Month: October 2022

Miklos, Zsuzsanna; Wafa, Dina; Nadasy, Gyorgy L.; Toth, Zsuzsanna E.; Besztercei, Balazs; Dornyei, Gabriella; Laska, Zsofia; Benyo, Zoltan; Ivanics, Tamas; Hunyady, Laszlo; Szekeres, Maria published the artcile< Angiotensin II-induced cardiac effects are modulated by endocannabinoid-mediated CB1 receptor activation>, Quality Control of 96829-58-2, the main research area is Angiotensin II; CB1 cannabinoid receptor; cardiac; coronary flow; endocannabinoid; myocardial function; vasoconstriction.

Angiotensin II (Ang II) has various cardiac effects and causes vasoconstriction. Ang II activates the type-1 angiotensin receptor-Gq/11 signaling pathway resulting in the release of 2- arachidonoylglycerol (2-AG). We aimed to investigate whether cardiac Ang II effects are modulated by 2-AG-release and to identify the role of type-1 cannabinoid receptors (CB1R) in these effects. Expression of CB1R in rat cardiac tissue was confirmed by immunohistochem. To characterize short-term Ang II effects, increasing concentrations of Ang II (10-9-10-7 M); whereas to assess tachyphylaxis, repeated infusions of Ang II (10-7 M) were administered to isolated Langendorff-perfused rat hearts. Ang II infusions caused a decrease in coronary flow and ventricular inotropy, which was more pronounced during the first administration. CB agonist 2-AG and WIN55,212-2 administration to the perfusate enhanced coronary flow. The flow-reducing effect of Ang II was moderated in the presence of CB1R blocker O2050 and diacylglycerol-lipase inhibitor Orlistat. Our findings indicate that Ang II-induced cardiac effects are modulated by simultaneous CB1R-activation, most likely due to 2-AG-release during Ang II signalling. In this combined effect, the response to 2-AG via cardiac CB1R may counteract the pos. inotropic effect of Ang II, which may decrease metabolic demand and augment Ang II-induced coronary vasoconstriction.

Cells published new progress about 96829-58-2. 96829-58-2 belongs to class amides-buliding-blocks, and the molecular formula is C29H53NO5, Quality Control of 96829-58-2.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Lange, Jos H. M.; Van Stuivenberg, Herman H.; Veerman, Willem; Wals, Henri C.; Stork, Bob; Coolen, Hein K. A. C.; McCreary, Andrew C.; Adolfs, Tiny J. P.; Kruse, Chris G. published the artcile< Novel 3,4-diarylpyrazolines as potent cannabinoid CB1 receptor antagonists with lower lipophilicity>, Application In Synthesis of 25999-04-6, the main research area is aminosulfonyl isothiocyanate diarylpyrazoline addition; aminosulfonylcarbamoyl diarylpyrazoline preparation chlorination amination; diarylpyrazoline derivative cannabinoid CB1 receptor antagonist.

3,4-Diarylpyrazolines as potent CB1 receptor antagonists with lipophilicity lower than that of SLV319 are described. The key change was the replacement of the arylsulfonyl group in the original series by a dialkylaminosulfonyl moiety. The absolute configuration (4S) of enantiomer I was established by X-ray diffraction anal. and I showed a close mol. fit with rimonabant in a CB1 receptor-based model. II exhibited the highest CB1 receptor affinity (Ki = 24 nM) in this series, as well as very potent CB1 antagonistic activity (pA 2 = 8.8) and a high CB1/CB2 subtype selectivity (∼147-fold).

Bioorganic & Medicinal Chemistry Letters published new progress about Cannabinoid receptor 1 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 25999-04-6 belongs to class amides-buliding-blocks, and the molecular formula is C4H10N2O3S, Application In Synthesis of 25999-04-6.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Tomaru, Atsuko; Toshimoto, Kota; Lee, Wooin; Ishigame, Keiko; Sugiyama, Yuichi published the artcile< A Simple Decision Tree Suited for Identification of Early Oral Drug Candidates With Likely Pharmacokinetic Nonlinearity by Intestinal CYP3A Saturation>, Product Details of C10H13ClN2O3S, the main research area is CYP3A pharmacokinetic Intestinal absorption type I nonlinearity; Cytochrome P450 (CYP) 3A; First-pass metabolism; Intestinal absorption; Nonlinear pharmacokinetics; Oral absorption.

To identify oral drugs that likely display nonlinear pharmacokinetics due to saturable metabolism by intestinal CYP3A, our previous report using CYP3A substrate drugs proposed an approach using thresholds for the linear index number (LIN3A = dose/Km; Km, Michaelis-Menten constant for CYP3A) and the intestinal availability (FaFg). Here, we aimed to extend the validity of the previous approach using both CYP3A substrate and non-substrate drugs and to devise a decision tree suited for early drug candidates using in vitro metabolic intrinsic clearance (CLint, vitro) instead of FaFg. Out of 152 oral drugs (including 136 drugs approved in Japan, US or both), type I nonlinearity (in which systemic drug exposure increases in a more than dose-proportional manner) was noted with 82 drugs (54%), among which 58 drugs were identified as CYP3A substrates based on public information. Based on practical feasibility, 41 drugs were selected from CYP3A substrates and subjected to inhouse metabolic assessment. The results were used to determine the thresholds for CLint, vitro (0.45μL/min/pmol CYP3A4) and LIN3A (1.0 L). For four drugs incorrectly predicted, potential mechanisms were looked up. Overall, our proposed decision tree may aid in the identification of early drug candidates with intestinal CYP3A-derived type I nonlinearity.

Journal of Pharmaceutical Sciences (Philadelphia, PA, United States) published new progress about Cytochrome P450 CYP3A inhibitors. 94-20-2 belongs to class amides-buliding-blocks, and the molecular formula is C10H13ClN2O3S, Product Details of C10H13ClN2O3S.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Gatrone, Ralph C.; Kaplan, Louis; Horwitz, E. Philip published the artcile< N,N-diisobutyl-2-(octylphenylphosphinyl)acetamide (CMPO)>, Application of C10H20ClNO, the main research area is phosphinylacetamide preparation; acetamide octylphenylphosphinyl diisobutyl preparation; safety preparation octylphenylphosphinyldiisobutylacetamide.

PhRP(O)CH2CONBu-i2 (R = octyl throughout this abstract) (CMPO) was prepared by the Grignard reaction of RBr with PhP(O)(H)(OEt) to give PhRP(O)MgBr followed by treatment with ClCH2CONBu-i2. ClCH2CONBu-i2 was prepared in 91-3% yields by treatment of ClCH2COCl with i-Bu2NH. PhP(O)(H)(OEt) was prepared in 91% yield by treatment of PhP(O)(H)(OH) with (EtO)3P.

Inorganic Syntheses published new progress about Safety. 5326-82-9 belongs to class amides-buliding-blocks, and the molecular formula is C10H20ClNO, Application of C10H20ClNO.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Vakhitov, D; Mella, M; Hakovirta, H; Suominen, V; Oksala, N; Saarinen, E; Romsi, P published the artcile< Prognostic Risk Factors for the Development of Compartment Syndrome in Acute Lower Limb Ischemia Patients Treated With Catheter-Directed Thrombolysis.>, Safety of (S)-(S)-1-((2S,3S)-3-Hexyl-4-oxooxetan-2-yl)tridecan-2-yl 2-formamido-4-methylpentanoate, the main research area is Compartment syndrome; Compartment syndrome after CDT; Compartment syndrome after catheter-directed thrombolysis.

BACKGROUND: To determine predisposing factors that may lead to the development of compartment syndrome (CS) in patients with acute lower limb ischemia (ALLI) managed with intra-arterial catheter-directed thrombolysis (CDT). METHODS: This is a retrospective study of patients admitted between 01/2002 and 12/2015 to three university hospitals in Tampere, Turku, and Oulu, Finland, with acute or acute-on-chronic lower limb ischemia (Rutherford I-IIb). Patients managed with CDT and aspiration thrombectomies (AT) as an adjunct to CDT were included in the study. Multivariable binary logistic regression models were used to detect possible risk factors for the development of CS and its impact on the limb salvage and survival. Amputation-free survival (AFS) rates of CS and non-CS patients were compared using Kaplan-Meier survival analysis. The length of hospitalization was calculated and compared between the CS and non-CS groups. RESULTS: A total of 292 CDTs with or without ATs were performed on patients with a mean age of 71 years (standard deviation 13 years), 151 (51.7%) being male. Altogether, 12/292 (4.1%) treatment-related CS cases were registered. Renal insufficiency (odds ratio [OR] 4.27, P = 0.07) was associated with an increased risk of CS. All CS cases were managed with fasciotomies. Treatment with fasciotomy was associated with a prolonged hospitalization of a median of 7 days versus the 4 days for non-CS patients, P < 0.001. During the median follow-up of 51 months (interquartile range 72 months), 152/292 (52.1%) patients died and 51/292 (17.5%) underwent major amputations. CS was not associated with an increased risk of mortality, but it was associated with a higher risk of major amputation (OR 3.87, P = 0.027). The AFS rates of patients with or without CS did not significantly differ from each other in the long term. CONCLUSIONS: CS after CDT for the treatment of ALLI is uncommon. Renal insufficiency is associated with an increased risk of CS. Fasciotomy prolongs the hospitalization. Patients with CS are exposed to an increased risk of major amputation. Annals of vascular surgery published new progress about 96829-58-2. 96829-58-2 belongs to class amides-buliding-blocks, and the molecular formula is C29H53NO5, Safety of (S)-(S)-1-((2S,3S)-3-Hexyl-4-oxooxetan-2-yl)tridecan-2-yl 2-formamido-4-methylpentanoate.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Liu, Xing-Ping; Narla, Rama Krishna; Uckun, Fatih M. published the artcile< Organic phenyl arsonic acid compounds with potent antileukemic activity>, Product Details of C9H12N2O3, the main research area is phenyl arsonic acid quinazoline preparation potent antileukemic activity; chlorodimethoxyquinazoline condensation reaction aminophenylazo phenylarsonic acid.

12 Organic arsonic acid compounds, e.g. I, were synthesized and evaluated against human B-lineage (NALM-6) and T-lineage (MOLT-3) acute lymphoblastic leukemia (ALL) cell lines. E.g., I was prepared from condensation of 4-chloro-6,7-dimethoxyquinazoline and 4-(4′-aminophenylazo)phenylarsonic acid. The lead compounds 2-trichloromethyl-4-[4′-(4”-phenylazo)phenylarsonic acid]aminoquinazoline (compound 19, PHI-P518; IC50=1.1 ± 0.5 μM against NALM-6 and 2.0 ± 0.8 μM against MOLT-3) and 2-methylthio-4-(2′-phenylarsonic acid)aminopyrimidine (compound 15, PHI-P381; IC50=1.5 ± 0.3 μM against NALM-6 and 2.3 ± 0.5 μM against MOLT-3) exhibited potent antileukemic activity at low micromolar concentrations

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 5004-88-6 belongs to class amides-buliding-blocks, and the molecular formula is C9H12N2O3, Product Details of C9H12N2O3.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Cheng, Ching-Feng; Ku, Hui-Chen; Cheng, Jing-Jy; Chao, Shi-Wei; Li, Hsiao-Fen; Lai, Pei-Fang; Chang, Che-Chang; Don, Ming-Jaw; Chen, Hsi-Hsien; Lin, Heng published the artcile< Adipocyte browning and resistance to obesity in mice is induced by expression of ATF3.>, Computed Properties of 96829-58-2, the main research area is Diabetes; Drug discovery; Medical research; Obesity; Transcription.

Billions of people have obesity-related metabolic syndromes such as diabetes and hyperlipidemia. Promoting the browning of white adipose tissue has been suggested as a potential strategy, but a drug still needs to be identified. Here, genetic deletion of activating transcription factor 3 (ATF3-/- ) in mice under a high-fat diet (HFD) resulted in obesity and insulin resistance, which was abrogated by virus-mediated ATF3 restoration. ST32da, a synthetic ATF3 inducer isolated from Salvia miltiorrhiza, promoted ATF3 expression to downregulate adipokine genes and induce adipocyte browning by suppressing the carbohydrate-responsive element-binding protein-stearoyl-CoA desaturase-1 axis. Furthermore, ST32da increased white adipose tissue browning and reduced lipogenesis in HFD-induced obese mice. The anti-obesity efficacy of oral ST32da administration was similar to that of the clinical drug orlistat. Our study identified the ATF3 inducer ST32da as a promising therapeutic drug for treating diet-induced obesity and related metabolic disorders.

Communications biology published new progress about 96829-58-2. 96829-58-2 belongs to class amides-buliding-blocks, and the molecular formula is C29H53NO5, Computed Properties of 96829-58-2.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Vaskevych, Alla I.; Savinchuk, Nataliia O.; Vaskevych, Ruslan I.; Rusanov, Eduard B.; Grygorenko, Oleksandr O.; Vovk, Mykhailo V. published the artcile< The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones - an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones>, Application In Synthesis of 5004-88-6, the main research area is hydroxymethyl dihydropyrroloquinazolinone preparation regioselective; butenyl quinazolinone oxidative exo trig cyclization PIFA; [bis(trifluoroacetoxy)iodo]benzene PIFA; nitrogen heterocycles; oxidative cyclization; pyrrolo[1,2-a]quinazolines.

A regioselective method for the synthesis of 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones – close structural analogs of naturally occurring vasicinone alkaloids – is described. The procedure is based on PIFA-initiated oxidative 5-exo-trig cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones, in turn prepared by thermal cyclocondensation of the corresponding 2-(pent-4-enamido)benzamides. The products obtained have a good natural product likeness (NPL) score and therefore can be useful for the design of natural product-like compound libraries.

Beilstein Journal of Organic Chemistry published new progress about Benzamides Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 5004-88-6 belongs to class amides-buliding-blocks, and the molecular formula is C9H12N2O3, Application In Synthesis of 5004-88-6.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Yuan, Shuo; Wang, Bo; Dai, Qing-Qing; Zhang, Xiao-Nan; Zhang, Jing-Ya; Zuo, Jia-Hui; Liu, Hui; Chen, Zhe-Sheng; Li, Guo-Bo; Wang, Shaomeng; Liu, Hong-Min; Yu, Bin published the artcile< Discovery of New 4-Indolyl Quinazoline Derivatives as Highly Potent and Orally Bioavailable P-Glycoprotein Inhibitors>, Related Products of 5004-88-6, the main research area is indolyl quinazoline derivative preparation oral P glycoprotein inhibitor cancer.

The major drawbacks of P-glycoprotein (P-gp) inhibitors at the clin. stage make the development of new P-gp inhibitors challenging and desirable. In this study, we reported our structure-activity relationship studies of 4-indolyl quinazoline, which led to the discovery of a highly effective and orally active P-gp inhibitor, YS-370. YS-370 effectively reversed multidrug resistance (MDR) to paclitaxel and colchicine in SW620/AD300 and HEK293T-ABCB1 cells. YS-370 bound directly to P-gp, did not alter expression or subcellular localization of P-gp in SW620/AD300 cells, but increased the intracellular accumulation of paclitaxel. Furthermore, YS-370 stimulated the P-gp ATPase activity and had moderate inhibition against CYP3A4. Significantly, oral administration of YS-370 in combination with paclitaxel achieved much stronger antitumor activity in a xenograft model bearing SW620/Ad300 cells than either drug alone. Taken together, our data demonstrate that YS-370 is a promising P-gp inhibitor capable of overcoming MDR and represents a unique scaffold for the development of new P-gp inhibitors.

Journal of Medicinal Chemistry published new progress about Antitumor agent resistance. 5004-88-6 belongs to class amides-buliding-blocks, and the molecular formula is C9H12N2O3, Related Products of 5004-88-6.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Ruhela, R.; Panja, S.; Singh, A. K.; Dhami, P. S.; Gandhi, P. M. published the artcile< BenzoDODA grafted polymeric resin-Plutonium selective solid sorbent>, Recommanded Product: 2-Chloro-N,N-diisobutylacetamide, the main research area is wastewater treatment sorption plutonium polymeric resin; BenzoDODA SDVB resin; Plutonium; Selective; Separation; Sorption.

A new ligand grafted polymeric resin (BenzoDODA SDVB) was synthesized by covalently attaching plutonium selective ligand (BenzoDODA) on to styrene divinyl benzene (SDVB) polymer matrix. BenzoDODA SDVB resin was evaluated for separation and recovery of plutonium(IV) from nitric acid medium. Sorption of Pu(IV) was found to decrease with the increase in nitric acid concentration, with very small sorption above 7.0 M HNO3. Sorption kinetics was fast enough to achieve the equilibrium within 60 min of contact where the kinetic data fitted well to pseudo-second-order model. Sorption isotherm data fitted well to Langmuir model suggesting chem. interaction between the BenzoDODA moiety and plutonium(IV) ions. Sorption studies with some of representative radionuclides of high level waste showed that BenzoDODA SDVB is selective and therefore could be a promising solid sorbent for separation and recovery of plutonium. Further, the theor. calculations done on BenzoDODA SDVB resin suggested Pu(NO3)4·BenzoDODA (1:1) sorbed complex conformed to generally observed square antiprism geometry of the plutonium complexes, with contributions from oxygen atoms of four nitrate ions as well as from four oxygen atoms present in BenzoDODA (two phenolic ether oxygen atoms and two carbonyl oxygen atoms of amidic moiety).

Journal of Hazardous Materials published new progress about Sorptive wastewater treatment. 5326-82-9 belongs to class amides-buliding-blocks, and the molecular formula is C10H20ClNO, Recommanded Product: 2-Chloro-N,N-diisobutylacetamide.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics