Tag: M.W=150-200

Rosemeyer, Helmut; Kaiser, Klaus; Seela, Frank published the artcile< Dextran-linked 7-deazaguanine - a polymer-bound inhibitor of xanthine oxidase>, Related Products of 84955-32-8, the main research area is xanthine oxidase deazaguanine dextran inhibitor; immobilized deazaguanine xanthine oxidase inhibition.

Dextran-linked 7-deazaguanine as well as 7-deazahypoxanthine and allopurinol derivatives were prepared by carbodiimide condensation of the 2-carboxyethyl intermediates with N-(6-aminohexyl)carbamoylmethylated dextran T80. The dextran-linked bases are degradable by endo-dextranase (EC 3.2.1.11) as demonstrated by time-dependent viscosity measurements. Monomeric as well as polymer-linked purine analogs were tested as inhibitors of xanthine oxidase (EC 1.2.3.1) from cow’s milk. Whereas the allopurinol- and 7-deazahypoxanthine derivatives no longer bind to the enzyme, the 7-deazaguanine derivatives are strong competitive inhibitors of xanthine oxidase even in the polymer-linked state.

International Journal of Biological Macromolecules published new progress about Enzyme kinetics. 84955-32-8 belongs to class pyrimidines, and the molecular formula is C7H8N4O, Related Products of 84955-32-8.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Beck, Hartmut; Jeske, Mario; Thede, Kai; Stoll, Friederike; Flamme, Ingo; Akbaba, Metin; Ergueden, Jens-Kerim; Karig, Gunter; Keldenich, Joerg; Oehme, Felix; Militzer, Hans-Christian; Hartung, Ingo V.; Thuss, Uwe published the artcile< Discovery of Molidustat (BAY 85-3934): A Small-Molecule Oral HIF-Prolyl Hydroxylase (HIF-PH) Inhibitor for the Treatment of Renal Anemia>, HPLC of Formula: 5018-38-2, the main research area is diheteroaryldihydropyrazolone preparation HIF prolyl hydroxylase inhibitor kidney disease anemia; molidustat BAY3934 preparation HIF prolyl hydroxylase inhibitor kidney anemia; BAY 85-3934; HIF-PH; inhibitors; metalloenzymes; molidustat.

Small-mol. inhibitors of hypoxia-inducible factor prolyl hydroxylases (HIF-PHs) are currently under clin. development as novel treatment options for chronic kidney disease (CKD) associated anemia. Inhibition of HIF-PH mimics hypoxia and leads to increased erythropoietin (EPO) expression and subsequently increased erythropoiesis. Herein the authors describe the discovery, synthesis, structure-activity relationship (SAR), and proposed binding mode of novel 2,4-diheteroaryl-1,2-dihydro-3H-pyrazol-3-ones as orally bioavailable HIF-PH inhibitors for the treatment of anemia. High-throughput screening of the authors’ corporate compound library identified BAY-908 as a promising hit. The lead optimization program then resulted in the identification of molidustat (BAY 85-3934), a novel small-mol. oral HIF-PH inhibitor. Molidustat is currently being investigated in clin. phase III trials as molidustat sodium for the treatment of anemia in patients with CKD.

ChemMedChem published new progress about Anemia (chronic kidney disease associated). 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, HPLC of Formula: 5018-38-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Suwal, Sujit; Rahman, Mahmuda; O’Brien, Gregory; Karambizi, Victoire G.; Wrotny, Matthew; Scott Goodman, M. published the artcile< Chemo-selective syntheses of N-t-boc-protected amino ester analogs through Buchwald-Hartwig amination>, Recommanded Product: Ethyl 2-chloropyrimidine-5-carboxylate, the main research area is amino ester preparation chemoselective; heterocyclic halo ester amine Buchwald Hartwig amination.

Synthesis of N-protected amino esters, e.g., I is achieved via a chemo-selective Buchwald Hartwig cross-coupling reaction using PEPPSI-IPr Pd-catalyst. Nearly two dozen functionally and structurally diverse mols. are created by individually cross-coupling eight II (R = Me, Et; Y = CH, N; X = Cl, Br) and three different secondary amines, e.g., tert-Bu piperazine-1-carboxylate. It was the observed that product formation is more facile in those heterocyclic esters II where nitrogen is present ortho to the halo substituent in the heteroaromatic ring. Based on this observation, a possible intermediate step in the cross-coupling cycle is proposed, where the nitrogen electron lone pair in the heterocycle may play an important role leading to a higher reaction yield.

New Journal of Chemistry published new progress about Amino esters Role: SPN (Synthetic Preparation), PREP (Preparation). 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Recommanded Product: Ethyl 2-chloropyrimidine-5-carboxylate.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Angst, Daniela; Gessier, Francois; Janser, Philipp; Vulpetti, Anna; Walchli, Rudolf; Beerli, Christian; Littlewood-Evans, Amanda; Dawson, Janet; Nuesslein-Hildesheim, Barbara; Wieczorek, Grazyna; Gutmann, Sascha; Scheufler, Clemens; Hinniger, Alexandra; Zimmerlin, Alfred; Funhoff, Enrico G.; Pulz, Robert; Cenni, Bruno published the artcile< Discovery of LOU064 (Remibrutinib), a Potent and Highly Selective Covalent Inhibitor of Bruton's Tyrosine Kinase>, Synthetic Route of 5018-38-2, the main research area is LOU064 remibrutinib Bruton tyrosine kinase inhibitor autoimmune diseases antiinflammatory.

Bruton’s tyrosine kinase (BTK), a cytoplasmic tyrosine kinase, plays a central role in immunity and is considered an attractive target for treating autoimmune diseases. The use of currently marketed covalent BTK inhibitors is limited to oncol. indications based on their suboptimal kinase selectivity. We describe the discovery and preclin. profile of LOU064 (remibrutinib, 25), a potent, highly selective covalent BTK inhibitor. LOU064 exhibits an exquisite kinase selectivity due to binding to an inactive conformation of BTK and has the potential for a best-in-class covalent BTK inhibitor for the treatment of autoimmune diseases. It demonstrates potent in vivo target occupancy with an EC90 of 1.6 mg/kg and dose-dependent efficacy in rat collagen-induced arthritis. LOU064 is currently being tested in phase 2 clin. studies for chronic spontaneous urticaria and Sjoegren’s syndrome.

Journal of Medicinal Chemistry published new progress about Anti-inflammatory agents. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, Synthetic Route of 5018-38-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Gruessner, A.; Montavon, M.; Schnider, O. published the artcile< Disubstituted 4-sulfanilamidopyrimidines>, Formula: C5H4Cl2N2O, the main research area is .

A series of 5,6-dialkoxy-4-sulfanilamidopyrimidines was prepared and tested for chemotherapeutic activity. Thus, to a mixture of 1 mole ROCH2CO2Me, 1200 ml. benzene, and 1.5 moles oxalic acid dialkyl ester was added in small portions at 22° during 3 hrs. with cooling and stirring 60 g. NaOMe. The mixture was stirred overnight, worked up, the crude product heated with 3 g. glass powder and 5 mg. Fe powder at 210°/400 mm. for 3 hrs. followed by distillation at 11 mm. After distillation was complete the residue was heated with an addnl. 5 g. glass powder and 5 mg. iron powder for 3 hrs. at 210° and then distilled at 11 mm. The successive distillations gave ROCH(CO2Me)2 (I). I was converted to the diamide ROCH(CONH2)2 (II) by treatment with liquid NH3 for 14 hrs. at room temperature The table lists the methyl esters and amides prepared I, II; R, b11, % yield, M.p. (H2O), % yield; Me, 103-4°, 78, 217-18°, 97; Et, 114-16°, 80, 202°, 97; iso-Pr, 118-21°, 72, 218-19°, 94; Pr, 124-8°, 65, –, –; Bu, 128-30°, 63, 174-6°, 85; To a solution of 20.4 g. Na in 410 ml. absolute alc. was added 42 g. II (R = Me) followed by 20.4 ml. formamide. The solution was heated for 3 hrs. After cooling the Na salt of 4,6-dihydroxypyrimidine was filtered off, washed with absolute alc., and dried in vacuo at 50°. The crude Na salt (72.4 g.) was added slowly to 314 ml. POCl3 below 30°, followed by 31 ml. PhNMe2. The mixture was heated at 130° for 3 hrs. to give 4,6-dichloro-5-methoxypyrimidine (III), m. 57-8°. Similarly prepared were the following IV (R and b12 given): Et, 102-7°; iso-Pr, 108-13°; Bu, 128-33°. A mixture of 48 g. III and 170 ml. liquid NH3 under N at 20 atm. was shaken in an autoclave overnight to give 82% 4-amino-5-methoxy-6-chloropyrimidine (V), m. 176-8°. The 5-ethoxy, m. 119-20° (MeCN), 5-isopropoxy, m. 139-41° (MeCN), and 5-butoxy, m. 103-4°, analogs were prepared To a solution of 29.4 g. Na in 1 l. MeOH was added 170 g. V and the solution heated 18 hrs. to yield 94% 4-amino-5,6-dimethoxypyrimidine (VI), m. 88-9° (isopropyl ether). Similarly prepared were the following VIa (R, R1, and m.p. given): Me, Et, 64-58°; Me, iso-Pr, 111-12°; Me, Pr, 70-1°; Me, CH2CH:CH2, 41-2°; Me, C10H21, 53-4°; Et, Et, 83-4°; Bu, C10H21, 32-3°; Bu, CH2CH2OCH2Me, 98-9°. To a solution of 62 g. VI in 160 ml. absolute pyridine was added over 3 hrs. 130 g. 4-acetamidobenzenesulfonyl chloride at 3-4° and the solution kept overnight to yield 89.5% VII (R = Me, R1 = OMe, X = Ac), m. 230-1° (HOAc), hydrolysis of which with 2N NaOH gave VII (R = Me, R1 = OMe, X = H), m. 201-2°. The following VII (R = Me) were similarly prepared (R1, X, and m.p. given): EtO, Ac, 201-2°; EtO, H, 170-1°; PrO, Ac, 186-7°; PrO, H, 142-3°; iso-PrO, Ac, 195-7°; iso-PrO, H, 136-7°; MeO, HCO, 194-5°. Also prepared were the following VII (X = H) (R, R1, and m.p. given): Me, OC10H21, 94-6°; Me, OPr-iso, 136-7°; Et, Cl, 215-16°; Et, OMe, 228-9°; Et, OEt, 173-4°; Et, OCH2CH:CH2, 152°; Et, OPr, 162°; Et, OPr-iso, 181-3°; Me, OCH2CH:CH2, 145-6°; iso-Pr, OMe, 193-5°; iso-Pr, OEt, 183-4°; iso-Pr, OPr-iso, 170-1°; Bu, Cl, 172-4°; iso-Pr, OCH2CH:CH2, 146-8°; Bu, OMe, 192-3°; H, OC10H21, 142-4°; Cl, OPr-iso, 172-4°. To a solution of 155 g. Na sulfanilamide in 500 ml. Me2NCHO was added slowly 71.6 g. III at 100°. Work-up gave 82% 4-sulfanilamido-5-methoxy-6-chloropyrimidine (VIII), m. 200-2° (alc.-H2O). To a solution of 5.75 g. Na in 200 ml. allyl alc. was added 31.4 g. VIII to give 4-sulfanilamido-5-methoxy-6-allyloxypyrimidine, m. 145 (BuOAc). To 31 g. VI in 140 ml. absolute pyridine was added 88 g. p-nitrobenzenesulfonyl chloride to give 105 g. 4-[bis(4-nitrophenylsulfonyl)amino]-5,6-dimethoxypyrimidine (IX), m. 216-17° (glacial HOAC). Partial hydrolysis of IX with NaOH in absolute MeOH gave 4-(4-nitrobenzenesulfonamido)-5,6-dimethoxypyrimidine (X), m. 136-8° (MeCN). Treatment of X with Ac2O in absolute pyridine for 3 hrs. on a steam bath gave 4-(N-acetyl-4-nitrobenzenesulfonamido)-5,6-dimethoxypyrimidine (XI), m. 160-2° (MeCN). Reduction of 13 g. XI in 540 ml. HOAc in the presence of 13 g. 5% Pd-C at room temperature gave 8.5 g. 4-(N’-acetylsulfanilamido)-5,6-dimethoxypyrimidine, m. 196-8 (MeCN). The following XII were similarly prepared (R, R1, X, and m.p. given): OMe, C10H21, 4-O2NC6H4SO2, 112-13°; OMe, C10H21, H, 114-15°; OBu, OCH2CH2OEt, 4-O2NC6H4SO2, 124-5°; OBu, OCH2CH2OEt, H, 96-8°.

Monatshefte fuer Chemie published new progress about 5018-38-2. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, Formula: C5H4Cl2N2O.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Picazo, Edwige M. H.; Heptinstall, Amy B.; Wilson, David M.; Cano, Celine; Golding, Bernard T.; Waring, Michael J. published the artcile< Cyclizations and fragmentations in the alkylation of 6-chloro-5-hydroxy-4-aminopyrimidines with aminoalkyl chlorides>, Electric Literature of 5018-38-2, the main research area is polysubstituted aminopyrimidine preparation; chlorohydroxyaminopyrimidine aminoalkyl chloride alkylation.

Substituted aminopyrimidines are an important class of compounds, in part because they frequently show biol. activity. Facile synthesis of polysubstituted aminopyrimidines is highly desirable for the synthesis of screening libraries. Authors describe a route to 4,6-diamino-5-alkoxypyrimidines via a SNAr-alkylation-SNAr sequence from readily available 4,6-dichloro-5-methoxypyrimidine, which allows the synthesis of such compounds with regiochem. control. The extension of this approach to alkylating agents bearing amino substituents led to unexpected and, in some cases, unprecedented products resulting from intramol. SNAr cyclization and subsequent fragmentation.

Journal of Heterocyclic Chemistry published new progress about Alkylation. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, Electric Literature of 5018-38-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

von Angerer, S. published the artcile< Product class 12: pyrimidines>, Synthetic Route of 99469-85-9, the main research area is review pyrimidine preparation cyclization ring transformation aromatization.

A review. Methods for preparing pyrimidines are reviewed including cyclization, ring transformation, aromatization and substituent modification.

Science of Synthesis published new progress about Aromatization. 99469-85-9 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2S, Synthetic Route of 99469-85-9.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

La Colla, Paolo; Marcialis, Maria A.; Flore, Ornella; Sau, Mario; Garzia, Aldo; Loddo, Bernardo published the artcile< Specific inhibition of virus multiplication by bichlorinated pyrimidines>, COA of Formula: C5H4Cl2N2O, the main research area is antiviral dichloro pyrimidine derivative; viricidal dichloropyrimidine derivative.

None of the 13 nonchlorinated or monochlorinated pyrimidines tested had any inhibitory effect on polio 1, vaccinia, and herpes simplex viruses, but all 8 dichloro derivatives inhibited growth of all 3 viruses, with 2-amino-4,6-dichloropyrimidine (I) [56-05-3] being the most active. 2-Mercaptoethanol enhanced the antiviral effect of the dichloropyrimidines. The compounds also inhibited coxsackie B1 virus, but had no effect on vesicular stomatitis or Newcastle disease viruses. Results from the effect of protein and RNA precursors on the antipolio action of I and from the effects of I on poliovirus synthesis and organization are also given. The mechanism of action of I and the structure-activity relation for the dichloropyrimidines are discussed.

Annals of the New York Academy of Sciences published new progress about Antiviral agents. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, COA of Formula: C5H4Cl2N2O.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia