Tag: 100-200

灏?Secretase (BACE1) Inhibitors with High in Vivo Efficacy Suitable for Clinical Evaluation in Alzheimer’s Disease was written by Hilpert, Hans;Guba, Wolfgang;Woltering, Thomas J.;Wostl, Wolfgang;Pinard, Emmanuel;Mauser, Harald;Mayweg, Alexander V.;Rogers-Evans, Mark;Humm, Roland;Krummenacher, Daniela;Muser, Thorsten;Schnider, Christian;Jacobsen, Helmut;Ozmen, Laurence;Bergadano, Alessandra;Banner, David W.;Hochstrasser, Remo;Kuglstatter, Andreas;David-Pierson, Pascale;Fischer, Holger;Polara, Alessandra;Narquizian, Robert. And the article was included in Journal of Medicinal Chemistry in 2013.Reference of 38275-61-5 This article mentions the following:

An extensive fluorine scan of 1,3-oxazines revealed the power of fluorine(s) to lower the pK_a and thereby dramatically change the pharmacol. profile of this class of BACE1 inhibitors. The CF₃ substituted oxazine 89, a potent and highly brain penetrant BACE1 inhibitor, was able to reduce significantly CSF A灏?0 and 42 in rats at oral doses as low as 1 mg/kg. The effect was long lasting, showing a significant reduction of A灏?0 and 42 even after 24 h. In contrast to 89, compound 1b lacking the CF₃ group was virtually inactive in vivo. In the experiment, the researchers used many compounds, for example, 5-Chloropyrimidine-2-carboxylic acid (cas: 38275-61-5Reference of 38275-61-5).

5-Chloropyrimidine-2-carboxylic acid (cas: 38275-61-5) belongs to pyrimidine derivatives. Heterocyclic compounds bearing the pyrimidine core are of tremendous interest as they constitute an important class of natural and synthetic compounds exhibiting diverse useful biological activities that hold attractive potential for clinical translation as therapeutic agents in alleviation of a myriad of diseases. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own.Reference of 38275-61-5

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Pteridines, LXIV. Synthesis and properties of thiolumazines was written by Southon, Ian W.;Pfleiderer, Wolfgang. And the article was included in Chemische Berichte in 1978.Application of 54030-56-7 This article mentions the following:

Thiolumazines I (R = Me, R¹ = H, Me, Ph, 2-pyridyl) were prepared in 82, 70, 50, and 8% yields by cyclizing diaminopyrimidine II with R¹COCOR¹. Cyclization of I (R = H, R¹ = H, Me, Ph) with Br(CH₂)_nBr (n = 2, 3) in aqueous N NaOH or DMF-K₂CO₃ gave preferentially, 44, 35, and 88% thiazolo- (III, R¹ = H, Me, Ph, n = 2) and 14 and 68% thiazinopteridines III (R¹ = H, Ph, n = 3), with the [3,2-a]isomers as minor products (thiazolopteridine IV was isolated in 5% yield). Stirring I (R = Me, R¹ = Me, Ph) with CH₂Br₂ and K₂CO₃ in DMF 4.5 h at 60鎺?gave 87 and 53% sulfide V (R¹ = Me, Ph; m = 1), whereas refluxing with THF 2 h gave 56 and 22% V (R¹ = Me, Ph; m = 0), 7% VI (R = R¹ = Me), and 11% pteridine VII. In the experiment, the researchers used many compounds, for example, 6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one (cas: 54030-56-7Application of 54030-56-7).

6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one (cas: 54030-56-7) belongs to pyrimidine derivatives. The aromatic compound pyrimidine, and its derivatives, are ubiquitous in nature. They are found in nucleic acids, vitamins, amino acids, antibiotics, alkaloids, and a variety of toxins. Pyrimidine derivatives 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.Application of 54030-56-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Solventless synthesis of the 2,2′-bipyrimidine derivatives was written by Cai, Chun;Lue, Chun-Xu. And the article was included in Yingyong Huaxue in 2004.Application In Synthesis of 2-Bromo-4,6-dimethylpyrimidine This article mentions the following:

A non-solvent synthesis procedure for the preparation of 2,2′-bipyrimidine, 4,4′,6,6′-tetramethyl-2,2′-bipyrimidine and 4,4′, 6,6′-tetraphenyl-2,2′-bipyrimidine in high yields was developed using fresh copper powder as catalyst. In the experiment, the researchers used many compounds, for example, 2-Bromo-4,6-dimethylpyrimidine (cas: 16879-39-3Application In Synthesis of 2-Bromo-4,6-dimethylpyrimidine).

2-Bromo-4,6-dimethylpyrimidine (cas: 16879-39-3) belongs to pyrimidine derivatives. The pyrimidine nitrogenous bases are derived from the organic compound pyrimidine through the addition of various functional groups. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own.Application In Synthesis of 2-Bromo-4,6-dimethylpyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

1-Aryl-3-[4-(thieno[3,2-d]pyrimidin-4-yloxy)phenyl]ureas as VEGFR-2 tyrosine kinase inhibitors: synthesis, biological evaluation, and molecular modelling studies was written by Soares, Pedro;Costa, Raquel;Froufe, Hugo J. C.;Calhelha, Ricardo C.;Peixoto, Daniela;Ferreira, Isabel C. F. R.;Abreu, Rui M. V.;Soares, Raquel;Queiroz, Maria-Joao R. P.. And the article was included in BioMed Research International in 2013.Category: pyrimidines This article mentions the following:

The vascular endothelial growth factor receptor-2 (VEGFR-2) is a tyrosine kinase receptor involved in the growth and differentiation of endothelial cells that are implicated in tumor-associated angiogenesis. In this study, novel 1-aryl-3-[4-(thieno[3,2-d]pyrimidin-4-yloxy)phenyl]ureas, e.g., I, were synthesized and evaluated for the VEGFR-2 tyrosine kinase inhibition. Three of these compounds showed good VEGFR-2 inhibition presenting low IC₅₀ values (150-199 nM) in enzymic assays, showing also a significant proliferation inhibition of VEGF-stimulated human umbilical vein endothelial cells (HUVECs) at low concentrations (0.5-1 娓璏), using the Bromodeoxyuridine (BrdU) assay, not affecting cell viability. The determination of the total and phosphorylated (active) VEGFR-2 was performed by western blot, and it was possible to conclude that the compounds significantly inhibit the phosphorylation of the receptor at 1 娓璏 pointing to their antiproliferative mechanism of action in HUVECs. The mol. rationale for inhibiting the tyrosine kinase domain of VEGFR-2 was also performed and discussed using mol. docking studies. In the experiment, the researchers used many compounds, for example, 4-Chloro-7-methylthieno[3,2-d]pyrimidine (cas: 175137-21-0Category: pyrimidines).

4-Chloro-7-methylthieno[3,2-d]pyrimidine (cas: 175137-21-0) belongs to pyrimidine derivatives. Pyrimidines are isomeric with two other forms of diazines: pyridazine, with the nitrogen atoms in the 1 and 2 positions; and pyrazine, with the nitrogen atoms in the 1 and 4 positions. We all know its importance to life – pyrimidine and purine bases are included in the structure of DNA and RNA.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Suzuki-Miyaura cross-coupling reaction of aryl and heteroaryl pinacol boronates for the synthesis of 2-substituted pyrimidines was written by Asano, Shigehiro;Kamioka, Seiji;Isobe, Yoshiaki. And the article was included in Tetrahedron in 2012.Computed Properties of C8H10ClN3O This article mentions the following:

Suzuki-Miyaura cross-coupling reaction with 2-heteroarylboronic acids is generally challenging due to easy decomposition of these acids. To overcome this problem, we developed a coupling method that uses 2-heteroaryl pinacol boronates in the presence of 1.0 mol % Pd(OAc)₂ and 2.0 mol % S-Phos with 4 equiv amount of LiOH in dioxane and H₂O at 80 鎺矯 for 30 min. This developed method allowed for the synthesis of a wide variety of 2-heteroaryl pyrimidines from 2-chloropyrimidyl derivatives in high yields, and is also useful in the preparation of various biaryl derivatives from heteroaryl chlorides. In the experiment, the researchers used many compounds, for example, 4-(2-Chloropyrimidin-4-yl)morpholine (cas: 62968-37-0Computed Properties of C8H10ClN3O).

4-(2-Chloropyrimidin-4-yl)morpholine (cas: 62968-37-0) belongs to pyrimidine derivatives. The pyrimidine derivatives can easily interact with enzymes, genetic materials, and bio components within the cell. For example, the neurotoxin tetrodotoxin is a pyrimidine derivative. It is found in a number of species including the Japanese puffer fish, the blue-ringed octopus, and the orange-bellied newt. Tetrodotoxin prevents the transmission of nerve signals and can result in paralysis and death.Computed Properties of C8H10ClN3O

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Casein Kinase 1鏈?钄?Inhibitor PF-5006739 Attenuates Opioid Drug-Seeking Behavior was written by Wager, Travis T.;Chandrasekaran, Ramalakshmi Y.;Bradley, Jenifer;Rubitski, David;Berke, Helen;Mente, Scot;Butler, Todd;Doran, Angela;Chang, Cheng;Fisher, Katherine;Knafels, John;Liu, Shenping;Ohren, Jeff;Marconi, Michael;DeMarco, George;Sneed, Blossom;Walton, Kevin;Horton, David;Rosado, Amy;Mead, Andy. And the article was included in ACS Chemical Neuroscience in 2014.Application In Synthesis of 4-Dimethoxymethylpyrimidin-2-ylamine This article mentions the following:

Casein kinase 1 delta (CK1鏈? and casein kinase 1 epsilon (CK1钄? inhibitors are potential therapeutic agents for a range of psychiatric disorders. The feasibility of developing a CNS kinase inhibitor has been limited by an inability to identify safe brain-penetrant compounds with high kinome selectivity. Guided by structure-based drug design, potent and selective CK1鏈?钄?inhibitors have now been identified that address this gap, through the design and synthesis of novel 4-[4-(4-fluorophenyl)-1-(piperidin-4-yl)-1H-imidazol-5-yl]pyrimidin-2-amine derivatives PF-5006739 (6) possesses a desirable profile, with low nanomolar in vitro potency for CK1鏈?钄?(IC₅₀ = 3.9 and 17.0 nM, resp.) and high kinome selectivity. In vivo, 6 demonstrated robust centrally mediated circadian rhythm phase-delaying effects in both nocturnal and diurnal animal models. Further, 6 dose-dependently attenuated opioid drug-seeking behavior in a rodent operant reinstatement model in animals trained to self-administer fentanyl. Collectively, our data supports further development of 6 as a promising candidate to test the hypothesis of CK1鏈?钄?inhibition in treating multiple indications in the clinic. In the experiment, the researchers used many compounds, for example, 4-Dimethoxymethylpyrimidin-2-ylamine (cas: 165807-05-6Application In Synthesis of 4-Dimethoxymethylpyrimidin-2-ylamine).

4-Dimethoxymethylpyrimidin-2-ylamine (cas: 165807-05-6) belongs to pyrimidine derivatives. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives. Therapy for fungal infections is based mainly on four classes of antifungals: azoles, echinocandins, polyenes, and pyrimidine analogs.Application In Synthesis of 4-Dimethoxymethylpyrimidin-2-ylamine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Macrocyclization as a Source of Desired Polypharmacology. Discovery of Triple PI3K/mTOR/PIM Inhibitors was written by Martinez-Gonzalez, Sonia;Alvarez, Rosa M.;Martin, Jose I.;Garcia, Ana Belen;Riesco-Fagundo, Concepcion;Varela, Carmen;Rodriguez Hergueta, Antonio;Gonzalez Cantalapiedra, Esther;Albarran, M. I.;Gomez-Casero, Elena;Cebria, Antonio;Aguirre, Enara;Ajenjo, Nuria;Cebrian, David;Di Geronimo, Bruno;Cunningham, Darren;O閳ョ澇eill, Michael;Dave, Harish P. G.;Blanco-Aparicio, Carmen;Pastor, Joaquin. And the article was included in ACS Medicinal Chemistry Letters in 2021.Recommanded Product: 4-Chloro-7-methylthieno[3,2-d]pyrimidine This article mentions the following:

The PI3K/AKT/mTOR and PIM kinase pathways contribute to the development of several hallmarks of cancer. Cotargeting of these pathways has exhibited promising synergistic therapeutic effects in liquid and solid tumor types. To identify mols. with combined activities, we cross-screened our collection of PI3K/(鍗TOR) macrocycles (MCXs) and identified the MCX thieno[3,2-d]pyrimidine derivative 2 as a moderate dual PI3K/PIM-1 inhibitor. We report the medicinal chem. exploration and biol. characterization of a series of thieno[3,2-d]pyrimidine MCXs, which led to the discovery of IBL-302 (31), a potent, selective, and orally bioavailable triple PI3K/mTOR/PIM inhibitor. IBL-302, currently in late preclin. development (AUM302), has recently demonstrated efficacy in neuroblastoma and breast cancer xenografts. Addnl., during the course of our experiments, we observed that macrocyclization was essential to obtain the desired multitarget profile. As a matter of example, the open precursors 35-37 were inactive against PIM whereas MCX 28 displayed low nanomolar activity. In the experiment, the researchers used many compounds, for example, 4-Chloro-7-methylthieno[3,2-d]pyrimidine (cas: 175137-21-0Recommanded Product: 4-Chloro-7-methylthieno[3,2-d]pyrimidine).

4-Chloro-7-methylthieno[3,2-d]pyrimidine (cas: 175137-21-0) belongs to pyrimidine derivatives. Pyrimidine also found in many synthetic compounds such as barbiturates and the HIV drug, zidovudine. A Cu-catalyzed and 4-HO-TEMPO-mediated [3 + 3] annulation of commercially available amidines with saturated ketones enables an efficient and facile synthesis of structurally important pyrimidines via a cascade reaction of oxidative dehydrogenation/annulation/oxidative aromatization.Recommanded Product: 4-Chloro-7-methylthieno[3,2-d]pyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Synthesis and herbicidal activity of 2-benzoyliminopyrimido[3,2-b]-1,2,4-thiadiazolines was written by Xue, Si Jia;Tan, Dong Yun;Sun, Chang You. And the article was included in Chinese Chemical Letters in 1998.Category: pyrimidines This article mentions the following:

The title compounds, i.e., N-([1,2,4]thiadiazolo[2,3-a]pyrimidinylidene)benzamides [2-benzoyliminopyrimido[3,2-b]-1,2,4-thiadiazolines], were synthesized and tested for herbicidal effects. All of them are new compounds and their structures were confirmed by ¹HNMR, IR, MS. The preliminary herbicidal tests show that some of the target compounds have potent activity and very good selectivity to rice. Of the target compounds thus prepared and tested was N-(6,7-Dimethoxy-2H-[1,2,4]thiadiazolo[2,3-a]pyrimidin-2-ylidene)benzamide. In the experiment, the researchers used many compounds, for example, 4,5-Dimethylpyrimidin-2-amine (cas: 1193-74-4Category: pyrimidines).

4,5-Dimethylpyrimidin-2-amine (cas: 1193-74-4) belongs to pyrimidine derivatives. Pyrimidine is an aromatic heterocyclic organic compound similar to pyridine. Pyrimidine derivatives 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.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Proton and carbon-13 nuclear magnetic resonance studies of substituted pyrimidines. 2. Monoprotonation of methyl- and aminopyrimidines was written by Riand, J.;Chenon, M. T.;Lumbroso-Bader, N.. And the article was included in Journal of the American Chemical Society in 1977.Category: pyrimidines This article mentions the following:

The monoprotonation of methyl- and aminopyrimidines was studied by C13 NMR spectroscopy. The chem.-shift parameters associated with the protonation of methylpyrimidines were determined for the aromatic and Me group C atoms from the salts of certain sym. compounds A significant difference exists for certain parameters for a given C, depending on whether a H atom or a Me group is attached to it. An especially large solvent effect exists for C atoms bearing a Me group para to the site of protonation. The percentages of the forms monoprotonated at sites N-1 or N-3 of pyrimidines were evaluated from their chem. shifts in F3CCO2H and Me2SO. For methylpyrimidines a higher percentage (鈭?1%) of the form in which the protonated N is in the para position to the Me group is found. For the 4-amino-6-methylpyrimidines, the influence of the amino group is greater than that of the Me group, and the percentage reaches 鈭?4% for the form in which the protonated N is in the para position to the amino group. In the experiment, the researchers used many compounds, for example, 4,5-Dimethylpyrimidin-2-amine (cas: 1193-74-4Category: pyrimidines).

4,5-Dimethylpyrimidin-2-amine (cas: 1193-74-4) belongs to pyrimidine derivatives. Pyrimidine also found in many synthetic compounds such as barbiturates and the HIV drug, zidovudine. Drugs having the pyrimidine motif have manifested to exhibit gratifying biological activity like anticancer, antiviral, anti-inflammatory, antibacterial, and antihypertensive activities.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Synthesis of novel pyrimido[4,5-b]quinolin-4-ones with potential antitumor activity was written by Insuasty, Braulio;Becerra, Diana;Quiroga, Jairo;Abonia, Rodrigo;Nogueras, Manuel;Cobo, Justo. And the article was included in Journal of Heterocyclic Chemistry in 2013.Recommanded Product: 54030-56-7 This article mentions the following:

5,6,7,8,9,10-Hexahydro-2-(methylthio)pyrimido[4,5-b]quinolines and their oxidized forms, the corresponding 6,7,8,9-tetrahydropyrimido[4,5-b]quinolin-4(3H)-ones, were obtained from the reaction of 6-amino-2-(methylthio)pyrimidin-4(3H)-one or its 3-Me derivative and 伪,尾-unsaturated ketones using BF₃.OEt₂ as catalyst and 4-chloranil as oxidizing agent. Some of the new compounds were evaluated in the US National Cancer Institute (NCI), where (9E)-9-benzylidene-3-methyl-2-(methylthio)-5-phenyl-5,6,7,8,9,10-hexahydropyrimido[4,5-b]quinolin-4(3H)-one presented remarkable activity against cancer cell lines, with the most important GI₅₀ values of 0.72-18.4 渭M from in vitro assays. In the experiment, the researchers used many compounds, for example, 6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one (cas: 54030-56-7Recommanded Product: 54030-56-7).

6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one (cas: 54030-56-7) belongs to pyrimidine derivatives. The aromatic compound pyrimidine, and its derivatives, are ubiquitous in nature. They are found in nucleic acids, vitamins, amino acids, antibiotics, alkaloids, and a variety of toxins. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own.Recommanded Product: 54030-56-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia