Structure of 30741-72-1
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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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CAS No. : | 30741-72-1 |
Formula : | C12H12N2O4 |
M.W : | 248.23 |
SMILES Code : | O=C(O)CCC(C(N1)=O)(C2=CC=CC=C2)NC1=O |
MDL No. : | MFCD08445744 |
InChI Key : | RUWPCCQWDIAGAJ-UHFFFAOYSA-N |
Pubchem ID : | 236331 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 18 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 3.0 |
Molar Refractivity | 69.21 |
TPSA ? Topological Polar Surface Area: Calculated from |
95.5 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.78 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.49 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.28 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.14 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.96 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.42 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.67 |
Solubility | 5.3 mg/ml ; 0.0214 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.07 |
Solubility | 2.14 mg/ml ; 0.00861 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.29 |
Solubility | 0.128 mg/ml ; 0.000518 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 |
No |
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 |
-7.47 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 |
0.56 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.31 |
* 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 ammonia; In ethanol; water; at 60℃; | A mixture of 3-benzoylpropionic acid (2.26 g), [NH4HC03] (3.63 g), and KCN (1.03 g) in a solution of 5 mL [ETOH] and 4 mL conc. NH4OH was heated to 60 C in an oil bath under a reflux condenser overnight. Water was added and the mixture extracted with ether, acidified with concentrated [HC1,] extracted with EtOAc and then CH2C12. The extracts of the acidified aqueous were reduced in vacuo to yield crude 2,5-dioxo-4-phenylimidazolidin-4-yl] propanoic acid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate; In DMF (N,N-dimethyl-formamide); | A mixture of [7-PROPYL-3-TRIFLUOROMETHYL-6- (3-BROMOPROPYLOXY)-1,] 2- benzisoxazole (54 mg), crude 2,5-dioxo-4-phenylimidazolidin-4-yl] propanoic acid (56 mg), and [CS2C03] (95 mg) in 3.0 mL DMF was allowed to react overnight. After aqueous workup, the mixture was separated by preparative scale TLC (40% EtOAc in hexanes with 1% [MEOH] added) to give the titled compound. Selected Signals: 1H NMR (400 MHz ; [CDC13)] 8 8.25 (s, 1H) ; 7.58 (d, [1H,] J=8.5 Hz); 7.54-7. 52 Hz (m, 2H); 7.43-7. 35 (m, 4H); 7.06 (d, [1H,] J=9.0 Hz); 4.32 (td, 2H, [JE=6.] 2 Hz, [J2=1.] 3 Hz) ; 4.16 (t, 2H, J=6.0 Hz); 2.92 (t, 2H, J=7.5 Hz) ; 2.53 (t, 2H, J=7.0 Hz); 2.45-2. 35 (m, 2H); 2.18 (p, 2H, J=6.5 Hz) ; 1.71 (sextet, 2H, 7.5 Hz); 0.97 (t, 3H, J=7.5 [HZ).] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; at 20℃; | A solution of acid (1 eq.), Et3N (3 to 4 eq.), HOBt (0.1 to 1.1 eq.) in DMF (or DCM) is stirred at r.t.. EDC.HC1 (1 to 1.2 eq.) is added, then amine (0.95 to 2 eq.) is added and the reaction mixture is stirred at r.t. for 5h to 2 days. The reaction mixture is partitioned between DCM (or EtOAC) and water, extracted with DCM (or EtOAc). The combined organic layers are washed with water and brine, dried over anhydrous Na2S04 (or MgS04), filtered, concentrated in vacuo and purified by flash chromatography on silica gel or preparative LCMS to afford the expected amide. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; N,N-dimethyl-formamide; at 20℃; for 24h; | A flask is charged with 3-(2,5-dioxo-4-phenyl-imidazolidin-4-yl)propionic acid (77 mg, 0.31 mmol, 1 eq.), l-(4-chloro-phenyl)-piperazine dihydrochloride (126 mg, 0.47 mmol, 1.5 eq.) and DMF DCM (lmL/4mL). Et3N (169 mu,, 1.25 mmol, 4 eq.) and PS-Mukaiyama reagent (load 1.17 mmol g, 540 mmg, 0.63 mmol, 2 eq.) are added and the reaction mixture is stirred at r.t. for 24h. Reaction mixture is filtered, washed with DCM and the filtrate is concentrated in vacuo and purified by preparative LCMS to afford the expected product. LCMS: MW (calcd): 427; m/z MW (obsd): 427-429 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A solution of 3-(4-Phenyl-2,5-dioxo-imidazolidin-4-yl)propionic acid (30mg, 0.12 mmol, 1 eq.), TEA (51 jiL, 0.35 mmol, 3eq.) and HOBT (18mg, 0.13 mmol, 1.1 eq) in DMF is stirred at room temperature for 5 mm. EDC-HC1 (28mg, 0.1 Smmol, 1.2 eq) is then added and the mixture is stirred at room temperature for 15 mm. 4-phenylpiperidine in solution in minimum amount of DMF is then added, and the reaction mixture is stirred at room temperature overnight. Solvent are evaporated under reduced pressure, and crude compound is then purified by LC/MS preparative purification, to afford expected Cpd 3. LCMS: MW (calcd): 391; m/z MW (obsd): 392 (M+H). |
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