Day: October 17, 2022

COA of Formula: C6H3Cl2N3In 2017 ,《Novel pyrrolopyrimidines as Mps1/TTK kinase inhibitors for breast cancer》 appeared in Bioorganic & Medicinal Chemistry. The author of the article were Sugimoto, Yasuro; Sawant, Dwitiya B.; Fisk, Harold A.; Mao, Liguang; Li, Chenglong; Chettiar, Somsundaram; Li, Pui-Kai; Darby, Michael V.; Brueggemeier, Robert W.. The article conveys some information:

New targeted therapy approaches for certain subtypes of breast cancer, such as triple-neg. breast cancers and other aggressive phenotypes, are desired. High levels of the mitotic checkpoint kinase Mps1/TTK have correlated with high histol. grade in breast cancer, suggesting a potential new therapeutic target for aggressive breast cancers (BC). Novel small mols. targeting Mps1 were designed by computer assisted docking analyses, and several candidate compounds were synthesized. These compounds were evaluated in anti-proliferative assays of a panel of 15 breast cancer cell lines and further examined for their ability to inhibit a variety of Mps1-dependent biol. functions. The results indicate that the lead compounds have strong anti-proliferative potential through Mps1/TTK inhibition in both basal and luminal BC cell lines, exhibiting IC50 values ranging from 0.05 to 1.0 μM. In addition, the lead compounds 1 and 13 inhibit Mps1 kinase enzymic activity with IC50 values from 0.356 μM to 0.809 μM, and inhibited Mps1-associated cellular functions such as centrosome duplication and the spindle checkpoint in triple neg. breast cancer cells. The most promising analog, compound 13, significantly decreased tumor growth in nude mice containing Cal-51 triple neg. breast cancer cell xenografts. Using drug discovery technologies, computational modeling, medicinal chem., cell culture and in vivo assays, novel small mol. Mps1/TTK inhibitors have been identified as potential targeted therapies for breast cancers. In the experimental materials used by the author, we found 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4COA of Formula: C6H3Cl2N3)

2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. Pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics. COA of Formula: C6H3Cl2N3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Quality Control of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidineIn 2009 ,《Novel Class of LIM-Kinase 2 Inhibitors for the Treatment of Ocular Hypertension and Associated Glaucoma》 appeared in Journal of Medicinal Chemistry. The author of the article were Harrison, Bryce A.; Whitlock, N. Andrew; Voronkov, Michael V.; Almstead, Zheng Y.; Gu, Kun-Jian; Mabon, Ross; Gardyan, Michael; Hamman, Brian D.; Allen, Jason; Gopinathan, Suma; McKnight, Beth; Crist, Mike; Zhang, Yulian; Liu, Ying; Courtney, Lawrence F.; Key, Billie; Zhou, Julia; Patel, Nita; Yates, Phil W.; Liu, Qingyun; Wilson, Alan G. E.; Kimball, S. David; Crosson, Craig E.; Rice, Dennis S.; Rawlins, David B.. The article conveys some information:

The discovery of a pyrrolopyrimidine class of LIM-kinase 2 (LIMK2) inhibitors is reported. These LIMK2 inhibitors show good potency in enzymic and cellular assays and good selectivity against ROCK. After topical dosing to the eye in a steroid induced mouse model of ocular hypertension, the compounds reduce intraocular pressure to baseline levels. The compounds also increase outflow facility in a pig eye perfusion assay. These results suggest LIMK2 may be an effective target for treating ocular hypertension and associated glaucoma. In the experiment, the researchers used many compounds, for example, 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Quality Control of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine)

2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives, including the nucleotides cytosine, thymine and uracil, thiamine (vitamin B1) and alloxan. Quality Control of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Design and optimization leading to an orally active TTK protein kinase inhibitor with robust single agent efficacy》 was written by Riggs, Jennifer R.; Elsner, Jan; Cashion, Dan; Robinson, Dale; Tehrani, Lida; Nagy, Mark; Fultz, Kimberly E.; Krishna Narla, Rama; Peng, Xiaohui; Tran, Tam; Kulkarni, Ashutosh; Bahmanyar, Sogole; Condroski, Kevin; Pagarigan, Barbra; Fenalti, Gustavo; LeBrun, Laurie; Leftheris, Katerina; Zhu, Dan; Boylan, John F.. Application of 90213-66-4This research focused ontriple neg breast cancer antitumor TTK protein kinase pharmacokinetics. The article conveys some information:

Triple neg. breast cancer (TNBC) is an aggressive disease with high relapse rates and few treatment options. Outlined in previous publications, we identified a series of potent, dual TTK/CLK2 inhibitors with strong efficacy in TNBC xenograft models. Pharmacokinetic properties and kinome selectivity were optimized, resulting in the identification of a new series of potent, selective, and orally bioavailable TTK inhibitors. We describe here the structure-activity relationship of the 2,4-disubstituted-7H-pyrrolo[2,3-d]pyrimidine series, leading to significant single agent efficacy in a TNBC xenograft model without body weight loss. The design effort evolving an iv-dosed TTK/CLK2 inhibitor to an orally bioavailable TTK inhibitor is described. The results came from multiple reactions, including the reaction of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Application of 90213-66-4)

2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. Pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics. Application of 90213-66-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Pyrimidine reactions. XIV. The butylaminolysis of substituted methoxy- and methylthiopyrimidines》 was published in Australian Journal of Chemistry in 1966. These research results belong to Brown, Desmond J.; Foster, Roy V.. COA of Formula: C6H8N2O The article mentions the following:

cf. CA 65, 15374e Aminolyses of 2- and 4-methoxy (or methylthio) pyrimidines bearing C-methyl, CC’-dimethyl, 5-bromo, or 5-intro substituents have proved of value, in the absence of added solvent, for preparing the corresponding n- and tert-butylamino-pyrimidines. When these displacements are followed spectro-metrically, the apparent 1st-order rate constants indicate mild deactivation by addnl. methyl substituents, moderate activation by a bromo substituent, and profound activation by a nitro substituent. Ionization constants and uv spectra of relevant pyrimidines are recorded. 31 references. In addition to this study using 2-Methoxy-4-methylpyrimidine, there are many other studies that have used 2-Methoxy-4-methylpyrimidine(cas: 14001-60-6COA of Formula: C6H8N2O) was used in this study.

2-Methoxy-4-methylpyrimidine(cas: 14001-60-6) is a member of ether. Friedel Crafts reaction, for example, adds an alkyl or acyl group to aromatic ethers when they react with an alkyl or acyl halide in the presence of a Lewis acid as a catalyst.COA of Formula: C6H8N2O

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Pyrimidine reactions. XVI. Thermal rearrangement of substituted 2- and 4-alkoxyprimidines》 was published in Australian Journal of Chemistry in 1968. These research results belong to Brown, Desmond J.; Lee, Tzoong-Chyh. Category: pyrimidines The article mentions the following:

Thermal rearrangement of methyl, bromo, and nitro derivatives of 2- and 4- alkoxypyrimidines produced their N-alkyl isomers, identified by proton magnetic resonance spectral comparison with synthetic specimens of unambiguous or proven structure. The rates for such isomerizations were measured by changes in uv spectra. The C-methyl derivatives rearranged more slowly than the parent alkoxypyrimidines, but the bromo, and especially the nitro derivatives did so much more quickly. Among the derivatives of each methoxypyrimidine, the rate of rearrangement increased as the basic pKa value fell and as the methoxyl protons moved downfield, thus affording a qual. correlation with properties reflecting the electronic effect of each substituent. 32 references. The experimental process involved the reaction of 2-Methoxy-4-methylpyrimidine(cas: 14001-60-6Category: pyrimidines)

2-Methoxy-4-methylpyrimidine(cas: 14001-60-6) is a member of ether. When aromatic ethers are exposed to halogen in the presence or absence of a catalyst, they undergo halogenation, such as bromination.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Reaction of 4-chloropyrimidines with alkylisothioureas》 was written by Hurst, Derek T.. Application of 52854-14-5 And the article was included in Journal of Heterocyclic Chemistry on April 30 ,1995. The article conveys some information:

Reaction of 4,6-dichloro-5-nitropyrimidine with S-methylisothiouronium sulfate gave 1-(4-chloro-5-nitropyrimidinium-6-yl)-S-methylisothiourea by an unusual nucleophilic attack involving an isothiouronium nitrogen atom. Rearrangement of S-Methylisothiuronium sulfate with 4,6-dichloro-5-nitropyrimidine gave [4-(methylthio)-1,3,5-triazin-2(1H)-ylidene]nitroacetonitrile (>70% yield) and 4,6-bis(methylthio)-5-nitropyrimidine (6% yield). In the experiment, the researchers used many compounds, for example, 4-Chloro-6-methoxy-5-nitropyrimidine(cas: 52854-14-5Application of 52854-14-5)

4-Chloro-6-methoxy-5-nitropyrimidine(cas: 52854-14-5) is a member of organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. They are generally not present in crude oils and are typically the result of additives, cleaning solutions or chemicals used for oil recovery.Application of 52854-14-5

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Simple pyrimidines. XVI. A synthetic route to some 2-(pyrimidin-2′-yl)acetic acids and esters》 was published in Australian Journal of Chemistry in 1977. These research results belong to Brown, Desmond J.; Waring, Paul. Electric Literature of C8H10N2O2 The article mentions the following:

The pyrimidinylacetic acid derivatives I [R = CO2H, CONH2, C(:NH)OMe, CO2Et, C(:NH)OEt, CN, CO2Me; R1 = H, HO, Cl, MeO, Ph, Me; R2 = H, OH, Cl] were prepared Thus, H2NCOCH2C(:NH)NH2 was treated with PhCOCH2Et to give I (R = CONH2, R1 = Ph, R2 = OH) which with POCl3 gave I (R = CN, R1 = Ph, R2 = Cl). The nitrile was converted into the corresponding imidic ester and then into the carboxylic ester, which underwent dehalogenation to I (R = CO2Me, R1 = Ph, R2 = H) and subsequent hydrolysis to I (R = CO2H, R1 = Ph, R2 = H). After reading the article, we found that the author used Ethyl 2-(pyrimidin-2-yl)acetate(cas: 63155-11-3Electric Literature of C8H10N2O2)

Ethyl 2-(pyrimidin-2-yl)acetate(cas: 63155-11-3) is a member of pyrimidine. Pyrimidine derivatives are an important class of N-heterocycles. They are well-known for their wide spectrum of promising biological activities such as antitumors, bactericidals, and fungicidal.Electric Literature of C8H10N2O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Synthesis and characterization of Sant-75 derivatives as Hedgehog-pathway inhibitors》 was published in Beilstein Journal of Organic Chemistry in 2012. These research results belong to Che, Chao; Li, Song; Yang, Bo; Xin, Shengchang; Yu, Zhixiong; Shao, Taofeng; Tao, Chuanye; Lin, Shuo; Yang, Zhen. Application In Synthesis of 3-(Pyrimidin-5-yl)benzaldehyde The article mentions the following:

The previously described 3-chloro-N-[trans-4-(propylamino)cyclohexyl]-N-[[3-(4-pyridinyl)phenyl]methyl]benzo[b]thiophene-2-carboxamide [Sant-75] (I) is a newly identified potent inhibitor of the Hedgehog pathway [Smo receptor (Smoothened) antagonist]. The authors designed a diversity-oriented synthesis program and the synthesis of the target compounds (series of Sant-75 analogs) was achieved, which lays a foundation for further investigation of the structure-activity relationship of this important class of hedgehog-pathway inhibitors. The results came from multiple reactions, including the reaction of 3-(Pyrimidin-5-yl)benzaldehyde(cas: 640769-70-6Application In Synthesis of 3-(Pyrimidin-5-yl)benzaldehyde)

3-(Pyrimidin-5-yl)benzaldehyde(cas: 640769-70-6) belongs to pyrimidine. Pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics. Application In Synthesis of 3-(Pyrimidin-5-yl)benzaldehyde

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Synthetic Route of C11H8N2O4On May 1, 2018 ,《Pharmacophore requirements for HIV-1 reverse transcriptase inhibitors that selectively “”Freeze”” the pre-translocated complex during the polymerization catalytic cycle》 appeared in Bioorganic & Medicinal Chemistry. The author of the article were Lacbay, Cyrus M.; Menni, Michael; Bernatchez, Jean A.; Gotte, Matthias; Tsantrizos, Youla S.. The article conveys some information:

Reverse transcriptase (RT) is responsible for replicating the HIV-1 genome and is a validated therapeutic target for the treatment of HIV infections. During each cycle of the RT-catalyzed DNA polymerization process, inorganic pyrophosphate is released as the byproduct of nucleotide incorporation. Small mols. were identified that act as bioisosteres of pyrophosphate and can selectively freeze the catalytic cycle of HIV-1 RT at the pre-translocated stage of the DNA- or RNA-template-primer-enzyme complex. In the experiment, the researchers used 5,6-Dihydroxy-2-phenylpyrimidine-4-carboxylic acid(cas: 62222-38-2Synthetic Route of C11H8N2O4)

5,6-Dihydroxy-2-phenylpyrimidine-4-carboxylic acid(cas: 62222-38-2) belongs to pyrimidine. Pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics. Synthetic Route of C11H8N2O4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

SDS of cas: 944401-55-2On September 14, 2017 ,《5-(4,6-Dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine (PQR309), a Potent, Brain-Penetrant, Orally Bioavailable, Pan-Class I PI3K/mTOR Inhibitor as Clinical Candidate in Oncology》 was published in Journal of Medicinal Chemistry. The article was written by Beaufils, Florent; Cmiljanovic, Natasa; Cmiljanovic, Vladimir; Bohnacker, Thomas; Melone, Anna; Marone, Romina; Jackson, Eileen; Zhang, Xuxiao; Sele, Alexander; Borsari, Chiara; Mestan, Jurgen; Hebeisen, Paul; Hillmann, Petra; Giese, Bernd; Zvelebil, Marketa; Fabbro, Doriano; Williams, Roger L.; Rageot, Denise; Wymann, Matthias P.. The article contains the following contents:

Phosphoinositide 3-kinase (PI3K) is deregulated in a wide variety of human tumors and triggers activation of protein kinase B (PKB/Akt) and mammalian target of rapamycin (mTOR). Here we describe the preclin. characterization of compound 1 (PQR309, bimiralisib), a potent 4,6-dimorpholino-1,3,5-triazine-based pan-class I PI3K inhibitor, which targets mTOR kinase in a balanced fashion at higher concentrations No off-target interactions were detected for 1 in a wide panel of protein kinase, enzyme, and receptor ligand assays. Moreover, 1 did not bind tubulin, which was observed for the structurally related 4 (BKM120, buparlisib). Compound 1 is orally available, crosses the blood-brain barrier, and displayed favorable pharmacokinetic parameters in mice, rats, and dogs. Compound 1 demonstrated efficiency in inhibiting proliferation in tumor cell lines and a rat xenograft model. This, together with the compound’s safety profile, identifies 1 as a clin. candidate with a broad application range in oncol., including treatment of brain tumors or CNS metastasis. Compound 1 is currently in phase II clin. trials for advanced solid tumors and refractory lymphoma. In the experiment, the researchers used many compounds, for example, 4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine(cas: 944401-55-2SDS of cas: 944401-55-2)

4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine(cas: 944401-55-2) belongs to pyrimidine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. SDS of cas: 944401-55-2They have been used in a wide variety of pharmaceuticals including general anesthetics, anti-epilepsy medication, anti-malaria medication, drugs for treating high blood pressure, and HIV medication.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia