Tag: 100-200

The Significance of Chirality in Drug Design and Synthesis of Bitopic Ligands as D₃ Receptor (D₃R) Selective Agonists was written by Battiti, Francisco O.;Cemaj, Sophie L.;Guerrero, Adrian M.;Shaik, Anver Basha;Lam, Jenny;Rais, Rana;Slusher, Barbara S.;Deschamps, Jeffery R.;Imler, Greg H.;Newman, Amy Hauck;Bonifazi, Alessandro. And the article was included in Journal of Medicinal Chemistry in 2019.Recommanded Product: 68867-17-4 This article mentions the following:

Because of the large degree of homol. among dopamine D₂-like receptors, discovering ligands capable of discriminating between the D₂, D₃, and D₄ receptor subtypes remains a significant challenge. Previous work has exemplified the use of bitopic ligands as a powerful strategy in achieving subtype selectivity for agonists and antagonists alike. Inspired by the potential for chem. modification of the D₃ preferential agonists (+)-PD128,907 (1) and PF592,379 (2), we synthesized bitopic structures to further improve their D₃R selectivity. We found that the (2S,5S) conformation of scaffold 2 resulted in a privileged architecture with increased affinity and selectivity for the D₃R. In addition, a cyclopropyl moiety incorporated into the linker and full resolution of the chiral centers resulted in lead compound 53 and eutomer 53a that demonstrate significantly higher D₃R binding selectivities than the reference compounds Moreover, the favorable metabolic stability in rat liver microsomes supports future studies in in vivo models of dopamine system dysregulation. In the experiment, the researchers used many compounds, for example, Benzothiazole-5-carboxylic acid (cas: 68867-17-4Recommanded Product: 68867-17-4).

Benzothiazole-5-carboxylic acid (cas: 68867-17-4) belongs to thiazole derivatives. Thiazole rings are planar and aromatic. Thiazoles are characterized by larger pi-electron delocalization than the corresponding oxazoles and have therefore greater aromaticity. There are numerous natural products that possess a thiazole ring with broad pharmacological activities. Thiamine, also known as vitamin B1, possesses a thiazole ring linked with 2-methylpyrimidine-4-amine as hydrochloride salt.Recommanded Product: 68867-17-4

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Novel and Potent Dopamine D₂ Receptor Go-Protein Biased Agonists was written by Bonifazi, Alessandro;Yano, Hideaki;Guerrero, Adrian M.;Kumar, Vivek;Hoffman, Alexander F.;Lupica, Carl R.;Shi, Lei;Newman, Amy Hauck. And the article was included in ACS Pharmacology & Translational Science in 2019.SDS of cas: 68867-17-4 This article mentions the following:

The discovery of functionally biased and physiol. beneficial ligands directed toward G-protein coupled receptors (GPCRs) has provided the impetus to design dopamine D₂ receptor (D₂R) targeted mols. that may be therapeutically advantageous for the treatment of certain neuropsychiatric or basal ganglia related disorders. Here we describe the synthesis of a novel series of D₂R agonists linking the D₂R unbiased agonist sumanirole with privileged secondary mol. fragments. The resulting ligands demonstrate improved D₂R affinity and selectivity over sumanirole. Extensive in vitro functional studies and bias factor anal. led to the identification of a novel class of highly potent Go-protein biased full D₂R agonists with more than 10-fold and 1000-fold bias selectivity toward activation of specific G-protein subtypes and β-arrestin, resp. Intracellular electrophysiol. recordings from midbrain dopamine neurons demonstrated that Go-protein selective agonists can elicit prolonged ligand-induced GIRK activity via D₂Rs, which may be beneficial in the treatment of dyskinesias associated with dopamine system dysfunction. In the experiment, the researchers used many compounds, for example, Benzothiazole-5-carboxylic acid (cas: 68867-17-4SDS of cas: 68867-17-4).

Benzothiazole-5-carboxylic acid (cas: 68867-17-4) belongs to thiazole derivatives. Thiazoles frequently appear in peptide studies. Thiazoles can also be used as protected formyl groups, which can be released in later stages of complex natural product synthesis. Thiazole sulfonation occurs only under forcing conditions: the action of oleum at 250 °C for 3 hours in the presence of mercury(II) sulfate leads to 65% formation of 5-thiazole sulfonic acid.SDS of cas: 68867-17-4

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Identification of ortho-amino benzamides and nicotinamides as MCHr1 antagonists was written by Vasudevan, Anil;LaMarche, Matthew J.;Blackburn, Christopher;Che, Jennifer Lee;Luchaco-Cullis, Courtney A.;Lai, Sujen;Marsilje, Thomas H.;Patane, Michael A.;Souers, Andrew J.;Wodka, Derek;Geddes, Bradley;Chen, Sumiao;Brodjian, Seven;Falls, Doug H.;Dayton, Brian D.;Bush, Eugene;Brune, Michael;Shapiro, Robin D.;Marsh, Kennan C.;Hernandez, Lisa E.;Sham, Hing L.;Collins, Christine A.;Kym, Philip R.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2005.Recommanded Product: 55661-33-1 This article mentions the following:

Several potent and efficacious MCHr1 antagonists containing an ortho-amino benzamide or nicotinamide chemotype have been identified, exemplified by compounds (I) and (II). In the experiment, the researchers used many compounds, for example, Thiazol-2-ylmethanamine (cas: 55661-33-1Recommanded Product: 55661-33-1).

Thiazol-2-ylmethanamine (cas: 55661-33-1) belongs to thiazole derivatives. Thiazole is a five-membered, unsaturated, planar, π-excessive heteroaromatic containing one sulfur atom and one pyridine-type nitrogen atom at position 3 of the cyclic ring system. Electrophilic attack at nitrogen depends on the presence of electron density at nitrogen as well as the position and nature of substituent linked to the thiazole ring.Recommanded Product: 55661-33-1

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Photoredox-Mediated C-H Functionalization and Coupling of Tertiary Aliphatic Amines with 2-Chloroazoles was written by Singh, Anuradha;Arora, Amandeep;Weaver, Jimmie D.. And the article was included in Organic Letters in 2013.Synthetic Route of C9H6ClNS This article mentions the following:

Herein, conditions for C-H functionalization of tertiary aliphatic amines and their subsequent coupling with a number of 2-chloroazole derivatives are reported. The reaction is facilitated by a catalytic amount of tris-fac-Ir(ppy)₃, with blue light irradiation and takes place under mild and convenient conditions. Most couplings take place with excellent regioselectivity. The reaction is tolerant of a number of functional groups and allows for rapid access to α-azole carbinamines e. g., I and II commonly found in post-translationally modified peptides. In the experiment, the researchers used many compounds, for example, 2-Chloro-5-phenylthiazole (cas: 329794-40-3Synthetic Route of C9H6ClNS).

2-Chloro-5-phenylthiazole (cas: 329794-40-3) belongs to thiazole derivatives. The thiazole ring has been identified as a central feature of numerous natural products, perhaps the most famous example of which is epothilone. Thiazole is a versatile building block for the construction and lead generation of new drug discoveries. Numerous diazole-based compounds are in clinical use as anticancer, antileukemic, antiinflammatory, antiviral, antifungal, antirheumatic, immunomodulator, and antiparasitic agents.Synthetic Route of C9H6ClNS

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Synthesis, biological evaluation and in silico modeling of novel integrase strand transfer inhibitors (INSTIs) was written by Ivashchenko, Andrey A.;Ivanenkov, Yan A.;Koryakova, Angela G.;Karapetian, Ruben N.;Mitkin, Oleg D.;Aladinskiy, Vladimir A.;Kravchenko, Dmitry V.;Savchuk, Nikolai P.;Ivashchenko, Alexander V.. And the article was included in European Journal of Medicinal Chemistry in 2020.Application In Synthesis of Thiazol-2-ylmethanamine This article mentions the following:

Although a relatively wide range of therapeutic options is currently available for the treatment of HIV/AIDS, it is still among the most serious and virulent diseases and is associated with a high mortality rate. Integrase strand transfer inhibitors (INSTIs), e.g., FDA-approved dolutegravir (DTG), bictegravir (BIC) and cabotegravir (CAB), have recently been included in standard highly active antiretroviral therapy (HAART) schemes as one of the five major components responsible for the most beneficial clin. outcome. In this paper, we describe a combinatorial amide synthesis, biol. evaluation and in silico modeling of new INSTIs containing heteroaromatic bioisosteric substitution instead of the well-studied halogen-substituted benzyl fragment. With the focus on the mentioned diversity point, a medium-sized library of compounds was selected for synthesis. A biol. study revealed that many mols. were highly active INSTIs (EC₅₀ < 10 nM). Two compounds 1{4} and 1{26} demonstrated picomolar antiviral activity that was comparable with CAB and were more active than DTG and BIC. Mol. docking study was performed to evaluate the binding mode of compounds in the active site of HIV-1 IN. In rats, lead compound 1{26} showed two-fold greater bioavailability than CAB and had a similar half-life. Compound 1{26} and its sodium salt were considerably more soluble in water than the parent drugs. Both mols. were very stable in human liver microsomes and plasma, demonstrated high affinity towards plasma proteins and did not show cytochrome (CYP) inhibition. This benefit profile indicates the great potential of these mols. as attractive candidates for subsequent evaluation as oral long-acting drugs and long-acting nanosuspension formulations for i.m. injection. In the experiment, the researchers used many compounds, for example, Thiazol-2-ylmethanamine (cas: 55661-33-1Application In Synthesis of Thiazol-2-ylmethanamine).

Thiazol-2-ylmethanamine (cas: 55661-33-1) belongs to thiazole derivatives. The thiazole ring has been identified as a central feature of numerous natural products, perhaps the most famous example of which is epothilone. Electrophilic attack at nitrogen depends on the presence of electron density at nitrogen as well as the position and nature of substituent linked to the thiazole ring.Application In Synthesis of Thiazol-2-ylmethanamine

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Efficient Synthesis of Benzothiazolone Derivatives by a Domino Reaction of Disulfide and COS under Mild Conditions was written by Zhou, Bohao;Hong, Hailong;Wang, Hongcai;Zhang, Tianmiao;Han, Limin;Zhu, Ning. And the article was included in European Journal of Organic Chemistry in 2018.Electric Literature of C7H4ClNOS This article mentions the following:

Carbonyl sulfide (COS), whose mol. structure is similar to CO₂ and CS₂, could be used as a better alternative carbonyl reagent due to its high chem. activity. However, the unfriendly byproduct H₂S would be generated when COS is used as a carbonyl reagent in the carbonylation reaction. In this report, the odorless and stable disulfide was used to replace the traditional foul smelling and unstable o-aminobenzenethiol to react with COS for preparing benzothiazolone derivatives in excellent yield, in which coupling reaction of H₂S generation and S-S bond cleavage was firstly designed. Notably, the C=O of COS was converted into benzothiazolone derivatives by carbonylation reaction and the sulfur of COS was transformed into sulfur and sulfide after cleaving the S-S bond by a domino reaction of disulfide and COS under mild conditions. This efficient synthetic methodol. provided a promising process for the utilization of COS. In the experiment, the researchers used many compounds, for example, 6-Chlorobenzo[d]thiazol-2(3H)-one (cas: 62266-81-3Electric Literature of C7H4ClNOS).

6-Chlorobenzo[d]thiazol-2(3H)-one (cas: 62266-81-3) belongs to thiazole derivatives. Thiazoles are a class of five-membered rings containing nitrogen and sulfur with excellent antitumor, antiviral and antibiotic activities. Thiazole sulfonation occurs only under forcing conditions: the action of oleum at 250 °C for 3 hours in the presence of mercury(II) sulfate leads to 65% formation of 5-thiazole sulfonic acid.Electric Literature of C7H4ClNOS

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Amphiphilic π-Allyliridium C,O-Benzoates Enable Regio- and Enantioselective Amination of Branched Allylic Acetates Bearing Linear Alkyl Groups was written by Meza, Arismel Tena;Wurm, Thomas;Smith, Lewis;Kim, Seung Wook;Zbieg, Jason R.;Stivala, Craig E.;Krische, Michael J.. And the article was included in Journal of the American Chemical Society in 2018.Safety of Thiazol-2-ylmethanamine This article mentions the following:

The first examples of amphiphilic reactivity in the context of enantioselective catalysis are described. Com. available π-allyliridium C,O-benzoates, which are stable to air, water and SiO₂ chromatog., and are well-known to catalyze allyl acetate-mediated carbonyl allylation, are now shown to catalyze highly chemo-, regio- and enantioselective substitutions of branched allylic acetates bearing linear alkyl groups with primary amines. In the experiment, the researchers used many compounds, for example, Thiazol-2-ylmethanamine (cas: 55661-33-1Safety of Thiazol-2-ylmethanamine).

Thiazol-2-ylmethanamine (cas: 55661-33-1) belongs to thiazole derivatives. Thiazole is a five-membered, unsaturated, planar, π-excessive heteroaromatic containing one sulfur atom and one pyridine-type nitrogen atom at position 3 of the cyclic ring system. Electrophilic attack at nitrogen depends on the presence of electron density at nitrogen as well as the position and nature of substituent linked to the thiazole ring.Safety of Thiazol-2-ylmethanamine

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Development of Glucose Regulated Protein 94-Selective Inhibitors Based on the BnIm and Radamide Scaffold was written by Crowley, Vincent M.;Khandelwal, Anuj;Mishra, Sanket;Stothert, Andrew R.;Huard, Dustin J. E.;Zhao, Jinbo;Muth, Aaron;Duerfeldt, Adam S.;Kizziah, James L.;Lieberman, Raquel L.;Dickey, Chad A.;Blagg, Brian S. J.. And the article was included in Journal of Medicinal Chemistry in 2016.Related Products of 55661-33-1 This article mentions the following:

(Arylmethyl)imidazolylethyl chlorodihydroxybenzoates I (R = Ph, 4-FC₆H₄, 4-ClC₆H₄, 4-BrC₆H₄, 4-IC₆H₄, 4-MeC₆H₄, 4-EtC₆H₄, 4-i-PrC₆H₄, 4-NCC₆H₄, 4-HCCC₆H₄, 4-F₃CC₆H₄, 4-PhC₆H₄, 4-MeOC₆H₄, 3,4-Cl₂C₆H₃, 1-naphthyl, 2-naphthyl, 5-quinolinyl, 3-FC₆H₄, 3-ClC₆H₄, 3-BrC₆H₄, 3-IC₆H₄, 3-MeOC₆H₄, 3-MeC₆H₄, 3-PhC₆H₄, 2-FC₆H₄, 2-ClC₆H₄, 2-BrC₆H₄, 2-MeC₆H₄, 2-H₂NC₆H₄, 2-MeOC₆H₄, 2-EtC₆H₄, 2-EtOC₆H₄, 2-i-PrOC₆H₄, 2-n-PrOC₆H₄, 2-F₃CC₆H₄, 2-MeO-4-MeC₆H₃, 3-furanyl, 2-furanyl, 5-Me-2-furanyl, 5-Cl-2-furanyl, 3,5-dimethyl-2-furanyl, 2-thienyl, 3-thienyl, 5-Me-2-thienyl, 5-Cl-2-thienyl, 4-Cl-2-thienyl, 3-Cl-2-thienyl, 5-isoxazolyl, 2-thiazolyl, 3-vinyl-2-thienyl, 3-vinyl-2-furanyl, 3-Et-2-thienyl, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 5-pyrimidinyl) were prepared as selective inhibitors of glucose regulated protein 94 (Grp94), the endoplasmic reticulum-resident isoform of the heat shock protein 90 (Hsp90), for potential use in the treatment of glaucoma and cancer; the effect of the aryl substituents on Grp94 binding and selectivity was determined I were prepared by the cyclocondensation of a bissilylated chloro(oxopropyl)dihydroxybenzoate with glyoxal and arylmethylamines RCH₂NH₂ (R = Ph, 4-FC₆H₄, 4-ClC₆H₄, 4-BrC₆H₄, 4-IC₆H₄, 4-MeC₆H₄, 4-EtC₆H₄, 4-i-PrC₆H₄, 4-NCC₆H₄, 4-HCCC₆H₄, 4-F₃CC₆H₄, 4-PhC₆H₄, 4-MeOC₆H₄, 3,4-Cl₂C₆H₃, 1-naphthyl, 2-naphthyl, 5-quinolinyl, 3-FC₆H₄, 3-ClC₆H₄, 3-BrC₆H₄, 3-IC₆H₄, 3-MeOC₆H₄, 3-MeC₆H₄, 3-PhC₆H₄, 2-FC₆H₄, 2-ClC₆H₄, 2-BrC₆H₄, 2-MeC₆H₄, 2-H₂NC₆H₄, 2-MeOC₆H₄, 2-EtC₆H₄, 2-EtOC₆H₄, 2-i-PrOC₆H₄, 2-n-PrOC₆H₄, 2-F₃CC₆H₄, 2-MeO-4-MeC₆H₃, 3-furanyl, 2-furanyl, 5-Me-2-furanyl, 5-Cl-2-furanyl, 3,5-dimethyl-2-furanyl, 2-thienyl, 3-thienyl, 5-Me-2-thienyl, 5-Cl-2-thienyl, 4-Cl-2-thienyl, 3-Cl-2-thienyl, 5-isoxazolyl, 2-thiazolyl, 3-vinyl-2-thienyl, 3-vinyl-2-furanyl, 3-Et-2-thienyl, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 5-pyrimidinyl) followed by desilylation. I (R = 2-MeO-4-MeC₆H₃CH₂, 5-chloro-2-furanylmethyl) were tested as inhibitors of cell migration in a cancer metastasis model and for their enhancement of the degradation of mutants of the protein myocilin in a glaucoma model. The structures of the lead compound radamide bound to Hsp82 and Grp94 and of I (R = 5-chloro-2-furanyl) bound to the N-terminal domain of Hsp94 lacking its acidic linker were determined by X-ray crystallog. In the experiment, the researchers used many compounds, for example, Thiazol-2-ylmethanamine (cas: 55661-33-1Related Products of 55661-33-1).

Thiazol-2-ylmethanamine (cas: 55661-33-1) belongs to thiazole derivatives. The thiazole ring is notable as a component of the vitamin thiamine (B1). Various laboratory methods exist for the organic synthesis of thiazoles. Prominent is the Hantzsch thiazole synthesis is a reaction between haloketones and thioamides.Related Products of 55661-33-1

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Synthesis and SAR study of novel 7-(pyridinium-3-yl)-carbonyl imidazo[5,1-b]thiazol-2-yl carbapenems was written by Maruyama, Takahisa;Kano, Yuko;Yamamoto, Yasuo;Kurazono, Mizuyo;Iwamatsu, Katsuyoshi;Atsumi, Kunio;Shitara, Eiki. And the article was included in Bioorganic & Medicinal Chemistry in 2007.Related Products of 55661-33-1 This article mentions the following:

A new series of 1β-Me carbapenems, possessing a 7-substituted imidazo[5,1-b]thiazol-2-yl group directly attached to the C-2 position of the carbapenem nucleus, was synthesized and evaluated for antibacterial activity. These compounds showed potent activities against Gram-pos. bacteria, in particular methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae (PRSP). They also exhibited potent activity against β-lactamase-neg. ampicillin-resistant Haemophilus influenzae (BLNAR). In the experiment, the researchers used many compounds, for example, Thiazol-2-ylmethanamine (cas: 55661-33-1Related Products of 55661-33-1).

Thiazol-2-ylmethanamine (cas: 55661-33-1) belongs to thiazole derivatives. Thiazoles are a class of five-membered rings containing nitrogen and sulfur with excellent antitumor, antiviral and antibiotic activities. Electrophilic attack at nitrogen depends on the presence of electron density at nitrogen as well as the position and nature of substituent linked to the thiazole ring.Related Products of 55661-33-1

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

radicAl rEactivity in thiazoles. i. comparison of the reactivity of thiazole, mono- and dialkylthiazoles and mono- and diphenylthiazoles in was written by Vernin, Gaston;Dou, Henri J. M.;Metzger, Jacques. And the article was included in Bulletin de la Societe Chimique de France in 1967.SDS of cas: 1826-13-7 This article mentions the following:

The radical reactivity in thiazoles (I) was studied by examining the products formed by the decomposition of Bz2O2 in I. Thus, thiazole (85 g.) was treated with 10 g. Bz2O2 20 hrs. at 78°, according to method described by G. Vernin and J. Metzger (1963), to give the following compounds: CO2 0.5, BzOH and phenylbenzoic acid 7, basic fractions (containing phenylthiazoles 80, dithiazolyls 15, and others 5%) 1, and resins 1 g. 4-Methylthiazole and 2,4-dimethylthiazole were treated similarly and showed an increase in the formation of secondary products due to the dimerization of thiazolyl methylene radical produced. The determination of I isomers in the basic fraction at position 2, 4, and 5 was carried out by gas chromatog. using 5% diethylene glycol succinate at 200° or by Al2O3 column using C6H6 as eluant. Column chromatog. gave 4 sep. fractions: the 1st was rich in 2-phenyl- and 4-phenylthiazole (II); the 2nd contained 2,2′- and 2,5′-dithiazolyls; the 3rd contained 5-phenylthiazole (III); and the 4th (eluted by 10% MeOH in C6H6) contained polythiazolyls, polyphenylthiazoles, and hydroxythiazoles. The 3 first fraction isomers were further separated by gas chromatog. using by 10% Carbowax 20M. The effect of temperature and Bz2O2 concentration on the % of phenylthiazole isomers was studied at 80-115° and 0.01-0.1 mole Bz2O2/mole I. The results show the highest percentages of II and III were obtained at 115-20° and 0.1 mole Bz2O2. The phenylation of I was also carried out in presence of AcOH. The results showed an increased activity of position 2 of the ring. The steric effect of substituents at the 2 and 4 position of thiazole ring on % isomers and radical reactivity was examined in acidic and neutral media. Radical phenylation of thiazole-2-d was carried in acid media. No isotopic effect was shown on % of 4- and 5- isomers. The phenylation of phenylthiazoles was carried in acidic and neutral media in the presence of 0.001 mole Bz2O2. The results showed that the decomposition of Bz2O2 in both media is the same. The following are % triphenylthiazoles obtained from 2,4-diphenylthiazole 17, 2,5-diphenylthiazole 3, and 4,5-diphenylthiazole 25%. The relative rates of arylation of I were determined by the competitive Ingold method using 5% Bz2O2 solutions and PhNO2 as a reference substrate at 120° in both acidic and neutral media. The reaction products were analyzed by gas chromatog. using Silicone SE-30 and Carbowax 20M columns. The % of nitrobiphenyls and phenylthiazoles were determined by Bartlet and Smith method (1960). The results showed the exptl. reactivity of I in phenylation reactions are in the order of -5>-2>-4 positions in the ring. In the experiment, the researchers used many compounds, for example, 5-Phenylthiazole (cas: 1826-13-7SDS of cas: 1826-13-7).

5-Phenylthiazole (cas: 1826-13-7) belongs to thiazole derivatives. The thiazole ring is notable as a component of the vitamin thiamine (B1). Electrophilic attack at nitrogen depends on the presence of electron density at nitrogen as well as the position and nature of substituent linked to the thiazole ring.SDS of cas: 1826-13-7

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica