Month: March 2022

Most of the compounds have physiologically active properties, and their biological properties are often attributed to the heteroatoms contained in their molecules, and most of these heteroatoms also appear in cyclic structures. A Journal, Article, Journal of Medicinal Chemistry called Discovery of Potent, Selective, and State-Dependent NaV1.7 Inhibitors with Robust Oral Efficacy in Pain Models: Structure-Activity Relationship and Optimization of Chroman and Indane Aryl Sulfonamides, Author is Ramdas, Vidya; Talwar, Rashmi; Kanoje, Vijay; Loriya, Rajesh M.; Banerjee, Moloy; Patil, Pradeep; Joshi, Advait Arun; Datrange, Laxmikant; Das, Amit Kumar; Walke, Deepak Sahebrao; Kalhapure, Vaibhav; Khan, Talha; Gote, Ganesh; Dhayagude, Usha; Deshpande, Shreyas; Shaikh, Javed; Chaure, Ganesh; Pal, Ravindra R.; Parkale, Santosh; Suravase, Sachin; Bhoskar, Smita; Gupta, Rajesh V.; Kalia, Anil; Yeshodharan, Rajesh; Azhar, Mahammad; Daler, Jagadeesh; Mali, Vinod; Sharma, Geetika; Kishore, Amitesh; Vyawahare, Rupali; Agarwal, Gautam; Pareek, Himani; Budhe, Sagar; Nayak, Arun; Warude, Dnyaneshwar; Gupta, Praveen Kumar; Joshi, Parag; Joshi, Sneha; Darekar, Sagar; Pandey, Dilip; Wagh, Akshaya; Nigade, Prashant B.; Mehta, Maneesh; Patil, Vinod; Modi, Dipak; Pawar, Shashikant; Verma, Mahip; Singh, Minakshi; Das, Sudipto; Gundu, Jayasagar; Nemmani, Kumar; Bock, Mark G.; Sharma, Sharad; Bakhle, Dhananjay; Kamboj, Rajender Kumar; Palle, Venkata P., which mentions a compound: 591-54-8, SMILESS is C1=CN=CN=C1N, Molecular C4H5N3, Recommanded Product: 591-54-8.

Voltage-gated sodium channel NaV1.7 is a genetically validated target for pain. Identification of NaV1.7 inhibitors with all of the desired properties to develop as an oral therapeutic for pain has been a major challenge. Herein, we report systematic structure-activity relationship (SAR) studies carried out to identify novel sulfonamide derivatives as potent, selective, and state-dependent NaV1.7 inhibitors for pain. Scaffold hopping from benzoxazine to chroman and indane bicyclic system followed by thiazole replacement on sulfonamide led to identification of lead mols. with significant improvement in solubility, selectivity over NaV1.5, and CYP2C9 inhibition. The lead mols. 13, 29, 32, 43, and 51 showed a favorable pharmacokinetics (PK) profile across different species and robust efficacy in veratridine and formalin-induced inflammatory pain models in mice. Compound 51 also showed significant effects on the CCI-induced neuropathic pain model. The profile of 51 indicated that it has the potential for further evaluation as a therapeutic for pain.

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Formula: C4H5N3. Aromatic compounds can be divided into two categories: single heterocycles and fused heterocycles. Compound: 4-Aminopyrimidine, is researched, Molecular C4H5N3, CAS is 591-54-8, about Recent progress in small-molecule inhibitors for critical therapeutic targets of necroptosis. Author is Fang, Zhennan; Wei, Huiqiang; Gou, Wenfeng; Chen, Leyuan; Bi, Changfen; Hou, Wenbin; Li, Yiliang.

A review. Nonapoptotic types of regulated cell death have attracted widespread interest since the discovery that certain forms of cell necrosis can be regulated. In particular, research into cell necroptosis has made significant progress in connection with kidney, inflammatory, degenerative and neoplastic diseases. Inhibitors targeting the critical necroptosis-associated proteins RIPK1/3 and MLKL have been in development for more than a decade. Herein the authors compile a list of the known small-mol. inhibitors of these enzymes and representative structures of compounds co-crystallized with these proteins and put forward some thoughts regarding their future development.

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Application of 591-54-8. The fused heterocycle is formed by combining a benzene ring with a single heterocycle, or two or more single heterocycles. Compound: 4-Aminopyrimidine, is researched, Molecular C4H5N3, CAS is 591-54-8, about Bidentate geometry-constrained iminopyridyl nickel-catalyzed synthesis of amines or imines via borrowing hydrogen or dehydrogenative condensation. Author is Jiang, Yong; Hu, Miao; Sun, Nan; Hu, Baoxiang; Shen, Zhenlu; Hu, Xinquan; Jin, Liqun.

The efficient Ni-catalyzed N-alkylation of various anilines with alcs. via borrowing hydrogen was reported using a bidentate geometry-constrained iminopyridyl nickel complex as the catalyst. Substituted benzylic alcs. and short/long chain aliphatic alcs. could be applied as the alkylation sources to couple with aromatic and heteroaromatic amines to give a diverse set of N-alkylation outcomes in moderate to excellent yields. The nickel catalytic system was also suitable for aliphatic amines, selectively delivering the corresponding imines via an acceptorless dehydrogenative condensation strategy.

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Most of the natural products isolated at present are heterocyclic compounds, so heterocyclic compounds occupy an important position in the research of organic chemistry. A compound: 2150-55-2, is researched, SMILESS is O=C(C1N=C(N)SC1)O, Molecular C4H6N2O2SJournal, Article, Pharmazie called Studies on the relation between 2-iminothiazolidine-4-carboxylic acid and the thiocyanate metabolism in the guinea pig, Author is Weuffen, W.; Jess, G.; Juelich, W. D.; Bernhardt, D., the main research direction is iminothiazolidine carboxylate metabolism; thiocyanate iminothiazolidine carboxylate metabolite.HPLC of Formula: 2150-55-2.

In vitro and in vivo experiments have been carried out to elucidate the metabolism of 2-iminothiazolidine-4-carboxylic acid (I) [2150-55-2]. By using I-35S, the formation. of 35SCN as well as of 35S-containing I metabolites could be excluded. As compared to the findings from control animals, the serum SCN levels determined in guinea pigs after oral administration of I were unchanged.

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Most of the natural products isolated at present are heterocyclic compounds, so heterocyclic compounds occupy an important position in the research of organic chemistry. A compound: 91912-53-7, is researched, SMILESS is NC1=CC(C2=CC=NC=C2)=NN1, Molecular C8H8N4Journal, Article, ACS Medicinal Chemistry Letters called Aminopyrazole-Phenylalanine Based GPR142 Agonists: Discovery of Tool Compound and in Vivo Efficacy Studies, Author is Yu, Ming; Lizarzaburu, Mike; Motani, Alykhan; Fu, Zice; Du, Xiaohui; Liu, Jiwen; Jiao, Xianyun; Lai, SuJen; Fan, Peter; Fu, Angela; Liu, Qingxiang; Murakoshi, Michiko; Nara, Futoshi; Oda, Kozo; Okuyama, Ryo; Reagan, Jeff D.; Watanabe, Nobuaki; Yamazaki, Mami; Xiong, Yumei; Zhang, Ying; Zhuang, Run; Lin, Daniel C.-H.; Houze, Jonathan B.; Medina, Julio C.; Li, Leping, the main research direction is amrinone phenylalanine carboxylic acid preparation GPR142 agonist structure design; pharmacokinetics bioavailability diabetes amrinone phenylalanine carboxylic acid antidiabetic prodrug; glucose tolerance insulin secretagogue human islet transplant CYP450 hERG; GPR142 agonist; aminopyrazole−phenylalanine; human islet transplant; insulin secretagogue; oral glucose tolerance test; prodrug; type 2 diabetes.Application of 91912-53-7.

Herein, we report the lead optimization of amrinone-phenylalanine based GPR142 agonists. Structure-activity relationship studies led to the discovery of aminopyrazole-phenylalanine carboxylic acid I, which exhibited good agonistic activity, high target selectivity, desirable pharmacokinetic properties, and no cytochrome P 450 or hERG liability. Compound I, together with its orally bioavailable Et ester prodrug II, were found to be suitable for in vivo proof-of-concept studies. Compound II displayed good efficacy in a mouse oral glucose tolerance test (OGTT). CompoundI showed GPR142 dependent stimulation of insulin secretion in isolated mouse islets and demonstrated a statistically significant glucose lowering effect in a mouse model bearing transplanted human islets.

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Application of 591-54-8. The mechanism of aromatic electrophilic substitution of aromatic heterocycles is consistent with that of benzene. Compound: 4-Aminopyrimidine, is researched, Molecular C4H5N3, CAS is 591-54-8, about Synthesis of novel structural hybrids between aza-heterocycles and azelaic acid moiety with a specific activity on osteosarcoma cells. Author is Micheletti, Gabriele; Calonghi, Natalia; Farruggia, Giovanna; Strocchi, Elena; Palmacci, Vincenzo; Telese, Dario; Bordoni, Silvia; Frisco, Giulia; Boga, Carla.

Nine compounds bearing pyridinyl (or piperidinyl, benzimidazolyl, benzotriazolyl) groups bound to an azelayl moiety through an amide bond were synthesized. The structural analogy with some histone deacetylase inhibitors inspired their syntheses, seeking new selective histone deacetylase inhibitors (HDACi). The azelayl moiety recalls part of 9-hydroxystearic acid, a cellular lipid showing antiproliferative activity toward cancer cells with HDAC as a mol. target. Azelayl derivatives bound to a benzothiazolyl moiety further proved to be active as HDACi. The novel compounds were tested on a panel of both normal and tumor cell lines. Non-specific induction of cytotoxicity was observed in the normal cell line, while three of them induced a biol. effect only on the osteosarcoma (U2OS) cell line. One of them induced a change in nuclear shape and size. Cell-cycle alterations are associated with post-transcriptional modification of both H2/H3 and H4 histones. In line with recent studies, revealing unexpected HDAC7 function in osteoclasts, mol. docking studies on the active mols. predicted their proneness to interact with HDAC7. By reducing side effects associated with the action of the first-generation inhibitors, the herein reported compounds, thus, sound promising as selective HDACi.

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Most of the compounds have physiologically active properties, and their biological properties are often attributed to the heteroatoms contained in their molecules, and most of these heteroatoms also appear in cyclic structures. A Journal, Article, Research Support, Non-U.S. Gov’t, Organic & Biomolecular Chemistry called Palladium-catalyzed direct C2-arylation of azoles with aromatic triazenes, Author is Liu, Can; Wang, Zhiming; Wang, Lei; Li, Pinhua; Zhang, Yicheng, which mentions a compound: 118994-89-1, SMILESS is O=C(C1=CN=CO1)OCC, Molecular C6H7NO3, Recommanded Product: Ethyl oxazole-5-carboxylate.

A highly efficient palladium-catalyzed arylation of azoles at the C2-position using 1-aryltriazenes as aryl reagents was developed for the synthesis of aryl azoles, e.g., I. Azoles including oxazoles, thiazoles, imidazoles, 1,3,4-oxadiazoles and oxazolines reacted with 1-aryltriazenes smoothly to generate the corresponding products in good to excellent yields and various substitution patterns were tolerated toward the reaction.

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Pyrazine – Wikipedia,
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Most of the compounds have physiologically active properties, and their biological properties are often attributed to the heteroatoms contained in their molecules, and most of these heteroatoms also appear in cyclic structures. A Journal, Article, European Journal of Medicinal Chemistry called Design, synthesis of novel celastrol derivatives and study on their antitumor growth through HIF-1α pathway, Author is Shang, Fan-Fan; Wang, Jing Ying; Xu, Qian; Deng, Hao; Guo, Hong-Yan; Jin, Xuejun; Li, Xiaoting; Shen, Qing-Kun; Quan, Zhe-Shan, which mentions a compound: 1827-27-6, SMILESS is NC1=CN=C(C=C1)F, Molecular C5H5FN2, Recommanded Product: 1827-27-6.

Four series of hypoxia-inducible factor-1 alpha (HIF-1α) functioning derivatives stemming from modifications to the C-29 carboxyl group of celastrol were designed and synthesized, and their anticancer activities were evaluated. To address the structure and activity relationship of each derivative, extensive structural changes were made. HRE luciferase reporter assay demonstrated that 12 modified compounds showed superior HIF-1α inhibitory activity. Among them, quinolin-7-yloxy derivative I exhibited the best features: first, it had the strongest HIF-1α inhibitory activity (IC50 = 0.05μM, 5-fold higher than that of celastrol), and second, it possessed lower cytotoxicity (22-fold lower, I 16.85μM vs. celastrol 0.76μM). Thus, the safety factor of C6 was about 112 times higher than that of celastrol. Western blot assay indicated that I may inhibit the expression of HIF-1α protein in cells. Addnl., I hindered tumor cell cloning, migration and induced cell apoptosis. It is worth mentioning that in the mouse tumor xenograft model, I (10 mg/kg) displayed good antitumor activity in vivo, showing a better inhibition rate (74.03%) than the reference compound 5-fluorouracil (inhibition rate, 59.58%). However, the celastrol treatment group experienced collective death after four doses of the drug. Moreover, I minimally affected the mouse weight, indicating that its application in vivo has little toxic effect. H&E staining experiments show that it could also exacerbate the degree of tumor cell damage. The results of water solubility experiment show that the solubility of I is increased by 1.36 times than that of celastrol. In conclusion, I is a promising antitumor agent through the HIF-1α pathway.

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Hu, Liu; Cai, Xing; Dong, Suzhen; Zhen, Yongjia; Hu, Jidi; Wang, Shenjun; Jiang, Jingwen; Huang, Jiawu; Han, Yuqiao; Qian, Yu; Yuan, Yanqiu; Hu, Wenhao published the article 《Synthesis and anticancer activity of novel Actinonin derivatives as HsPDF inhibitors》. Keywords: peptidomimetic actinonin peptide synthesis antitumor structure activity HsPDF inhibitor; acyl chloride coupling chiral auxiliary alkylation bromoacetate oxidative hydrolysis; aromatic amine coupling proline nucleophilic addition nitrile hydroxylamine cyclization; amide amine peptide coupling hydrolysis Suzuki coupling mol docking; drug design target mechanism action.They researched the compound: 4-Aminopyrimidine( cas:591-54-8 ).Related Products of 591-54-8. Aromatic heterocyclic compounds can be divided into two categories: single heterocyclic and fused heterocyclic. In addition, there is a lot of other information about this compound (cas:591-54-8) here.

Human mitochondrial peptide deformylase (HsPDF) is responsible for removing the formyl group from N-terminal formylmethionines of newly synthesized mitochondrial proteins and plays important roles in maintaining mitochondria function. It is overexpressed in various cancers and has been proposed as a novel therapeutic target. Actinonin, a naturally occurring peptidomimetic HsPDF inhibitor, was reported to inhibit the proliferation of a broad spectrum of human cancer cells in vitro. However, its efficacy and pharmacokinetic profile requires significant improvement for therapeutic purposes. To obtain HsPDF inhibitors as anticancer therapeutics, we screened an inhouse collection of actinonin derivatives and found two initial hits with antiproliferation activity. Further optimization along the peptidomimetic backbone lead to two series of compounds containing substituted Ph moieties. They are potent HsPDF inhibitors and exhibited greatly improved antiproliferation activity in selected cancer cell lines. Finally, compound (I) significantly inhibited the growth of human colon cancer in xenograft animal models.

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Wieczorkiewicz, Pawel A.; Szatylowicz, Halina; Krygowski, Tadeusz M. published an article about the compound: 4-Aminopyrimidine( cas:591-54-8,SMILESS:C1=CN=CN=C1N ).Name: 4-Aminopyrimidine. Aromatic heterocyclic compounds can be classified according to the number of heteroatoms or the size of the ring. The authors also want to convey more information about this compound (cas:591-54-8) through the article.

Variously substituted N-heterocyclic compounds are widespread across bio- and medicinal chem. The work aims to computationally evaluate the influence of the type of N-heterocyclic compound and the substitution position on the properties of three model substituents: NO2, Cl, and NH2. For this reason, the energetic descriptor of global substituent effect (Erel), geometry of substituents, and electronic descriptors (cSAR, pEDA, sEDA) are considered, and interdependences between these characteristics are discussed. Furthermore, the existence of an endocyclic N atom may induce proximity effects specific for a given substituent. Therefore, various quantum chem. methods are used to assess them: the quantum theory of atoms in mols. (QTAIM), anal. of non-covalent interactions using reduced d. gradient (RDG) function, and electrostatic potential maps (ESP). The study shows that the energetic effect associated with the substitution is highly dependent on the number and position of N atoms in the heterocyclic ring. Moreover, this effect due to interaction with more than one endo N atom (e.g., in pyrimidines) can be assessed with reasonable accuracy by adding the effects calculated for interactions with one endo N atom in substituted pyridines. Finally, all possible cases of proximity interactions for the NO2, Cl, and NH2 groups are thoroughly discussed.

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Pyrazine – Wikipedia,
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