124499-18-9

Upstream product

• 1122-91-4 4-bromo-benzaldehyde 
• 3156-37-4 4-bromo-β-nitrostyrene 
• 85-44-9 phthalic anhydride 
• 73918-56-6 4-Bromophenethylamine 
• 136918-14-4 phthalimide 
• 4654-39-1 4-bromophenethanol 

Downstream Products

• 885229-51-6 2-[2-(4-morpholin-4-ylphenyl)ethyl]-1H-isoindole-1,3(2H)-dione 
• 1377838-26-0 2-(2-(4-(pyrrolidin-1-yl)phenyl)ethyl)isoindoline-1,3-dione 
• 1377838-25-9 2-(4-(piperidin-1-yl)phenethyl)isoindoline-1,3-dione 
• 1377838-27-1 2-(2-(4-(4-methylpiperazin-1-yl)phenyl)ethyl)isoindoline-1,3-dione 
• 794-43-4 2-(2-(4-bromophenyl)-2-oxoethyl)isoindoline-1,3-dione 
• 308846-03-9 4-[2-(1,3-dioxoisoindolin-2-yl)ethyl]benzonitrile 
• 187283-19-8 tert-butyl N-[[4-(2-aminoethyl)phenyl]methyl]carbamate 
• 1595285-39-4 C₆₆H₈₇N₃S₆ 
• 1595285-29-2 C₇₁H₉₁N₃S₄ 
• 663926-22-5 2-(4-(pyrrolidin-1-yl)phenyl)ethanamine 
• 868273-06-7 Org 27569 
• 124498-90-4 (2R,3R,4S,5R)-2-{6-Amino-2-[2-(4-phenethyl-phenyl)-ethylamino]-purin-9-yl}-5-hydroxymethyl-tetrahydro-furan-3,4-diol 
• 124498-92-6 2-[2-(p-2-cyclohexylethyl-phenyl)-ethylamino]-adenosine 

Relevant academic research and scientific papers

Stabilization of G-quadruplex DNA, inhibition of telomerase activity, and tumor cell apoptosis by organoplatinum(II) complexes with oxoisoaporphine

Two G-quadruplex ligands [Pt(La)(DMSO)Cl] (Pt1) and [Pt(Lb)(DMSO)Cl] (Pt2) have been synthesized and fully characterized. The two complexes are more selective for SK-OV-3/DDP tumor cells versus normal cells (HL-7702). It was found that both Pt1 and Pt2 could be a telomerase inhibitor targeting G-quadruplex DNA. This is the first report demonstrating that telomeric, c-myc, and bcl-2 G-quadruplexes and caspase-3/9 preferred to bind with Pt2 rather than Pt1, which also can induce senescence and apoptosis. The different biological behavior of Pt1 and Pt2 may correlate with the presence of a 6-hydroxyl group in Lb. Importantly, Pt1 and Pt2 exhibited higher safety in vivo and more effective inhibitory effects on tumor growth in the HCT-8 and NCI-H460 xenograft mouse model, compared with cisplatin. Taken together, these mechanistic insights indicate that both Pt1 and Pt2 display low toxicity and could be novel anticancer drug candidates.

IRAK DEGRADERS AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same.

COMPOUNDS, COMPOSITIONS, AND METHODS FOR PROTEIN DEGRADATION

Disclosed herein are compounds that target SMARCA2 and SMARCA4, causing their degradation. Also disclosed herein are compositions and methods of use in treating associated disorders and diseases.

Combined Photoredox/Enzymatic C?H Benzylic Hydroxylations

Chemical transformations that install heteroatoms into C?H bonds are of significant interest because they streamline the construction of value-added small molecules. Direct C?H oxyfunctionalization, or the one step conversion of a C?H bond to a C?O bond, could be a highly enabling transformation due to the prevalence of the resulting enantioenriched alcohols in pharmaceuticals and natural products,. Here we report a single-flask photoredox/enzymatic process for direct C?H hydroxylation that proceeds with broad reactivity, chemoselectivity and enantioselectivity. This unified strategy advances general photoredox and enzymatic catalysis synergy and enables chemoenzymatic processes for powerful and selective oxidative transformations.

Structure-based design, synthesis, PPAR-γ activation, and molecular docking of N-substituted phthalimides

N-substituted phthalimides showed peroxisome proliferator-activated receptors-γ activation in rat liver epithelial Ac2F cells in our previous study. In order to explore better peroxisome proliferator-activated receptors-γ agonists, new N-substituted phthalimide derivatives were designed and synthesized based on a pharmacophore study of natural peroxisome proliferator-activated receptors-γ agonist paecilocin A and synthetic leads. Peroxisome proliferator-activated receptors-γ activation by the new derivatives was evaluated using rat liver epithelial Ac2F cells at a concentration of 10 μM (same as previous study). All the new derivatives showed comparable or better activities than that of rosiglitazone, in which 3-hydroxy-N-(p-methoxy-phenethyl) phthalimide (compound 6) appeared as the best. Molecular docking suggested that the free hydroxyl group on the phthalimide head, a proper hydrophobic tail including a phenyl linker, were beneficial for peroxisome proliferator-activated receptors-γ activation. These N-substituted phthalimide derivatives are valuable as scaffolds for new peroxisome proliferator-activated receptors-γ agonists.

Pyrazolo[1, 5-a]pyridine compound and use thereof

The invention discloses a pyrazolo[1, 5-a]pyridine compound with the structure characteristic shown in the formula (I) or its pharmaceutically acceptable salt, stereoisomer or prodrug molecule and a use thereof. The compound has good in-vitro anti-tubercle bacillus activity, has the minimal inhibitory concentration (MIC) less than 0.1 micrograms per milliliter and partial MIC of 0.01 micrograms per milliliter and has strong inhibition effects on a clinically sorted multi-drug-resistant tuberculosis (MDR-TB) strain. In an in-vivo experiment, at a dosage of 20mg/kg/d, the pyrazolo[1, 5-a]pyridine compound can effectively eliminate H37Ra infection in a mouse and is a novel anti-tuberculosis compound.

Site-specific radioiodination of HER2-targeting affibody molecules using 4-iodophenethylmaleimide decreases renal uptake of radioactivity

Affibody molecules are small scaffold-based affinity proteins with promising properties as probes for radionuclide-based molecular imaging. However, a high reabsorption of radiolabeled Affibody molecules in kidneys is an issue. We have shown that the use of 125I-3-iodo-((4-hydroxyphenyl)ethyl)maleimide (IHPEM) for site-specific labeling of cysteine-containing Affibody molecules provides high tumor uptake but low radioactivity retention in kidneys. We hypothesized that the use of 4-iodophenethylmaleimide (IPEM) would further reduce renal retention of radioactivity because of higher lipophilicity of radiometabolites. An anti-human epidermal growth factor receptor type 2 (HER2) Affibody molecule (ZHER2:2395) was labeled using 125I-IPEM with an overall yield of 45±3 %. 125I-IPEM-ZHER2:2395 bound specifically to HER2-expressing human ovarian carcinoma cells (SKOV-3 cell line). In NMRI mice, the renal uptake of 125I-IPEM-ZHER2:2395 (24±2 and 5.7±0.3 % IA g-1at 1 and 4 h after injection, respectively) was significantly lower than uptake of 125I-IHPEM-ZHER2:2395 (50±8 and 12±2 % IA g-1at 1 and 4 h after injection, respectively). In conclusion, the use of a more lipophilic linker for the radioiodination of Affibody molecules reduces renal radioactivity.

Perylenediimide-based donor-acceptor dyads and triads: Impact of molecular architecture on self-assembling properties

Perylenediimide-based donor-acceptor co-oligomers are particularly attractive in plastic electronics because of their unique electro-active properties that can be tuned by proper chemical engineering. Herein, a new class of co-oligomers has been synthesized with a dyad structure (AD) or a triad structure (DAD and ADA) in order to understand the correlations between the co-oligomer molecular architecture and the structures formed by self-assembly in thin films. The acceptor block A is a perylene tetracarboxyl diimide (PDI), whereas the donor block D is made of a combination of thiophene, fluorene, and 2,1,3-benzothiadiazole derivatives. D and A blocks are linked by a short and flexible ethylene spacer to ease self-assembling in thin films. Structural studies using small and wide X-ray diffraction and transmission electron microscopy demonstrate that AD and ADA lamellae are made of a double layer of co-oligomers with overlapping and strongly π-stacked PDI units because the sectional area of the PDI is about half that of the donor block. These structural models allow rationalizing the absence of organization for the DAD co-oligomer and therefore to draw general rules for the design of PDI-based dyads and triads with proper self-assembling properties of use in organic electronics.

Indole-2-carboxamides as allosteric modulators of the cannabinoid CB 1 receptor

We synthesized new N-phenylethyl-1H-indole-2-carboxamides as the first SAR study of allosteric modulators of the CB1 receptor. The presence of the carboxamide functionality was required in order to obtain a stimulatory effect. The maximum stimulatory activity on CB1 was exerted by carboxamides 13 (EC50 = 50 nM) and 21 (EC50 = 90 nM) bearing a dimethylamino or piperidinyl group, respectively, at position 4 of the phenethyl moiety and a chlorine atom at position 5 of the indole.

Highly Selective Adenosine A2 Receptor Agonists in a Series of N-Alkylated 2-Aminoadenosines

A wide variety of 2-substituted aminoadenosines were prepared for comparison with the moderately A2 receptor selective adenosine agonist 2-anilinoadenosine (CV-1808).High selectivity combined with significant affinity at the A2 receptor in rat membranes was observed for those amines bearing a two-carbon chain to which was attached an aryl, heteroaryl, or alicyclic moiety. 2-(2-Phenethylamino)adenosine (3d), a 14-fold A2 selective compound, was modified by introduction of a variety of substituents in the benzene ring and the side chain.Some of these changes led to improved A2 affinity and increased selectivity.Replacement of the phenyl moiety by cyclohexenyl produced a 210-fold selective agonist 3ag (CGS 22989) whereas the cyclohexanyl analogue 3af (CGS 22492) was 530-fold selective at the A2 site.These compounds showed hypotensive activity in rat models over a range of doses without the bradycardia observed with less selective agonists.