Month: October 2022

On January 1, 2020, Semenov, Vyacheslav E.; Zueva, Irina V.; Lushchekina, Sofya V.; Lenina, Oksana A.; Gubaidullina, Lilya M.; Saifina, Lilya F.; Shulaeva, Marina M.; Kayumova, Ramilya M.; Saifina, Alina F.; Gubaidullin, Aidar T.; Kondrashova, Svetlana A.; Latypov, Shamil K.; Masson, Patrick; Petrov, Konstantin A. published an article.Safety of 6-Methylpyrimidine-2,4(1H,3H)-dione The title of the article was 6-Methyluracil derivatives as peripheral site ligand-hydroxamic acid conjugates: Reactivation for paraoxon-inhibited acetylcholinesterase. And the article contained the following:

New uncharged conjugates of 6-methyluracil derivatives with imidazole-2-aldoxime I (n = 1, 2, 3, 4) and 1,2,4-triazole-3-hydroxamic acid units II (n = 2, 3, 4) were synthesized and studied as reactivators of organophosphate-inhibited cholinesterase. Using paraoxon (POX) as a model organophosphate, it was shown that 6-methyluracil derivatives linked with hydroxamic acid are able to reactivate POX-inhibited human acetylcholinesterase (AChE) in vitro. The reactivating efficacy of one compound II (n = 3) is lower than that of pyridinium-2-aldoxime (2-PAM). Meanwhile, unlike 2-PAM, in vivo study showed that the lead compound II (n = 3) is able: (1) to reactivate POX-inhibited AChE in the brain; (2) to decrease death of neurons and, (3) to prevent memory impairment in rat model of POX-induced neurodegeneration. The experimental process involved the reaction of 6-Methylpyrimidine-2,4(1H,3H)-dione(cas: 626-48-2).Safety of 6-Methylpyrimidine-2,4(1H,3H)-dione

The Article related to methyluracil imidazole aldoxime triazole hydroxamic acid preparation mol docking, reactivator paraoxon acetylcholinesterase butyrylcholinesterase inhibitor, 3,6-dimethyluracil, acetylcholinesterase, hydroxamic acids, molecular modeling, paraoxon, reactivator and other aspects.Safety of 6-Methylpyrimidine-2,4(1H,3H)-dione

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Hrabina, Ondrej; Brabec, Viktor; Novakova, Olga published an article in 2019, the title of the article was Translesion DNA synthesis across lesions induced by oxidative products of pyrimidines: an insight into the mechanism by microscale thermophoresis.Quality Control of 5-(Hydroxymethyl)pyrimidine-2,4(1H,3H)-dione And the article contains the following content:

Oxidative stress in cells can lead to the accumulation of reactive oxygen species and oxidation of DNA precursors. Oxidized nucleotides such as 2′-deoxyribo-5-hydroxyuridin (HdU) and 2′-deoxyribo-5-hydroxymethyluridin (HMdU) can be inserted into DNA during replication and repair. HdU and HMdU have attracted particular interest because they have different effects on damaged-DNA processing enzymes that control the downstream effects of the lesions. Herein, we studied the chem. simulated translesion DNA synthesis (TLS) across the lesions formed by HdU or HMdU using microscale thermophoresis (MST). The thermodn. changes associated with replication across HdU or HMdU show that the HdU paired with the mismatched deoxyribonucleoside triphosphates disturbs DNA duplexes considerably less than thymidine (dT) or HMdU. Moreover, we also demonstrate that TLS by DNA polymerases across the lesion derived from HdU was markedly less extensive and potentially more mutagenic than that across the lesion formed by HMdU. The equilibrium thermodn. data obtained by MST can explain the influence of the thermodn. alterations on the ability of DNA polymerases to bypass lesions induced by oxidative products of pyrimidines. The results also highlighted the usefulness of MST in evaluating the impact of oxidative products of pyrimidines on the processing of these lesions by damaged DNA processing enzymes. The experimental process involved the reaction of 5-(Hydroxymethyl)pyrimidine-2,4(1H,3H)-dione(cas: 4433-40-3).Quality Control of 5-(Hydroxymethyl)pyrimidine-2,4(1H,3H)-dione

The Article related to translesion dna synthesis deoxyribo hydroxyuridine hydroxymethyluridine polymerase oxidative stress, 2’-deoxyribo-5-hydroxymethyl- uridin, 2’-deoxyribo-5-hydroxyuridin, dna polymerases, microscale thermophoresis, oxidized nucleotides, translesion dna synthesis and other aspects.Quality Control of 5-(Hydroxymethyl)pyrimidine-2,4(1H,3H)-dione

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Fu, Suhong; Xiang, Wei; Chen, Jinying; Ma, Liang; Chen, Lijuan published an article in 2017, the title of the article was Synthesis and biological evaluation of 1, 2, 4-oxadiazole derivatives as novel GPR119 agonists.Application of 596114-50-0 And the article contains the following content:

Aryloxymethyl piperidinyl 1,2,4-oxadiazoles I [R = Boc, 5-R2-2-pyrimidinyl; R1 = 5-formyl-2-furanyl, 5-formyl-2-thienyl, 5-acetyl-2-thienyl, 4-MeOC6H4, 4-MeSO2C6H4, 1-cyclopropyl-3-pyrazolyl, 1-methyl-3-pyrazolyl, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 2-chloro-4-pyridinyl, 6-methoxy-3-pyridinyl, 6-fluoro-3-pyridinyl, 6-methyl-3-pyridinyl, 2-pyrimidinyl, 5-pyrimidinyl, 2-pyrazinyl, 5-oxazolyl, 4-(ethoxycarbonyl)-5-methyl-2-thiazolyl, 4-(ethoxycarbonyl)-2-thiazolyl, 2-ethyl-1,2,4-oxadiazol-5-yl; R2 = Et, i-Pr, EtO] were prepared as potential GPR119 agonists; agonism of GPR119 in human cells expressing GPR119, comparison to the pos. control GSK1292263, and their calculated lipophilicities were determined The prepared compounds showed acceptable agonistic effects at GPR119; I (R = Boc; R1 = 5-pyrimidinyl) was the most active GPR119 agonist tested with an EC50 value of 20.6 nM, comparable to that of the pos. control. The structure-activity relationship of the prepared 1,2,4-oxadiazole derivatives for GPR119 agonism was determined The experimental process involved the reaction of 2-Chloro-5-isopropylpyrimidine(cas: 596114-50-0).Application of 596114-50-0

The Article related to butoxycarbonylpiperidinyl pyrimidinylpiperidinyl aryloxymethyl oxadiazole preparation gpr119 agonism lipophilicity, structure butoxycarbonylpiperidinyl pyrimidinylpiperidinyl aryloxymethyl oxadiazole gpr119 agonism, gpcr, gpr119, sar study, agonistic activity, camp and other aspects.Application of 596114-50-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On February 5, 2015, Blinn, James Robert; Flick, Andrew Christopher; Wennerstaal, Goeran Mattias; Jones, Peter; Kaila, Neelu; Kiefer, James Richard, Jr.; Kurumbail, Ravi G.; Mente, Scot Richard; Meyers, Marvin Jay; Schnute, Mark Edward; Thorarensen, Atli; Xing, Li; Zamaratski, Edouard; Zapf, Christoph Wolfgang published a patent.Safety of 2-Chloro-5-isopropylpyrimidine The title of the patent was Preparation of N-heteroaryl amides as RORC2 inhibitors. And the patent contained the following:

The present invention provides compounds I-VII [Y = H, halo, CN, etc.; R1 = H, alkyl, hydroxyalkyl, haloalkyl; X = NHC(O)R2, NHC(O)NHR2, NHSO2R2, etc.; R2 = alkyl, cycloalkyl, aryl, etc.; W = N-substituted 4-piperidinyl, 3-piperidinyl, 3-pyrrolidinyl, 3-azetidinyl], pharmaceutical compositions, methods of inhibiting RORγ activity and/or reducing the amount of IL-17 in a subject, and methods of treating various medical disorders using such compounds I-VII and pharmaceutical compositions Ninety-five compounds I-VII were prepared E.g., a multi-step synthesis of VIII, starting from 5-nitroindole and tert-Bu 4-oxopiperidine-1-carboxylate, was described. Exemplified compounds I were evaluated for RORC2 activity (data given). The experimental process involved the reaction of 2-Chloro-5-isopropylpyrimidine(cas: 596114-50-0).Safety of 2-Chloro-5-isopropylpyrimidine

The Article related to heteroaryl amide preparation rorc2 inhibitor immune inflammatory disorder treatment, antiinflammatory immunomodulator antiarthritic antirheumatic heteroaryl amide preparation interleukin17 decrease, sulfonamide urea amide heteroaryl indolyl pyrrolopyridinyl preparation rorc2 inhibitor and other aspects.Safety of 2-Chloro-5-isopropylpyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On August 15, 2015, Li, Wei; Liu, Yucan; Duan, Jinming; van Leeuwen, John; Saint, Christopher P. published an article.Computed Properties of 626-48-2 The title of the article was UV and UV/H2O2 treatment of diazinon and its influence on disinfection byproduct formation following chlorination. And the article contained the following:

Incomplete oxidation of organic micro-pollutants may result in diverse, intermittent oxidation byproducts, significantly affecting disinfection byproduct (DBP) formation from the original solutions following chlorination. This work assessed DBP formation from diazinon in solution due to the formation of intermittent oxidation byproducts by UV and UV/H2O2 pre-oxidation Monochloroacetic acid (MCAA), dichloroacetic acid (DCAA), trichloroacetic acid (TCAA), chloroform (TCM), dichloroacetonitrile (DCAN), and 1,1,1-trichloroacetone (1,1,1-TCP) were detected for chlorinated diazinon solutions which were treated by UV and UV/H2O2 oxidation DBP formation significantly increased in diazinon solutions treated by UV irradiation Solution pH and H2O2 dose also had distinct effects on DBP formation, depending on the individual DBP species. Speciation and mol. structures of oxidation byproducts were analyzed by mass spectrometry and tandem mass spectrometry. Four main UV oxidation byproducts (2-isopropyl-6-methyl-4-pyrimidinol [IMP], O-analog diazinon [diazoxon], di-Et thiophosphate [DETP], di-Et phosphate [DEP]) were examined individually to identify their relative contribution to DBP formation. Increased total DBP formation of treated diazinon solutions was mainly attributable to its oxidation product, IMP, and its secondary oxidation products; the other 2 fragments, DETP and DEP, had little effect. Its oxidation fragment, diazoxon, intensified MCAA, DCAA, and TCAA formation under UV/H2O2 pre-oxidation conditions. The experimental process involved the reaction of 6-Methylpyrimidine-2,4(1H,3H)-dione(cas: 626-48-2).Computed Properties of 626-48-2

The Article related to water purification chlorination pre oxidation disinfection, hydrogen peroxide uv irradiation pre oxidation water purification, disinfection byproduct formation diazinon containing water chlorination oxidation disinfection, intermittent oxidation product effect disinfection byproduct formation and other aspects.Computed Properties of 626-48-2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On May 20, 1999, Smaill, Jeff B.; Palmer, Brian D.; Rewcastle, Gordon W.; Denny, William A.; McNamara, Dennis J.; Dobrusin, Ellen M.; Bridges, Alexander J.; Zhou, Hairong; Showalter, H. D. Hollis; Winters, R. Thomas; Leopold, Wilbur R.; Fry, David W.; Nelson, James M.; Slintak, Veronika; Elliot, William L.; Roberts, Billy J.; Vincent, Patrick W.; Patmore, Sandra J. published an article.Name: 4-Chloro-6-fluoropyrido[3,4-d]pyrimidine The title of the article was Tyrosine kinase inhibitors. 15. 4-(Phenylamino)quinazoline and 4-(phenylamino)pyrido[d]pyrimidine acrylamides as irreversible inhibitors of the ATP binding site of the epidermal growth factor receptor. And the article contained the following:

A series of 6- and 7-acrylamide derivatives of the 4-(phenylamino)quinazoline and -pyridopyrimidine classes of epidermal growth factor receptor (EGFR) inhibitors, I (R = Br, Cl, Me, X = CH, N), II (R = 3-Br, 3-Cl, 3-Me, 3-CF3, 3-Br-4-F, 3-Cl-4-F, 4-OPh, 4-OCH2Ph), III (R = 3-Br, 3-Br-4-F, 3-Cl-4-F), and IV, were prepared from the corresponding amino compounds by reaction with either acryloyl chloride/base or acrylic acid/1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. All of the 6-acrylamides, but only the parent quinazoline 7-acrylamide, were irreversible inhibitors of the isolated enzyme, confirming that the former are better-positioned, when bound to the enzyme, to react with the critical cysteine-773. Quinazoline, pyrido[3,4-d]pyrimidine, and pyrido[3,2-d]pyrimidine 6-acrylamides were all irreversible inhibitors and showed similar high potencies in the enzyme assay (likely due to titration of the available enzyme). However, the pyrido[3,2-d]pyrimidine analogs were 2-6-fold less potent than the others in a cellular autophosphorylation assay for EGFR in A431 cells. The quinazolines were generally less potent overall toward inhibition of heregulin-stimulated autophosphorylation of erbB2 (in MDA-MB-453-cells), whereas the pyridopyrimidines were equipotent. Selected compounds were evaluated in A431 epidermoid and H125 non-small-cell lung cancer human tumor xenografts. The compounds showed better activity when given orally than i.p. All showed significant tumor growth inhibition (stasis) over a dose range. The poor aqueous solubility of the compounds was a drawback, requiring formulation as fine particulate emulsions. The experimental process involved the reaction of 4-Chloro-6-fluoropyrido[3,4-d]pyrimidine(cas: 175357-98-9).Name: 4-Chloro-6-fluoropyrido[3,4-d]pyrimidine

The Article related to phenylaminoquinazoline acrylamide preparation egfr inhibitor, phenylaminopyridopyrimidine acrylamide preparation egfr inhibitor, epidermal growth factor receptor inhibitor acrylamide, antitumor quinazoline pyridopyrimidine acrylamide, acrylamide quinazoline pyridopyrimidine egfr inhibitor antitumor and other aspects.Name: 4-Chloro-6-fluoropyrido[3,4-d]pyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On October 20, 2011, Barba, Oscar; Gattrell, William; Smyth, Donald; Swain, Simon published a patent.Recommanded Product: 596114-50-0 The title of the patent was Preparation of 3-substituted 5-(pyrrolidine-1-carbonyl)pyrrolidine and its derivatives for use in the treatment of metabolic disorders. And the patent contained the following:

The title compounds I [p, q = 1-2; Z = NC(O)OR4, NC(O)NR4R5, N-heteroaryl, etc.; Y = CH2, CF2, CHF, O, NR1, C(O) or B (wherein B = 5-membered heteroaryl containing one or more heteroatoms selected from N, O and S); when Y = CH2, CF2, CHF, O, NR1 or C(O), X = (un)branched alkylene; or when Y = O or NR1, X may also be -ACHR2- (wherein A = 5-membered heteroaryl containing one or more heteroatoms selected from N, O and S); and when Y = B, X = OCHR3; Ar = (un)substituted para-substituted 6-membered heteroaryl containing one or two N atoms; R1-R3 = H, alkyl; R4 = aryl, heteroaryl, alkyl,(un)substituted cycloalkyl; R5 = H or alkyl; V = II (T = CH2, or, when m = 1, T may also be S; when T = CH2, R6 = F or CN, and when T = S, R6 = CN; R7 = H, alkyl; m = 0-1; s = 0-2); n = 0-1] which have activity as agonists of GPR119 and are useful for the treatment of metabolic disorders including type II diabetes, were prepared For example, Pd-catalyzed coupling 2-bromo-5-{3-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)piperidin-4-yl]propoxy}pyridine with tert-Bu (2S,4S)-4-amino-2-(pyrrolidine-1-carbonyl)pyrrolidine-1-carboxylate (preparations given) followed by Boc-deprotection afforded (2S,4S)-III. Compounds I produced a concentration-dependent increase in intracellular cAMP level and generally had an EC50 of <10 μM when tested in GPR119 cAMP assay. All exemplified compounds I showed activity in DPP-IV assay having an IC50 of <20 μM. Pharmaceutical composition comprising compound I is disclosed. The experimental process involved the reaction of 2-Chloro-5-isopropylpyrimidine(cas: 596114-50-0).Recommanded Product: 596114-50-0

The Article related to pyrrolidinecarbonylpyrrolidine preparation glucose dependent insulinotropic polypeptide receptor gpr119 agonist, metabolic disorder type ii diabetes treatment pyrrolidinecarbonylpyrrolidine preparation, antidiabetic pyrrolidinecarbonylpyrrolidine preparation gpr119 agonist dipeptidyl peptidase dppiv modulator and other aspects.Recommanded Product: 596114-50-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On June 28, 2012, Bohno, Ayako; Matsuda, Daisuke; Otake, Norikazu; Kakinuma, Hiroyuki; Kobashi, Yohei; Kawamura, Madoka; Shiozawa, Fumiyasu; Kawabe, Kenichi; Iwata, Yuki; Hamada, Makoto published a patent.Name: 2-Chloro-5-isopropylpyrimidine The title of the patent was Preparation of 4-piperidinyl-condensed heterocyclic compounds as GPR119 agonists. And the patent contained the following:

The title compounds represented by general formula [I; group A = each (un)substituted Ph or 5 or 6-membered heteroaryl; W = a single bond, O, NH, OCH2, or CH2O; X = a nitrogen atom or CR21; Y1 = a nitrogen atom or CR22; Y2 = a nitrogen atom or CR23; Y3 = a nitrogen atom or CR24; R21, R22, R23, R24 = a hydrogen atom or C1-6 alkyl; group B = C2-6 alkyl, C3-8 cycloalkyl, (C3-8 cycloalkyl)C1-6 alkyl, (aryl)C1-6 alkyl, (saturated heterocyclyl)C1-6 alkyl, CO2R31 (R31 = C1-6 alkyl, C3-8 cycloalkyl, aryl or saturated heterocyclyl), or 5 or 6-membered heteroaryl] or pharmaceutically permitted salts thereof are prepared These compounds including indazolylpiperidine, benzotriazolylpiperidine, pyrazolopyridinylpiperidine, and triazolopyridinylpiperidine compounds have an outstanding glucose-dependent insulinotropic polypeptide receptors (GPR119) agonist action. They are useful as blood-sugar lowering agents for the prevention and/or treatment of diabetes. Thus, a solution of 150 mg tert-Bu 4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazol-1-yl]piperidine-1-carboxylate in 1.5 mL DMF was treated with 155 mg 4-(1H-Tetrazol-1-yl)phenyl trifluoromethanesulfonate, [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride and 525 μL 2 M aqueous Na2CO3 solution, stirred at 100° for 1.5 h, and concentrated under reduced pressure to give, after silica gel chromatog., 100 mg tert-Bu 4-(5-[4-(1H-tetrazol-1-yl)phenyl]-1H-indazol-1-yl)piperidine-1-carboxylate (II). II and 4-[3-[1-(5-Chloropyrimidin-2-yl)piperidin-4-yl]-3H-[1,2,3]triazolo[4,5-c]pyridin-6-yl]-N-ethyl-2,3-difluorobenzamide(III) in vitro promoted the cellular production of cAMP with ED50 of 13 and 2 nM, resp., in cells expressing human GPR119. The experimental process involved the reaction of 2-Chloro-5-isopropylpyrimidine(cas: 596114-50-0).Name: 2-Chloro-5-isopropylpyrimidine

The Article related to diabetes prevention treatment piperidinyl condensed heterocyclic compound preparation, piperidinyl condensed heterocyclic compound preparation gpr119 agonist, indazolylpiperidine benzotriazolylpiperidine preparation gpr119 agonist, pyrazolopyridinylpiperidine triazolopyridinylpiperidine preparation gpr119 agonist and other aspects.Name: 2-Chloro-5-isopropylpyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On November 4, 2021, Xu, Qing; Alt, Carsten; Li, Zhe; Nilar, Shahul; Rademacher, Peter Michael; Yee, Calvin Wesley published a patent.Category: pyrimidines The title of the patent was Prepartion of pyrimidines as ferroportin inhibitors. And the patent contained the following:

The invention is related to a method of inhibiting iron transport mediated by ferroportin in a subject, comprising administering to the subject an effective amount of a compound I [Z= N, CR5; R5 = H, halo, alkyl; R6 = independently at each occurrence halo, OH, (un)substituted alkoxy, alkyl, etc.; or two R6 groups, taken together with the atom to which each is attached, form an (un)substituted 5- or 6-membered monocyclic heterocyclyl fused with ring B, a C4-C7 cycloalkyl fused with ring B, a Ph fused with ring B, or a 5- to 6-membered monocyclic heteroaryl fused with ring B; n = 0-3; Y = (Y1)0-1; Y1-4 = independently CH, N, NH, O, S, SH, SR6, NR6, CR6; provided that 1 or 2 of Y1-4 can be N, NR6, NH, O, SH or SR6; R1, R2 = independently H, alkyl, haloalkyl, alkoxy, and OH; R1 and R2 taken together with the atom to which each is attached form ring A; wherein A = (un)substituted C5-C6 cycloalkyl, 5- or 6-membered heterocyclyl, Ph, and 5- or 6-membered heteroaryl; R3 = H , optionally deuterated C1-C3 alkyl, hydroxyalkyl, C1-C3 alkoxyalkyl, haloalkyl, cyclopropyl, phenyl; R4 = CH2CONH2 and derivatives, cycloalkyl, alkylsulfonylalkyl, etc.; or R3NR4 = (un)substituted4- to 12-membered heterocyclyl] and their pharmaceutical salts. The invention is laos relates to methods of administering them for prophylaxis and/or treatment of diseases caused by a lack of hepcidin or iron metabolism disorders, particularly iron overload states, such as thalassemia, sickle cell disease and hemochromatosis, and also kidney injuries and to pharmaceutical compositions containing compounds I. Preparation of compounds I and their pharmaceutical acceptable salts is also given. Thus, II was prepared in 6 steps from 2-chloro-4-methylpyridine and diethylcarbonate using N-tert-Butyl-2-[(2-chloro-5H,6H,7H-cyclopenta[d]pyrimidin-4-yl)amino]acetamide (preparation given). II was tested in an in vitro ferroportin internalization assay (pEC50 = 7.7). The experimental process involved the reaction of 2,4-Dichloro-5,6-dimethylthieno[2,3-d]pyrimidine(cas: 42518-42-3).Category: pyrimidines

The Article related to pyrimdine cycloalkapyrimidine thienopyrimidine preparation ferroportin inhibitor, thienopyrimidine cyclopentapyrimidinyl amino acid amide preparation ferroportin inhibitor, hepcidin iron metabolism disorder cycloalkapyrimidine thienopyrimidine preparation, iron overload state thalassemia hemochromatosis treatment cycloalkapyridine thienopyrimidine preparation and other aspects.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia