Structure of 730980-51-5
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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. : | 730980-51-5 |
Formula : | C10H14ClNO |
M.W : | 199.68 |
SMILES Code : | N[C@@H]1CCC2=C1C=C(OC)C=C2.[H]Cl |
MDL No. : | MFCD16295033 |
InChI Key : | KJDASQBFJKUGFC-HNCPQSOCSA-N |
Pubchem ID : | 53484733 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.4 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 55.23 |
TPSA ? Topological Polar Surface Area: Calculated from |
35.25 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.98 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.12 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.73 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.92 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.55 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.6 |
Solubility | 0.5 mg/ml ; 0.00251 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.35 |
Solubility | 0.9 mg/ml ; 0.00451 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.75 |
Solubility | 0.351 mg/ml ; 0.00176 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) |
Yes |
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 |
-6.11 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 |
1.0 |
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 |
0.0 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) |
2.09 |
* 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 |
---|---|---|
Example 2-4LP N-[(R)-Carbamoylphenylmethyl]-N-[(R)-6-methoxyindan-1-yl]benzamide (0395) RT (min.): 3.332 (0396) MS (ESI, m/z): 399.1711 (M-H)- (0397) 1H-NMR (CDCl3) delta: 1.65-1.82 (1H, m), 1.96-2.11 (1H, m), 2.46-2.75 (2H, m), 3.90 (3H, s), 4.69 (1H, br s), 5.20-5.90 (3H, m), 6.78-6.87 (1H, m), 7.06 (1H, d, J=8.3 Hz), 7.24-7.67 (11H, m). N-[(S)-Carbamoylphenylmethyl]-N-[(R)-5-chloroindan-1-yl]benzamide To a solution of (R)-5-chloroindan-1-ylamine hydrochloride (0.05 g) in methanol (1 mL) were added triethylamine (35 muL) and benzaldehyde (0.026 g), and the mixture was stirred for 1.5 hours at 50 C. The reaction mixture was allowed to cool to room temperature, and to the mixture were added benzoic acid (0.03 g) and 4-phenylcyclohexen-1-ylisocyanide (0.045 g). The mixture was stirred for 3 days at 50 C., then allowed to cool to room temperature, and concentrated under reduced pressure. To the obtained residue were added tetrahydrofuran (2 mL), water (5 muL) and a solution of 4 mol/L hydrogen chloride in 1,4-dioxane (185 muL), and the mixture was stirred for 1 hour at room temperature. To the reaction mixture were added water and a saturated aqueous solution of sodium bicarbonate, and the crude product was extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (eluent:ethyl acetate/n-hexane=55/45 to 75/25 to 100/0) to afford N-[(R)-carbamoylphenylmethyl]-N-[(R)-5-chloroindan-1-yl]benzamide (Example 2-1LP, 0.040 g) as low polarity product and N-[(S)-carbamoylphenylmethyl]-N-[(R)-5-chloroindan-1-yl]benzamide (Example 2-1HP, 0.023 g) as high polarity product. The structural formulae are shown in Table 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: To a solution of (R)-5-chloroindan-1-ylamine hydrochloride (0.05 g) in methanol (1 mL) were added triethylamine (35 muL) and benzaldehyde (0.026 g), and the mixture was stirred for 1.5 hours at 50 C. The reaction mixture was allowed to cool to room temperature, and to the mixture were added benzoic acid (0.03 g) and 4-phenylcyclohexen-1-ylisocyanide (0.045 g). The mixture was stirred for 3 days at 50 C., then allowed to cool to room temperature, and concentrated under reduced pressure. To the obtained residue were added tetrahydrofuran (2 mL), water (5 muL) and a solution of 4 mol/L hydrogen chloride in 1,4-dioxane (185 muL), and the mixture was stirred for 1 hour at room temperature. To the reaction mixture were added water and a saturated aqueous solution of sodium bicarbonate, and the crude product was extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (eluent:ethyl acetate/n-hexane=55/45 to 75/25 to 100/0) to afford N--[(R)-carbamoylphenylmethyl]-N--[(R)-5-chloroindan-1-yl]benzamide (Example 2-1LP, 0.040 g) as low polarity product and N--[(S)-carbamoylphenylmethyl]-N--[(R)-5-chloroindan-1-yl]benzamide (Example 2-1HP, 0.023 g) as high polarity product. Examples 2-2 to 2-260 were synthesized in a manner similar to that of Example 2-1 by using the corresponding starting materials. |
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