Structure of Boc-β-iodo-Ala-OMe
CAS No.: 93267-04-0
*Storage: {[sel_prStorage]}
*Shipping: {[sel_prShipping]}
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.
Synonyms: Methyl (R)-2-((tert-butoxycarbonyl)amino)-3-iodopropanoate
4.5
*For Research Use Only !
Change View
| Size | Price | VIP Price |
DE Stock US Stock |
Asia Stock Global Stock |
In Stock |
| {[ item.pr_size ]} |
Inquiry
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price, item.discount_usd) ]} {[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]} |
Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]} | {[ item.p_spot_brand_remark ]} 1-2 weeks {[ item.pr_usastock ]} In Stock Inquiry - | {[ item.p_spot_brand_remark ]} 1-2 weeks {[ item.pr_chinastock ]} {[ item.pr_remark ]} In Stock Inquiry - | Login - + |
Please Login or Create an Account to: See VIP prices and availability
Asia Stock: Ship in 3-5 business days
EU Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days
US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days
{[ item.p_spot_brand_remark ]}
1-2weeks
Inquiry
Inquiry
{[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ getRatePrice(item.pr_usd,1,item.mem_rate,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ item.p_spot_brand_remark ]}
1-2weeks
Inquiry
Inquiry
{[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price, item.vip_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
In Stock
- +
Please Login or Create an Account to: See VIP prices and availability
Asia Stock: Ship in 3-5 business days
EU Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days
US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
A µ-opioid receptor modulator that works cooperatively with naloxone
Evan S. O& ; amp ; amp ; #39 ; Brien ; Vipin Ashok Rangari , et al.
Abstract: The µ-opioid receptor (µOR) is a well-established target for analgesia1, yet conventional opioid receptor agonists cause serious adverse efects, notably addiction and respiratory depression. These factors have contributed to the current opioid overdose epidemic driven by fentanyl2, a highly potent synthetic opioid. µOR negative allosteric modulators (NAMs) may serve as useful tools in preventing opioid overdose deaths, but promising chemical scafolds remain elusive. Here we screened a large DNA-encoded chemical library against inactive µOR, counter-screening with active, G-protein and agonist-bound receptor to ‘steer’ hits towards conformationally selective modulators. We discovered a NAM compound with high and selective enrichment to inactive µOR that enhances the afnity of the key opioid overdose reversal molecule, naloxone. The NAM works cooperatively with naloxone to potently block opioid agonist signalling. Using cryogenic electron microscopy, we demonstrate that the NAM accomplishes this efect by binding a site on the extracellular vestibule in direct contact with naloxone while stabilizing a distinct inactive conformation of the extracellular portions of the second and seventh transmembrane helices. The NAM alters orthosteric ligand kinetics in therapeutically desirable ways and works cooperatively with low doses of naloxone to efectively inhibit various morphine-induced and fentanyl-induced behavioural efects in vivo while minimizing withdrawal behaviours. Our results provide detailed structural insights into the mechanism of negative allosteric modulation of the µOR and demonstrate how this can be exploited in vivo.
Show More >
| CAS No. : | 93267-04-0 |
| Formula : | C9H16INO4 |
| M.W : | 329.13 |
| SMILES Code : | O=C(OC)[C@@H](NC(OC(C)(C)C)=O)CI |
| Synonyms : |
Methyl (R)-2-((tert-butoxycarbonyl)amino)-3-iodopropanoate
|
| MDL No. : | MFCD00216579 |
| InChI Key : | UGZBFCCHLUWCQI-LURJTMIESA-N |
| Pubchem ID : | 10903591 |
| GHS Pictogram: |
|
| Signal Word: | Warning |
| Hazard Statements: | H302-H315-H319-H335 |
| Precautionary Statements: | P261-P305+P351+P338 |
| Num. heavy atoms | 15 |
| Num. arom. heavy atoms | 0 |
| Fraction Csp3 | 0.78 |
| Num. rotatable bonds | 7 |
| Num. H-bond acceptors | 4.0 |
| Num. H-bond donors | 1.0 |
| Molar Refractivity | 64.14 |
| TPSA ? Topological Polar Surface Area: Calculated from |
64.63 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.6 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.43 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.49 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.42 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.3 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.65 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-2.32 |
| Solubility | 1.58 mg/ml ; 0.00479 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-2.39 |
| Solubility | 1.33 mg/ml ; 0.00405 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.29 |
| Solubility | 1.71 mg/ml ; 0.00519 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
| BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
| P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
| CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
| CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
| CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
| CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
| CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
| Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-7.29 cm/s |
| Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
| Ghose? Ghose filter: implemented from |
None |
| Veber? Veber (GSK) filter: implemented from |
0.0 |
| Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
| Muegge? Muegge (Bayer) filter: implemented from |
0.0 |
| Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
| PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
| Brenk? Structural Alert: implemented from |
3.0 alert: heavy_metal |
| Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<0.0 |
| Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
3.09 |
* 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 |
|---|---|---|
| 63% | Degassed anhydrous DMF (42 mL) was added to zinc (13.72 g, 209.8 mmol) under a flow of argon. Chlorotrimethylsilane (5.30 mL, 42.0 mmol) was added and the mixture stirred vigorously for 30 min. Stirring was stopped and the zinc was allowed to settle. The supernatant was decanted under a flow of argon and the zinc washed with degassed DMF (2 × 20 mL). A solution of Boc-3-iodoalanine methyl ester (29.9 g, 90.9 mmol) in degassed DMF (75 mL) was added to the zinc. Upon addition an exotherm was observed. The cloudy gray solution was stirred for 30 min at room temperature and then the zinc was allowed to settle. This was repeated for a second batch of zincate. The two batches of zincate were combined by decanting the supernatant into a clean flask under a flow of argon. A solution of bromide 8 (40.0 g, 140 mmol) in degassed DMF (120 mL), palladium acetate (1.57 g, 6.99 mmol), and X-Phos (6.67 g, 14.0 mmol) were added sequentially. The reaction was heated at 40 C. After 16 h the reaction mixture was poured into water (400 mL) and ethyl acetate (250 mL) was added. The mixture was filtered through a pad of celite, washing the filter cake with ethyl acetate (2 × 50 mL). The layers were separated, the aqueous extracted with ethyl acetate (100 mL) and the organics combined. The organics were then washed with brine (5 × 400 mL), dried (MgSO4), and concentrated in vacuo. The resulting residue was purified by dry flash chromatography (2% ethyl acetate in heptane to 20%) to give compound 9 as a brown solid (35.95 g, 63%).1H NMR (400 MHz, CDCl3): 7.84 (s, 1H), 7.47-7.36 (m, 2H), 5.22-5.14 (m, 1H), 4.72-4.63 (m, 1H), 3.74 (s, 3H), 3.57 (dd, 1H), 3.25-3.15 (m, 1H), 1.33 (s, 9H). |
[ 3032-81-3 ]
[ 93267-04-0 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 0.16 g | With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; tris-(dibenzylideneacetone)dipalladium(0); iodine; zinc; In N,N-dimethyl-formamide; at 20℃; for 16h;Inert atmosphere; Sealed tube; | To an oven dried 8 mL vial with teflon cap purged with N2 was added Zinc dust (298 mg, 4.56 mmol), DMF(1.5 mL), and iodine (57.8 mg, 0.228 mmol). To this mixture was added (R)-methyl 2-((tert-butoxycarbonyl)amino)-3-iodopropanoate (500 mg, 1.519 mmol), immediately followed by iodine (57.8 mg, 0.228 mmol).Pd2(dba)3 (69.6 mg, 0.076 mmol), 2-DICYCLOHEXYLPHOSPHINO-2?,6?-DIMETHOXYBIPHENYL(62.4 mg, 0.152 mmol), <strong>[3032-81-3]1,3-dichloro-5-iodobenzene</strong> (622 mg, 2.279 mmol) and the reaction mixture wasallowed to stir at rt for 16 h. The crude mixture was diluted in EtOAc (30 mL) and DMF was removed withfour aqueous washes. The organic phase was dried over anhydrous sodium sulfate. The solution was filteredand concentrated, and the crude was purified by silica gel chromatography using 100percent hexanes to 30percentEtOAc/Hexanes. The desired product was obtained as a pale yellow oil, (S)-methyl 2-((tertbutoxycarbonyl)amino)-3-(3,5-dichlorophenyl)propanoate, 0.160 g yield in 77percent purity by LCMS analysis.Analysis LCMS condition F: Retention time=2.84 min; ESI-MS(+) m/z 348.1 (M+H). |
[ 326-62-5 ]
[ 93267-04-0 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Step A: Methyl N-(tert-butoxycarbonyl)-4-(2-fluorophenyl)-5-nitrilonorvalinate (0251) To a solution of methyl N-(tert-butoxycarbonyl)-3-iodo-D-alaninate (5.00 g, 15.2 mmol) in DMF (20 mL) was added cesium carbonate (5.44 g, 16.7 mmol) and the mixture was stirred at 23 C. for 2 hours. (2-Fluorophenyl)acetonitrile (5.87 mL, 45.6 mmol) and cesium carbonate (7.42 g, 22.8 mmol) were added and the resulting mixture was stirred for 1 hour. The mixture was filtered and water was added to the filtrate. The mixture was extracted with ethyl acetate (3×). The combined organic extracts were washed with water (3×), brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography (0% ethyl acetate?50% ethyl acetate/hexane) gave the title compound as a racemic mixture of cis and trans diastereomers. MS: m/z=378.1 (M+CH3CN+1). |