Category: amides-buliding-blocks

Protopopov, Mykola V. published the artcileIdentification of 1,3-thiazole-5-carboxylic Acid Derivatives as Inhibitors of Protein Kinase CK2, Name: 3-Methoxybenzothioamide, the publication is Current Enzyme Inhibition (2018), 14(2), 152-159, database is CAplus.

Serine/threonine protein kinase CK2 is involved in the regulation of a number of cellular functions such as cell growth, proliferation, differentiation and apoptosis. Increased activity of CK2 is associated with the development of different types of cancer, inflammatory response, pain and virus infections. Therefore, protein kinase CK2 is an attractive mol. target for the development of small-mol. inhibitors which can be important compounds for pharmaceutical application. The main aim of this research is to identify novel chem. class of CK2 inhibitors with good lead-like properties. In order to find novel CK2 inhibitors, virtual screening experiments were performed using Autodock software. Best-scored compounds were tested in vitro using P32 radioactive kinase assay. Small-mol. inhibitors of protein kinase CK2 were identified among the derivatives of 1,3-thiazole-5-carboxylic acid. The most active compound inhibited CK2 with IC₅₀ value of 0.4 μM. Ligand efficiency for studied derivatives of 1,3-thiazole-5-carboxylic acid was in the range from 0.45 to 0.56 kcal/mol/non-hydrogen atom. Considering the fact that the lower limit for ligand efficiency parameter is 0.3, the identified CK2 inhibitors among the derivatives of 1,3-thiazole-5-carboxylic acid are excellent candidates for further lead optimization.

Current Enzyme Inhibition published new progress about 64559-06-4. 64559-06-4 belongs to amides-buliding-blocks, auxiliary class Amine,Benzene,Amide,Ether, name is 3-Methoxybenzothioamide, and the molecular formula is C8H9NOS, Name: 3-Methoxybenzothioamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Coetzee, Nanika published the artcileEpigenetic inhibitors target multiple stages of Plasmodium falciparum parasites, Safety of 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, the publication is Scientific Reports (2020), 10(1), 2355, database is CAplus and MEDLINE.

Abstract: The epigenome of the malaria parasite, Plasmodium falciparum, is associated with regulation of various essential processes in the parasite including control of proliferation during asexual development as well as control of sexual differentiation. The unusual nature of the epigenome has prompted investigations into the potential to target epigenetic modulators with novel chemotypes. Here, we explored the diversity within a library of 95 compounds, active against various epigenetic modifiers in cancerous cells, for activity against multiple stages of P. falciparum development. We show that P. falciparum is differentially susceptible to epigenetic perturbation during both asexual and sexual development, with early stage gametocytes particularly sensitive to epi-drugs targeting both histone and non-histone epigenetic modifiers. Moreover, 5 compounds targeting histone acetylation and methylation show potent multistage activity against asexual parasites, early and late stage gametocytes, with transmission-blocking potential. Overall, these results warrant further examination of the potential antimalarial properties of these hit compounds

Scientific Reports published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C25H34N4O2S, Safety of 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Reichstein, Alexandra published the artcileSynthesis and Structure-Activity Relationships of Lapacho Analogues. 1. Suppression of Human Keratinocyte Hyperproliferation by 2-Substituted Naphtho[2,3-b]furan-4,9-diones, Activation by Enzymatic One- and Two-Electron Reduction, and Intracellular Generation of Superoxide, SDS of cas: 360-92-9, the publication is Journal of Medicinal Chemistry (2012), 55(16), 7273-7284, database is CAplus and MEDLINE.

A series of linearly annelated lapacho quinone analogs substituted at the 2-position of the tricyclic naphtho[2,3-b]furan-4,9-dione system were synthesized and evaluated for their ability to suppress keratinocyte hyperproliferation using HaCaT cells as the primary test system. While very good in vitro potency with IC₅₀ values in the submicromolar range was attained with electron-withdrawing substituents, some compounds were found to induce plasma membrane damage, as evidenced by the release of LDH activity from cytoplasm of the keratinocytes. The most potent analog against keratinocyte hyperproliferation was the 1,2,4-oxadiazole I, the potency of which was combined with comparably low cytotoxic membrane damaging effects. Structure-activity relationship studies with either metabolically stable or labile analogs revealed that the quinone moiety was required for activity. Selected compounds were studied in detail for their capability to generate superoxide radicals both in isolated enzymic one- and two-electron reduction assays as well as in a HaCaT cell-based assay.

Journal of Medicinal Chemistry published new progress about 360-92-9. 360-92-9 belongs to amides-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Amine,Aliphatic hydrocarbon chain,Amide, name is N,N-Diethyl-2,2,2-trifluoroacetamide, and the molecular formula is C6H10F3NO, SDS of cas: 360-92-9.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Staab, Heinz A. published the artcileN-Trifluoroacetyl- and N-trichloroacetylimidazole, Name: N,N-Diethyl-2,2,2-trifluoroacetamide, the publication is Chemische Berichte (1962), 2070-2, database is CAplus.

The syntheses and reactions of N-trifluoroacetylimidazole (I) and N-trichloroacetylimidazole (II) are described. N,N’-Carbonyldiimidazole (III) (20.5 g.) in 100 cc. dry THF treated dropwise with 28.8 g. CF₃CO₂H in 80 cc. THF, cooled several hrs., and filtered gave imidazolium trifluoroacetate (IV), m. 136-7° (tetrahydrofuran); distillation of the filtrate yielded 14.4 g. I, b₁₄ 45-6°. Imidazole (V) (25.8 g.) in 120 cc. dry THF treated dropwise with cooling with 39.9 g. (CF₃CO)₂O in 50 cc. THF, filtered from the IV, and distilled gave 24.8 g. I. CCl₃CO₂H (39.1 g.) and 19.5 g. III in C₆H₆ gave in the usual manner imidazolium trichloroacetate (VI), m. 93-4.5° (decomposition) (CHCl₃), and from the filtrate 18.5 g. II, b_0.001 60-2°, m. 38.5-40°. (CCl₃CO)₂O (31.3 g.) added dropwise with cooling to 17.8 g. V in 170 cc. C₆H₆, filtered from the VI, and distilled yielded 21.7 g. II. I treated in Et₂O or THF at room temperature with an equivalent amount of an appropriate alc. gave the following CF₃CO₂R (R, % yield, m.p. or b.p./mm., and n²⁰_D given): cyclohexyl, 73, 148-9°/760, 1.3839; iso-Am, 74, 119-20°/760, 1.3513; Me₃C, 73, 83°/760, 1.3302 (at 25°); Ph, 75, 48-9°/16, 1.4187 (at 25°). II gave similarly the following CCl₃CO₂R (same data given): cyclohexyl, 81, 122.5-3.5°/14, 1.4805; iso-Am, 84, 97.5-98°/15, 1.4520; Me₃C, 78, 25-6°, -; Ph, 79, 124.5-25°/14, 1.5253. I treated at room temperature with an equivalent amount of an appropriate amine in THF or Et₂O and evaporated, and the residue washed with H₂O gave the corresponding amides of CF₃CO₂H (% yield, and m.p. or b.p./mm. given): diethylamide, 74, 157-8°/760; anilide, 83, 89-90°; 2-naphthylamide, 83, 146-7.5°; p-nitranilide, 84, 151-3°; carbethoxymethylamide, 51, 51°. II gave similarly the following amides of CCl₃CO₂H (same data given): diethylamide, 82, 26-7°; anilide, 90, 94.5-5.5°; N-methylanilide, 87, 72-2.5°. p-H₂NC₆H₄CO₂H (4.12 g.) and 10 g. I in Et₂O at room temperature gave 5.5 g. p-CF₃CONHC₆H₄CO₂H (VII), m. 284-5° with resolidification to a solid which does not melt up to 350°. A similar run with equivalent amounts of reactants gave only 38% VII. VII heated 1 h. at 300° gave with the elimination of CF₃CO₂H a polyamide of p-H₂NC₆H₄CO₂H.

Chemische Berichte published new progress about 360-92-9. 360-92-9 belongs to amides-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Amine,Aliphatic hydrocarbon chain,Amide, name is N,N-Diethyl-2,2,2-trifluoroacetamide, and the molecular formula is C10H15ClO3S, Name: N,N-Diethyl-2,2,2-trifluoroacetamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Tauber, Carolin published the artcileChemical Evolution of Antivirals Against Enterovirus D68 through Protein-Templated Knoevenagel Reactions, Related Products of amides-buliding-blocks, the publication is Angewandte Chemie, International Edition (2021), 60(24), 13294-13301, database is CAplus and MEDLINE.

The generation of bioactive mols. from inactive precursors is a crucial step in the chem. evolution of life, however, mechanistic insights into this aspect of abiogenesis are scarce. Here, we investigate the protein-catalyzed formation of antivirals by the 3C-protease of enterovirus D68. The enzyme induces aldol condensations yielding inhibitors with antiviral activity in cells. Kinetic and thermodn. analyses reveal that the bioactivity emerges from a dynamic reaction system including inhibitor formation, alkylation of the protein target by the inhibitors, and competitive addition of non-protein nucleophiles to the inhibitors. The most active antivirals are slowly reversible inhibitors with elongated target residence times. The study reveals first examples for the chem. evolution of bio-actives through protein-catalyzed, non-enzymic C-C couplings. The discovered mechanism works under physiol. conditions and might constitute a native process of drug development.

Angewandte Chemie, International Edition published new progress about 15029-36-4. 15029-36-4 belongs to amides-buliding-blocks, auxiliary class Nitrile,Amine,Aliphatic hydrocarbon chain,Amide, name is 2-Cyano-N-ethylacetamide, and the molecular formula is C6H9NO3, Related Products of amides-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Wei, Congwen published the artcileHDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry, Application of [(2-Hexylcyclopentylidene)amino]thiourea, the publication is Nature Metabolism (2020), 2(12), 1391-1400, database is CAplus and MEDLINE.

Responsible for the ongoing coronavirus disease 19 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through binding of the viral spike protein (SARS-2-S) to the cell-surface receptor angiotensin-converting enzyme 2 (ACE2). Here we show that the high-d. lipoprotein (HDL) scavenger receptor B type 1 (SR-B1) facilitates ACE2-dependent entry of SARS-CoV-2. We find that the S1 subunit of SARS-2-S binds to cholesterol and possibly to HDL components to enhance viral uptake in vitro. SR-B1 expression facilitates SARS-CoV-2 entry into ACE2-expressing cells by augmenting virus attachment. Blockade of the cholesterol-binding site on SARS-2-S1 with a monoclonal antibody, or treatment of cultured cells with pharmacol. SR-B1 antagonists, inhibits HDL-enhanced SARS-CoV-2 infection. We further show that SR-B1 is coexpressed with ACE2 in human pulmonary tissue and in several extrapulmonary tissues. Our findings reveal that SR-B1 acts as a host factor that promotes SARS-CoV-2 entry and may help explain viral tropism, identify a possible mol. connection between COVID-19 and lipoprotein metabolism, and highlight SR-B1 as a potential therapeutic target to interfere with SARS-CoV-2 infection.

Nature Metabolism published new progress about 321673-30-7. 321673-30-7 belongs to amides-buliding-blocks, auxiliary class Immunology/Inflammation,Scavenger receptor, name is [(2-Hexylcyclopentylidene)amino]thiourea, and the molecular formula is C12H14IN, Application of [(2-Hexylcyclopentylidene)amino]thiourea.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Jiang, Jiaxuan published the artcileThe isonicotinamide cocrystal promotes inhibitory effects of naringenin on nonalcoholic fatty liver disease in mice, Application of Isonicotinamide, the publication is Journal of Drug Delivery Science and Technology (2020), 101874, database is CAplus.

Cocrystal formation can increase the solubility and dissolution rate of the poorly water-soluble drugs, thus enhancing their oral absorption and bioavailability. Our previous study demonstrates that a high dose (100 mg/kg) of naringenin (NGN) has a prominent inhibitory effect on nonalcoholic fatty liver disease (NAFLD) in mice. However, NGN is poorly soluble in water and has low oral bioavailability, which greatly limit its application. To increase solubility and dissolution rate of NGN, the naringenin-isonicotinamide cocrystal (NGN-INT) was prepared by solvent volatilization method. Compared to an equal dose (50 mg/kg) of the NGN crude drug, the NGN-INT significantly increased in vitro release rate as well as in vivo gastrointestinal absorption of NGN and thus more significantly alleviated liver deposition of triglycerides (TG) of the NAFLD mice induced by a methionine choline deficient (MCD) diet.

Journal of Drug Delivery Science and Technology published new progress about 1453-82-3. 1453-82-3 belongs to amides-buliding-blocks, auxiliary class Pyridine,Amine,Amide, name is Isonicotinamide, and the molecular formula is C6H6N2O, Application of Isonicotinamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Zhang, Xing published the artcileHPMC improves protective effects of naringenin and isonicotinamide co-crystals against abdominal aortic aneurysm, Quality Control of 1453-82-3, the publication is Cardiovascular Drugs and Therapy, database is CAplus and MEDLINE.

Abdominal aortic aneurysm (AAA) rupture is one of the most common causes of mortality in cardiovascular diseases, but currently there is no approved drug for AAA treatment or prevention in the clinic. Naringenin (NGN) has been reported to have anti-AAA effects. However, water solubility and in vivo absorption of NGN are not satisfactory, which leads to its low bioavailability, thus affecting its pharmacol. effects. In this project, the improving effects of isonicotinamide (INT) co-crystal and hydroxy Pr Me cellulose (HPMC) or polyvinyl pyrrolidone (PVP) on the solubility, in vivo absorption, and anti-AAA effects of NGN were evaluated. In the current study, co-crystals of naringenin-isonicotinamide (NGN-INT) were prepared, and effects of PVP or HPMC on precipitation rate, supersaturation, and bioavailability of NGN were explored. In addition, with or without HPMC supply, the effects of NGN-INT co-crystal on anti-AAA efficacy of NGN were investigated on an elastase-induced AAA mouse model, and the results were compared with the efficacy of the NGN crude drug. Our results demonstrate that NGN-INT formulation, compared to the NGN crude drug, enhanced the dissolution rate of NGN and significantly increased C_max and AUC_(0-∞) of NGN by 18 times and 1.97 times, resp. Addition of PVP or HPMC in NGN-INT co-crystal further increased bioavailability of NGN in NGN-INT. The in vivo pharmacodynamic study showed that NGN-INT with HPMC significantly improved the inhibitory effects of NGN against AAA. NGN-INT significantly improved the absorption and aortic protective effects of NGN. The supersaturation-prolonging effect of HPMC further enhanced bioavailability and anti-AAA effects of NGN-INT.

Cardiovascular Drugs and Therapy published new progress about 1453-82-3. 1453-82-3 belongs to amides-buliding-blocks, auxiliary class Pyridine,Amine,Amide, name is Isonicotinamide, and the molecular formula is C4H10OS, Quality Control of 1453-82-3.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Kang, Jianlei published the artcileSynthesis of 5-[[[4-methyl-2-(phenyl)-5-thiazolyl]methyl]thio]-1,3-benzodioxole-2,2-dicarboxylic acid derivatives and determination of their activity as PPARδ agonists, Safety of 2,4-Dichlorobenzamide, the publication is Zhongguo Yaowu Huaxue Zazhi (2006), 16(4), 193-197, 207, database is CAplus.

A series of novel 1,3-benzodioxole-2,2-dicarboxylic acid derivatives were synthesized from arylamides and pyrocatechol through a ten-step process and the target compounds were screened in a cell-based transient transactivation assay against human peroxisome proliferator-activated receptor-δ (PPARδ). A series of target compounds were confirmed by fast atom bombardment mass spectrometry (FAB-MS) and ¹H-NMR. The preliminary pharmacol. screening showed that these compounds exhibited definite human PPARδ agonist activity,.

Zhongguo Yaowu Huaxue Zazhi published new progress about 2447-79-2. 2447-79-2 belongs to amides-buliding-blocks, auxiliary class Chloride,Amine,Benzene,Amide, name is 2,4-Dichlorobenzamide, and the molecular formula is C7H5Cl2NO, Safety of 2,4-Dichlorobenzamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Tian, Wan-Fa published the artcileVisible-Light Photoredox-Catalyzed Iminyl Radical Formation by N-H Cleavage with Hydrogen Release and Its Application in Synthesis of Isoquinolines, Category: amides-buliding-blocks, the publication is Organic Letters (2018), 20(5), 1421-1425, database is CAplus and MEDLINE.

An unprecedented visible-light photoredox-catalyzed iminyl radical formation by N-H cleavage with H₂ release has been developed. Its application in the synthesis of various isoquinolines, e.g., I, and related polyaromatics in high atom economy at ambient temperature by applying a photosensitizer, Acr⁺-Mes ClO₄^–, and a new cobalt catalyst, Co(dmgH)₂(4-CONMe₂Py)Cl is reported. Mechanistic investigations indicated that the generated iminyl radical initiates the cascade C-N/C-C bonds formation and the catalytic cycle occurs by a simultaneous oxidative as well as reductive quenching pathway.

Organic Letters published new progress about 530-40-5. 530-40-5 belongs to amides-buliding-blocks, auxiliary class Pyridine,Amine,Amide, name is N,N-Diethylisonicotinamide, and the molecular formula is C15H14O3, Category: amides-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics