Tag: 100-200

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 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 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 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

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

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

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

Jakubiec, Dominika; Przypis, Lukasz; Suwinski, Jerzy W.; Walczak, Krzysztof Z. published an article in 2017, the title of the article was Synthesis of 5-hetaryluracil derivatives via 1,3-dipolar cycloaddition reaction.Synthetic Route of 4433-40-3 And the article contains the following content:

1,3-Dipolar cycloaddition was applied for the synthesis 5-hetaryluracil derivatives where substituted uracils played the role of 1,3-dipoles or dipolarophiles. Treatment of the nitrile oxide derived from 5-formyluracil and substituted alkenes gave the appropriate 5-(4,5-dihydroisoxazol-3-yl)pyrimidine-2,4(1H,3H)-diones, which by oxidation with N-bromosuccinimide were transformed into appropriate 5-(isoxazol-3-yl)uracils. When 5-cyanouracil was used as a dipolarophile in the reaction with nitrile oxides, generated from aromatic aldoximes, several 5-(1,2,4-oxadiazol-5-yl)uracils were obtained. An alternative reaction of 5-formyluracil with an excess of nitriles in the presence of cerium ammonium nitrate as an oxidant gave 1,2,4-oxadiazol-3-yl derivatives in moderate yields. The experimental process involved the reaction of 5-(Hydroxymethyl)pyrimidine-2,4(1H,3H)-dione(cas: 4433-40-3).Synthetic Route of 4433-40-3

The Article related to dioxopyrimidinyl aldoxime preparation alkene regioselective dipolar cycloaddition, dihydroisoxazolyl uracil preparation, nitrile dioxopyrimidinyl aldoxime dipolar cycloaddition, oxadiazoyl uracil preparation, phenyl aldoxime cyanouracil dipolar cycloaddition and other aspects.Synthetic Route of 4433-40-3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On October 26, 2020, Curti, Claudio; Rassu, Gloria; Lombardo, Marco; Zambrano, Vincenzo; Pinna, Luigi; Battistini, Lucia; Sartori, Andrea; Pelosi, Giorgio; Zanardi, Franca published an article.Application of 626-48-2 The title of the article was Unlocking Access to Enantiopure Fused Uracils by Chemodivergent [4+2] Cross-Cycloadditions: DFT-Supported Homo-Synergistic Organocatalytic Approach. And the article contained the following:

The discovery of chem. methods enabling the construction of carbocycle-fused uracils which embody a three-dimensional and functional-group-rich architecture is a useful tool in medicinal chem. oriented synthesis. In this work, an unprecedented amine-catalyzed [4+2] cross-cycloaddition is documented; it involves remotely enolizable 6-methyluracil-5-carbaldehydes and β-aryl enals, and chemoselectively produces two novel bicyclic and tricyclic fused uracil chemotypes in good yields with a maximum level of enantiocontrol. In-depth mechanistic investigations and control experiments support an intriguing homo-synergistic organocatalytic approach, where the same amine organocatalyst concomitantly engages both aldehyde partners in a stepwise eliminative [4+2] cycloaddition, whose vinylogous iminium ion intermediate product may diverge-depending upon conditions-to either bicyclic targets by hydrolysis or tricyclic products by a second homo-synergistic trienamine-mediated stepwise [4+2] cycloaddition The experimental process involved the reaction of 6-Methylpyrimidine-2,4(1H,3H)-dione(cas: 626-48-2).Application of 626-48-2

The Article related to uracil cinnamaldehyde chemoselective regioselective diastereoselective enantioselective organocatalysis cycloaddition, carbocycle fused uracil stereoselective preparation, asymmetric synthesis, cycloaddition, fused-ring systems, heterocycles, organocatalysis and other aspects.Application of 626-48-2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On February 26, 1998, Rewcastle, Gordon W.; Murray, Donna K.; Elliott, William L.; Fry, David W.; Howard, Curtis T.; Nelson, James M.; Roberts, Billy J.; Vincent, Patrick W.; Showalter, H. D. Hollis; Winters, R. Thomas; Denny, William A. published an article.Formula: C7H3ClFN3 The title of the article was Tyrosine Kinase Inhibitors. 14. Structure-Activity Relationships for Methyl- amino-Substituted Derivatives of 4-[(3-Bromophenyl)amino]-6-(methylamino)- pyrido[3,4-d]pyrimidine (PD 158780), a Potent and Specific Inhibitor of the Tyrosine Kinase Activity of Receptors for the EGF Family of Growth Factors. And the article contained the following:

PD 158780 (I) is a very potent in vitro inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) (IC50 = 0.08 nM), and other members of the erbB family, by competitive binding at the ATP site of these signal transduction enzymes. A series of analogs of PD 158780 bearing solubilizing functions off the 6-methylamino substituent were prepared by reaction of the 6-fluoro derivatives with appropriate amine nucleophiles. These were evaluated for their ability to inhibit the tyrosine phosphorylating action of EGF-stimulated full-length EGFR enzyme and for inhibition of autophosphorylation of the EGFR in A431 human epidermoid carcinoma cells in culture. The most effective analogs were those bearing weakly basic substituents through a secondary amine linkage, which proved water-soluble (>10 mM) and potent (IC50s generally <1 nM). No clear SAR could be discerned for these compounds with respect to amine base strength or the distance of the cationic center from the chromophore, suggesting that 6-substituents are in a favorable area of bulk tolerance in the enzyme binding site. More distinct SAR emerged for the ability of the compounds to inhibit EGFR autophosphorylation in A431 cells, where analogs bearing lipophilic weak bases were preferred. Representative analogs were evaluated for antitumor effectiveness against four in vivo tumor models. Significant in vivo activity was observed in estrogen-dependent MCF-7 breast and A431 epidermoid tumors. Marginal activity was seen in an EGFR-transfected tumor model, suggesting that while this cell line requires EGF for clone formation in soft agar, other growth factors may be able to replace EGF in vivo. Also, activity was seen against the SK-OV-3 ovarian cancer model, which is known to express other EGF receptor family members (although it is not clear whether these are absolutely required for growth in vivo). While substantial growth delays were seen in A431 and MCF-7 tumor models, the treated tumors remained approx. the same size throughout therapy, suggesting that the compounds are cytostatic rather than cytotoxic under these test conditions. It remains to be determined if more prolonged therapy has cytotoxic effects in vivo, resulting in net tumor cell kill. The experimental process involved the reaction of 4-Chloro-6-fluoropyrido[3,4-d]pyrimidine(cas: 175357-98-9).Formula: C7H3ClFN3

The Article related to pd 158780 analog preparation structure activity, antitumor activity pd 158780 analog preparation, tyrosine kinase inhibitor pd 158780 analog, autophosphorylation inhibitor pd 158780 analog preparation, epidermal growth factor receptor inhibitor preparation and other aspects.Formula: C7H3ClFN3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia