Category: pyrimidines

Doherty, Elizabeth M.; Fotsch, Christopher; Bannon, Anthony W.; Bo, Yunxin; Chen, Ning; Dominguez, Celia; Falsey, James; Gavva, Narender R.; Katon, Jodie; Nixey, Thomas; Ognyanov, Vassil I.; Pettus, Liping; Rzasa, Robert M.; Stec, Markian; Surapaneni, Sekhar; Tamir, Rami; Zhu, Jiawang; Treanor, James J. S.; Norman, Mark H. published an article in Journal of Medicinal Chemistry. The title of the article was 《Novel Vanilloid Receptor-1 Antagonists: 2. Structure-Activity Relationships of 4-Oxopyrimidines Leading to the Selection of a Clinical Candidate》.Related Products of 659729-09-6 The author mentioned the following in the article:

A series of novel 4-oxopyrimidine TRPV1 antagonists was evaluated in assays measuring the blockade of capsaicin or acid-induced influx of calcium into CHO cells expressing TRPV1. The investigation of the structure-activity relationships in the heterocyclic A-region revealed the optimum pharmacophoric elements required for activity in this series and resulted in the identification of subnanomolar TRPV1 antagonists. The most potent of these antagonists were thoroughly profiled in pharmacokinetic assays. Optimization of the heterocyclic A-region led to the design and synthesis of 23 (I), a compound that potently blocked multiple modes of TRPV1 activation. Compound 23 was shown to be effective in a rodent “”on-target”” biochem. challenge model (capsaicin-induced flinch, ED50 = 0.33 mg/kg p.o.) and was antihyperalgesic in a model of inflammatory pain (CFA-induced thermal hyperalgesia, MED = 0.83 mg/kg, p.o.). Based on its in vivo efficacy and pharmacokinetic profile, compound 23 (N-{4-[6-(4-trifluoromethyl-phenyl)-pyrimidin-4-yloxy]-benzothiazol-2-yl}-acetamide; AMG 517) was selected for further evaluation in human clin. trials. The experimental part of the paper was very detailed, including the reaction process of 4-Chloro-6-(4-(trifluoromethyl)phenyl)pyrimidine(cas: 659729-09-6Related Products of 659729-09-6)

4-Chloro-6-(4-(trifluoromethyl)phenyl)pyrimidine(cas: 659729-09-6) belongs to pyrimidine. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives, including the nucleotides cytosine, thymine and uracil, thiamine (vitamin B1) and alloxan. Related Products of 659729-09-6

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Reference of 6-Bromothieno[2,3-d]pyrimidin-4(3H)-oneOn March 15, 2020, Miao, Zhuang; Sun, Yu-meng; Zhao, Lan-ying; Li, Yue-shan; Wang, Yi-fei; Nan, Jin-shan; Qiao, Ze-en; Li, Lin-li; Yang, Sheng-yong published an article in Bioorganic & Medicinal Chemistry Letters. The article was 《Discovery of thieno[2,3-d]pyrimidin-4(3H)-one derivatives as a new class of ROCK inhibitors》. The article mentions the following:

Herein, we report the discovery of a series of thieno[2,3-d]pyrimidin-4(3H)-one derivatives as a new class of ROCK inhibitors. Structure-activity relationship studies of these compounds led to the identification of the most potent compound, 3-(3-methoxybenzyl)-6-(1H-pyrrolo[2,3-b]pyridin-4-yl)thieno[2,3-d]pyrimidin-4(3H)-one (8k), which showed IC50 values of 0.004μM and 0.001μM against ROCK I and ROCK II, resp. In vitro, 8k significantly reduced the phosphorylation level of ROCK downstream signaling protein and induce changes in cell morphol. and migration. Overall, this study provides a promising lead compound for drug discovery targeting ROCKs. After reading the article, we found that the author used 6-Bromothieno[2,3-d]pyrimidin-4(3H)-one(cas: 56844-40-7Reference of 6-Bromothieno[2,3-d]pyrimidin-4(3H)-one)

6-Bromothieno[2,3-d]pyrimidin-4(3H)-one(cas: 56844-40-7) belongs to pyrimidine. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives, including the nucleotides cytosine, thymine and uracil, thiamine (vitamin B1) and alloxan. Reference of 6-Bromothieno[2,3-d]pyrimidin-4(3H)-one

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Redox-Active Reagents for Photocatalytic Generation of the OCF3 Radical and (Hetero)Aryl C-H Trifluoromethoxylation》 was written by Zheng, Weijia; Lee, Johnny W.; Morales-Rivera, Cristian A.; Liu, Peng; Ngai, Ming-Yu. Category: pyrimidinesThis research focused ontrifluoromethoxyarene trifluoromethoxyheteroarene preparation; arene heteroarene radical trifluoromethoxylation ruthenium photocatalyst; arenes; photocatalysis; radicals; trifluoromethoxylating reagents; trifluoromethoxylation. The article conveys some information:

The trifluoromethoxy (OCF3) radical is of great importance in organic chem. Yet, the catalytic and selective generation of this radical at room temperature and pressure remains a longstanding challenge. Herein, the design and development of a redox-active cationic reagent (1) that enables the formation of the OCF3 radical in a controllable, selective, and catalytic fashion under visible-light photocatalytic conditions is reported. More importantly, the reagent allows catalytic, intermol. C-H trifluoromethoxylation of a broad array of (hetero)arenes and biorelevant compounds Exptl. and computational studies suggest single electron transfer (SET) from excited photoredox catalysts to 1 resulting in exclusive liberation of the OCF3 radical. Addition of this radical to (hetero)arenes gives trifluoromethoxylated cyclohexadienyl radicals that are oxidized and deprotonated to afford the products of trifluoromethoxylation. In the experiment, the researchers used many compounds, for example, 2,4,6-Trichloropyrimidine(cas: 3764-01-0Category: pyrimidines)

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. They are generally not present in crude oils and are typically the result of additives, cleaning solutions or chemicals used for oil recovery.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Design and synthesis of triple inhibitors of janus kinase (JAK), histone deacetylase (HDAC) and Heat Shock Protein 90 (HSP90)》 was written by Yao, Lianbin; Ohlson, Sten; Dymock, Brian W.. Reference of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidineThis research focused ontriple inhibitor JAK2 histone deacetylase HSP90 antitumor drug design; HDAC; HSP90; Janus kinase; Multiple ligand; Transient drug. The article conveys some information:

Inhibition of multiple signaling pathways in a cancer cell with a single mol. could result in better therapies that are simpler to administer. Efficacy may be achieved with reduced potency against individual targets if there is synergy through multiple pathway inhibition. To achieve this, it is necessary to be able to build multi-component ligands by joining together key pharmacophores in a way which maintains sufficient activity against the individual pathways. Designed triple inhibiting ligands are explored aiming to block three completely different target types: a kinase (JAK2), an epigenetic target (HDAC) and a chaperone (HSP90). Although these enzymes have totally different functions they are related through inter-dependent pathways in the developing cancer cell. Synthesis of several complex multi-inhibiting ligands are presented along with initial enzyme inhibition data against 3 biol. target classes of interest. A lead compound, 47 (I), was discovered which had low micromolar activity for all 3 targets. Further development of these complex trispecific designed multiple ligands could result in a ‘transient drug’, an alternative combination therapy for treating cancer mediated via a single mol. After reading the article, we found that the author used 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Reference of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine)

2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. Pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics. Reference of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Related Products of 90213-66-4In 2021 ,《Design and Synthesis of Pyrrolo[2,3-d]pyrimidine-Derived Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors Using a Checkpoint Kinase 1 (CHK1)-Derived Crystallographic Surrogate》 appeared in Journal of Medicinal Chemistry. The author of the article were Williamson, Douglas S.; Smith, Garrick P.; Mikkelsen, Gitte K.; Jensen, Thomas; Acheson-Dossang, Pamela; Badolo, Lassina; Bedford, Simon T.; Chell, Victoria; Chen, I-Jen; Dokurno, Pawel; Hentzer, Morten; Newland, Samantha; Ray, Stuart C.; Shaw, Terry; Surgenor, Allan E.; Terry, Lindsey; Wang, Yikang; Christensen, Kenneth V.. The article conveys some information:

Inhibitors of leucine-rich repeat kinase 2 (LRRK2) and mutants, such as G2019S, have potential utility in Parkinson’s disease treatment. Fragment hit-derived pyrrolo[2,3-d]pyrimidines underwent optimization using X-ray structures of LRRK2 kinase domain surrogates, based on checkpoint kinase 1 (CHK1) and a CHK1 10-point mutant. (2R)-2-Methylpyrrolidin-1-yl derivative I (LRRK2 G2019S cKi 0.7 nM, LE 0.66) was identified, with increased potency consistent with an X-ray structure of 18/CHK1 10-pt. mutant showing the 2-Me substituent proximal to Ala147 (Ala2016 in LRRK2). Further structure-guided elaboration of I gave the 2-[(1,3-dimethyl-1H-pyrazol-4-yl)amino] deriv II. Optimization of II afforded diastereomeric oxolan-3-yl derivatives III and IV, which demonstrated a favorable in vitro PK profile, although they displayed species disconnects in the in vivo PK profile, and a propensity for P-gp- and/or BCRP-mediated efflux in a mouse model. Compounds III and IV demonstrated high potency and exquisite selectivity for LRRK2 and utility as chem. probes for the study of LRRK2 inhibition. In the experiment, the researchers used many compounds, for example, 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Related Products of 90213-66-4)

2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. Pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics. Related Products of 90213-66-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Product Details of 90213-66-4In 2016 ,《An improved synthesis approach of the HIV-1 inhibitor RDEA427, a pyrrolo[2,3-d]pyrimidine derivative》 appeared in ARKIVOC (Gainesville, FL, United States). The author of the article were Huang, Boshi; Liu, Xinhao; Li, Wanzhuo; Chen, Zihui; Kang, Dongwei; Zhan, Peng; Liu, Xinyong. The article conveys some information:

A new method for the synthesis of HIV-1 inhibitor RDEA427, a pyrrolo[2,3-d]pyrimidine derivative I was developed. The total yield of the optimized route increased to 39%, over 20 times better than that of the original one. On the whole, the reaction conditions were relatively mild, environment-friendly and economic. In the experiment, the researchers used many compounds, for example, 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Product Details of 90213-66-4)

2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. Product Details of 90213-66-4They 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.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Reddy, Bhoomireddy Rajendra Prasad; Reddy, Motakatla Venkata Krishna; Reddy, Peddiahgari Vasu Govardhana; Kumar, Dharani Praveen; Shankar, Muthukonda V. published an article on February 10 ,2016. The article was titled 《Protonated trititanate nanotubes: an efficient catalyst for one-pot three-component coupling of benzothiazole amines, heterocyclic aldehydes, and dialkyl/diaryl phosphites with a greener perspective》, and you may find the article in Tetrahedron Letters.Product Details of 640769-70-6 The information in the text is summarized as follows:

Nano-size catalysts of TiO2, ZnO, CuO, and protonated trititanate nanotubes (H2Ti3O7) have been investigated for the one-pot three component synthesis of novel α-aminophosphonates from benzothiazole amines, heteroaldehydes, and dialkyl/diaryl phosphites via Kabachnik-Fields reaction. This methodol. provides a new and convenient approach to multicomponent reaction and the H2Ti3O7 nanotubes catalyst is recyclable up to seven cycles. The experimental process involved the reaction of 3-(Pyrimidin-5-yl)benzaldehyde(cas: 640769-70-6Product Details of 640769-70-6)

3-(Pyrimidin-5-yl)benzaldehyde(cas: 640769-70-6) belongs to pyrimidine. Pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics. Product Details of 640769-70-6

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Lim, Sang Min; Xie, Ting; Westover, Kenneth D.; Ficarro, Scott B.; Tae, Hyun Seop; Gurbani, Deepak; Sim, Taebo; Marto, Jarrod A.; Janne, Pasi A.; Crews, Craig M.; Gray, Nathanael S. published their research in Bioorganic & Medicinal Chemistry Letters on August 15 ,2015. The article was titled 《Development of small molecules targeting the pseudokinase Her3》.Related Products of 213743-31-8 The article contains the following contents:

Her3 is a member of the human epidermal growth factor receptor (EGFR) tyrosine kinase family, and it is often either overexpressed or deregulated in many types of human cancer. Her3 has not been the subject of small-mol. inhibitor development because it is a pseudokinase and does not possess appreciable kinase activity. We recently reported on the development of the first selective irreversible Her3 ligand (TX1-85-1) that forms a covalent bond with cysteine 721 which is unique to Her3 among all kinases. We also developed a bi-functional compound (TX2-121-1) containing a hydrophobic adamantane moiety and the same warhead of TX1-85-1 that is capable of inhibiting Her3-dependent signaling and growth. Here we report on the structure-based medicinal chem. effort that resulted in the discovery of these two compounds7-Cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine(cas: 213743-31-8Related Products of 213743-31-8) was used in this study.

7-Cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine(cas: 213743-31-8) belongs to pyrimidine. Pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics.Related Products of 213743-31-8

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia