Category: 2854-32-2

Liu, Tao published the artcileWater-removable ynamide coupling reagent for racemization-free syntheses of peptides, amides, and esters, Safety of 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone, the publication is Green Chemistry (2021), 23(24), 9916-9921, database is CAplus.

A novel ynamide coupling reagent, the byproduct of which can be removed by water, was reported. It promotes the direct coupling between carboxylic acids and amines, alcs. or thiols to provide amides, peptides, esters and thioesters, resp. No detectable racemization was observed for all the coupling reactions of carboxylic acids containing an α-chiral center. Importantly, a simple acidic aqueous work-up removed the byproduct readily to afford pure coupling products in good to excellent yields without the use of column chromatog., thus making this method more environmentally benign, user friendly and cost-effective. The robustness of the water-removable ynamide coupling reagent was further exemplified by the racemization/epimerization-free synthesis of carfilzomib, in which no column chromatog. purification was involved for the entire 12-step synthesis.

Green Chemistry published new progress about 2854-32-2. 2854-32-2 belongs to indole-building-block, auxiliary class GPCR/G Protein,Cannabinoid Receptor, name is 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone, and the molecular formula is C23H23ClN2O4, Safety of 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Wilkinson, Jonathan D. published the artcileCannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis, HPLC of Formula: 2854-32-2, the publication is Journal of Dermatological Science (2007), 45(2), 87-92, database is CAplus and MEDLINE.

Cannabinoids from cannabis (Cannabis sativa) are anti-inflammatory and have inhibitory effects on the proliferation of a number of tumorigenic cell lines, some of which are mediated via cannabinoid receptors. Cannabinoid (CB) receptors are present in human skin and anandamide, an endogenous CB receptor ligand, inhibits epidermal keratinocyte differentiation. Psoriasis is an inflammatory disease also characterized in part by epidermal keratinocyte hyper-proliferation. We investigated the plant cannabinoids Δ-9 tetrahydrocannabinol, cannabidiol, cannabinol and cannabigerol for their ability to inhibit the proliferation of a hyper-proliferating human keratinocyte cell line and for any involvement of cannabinoid receptors. A keratinocyte proliferation assay was used to assess the effect of treatment with cannabinoids. Cell integrity and metabolic competence confirmed using lactate-dehydrogenase and adenosine tri-phosphate assays. To determine the involvement of the receptors, specific agonist and antagonist were used in conjunction with some phytocannabinoids. Western blot and RT-PCR anal. confirmed presence of CB1 and CB2 receptors. The cannabinoids tested all inhibited keratinocyte proliferation in a concentration-dependent manner. The selective CB2 receptor agonists JWH015 and BML190 elicited only partial inhibition, the non-selective CB agonist HU210 produced a concentration-dependent response, the activity of theses agonists were not blocked by either CB1/CB2 antagonists. The results indicate that while CB receptors may have a circumstantial role in keratinocyte proliferation, they do not contribute significantly to this process. Our results show that cannabinoids inhibit keratinocyte proliferation, and therefore support a potential role for cannabinoids in the treatment of psoriasis.

Journal of Dermatological Science published new progress about 2854-32-2. 2854-32-2 belongs to indole-building-block, auxiliary class GPCR/G Protein,Cannabinoid Receptor, name is 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone, and the molecular formula is C19H14N2, HPLC of Formula: 2854-32-2.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

New, David C. published the artcileBML-190 and AM251 act as inverse agonists at the human cannabinoid CB₂ receptor: signalling via cAMP and inositol phosphates, Safety of 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone, the publication is FEBS Letters (2003), 536(1-3), 157-160, database is CAplus and MEDLINE.

The aminoalkylindole BML-190 and diarylpyrazole AM251 ligands have previously been shown to bind to cannabinoid CB₂ and CB₁ receptors, resp. In HEK-293 cells stably expressing the human CB₂ receptor, BML-190 and AM251 potentiated the forskolin-stimulated accumulation of cAMP. Moreover, the CB₂ receptor can interact productively with 16z44, a promiscuous Gα_16/z chimera. BML-190 and AM251 reduce the basal levels of inositol phosphate production in cells expressing the CB₂ receptor and 16z44. These results demonstrate that BML-190 and AM251 act as inverse agonists at the human CB₂ receptor acting via Gα_i/o and Gα_q family-coupled pathways.

FEBS Letters published new progress about 2854-32-2. 2854-32-2 belongs to indole-building-block, auxiliary class GPCR/G Protein,Cannabinoid Receptor, name is 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone, and the molecular formula is C23H23ClN2O4, Safety of 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Jones, Melissa published the artcileTherapeutic effect of the substrate-selective COX-2 inhibitor IMMA in the animal model of chronic constriction injury, Product Details of C23H23ClN2O4, the publication is Frontiers in Pharmacology (2018), 1481, database is CAplus and MEDLINE.

Enhancement of endocannabinoid signaling has emerged as an attractive strategy for the treatment of pain. In addition to the well-characterized hydrolytic pathways, cyclooxygenase-2 (COX-2) mediated oxygenation is thought to be an alternative route for endocannabinoid metabolism and therefore provides a new avenue for drug intervention. In this study, we examined the therapeutic effect of indomethacin morpholinamide (IMMA), a novel substrate-selective COX-2 inhibitor, in the chronic constriction injury (CCI) mouse model. Treatment with IMMA significantly alleviated hyperalgesia and mech. allodynia demonstrated by increased thermal withdrawal latency in Hargreaves test and tactile thresholds in Von Frey test. Accumulation of astrocytes and microglia in spinal cord dorsal horn and infiltration of macrophages into the dorsal root ganglion and sciatic nerve were reduced by drug treatment. Coadministration of the CB2 receptor antagonist, but not the CB1 receptor antagonist partially reversed the inhibitory effect of IMMA on pain sensitivity and inflammatory infiltrates. IMMA downregulated the mRNA expression of TNF- α and IL-1β and the production of IL-6 and MCP-1 proteins in the ipsilateral sciatic nerve. The enhanced NF- κB DNA binding activity in the CCI mouse dorsal spinal cord was also significantly reduced, suggesting that inactivation of NF- κB contributes to the anti-inflammatory property of IMMA. However, different from the previous reports showing that IMMA can increase endocannabinoids without interfering with arachidonic acid metabolism, treatment with IMMA failed to elevate the endogenous levels of AEA and 2-AG, but significantly reduced the production of prostaglandin E2 (PGE2). Furthermore, the mRNA expression of enzymes involved in PGE2 production, COX-2 and prostaglandin E synthase 2 in the ipsilateral sciatic nerve was also suppressed by IMMA treatment. Taken together, these results suggested that IMMA might exert anti-nociceptive effects through multiple mechanisms which include, but are not limited to, CB2 receptor activation and reduced PGE2 production

Frontiers in Pharmacology published new progress about 2854-32-2. 2854-32-2 belongs to indole-building-block, auxiliary class GPCR/G Protein,Cannabinoid Receptor, name is 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone, and the molecular formula is C23H23ClN2O4, Product Details of C23H23ClN2O4.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Ma, Chao published the artcileLiCABEDS II. Modeling of Ligand Selectivity for G-Protein-Coupled Cannabinoid Receptors, Quality Control of 2854-32-2, the publication is Journal of Chemical Information and Modeling (2013), 53(1), 11-26, database is CAplus and MEDLINE.

The cannabinoid receptor subtype 2 (CB2) is a promising therapeutic target for blood cancer, pain relief, osteoporosis, and immune system disease. The recent withdrawal of Rimonabant, which targets another closely related cannabinoid receptor (CB1), accentuates the importance of selectivity for the development of CB2 ligands to minimize their effects on the CB1 receptor. In the authors’ previous study, LiCABEDS (Ligand Classifier of Adaptively Boosting Ensemble Decision Stumps) was reported as a generic ligand classification algorithm for the prediction of categorical mol. properties. Here, the authors report extension of the application of LiCABEDS to the modeling of cannabinoid ligand selectivity with mol. fingerprints as descriptors. The performance of LiCABEDS was systematically compared with another popular classification algorithm, support vector machine (SVM), according to prediction precision and recall rate. In addition, the examination of LiCABEDS models revealed the difference in structure diversity of CB1 and CB2 selective ligands. The structure determination from data mining could be useful for the design of novel cannabinoid lead compounds More importantly, the potential of LiCABEDS was demonstrated through successful identification of newly synthesized CB2 selective compounds

Journal of Chemical Information and Modeling published new progress about 2854-32-2. 2854-32-2 belongs to indole-building-block, auxiliary class GPCR/G Protein,Cannabinoid Receptor, name is 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone, and the molecular formula is C23H23ClN2O4, Quality Control of 2854-32-2.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Holt, Sandra published the artcileInhibition of fatty acid amide hydrolase, a key endocannabinoid metabolizing enzyme, by analogues of ibuprofen and indomethacin, Product Details of C23H23ClN2O4, the publication is European Journal of Pharmacology (2007), 565(1-3), 26-36, database is CAplus and MEDLINE.

There is evidence in the literature that the nonsteroidal anti-inflammatory drugs indomethacin and ibuprofen can interact with the cannabinoid system both in vitro and in vivo. In the present study, a series of analogs of ibuprofen and indomethacin have been investigated with respect to their ability to inhibit fatty acid amide hydrolase, the enzyme responsible for the hydrolysis of the endogenous cannabinoid anandamide. Of the compounds tested, the 6-methyl-pyridin-2-yl analog of ibuprofen (“ibu-am5”) was selected for further study. This compound inhibited rat brain anandamide hydrolysis in a non-competitive manner, with IC₅₀ values of 4.7 and 2.5 μM being found at pH 6 and 8, resp. By comparison, the IC₅₀ values for ibuprofen were 130 and 750 μM at pH 6 and 8, resp. There was no measurable N-acylethanolamine hydrolyzing acid amidase activity in rat brain membrane preparations In intact C6 glioma cells, ibu-am5 inhibited the hydrolysis of anandamide with an IC₅₀ value of 1.2 μM. There was little difference in the potencies of ibu-am5 and ibuprofen towards cyclooxygenase-1 and -2 enzymes, and neither compound inhibited the activity of monoacylglycerol lipase. Ibu-am5 inhibited the binding of [³H]-CP55,940 to rat brain CB₁ and human CB₂ cannabinoid receptors more potently than ibuprofen, but the increase in potency was less than the corresponding increase in potency seen for inhibition of FAAH activity. It is concluded that ibu-am5 is an analog of ibuprofen with a greater potency towards fatty acid amide hydrolase but with a similar cyclooxygenase inhibitory profile, and may be useful for the study of the therapeutic potential of combined fatty acid amide hydrolase-cyclooxygenase inhibitors.

European Journal of Pharmacology published new progress about 2854-32-2. 2854-32-2 belongs to indole-building-block, auxiliary class GPCR/G Protein,Cannabinoid Receptor, name is 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone, and the molecular formula is C23H23ClN2O4, Product Details of C23H23ClN2O4.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Chin, Chen-Ni published the artcileThe third transmembrane helix of the cannabinoid receptor plays a role in the selectivity of aminoalkylindoles for CB2, peripheral cannabinoid receptor, Name: 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone, the publication is Journal of Pharmacology and Experimental Therapeutics (1999), 291(2), 837-844, database is CAplus and MEDLINE.

Two subtypes of the human cannabinoid receptor have been identified. The CB1 receptor is primarily distributed in the central nervous system, whereas the CB2 receptor is associated with peripheral tissue, including the spleen. These two subtypes are also distinguished by their ligand-binding profiles. The goal of this study was to identify critical residues in transmembrane region III (TM3) of the receptors that contribute to subtype specificity in ligand binding. For this purpose, a chimeric cannabinoid receptor [CB1/2(TM3)] was generated in which the TM3 of CB1 was replaced with the corresponding region of CB2. These receptors were stably expressed in Chinese hamster ovary cells for evaluation. The binding affinities of CB1/2(TM3) and the wild-type CB1 receptor to several prototype ligands were similar with one notable exception: the chimeric receptor exhibited a 4-fold enhancement in binding affinity to WIN 55212-2 (K_d = 4.8 nM) relative to that observed with CB1 (K_d = 21.7 nM). Two addnl. aminoalkylindoles, JWH 015 and JWH 018, also bound the chimeric receptor (K_i = 1.0 μM and 1.4 nM, resp.) with higher affinity compared with the wild-type CB1 (K_i = 5.2 μM and 9.8 nM, resp.). Furthermore, the increase in binding affinities of the aminoalkylindoles were reflected in the EC₅₀ values for the ligand-induced inhibition of intracellular cAMP levels mediated by the chimeric receptor. This pattern mirrors the selectivity of WIN 55212-2 binding to CB2 compared with CB1. Site-specific mutagenesis of the most notable amino acid changes in the chimeric receptor, Gly195 to Ser and Ala198 to Met, revealed that the enhancement in WIN 55212-2 binding is contributed to by the Ser but not by the Met residue. The data indicate that the amino acid differences in TM3 between CB1 and CB2 play a critical role in subtype selectivity for this class of compounds

Journal of Pharmacology and Experimental Therapeutics published new progress about 2854-32-2. 2854-32-2 belongs to indole-building-block, auxiliary class GPCR/G Protein,Cannabinoid Receptor, name is 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone, and the molecular formula is C23H23ClN2O4, Name: 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Schyman, Patric published the artcileGeneral Purpose 2D and 3D Similarity Approach to Identify hERG Blockers, Application In Synthesis of 2854-32-2, the publication is Journal of Chemical Information and Modeling (2016), 56(1), 213-222, database is CAplus and MEDLINE.

Screening compounds for human ether-á-go-go-related gene (hERG) channel inhibition is an important component of early stage drug development and assessment. In this study, we developed a high-confidence (p-value < 0.01) hERG prediction model based on a combined two-dimensional (2D) and three-dimensional (3D) modeling approach. We developed a 3D similarity conformation approach (SCA) based on examining a limited fixed number of pairwise 3D similarity scores between a query mol. and a set of known hERG blockers. By combining 3D SCA with 2D similarity ensemble approach (SEA) methods, we achieved a maximum sensitivity in hERG inhibition prediction with an accuracy not achieved by either method sep. The combined model achieved 69% sensitivity and 95% specificity on an independent external data set. Further validation showed that the model correctly picked up documented hERG inhibition or interactions among the Food and Drug Administration- approved drugs with the highest similarity scores-with 18 of 20 correctly identified. The combination of ascertaining 2D and 3D similarity of compounds allowed us to synergistically use 2D fingerprint matching with 3D shape and chem. complementarity matching.

Journal of Chemical Information and Modeling published new progress about 2854-32-2. 2854-32-2 belongs to indole-building-block, auxiliary class GPCR/G Protein,Cannabinoid Receptor, name is 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone, and the molecular formula is C25H23NO4, Application In Synthesis of 2854-32-2.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Zhang, Qiang published the artcileIn vitro metabolism of indomethacin morpholinylamide (BML-190), an inverse agonist for the peripheral cannabinoid receptor (CB₂) in rat liver microsomes, Safety of 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone, the publication is European Journal of Pharmaceutical Sciences (2010), 41(1), 163-172, database is CAplus and MEDLINE.

The in vitro metabolism of an inverse agonist of the peripheral cannabinoid receptor (CB₂), indomethacin morpholinylamide (BML-190), has been characterized using rat liver microsomal incubation. BML-190 was found to yield at least 15 metabolic products as identified by HPLC-MS/MS anal. Four major phase one metabolic pathways either individually, or in combination, were proposed to account for the identified metabolic products: (1) loss of the p-chlorobenzyl group, (2) hydroxylation on the indole or on the morpholine ring, (3) morpholinyl ring opening, and (4) demethylation of the methoxyl group on the indole ring.

European Journal of Pharmaceutical Sciences published new progress about 2854-32-2. 2854-32-2 belongs to indole-building-block, auxiliary class GPCR/G Protein,Cannabinoid Receptor, name is 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone, and the molecular formula is C8H7NO4, Safety of 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Kalgutkar, Amit S. published the artcileEster and Amide Derivatives of the Nonsteroidal Antiinflammatory Drug, Indomethacin, as Selective Cyclooxygenase-2 Inhibitors, COA of Formula: C23H23ClN2O4, the publication is Journal of Medicinal Chemistry (2000), 43(15), 2860-2870, database is CAplus and MEDLINE.

Recent studies from our laboratory have shown that derivatization of the carboxylate moiety in substrate analog inhibitors, such as 5,8,11,14-eicosatetraynoic acid, and in nonsteroidal antiinflammatory drugs (NSAIDs), such as indomethacin and meclofenamic acid, results in the generation of potent and selective cyclooxygenase-2 (COX-2) inhibitors (Kalgutkar et al. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 925-930). This paper summarizes details of the structure-activity studies involved in the transformation of the arylacetic acid NSAID, indomethacin, into a COX-2-selective inhibitor. Many of the structurally diverse indomethacin esters and amides inhibited purified human COX-2 with IC₅₀ values in the low-nanomolar range but did not inhibit ovine COX-1 activity at concentrations as high as 66 μM. Primary and secondary amide analogs of indomethacin were more potent as COX-2 inhibitors than the corresponding tertiary amides. Replacement of the 4-chlorobenzoyl group in indomethacin esters or amides with the 4-bromobenzyl functionality or hydrogen afforded inactive compounds Likewise, exchanging the 2-Me group on the indole ring in the ester and amide series with a hydrogen also generated inactive compounds Inhibition kinetics revealed that indomethacin amides behave as slow, tight-binding inhibitors of COX-2 and that selectivity is a function of the time-dependent step. Conversion of indomethacin into ester and amide derivatives provides a facile strategy for generating highly selective COX-2 inhibitors and eliminating the gastrointestinal side effects of the parent compound

Journal of Medicinal Chemistry published new progress about 2854-32-2. 2854-32-2 belongs to indole-building-block, auxiliary class GPCR/G Protein,Cannabinoid Receptor, name is 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone, and the molecular formula is C23H23ClN2O4, COA of Formula: C23H23ClN2O4.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles