Tag: 100-200

Pyrimidine derivatives. V. 5 was written by Inoue, Shoji. And the article was included in Chemical & Pharmaceutical Bulletin in 1958.Synthetic Route of C4H5N3O This article mentions the following:

Thiazolo[5,4-d]pyrimidine (I) and its 2-substituted derivatives are synthesized. The 4-HS derivative (II) of 5-aminopyrimidine (III) was 1st prepared from the 4-HO derivative (IV), the 6-Cl derivative (V), and the 6,4-Cl(HS) derivative (VI) of III. IV (1 g.) refluxed 8 hrs. with 3 g. P₂S₅ and 20 cc. xylene, the filtered solid from the cooled mixture dissolved in 20 cc. N NaOH, decolorized with C, and the filtrate neutralized with AcOH and extracted with AcOEt yielded 0.4-0.5 g. II, m. 207° (decomposition). The 4,6-Cl₂ derivative of 5-nitropyrimidine (5 g.) reduced with Fe powder and AcOH as above yielded 3 g. 4,6-Cl₂ derivative of III, m. 142°, which (5 g.) in 50 cc. EtOH heated 3 hrs. at 60° with the theoretical amount of KSH yielded 4.1 g. VI, m. above 300°, and this (1 g.) desulfurized with Raney Ni in NH₄OH (as was V in Part IV) yielded 0.2 g. V, m. 123° (decomposition). V (0.13 g.) in 5 cc. H₂O heated 2 hrs. at 60° with 0.2 g. KSH and the cooled mixture neutralized with AcOH yielded 0.1 g. II. VI (1 g.) refluxed 3 hrs. with 5 g. powd. Zn in 20 cc. H₂O and 3 cc. 28% NH₄OH, the filtrate from the mixture concentrated, neutralized, and extracted with AcOEt yielded 0.55 g. II. II was next cyclized as were similar compounds in the preceding abstracts (weight II, reagent, hrs. of refluxing, derivative of I formed, m.p., and g. yield given): 0.3 g., HCO₂H, 2, I, 144°, 0.1; 0.3 g., Ac₂O, 2, 2-Me, 77°, 0.16; 0.4 g., BzCl in C₅H₅N, 3, 2-Ph, 119-20°, 0.55; 0.2 g., K methylxanthate, 15, 2-HS (VII), 287° (decomposition), 0.21. The K salt of VII (0.2 g.) refluxed 30 min. with 0.12 g. PhCH₂Cl in 20 cc. 70% EtOH, the solvent distilled, the residue treated with 5 cc. N NaOH, and extracted with ether yielded 0.21 g. 2-PhCH₂S derivative of I, m. 101°. In the experiment, the researchers used many compounds, for example, 5-Aminopyrimidin-4(3H)-one (cas: 69785-94-0Synthetic Route of C4H5N3O).

5-Aminopyrimidin-4(3H)-one (cas: 69785-94-0) 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. We all know its importance to life – pyrimidine and purine bases are included in the structure of DNA and RNA.Synthetic Route of C4H5N3O

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Total Synthesis of (±)-Cylindrospermopsin was written by Xie, Chaoyu;Runnegar, Maria T. C.;Snider, Barry B.. And the article was included in Journal of the American Chemical Society in 2000.Recommanded Product: 59864-30-1 This article mentions the following:

The first total synthesis of the novel hepatotoxin (±)-cylindrospermopsin (I) has been accomplished in 20 steps from 4-methoxy-3-methylpyridine (II) in 3.5% overall yield. The substituted piperidine A ring III was generated stereospecifically by a four-step sequence using the addition of trimethylsilylethynylmagnesium bromide to II to give IV (Troc = CO₂CH₂CCl₃) and stereospecific addition of vinylcuprate to IV to form V. The reaction of diamine VI (R¹ = R² = H; TBDMS = SiMe₂CMe₃) with cyanogen bromide produced the cyclic guanidine C ring of VI (R¹R² = C:NH). The key step in the synthesis was bromination of ketone VII (Cbz = CO₂CH₂Ph), followed by hydrogenation to liberate the free guanidine, which underwent an intramol. S_N2 reaction to form the tetrahydropyrimidine ring B of VIII. Further hydrogenation reduced the ketone to yield 42% of VIII containing the fully functionalized tricyclic system and protected hydroxymethyluracil side chain of cylindrospermopsin. Hydrolysis of the pyrimidine in concentrated hydrochloric acid and selective monosulfation completed the synthesis of cylindrospermopsin. In the experiment, the researchers used many compounds, for example, 2,6-Dimethoxypyrimidine-4-carboxylic acid (cas: 59864-30-1Recommanded Product: 59864-30-1).

2,6-Dimethoxypyrimidine-4-carboxylic acid (cas: 59864-30-1) 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. 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.Recommanded Product: 59864-30-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Practical Asymmetric Synthesis of a Non-Peptidic α_vβ₃ Antagonist was written by Keen, Stephen P.;Cowden, Cameron J.;Bishop, Brian C.;Brands, Karel M. J.;Davies, Antony J.;Dolling, Ulf H.;Lieberman, David R.;Stewart, Gavin W.. And the article was included in Journal of Organic Chemistry in 2005.Recommanded Product: 90905-32-1 This article mentions the following:

The development of a practical and highly convergent synthesis of an α_vβ₃ antagonist I is described. The two key fragments present in this compound, a chiral 3-aryl-5-oxopentanoic acid II and a tetrahydropyrido[2,3-b]azepine ring system III (R= Boc), were constructed independently and then coupled at a late stage using a Wittig reaction. The pyridoazepine moiety was prepared from N-Boc 6-chloro-2-aminopyridine via directed ortho-metalation/alkylation followed by in situ cyclization. A Suzuki reaction was then used to attach the propionaldehyde side-chain required for Wittig coupling. The coupling partner was prepared from asym. methanolysis of a 3-substituted glutaric anhydride followed by elaboration of the acid moiety to the requisite β-keto phosphorane. Using this route, kilogram quantities of the desired drug candidate were prepared In the experiment, the researchers used many compounds, for example, 2-Methoxypyrimidine-5-carbaldehyde (cas: 90905-32-1Recommanded Product: 90905-32-1).

2-Methoxypyrimidine-5-carbaldehyde (cas: 90905-32-1) belongs to pyrimidine derivatives. The pyrimidine nitrogenous bases are derived from the organic compound pyrimidine through the addition of various functional groups. 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.Recommanded Product: 90905-32-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Design, synthesis, docking, molecular dynamics and bioevaluation studies on novel N-methylpicolinamide and thienopyrimidine derivatives with inhibiting NF-κB and TAK1 activities: Cheminformatics tools RDKit applied in drug design was written by Wang, Linxiao;Zhang, Qian;Wang, Zhe;Zhu, Wufu;Tan, Ninghua. And the article was included in European Journal of Medicinal Chemistry in 2021.Safety of 4-(2-Chloropyrimidin-4-yl)morpholine This article mentions the following:

Using cheminformatics tools RDKit and literature investigation, four series of 24 thienopyrimidine I [X = C, C=O; Y = H, N(Me)₂, N(Et)₂] II [R = H, Me; R² = pyrrolidin-1-yl, 1-piperidyl, morpholino, indolin-1-yl, 3,4-dihydro-1H-isoquinolin-2-yl] III and N-methylpicolinamide derivatives IV [R² = pyrrolidin-1-yl, 1-piperidyl, morpholino, 3,4-dihydro-1H-isoquinolin-2-yl] substituted with pyrimidine were designed, synthesized and evaluated for activities against three cancer cell lines (MDA-MB-231, HCT116 and A549), TAK1 kinase and NF-κB signaling pathway. Almost all compounds I, II, III, IV showed selectivity toward the A549 cell lines and the most promising compound IV [R² = 1-piperidyl] could inhibit TAK1 kinase and NF-κB signaling pathway with the IC₅₀ values of 0.58 and 0.84μM. Moreover, IV [R² = 1-piperidyl] could induce cell cycle arrest of A549 cells at the G2/M checkpoint with 30.57% and induce apoptosis (34.94%) in a concentration-dependent manner. And western blot showed that compound IV [R² = 1-piperidyl] could inhibit TNF-α-induced IκBα phosphorylation, IκBα degradation, p65 phosphorylation and TAK1 phosphorylation, and reduce the expression of p65. The studies of docking, mol. dynamics, MM/PBSA and frequency anal. theor. supported the conclusions of the bioevaluation. In the experiment, the researchers used many compounds, for example, 4-(2-Chloropyrimidin-4-yl)morpholine (cas: 62968-37-0Safety of 4-(2-Chloropyrimidin-4-yl)morpholine).

4-(2-Chloropyrimidin-4-yl)morpholine (cas: 62968-37-0) 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. 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.Safety of 4-(2-Chloropyrimidin-4-yl)morpholine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Mechanism of decarboxylation of 1,3-dimethylorotic acid. A model for orotidine 5′-phosphate decarboxylase was written by Beak, Peter;Siegel, Brock. And the article was included in Journal of the American Chemical Society in 1976.Recommanded Product: 59864-30-1 This article mentions the following:

The decarboxylation of 1,3-dimethylorotic acid (I) is shown to proceed by sep. pH-determined pathways in sulfolane at 180-220°. Although a process involving ionization of I is the major pathway in the presence of excess base, decarboxylation is initiated by zwitterion formation in the neutral solvent. Measurements of the rate of loss of CO2 from 6-carboxy-2,4-dimethoxypyrimidine and 1-methyl-2,4-dimethoxypyrimidinium-6-carboxylate betaine (II) are used to estimate the equilibrium and rate constants for the zwitterionic pathway. Comparison of the rate constant for decarboxylation of II with kcat for orotidine 5′-phosphate decarboxylase shows that the biol. catalysis can be satisfactorily accounted for if the enzyme provides a site which displaces the equilibrium in favor of the zwitterionic form of orotidylic acid. It is also noted that the inhibitor, 6-azauridine monophosphate, which has a greater affinity for the enzyme than does the substrate, provides a partial model for the intermediate formed on loss of CO2 from the zwitterion. In the experiment, the researchers used many compounds, for example, 2,6-Dimethoxypyrimidine-4-carboxylic acid (cas: 59864-30-1Recommanded Product: 59864-30-1).

2,6-Dimethoxypyrimidine-4-carboxylic acid (cas: 59864-30-1) belongs to pyrimidine derivatives. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives. As nucleotides in DNA and RNA, pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics.Recommanded Product: 59864-30-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Design and synthesis of potent and selective inhibitors of BRD7 and BRD9 bromodomains was written by Hay, Duncan A.;Rogers, Catherine M.;Fedorov, Oleg;Tallant, Cynthia;Martin, Sarah;Monteiro, Octovia P.;Muller, Susanne;Knapp, Stefan;Schofield, Christopher J.;Brennan, Paul E.. And the article was included in MedChemComm in 2015.Category: pyrimidines This article mentions the following:

Emerging evidence suggests bromodomain-containing proteins 7 and 9 (BRD7 and BRD9) have roles in the regulation of human transcription and disease including cancer. We describe potent and selective inhibitors of the BRD7 and BRD9 bromodomains intended for use as tools to elucidate the biol. roles of BRD7 and BRD9 in healthy and diseased cells. In the experiment, the researchers used many compounds, for example, 2-Ethynylpyrimidine (cas: 37972-24-0Category: pyrimidines).

2-Ethynylpyrimidine (cas: 37972-24-0) belongs to pyrimidine derivatives. Pyrimidine also found in many synthetic compounds such as barbiturates and the HIV drug, zidovudine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The octaethylporphyrin-dihexylbithiophene derivatives combined with pyridine and pyrimidine rings. Their syntheses and proton-mediated and heat-driven spectral changes was written by Higuchi, Hiroyuki;Hayashi, Naoto;Matsukihira, Takuya;Kawakami, Takanori;Takizawa, Toru;Saito, Junji;Miyabayashi, Keiko;Miyake, Mikio. And the article was included in Heterocycles in 2008.Synthetic Route of C6H4N2 This article mentions the following:

Nickel octaethylporphyrin (NiOEP)-dihexylbithiophene (DHBTh) derivatives combined with pyridine (Pyr) and pyrimidine (Pym) as proton-acceptable rings (PAR) were synthesized, describable as NiOEP-DHBTh-PAR, in which all the NiOEP, DHBTh, and PAR components are connected with diacetylene linkage. Their ¹H NMR and electronic spectral properties and electrochem. behaviors were studied under the neutral and acidic conditions. Reversible proton-mediated and heat-driven spectral changes of NiOEP-DHBTh-PAR were performed, reflecting both properties of PAR and DHBTh. In the experiment, the researchers used many compounds, for example, 2-Ethynylpyrimidine (cas: 37972-24-0Synthetic Route of C6H4N2).

2-Ethynylpyrimidine (cas: 37972-24-0) 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.Synthetic Route of C6H4N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Discovery of a potent and highly selective transforming growth factor β receptor-associated kinase 1 (TAK1) inhibitor by structure based drug design (SBDD) was written by Muraoka, Terushige;Ide, Mitsuaki;Morikami, Kenji;Irie, Machiko;Nakamura, Mitsuaki;Miura, Takaaki;Kamikawa, Takayuki;Nishihara, Masamichi;Kashiwagi, Hirotaka. And the article was included in Bioorganic & Medicinal Chemistry in 2016.Product Details of 175137-21-0 This article mentions the following:

A novel thienopyrimidinone analog was discovered as a potent and highly selective TAK1 inhibitor using the SBDD approach. TAK1 plays a key role in inflammatory and immune signaling, so TAK1 is considered to be an attractive mol. target for the treatment of human diseases (inflammatory disease, cancer, etc.). After the hit compound had been obtained, the authors’ modifications successfully increased TAK1 inhibitory activity and solubility, but metabolic stability was still unsatisfactory. To improve metabolic stability, the authors conducted metabolic identification. Although the obtained metabolite was fortunately a potent TAK1 inhibitor, its kinase selectivity was low. Subsequently, to achieve high kinase selectivity, the authors used SBDD to follow two strategies: one targeting unique amino acid residues in TAK1, especially the combination of Ser 111 and Asn 114; the other decreasing the interaction with Tyr 106 at the hinge position in TAK1. As expected, the authors’ designed compound (I) showed an excellent kinase selectivity profile in both an inhouse and a com. available panel assay of over 420 kinases and also retained its potent TAK1 inhibitory activity (TAK1 IC₅₀ = 11 nM). In the experiment, the researchers used many compounds, for example, 4-Chloro-7-methylthieno[3,2-d]pyrimidine (cas: 175137-21-0Product Details of 175137-21-0).

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. Drugs having the pyrimidine motif have manifested to exhibit gratifying biological activity like anticancer, antiviral, anti-inflammatory, antibacterial, and antihypertensive activities.Product Details of 175137-21-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

A new method for the synthesis of 2-glycosylaminopyridines. Tandem Diels-Alder/retro-Diels-Alder reactions in the synthesis of 2-amino- and 2-glycosylaminopyridines was written by Cobo, J.;Melguizo, M.;Sanchez, A.;Nogueras, M.. And the article was included in Synlett in 1993.Safety of 6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one This article mentions the following:

Several 2-amino- and 2-glycosylaminopyridines, I (X = O, S) and II (R’ = H, CH₂OAc, X = O, S), were synthesized through a tandem Diels-Alder/retro-Diels-Alder reaction starting from 6-amino-, e.g. III (R = H, Me, X = O, S), and 6-glycosylaminopyrimidines with di-Me acetylenedicarboxylate as dienophile. This approach constitutes a new method for the synthesis of nucleosides derived from 2-aminopyridines. In the experiment, the researchers used many compounds, for example, 6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one (cas: 54030-56-7Safety of 6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one).

6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one (cas: 54030-56-7) 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. 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.Safety of 6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Regioselectivity in the reactions of aryltriisopropoxytitanium with pyrimidinones was written by Rise, Frode;Undheim, Kjell. And the article was included in Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999) in 1985.Synthetic Route of C4H4Cl2N2O This article mentions the following:

Complete regioselectivity was observed in the 1:1 condensation between 4-RC₆H₄Ti(OCHMe₂)₃ (R = H, Cl, OMe) and pyrimidin-2(1H)ones I (R¹ = H; R² = Me, CH₂Ph, CH₂OCH₂Ph, CH₂SC₆H₄Cl-4; R³ = H, Cl, Br, iodo). The new C-C bond was formed at C-4 to yield product II. Subsequent dehydrogenation with MnO₂ or DDQ produced I (R¹ = C₆H₄R). In the experiment, the researchers used many compounds, for example, 5-Chloropyrimidin-2(1H)-one hydrochloride (cas: 42748-90-3Synthetic Route of C4H4Cl2N2O).

5-Chloropyrimidin-2(1H)-one hydrochloride (cas: 42748-90-3) 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.Synthetic Route of C4H4Cl2N2O

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia