Structure of 7787-70-4
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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Ang, Charles G ; Hyatt, Nadia L ; Le Minh, Giang ; Gupta, Monisha ; Kadam, Manali ; Hogg, Philip J , et al.
Abstract: Disulfide exchange is underexplored as a mechanism influencing HIV-1 entry. Prior studies demonstrated that redox enzyme inhibition can prevent HIV-1 infection but with limited mechanistic explanation. We hypothesize that ligand-driven rearrangement (“conformational activation”) enables enzyme-mediated disulfide exchange in Env residues (“disulfide trigger”) that promotes fusion transformations, enhancing virus entry. We tested soluble CD4 and CD4-binding site entry inhibitors as conformational activators and the ubiquitous redox enzyme thioredoxin-1 (Trx1) as disulfide trigger. We found that combination treatment caused fusion-like Env transformation and pseudovirus lysis, independent of cells. Notably, only compounds associated with gp120 shedding caused lysis when paired with Trx1. In each case, lysis was prevented by adding the fusion inhibitor T20, demonstrating that six-helix bundle formation is required as in virus-cell fusion. In contrast to conformationally activating ligands, neither the ground state stabilizer BMS-806 with Trx1 nor Trx1 alone caused lysis. Order of addition experiments reinforced conformational activation/disulfide trigger as a sequential process, with virus/activator preincubation transiently enhancing lysis and virus/Trx1 preincubation reducing lysis. Lastly, addition of exogenous Trx1 to typical pseudovirus infections exhibited dose-dependent enhancement of infection. Altogether, these data support conformational activation and disulfide triggering as a mechanism that can induce and enhance the fusogenic transformation of Env.
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Keywords: HIV-1 ; Env ; thioredoxins ; allosteric disulfides ; virus entry ; entry inhibitors ; thiols ; disulfide exchange
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CAS No. : | 7787-70-4 |
Formula : | BrCu |
M.W : | 143.45 |
SMILES Code : | [Cu+].[Br-] |
MDL No. : | MFCD00010969 |
InChI Key : | NKNDPYCGAZPOFS-UHFFFAOYSA-M |
Pubchem ID : | 24593 |
GHS Pictogram: |
![]() ![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H302-H315-H318-H335-H410 |
Precautionary Statements: | P261-P264-P270-P271-P280-P302+P352-P304+P340-P305+P351+P338-P310-P330-P362+P364-P403+P233-P501 |
Class: | 9 |
UN#: | 3077 |
Packing Group: | Ⅲ |
Num. heavy atoms | 2 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | None |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | None |
Num. H-bond donors | None |
Molar Refractivity | 8.93 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
None |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
None |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
None |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
None |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
None |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
None |
Log S (ESOL):? ESOL: Topological method implemented from |
None |
Solubility | None mg/ml ; None mol/l |
Class? Solubility class: Log S scale |
None |
Log S (Ali)? Ali: Topological method implemented from |
None |
Solubility | None mg/ml ; None mol/l |
Class? Solubility class: Log S scale |
None |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
None |
Solubility | None mg/ml ; None mol/l |
Class? Solubility class: Log S scale |
None |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
None |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
None |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
None |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
None |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
None |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
None |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
None |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
None |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
None cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
None |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
None |
Egan? Egan (Pharmacia) filter: implemented from |
None |
Muegge? Muegge (Bayer) filter: implemented from |
None |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
None |
PAINS? Pan Assay Interference Structures: implemented from |
None alert |
Brenk? Structural Alert: implemented from |
None alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
None |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen bromide; sodium nitrite; In sulfuric acid; water; acetic acid; | Reference Example 24 A solution of <strong>[64628-73-5]3-chloro4-trifluoromethoxyaniline</strong> (5.1 g) in acetic acid (31 ml) was stirred and treated with sodium nitrite (2.16 g) in concentrated sulphuric acid (14 ml) at below 18 C. After an additional 1 hour at 10 C., the solution was added to a mixture of copper (I) bromide (7.7 g) and hydrobromic acid (24.5 ml) in water at 40-50 C. The reaction was completed by heating at 50 C. for 2 hours, water was added and the mixture filtered. The filtrate was extracted with ether, washed with sodium bicarbonate, dried (magnesium sulphate) and evaporated to give 3-chloro-4-trifluoromethoxy-bromobenzene (6.05 g) as a brown oil, NMR (CDCl3) 7.10(m,1H), 7.35(m,1H), 7.55(d,1H). By proceeding in a similar manner 2-nitro-4-trifluoromethoxy-bromobenzene was prepared, NMR (CDCl3) 7.35(m,1H), 7.75(m,1H), 7.8(d,1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With tert.-butylnitrite; In hexane; ethyl acetate; acetonitrile; | (Step 1) Synthesis of 2-bromo-6-fluorobenzothiazole Copper (I) bromide (619 mg, 4.32 mmol) was suspended in acetonitrile (10 ml). To the resulting suspension was added tert-butyl nitrite (640 ael, 5.38 mmol), followed by stirring at 60ØC for 5 minutes. To the reaction mixture was added 2-amino-6-fluorobenzothiazole (605 mg, 3.60 mmol). The resulting mixture was stirred at 60ØC for 10 minutes. After cooling to the room temperature, the reaction mixture was diluted with ethyl acetate. The ethyl acetate solution was washed with 1N HCl, saturated brine, dried over anhydrous sodium sulfate, and distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from n-hexane/ ethyl acetate (5:1, v/v) eluate fractions, 2-bromo-6-fluorobenzothiazole (330 mg, 40%) was obtained as a brown solid. 1H-NMR (CDCl3) delta: 7.19-7.24 (m, 1H), 7.49-7.52 (m, 1H), 7.92-7.96 (m, 1H). MS (ESI) m/z 273.8 (M++1+MeCN). |
With sodium nitrite; In water; hydrogen bromide; | EXAMPLE 28 [(2-(6-Fluorobenzothiazolyl))carbonyl]-1-piperidinecarboxylic acid, 1,1-dimethylethyl ester STR36 Slurry 2-amino-6-fluorobenzothiazole (0.255 mol) in water (325 mL), heat to reflux and add 48% hydrobromic acid (130 mL). Maintain at reflux for 20 minutes, cool to 0 C. and add a solution of sodium nitrite (17.56 g, 0.255 mol) water (90 mL), maintaining a temperature of 0 C. Stir at 0 C. for 15 minutes and add by dropwise addition (while keeping cold) to a rapidly stirring mixture of copper (I) bromide (42.03 g, 0.293 mol) in 48% hydrobromic acid (86 mL) and water (225 mL). Stir at room temperature for 20 minutes. Allow to stand overnight, extract into methylene chloride and dry (MgSO4). Evaporate the solvent in vacuo and purify by chromatography to give 2-bromo-6-fluorobenzothiazole. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | at 20℃; for 24h; | General procedure: Prepared as described for 1 except CuBr (0.29g, 2.0mmol) and HBr (47%) were used. Yield: 0.25g (27%). Anal. Calcd for C4H7N3IOCuBr2 (MW=463.48): C, 10.37; H, 1.52; N, 9.07. Found: C, 10.28; H, 1.66; N, 8.91. FT-IR (cm-1): 3163(w), 2348(m), 1673(m), 1604(m), 1363(w), 1220(s), 868(s), 664(s). The color of crystal is purple. |
Tags: 7787-70-4 synthesis path| 7787-70-4 SDS| 7787-70-4 COA| 7787-70-4 purity| 7787-70-4 application| 7787-70-4 NMR| 7787-70-4 COA| 7787-70-4 structure
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