in five molecular orbitals, each of which is distorted by the presence of the nitrogen atoms causing an electron drift in that direction. Enoxacin, nalidixic acid, and trovafloxacin are 1,8-naphthyridine derivatives with antibacterial properties related to the fluoroquinolones.HPLC of Formula: 42971-09-5

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Neuroprotective effects of novel nanosystems simultaneously loaded with vinpocetine and piracetam after intranasal administration was written by Nasr, Maha;Wahdan, Sara A.. And the article was included in Life Sciences in 2019.Synthetic Route of C22H26N2O2 This article mentions the following:

The study aim was to test the efficacy of a novel created hybrid nanosystem compared to other nanosystems in treatment of scopolamine induced memory impairment. The fabrication and characterization of nanoformulations (microemulsion, liposomes, ethosomes, transfersomes and transethosomes) coencapsulating two cognitive enhancers; piracetam and vinpocetine delivered intranasally, in addition to a novel nanocomposite microemulsion/vesicular nanoformulation was described. Formulations delivered the drugs across sheep nasal mucosa, with cumulative percentage reaching 29.99% for vinpocetine and 57.78% for piracetam. While the solution form of the drugs was totally ineffective, the selected transethosomal, microemulsion and nanocomposite formulations reversed the scopolamine induced effect on the step through latency of passive avoidance test and the spontaneous alternation behavior in Y maze test, further confirmed by histopathlogical examination All three nanoformulations significantly decreased the acetylcholinesterase activity and the extent of lipid peroxidation by 32-42%. The nanocomposite formulation was superior to the microemulsion and transethosomal formulations in its anti-inflammatory and antiapoptotic effects, delineated by higher extent of inhibition of COX-2 and caspase 3 expression resp. Results support the hypothesis that the novel microemulsion/vesicular nanocomposite system is a promising neuroprotective modality for intranasal brain targeting which is worthy of exploitation in other brain diseases. In the experiment, the researchers used many compounds, for example, (41S,13aS)-Ethyl 13a-ethyl-2,3,41,5,6,13a-hexahydro-1H-indolo[3,2,1-de]pyrido[3,2,1-ij][1,5]naphthyridine-12-carboxylate (cas: 42971-09-5Synthetic Route of C22H26N2O2).

(41S,13aS)-Ethyl 13a-ethyl-2,3,41,5,6,13a-hexahydro-1H-indolo[3,2,1-de]pyrido[3,2,1-ij][1,5]naphthyridine-12-carboxylate (cas: 42971-09-5) belongs to naphthyridine derivatives. The naphthyridines have 10 delocalized π-electrons located in five molecular orbitals, each of which is distorted by the presence of the nitrogen atoms causing an electron drift in that direction. 1,6-Naphthyridine and some of its derivatives have been reported to have medicinal, electronic, and catalytic properties. But none of these investigations has yet resulted in any practical applications.Synthetic Route of C22H26N2O2

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem