Structure of 71432-55-8
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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. : | 71432-55-8 |
Formula : | C11H24N2O |
M.W : | 200.32 |
SMILES Code : | CC(N=C(OC(C)(C)C)NC(C)C)C |
MDL No. : | MFCD06657672 |
InChI Key : | FESDUDPSRMWIDL-UHFFFAOYSA-N |
Pubchem ID : | 11041782 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.91 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 62.6 |
TPSA ? Topological Polar Surface Area: Calculated from |
33.62 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.98 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.61 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.56 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.4 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.14 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.54 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.4 |
Solubility | 0.804 mg/ml ; 0.00402 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.97 |
Solubility | 0.217 mg/ml ; 0.00108 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.63 |
Solubility | 0.473 mg/ml ; 0.00236 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 |
-5.67 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 |
2.0 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) |
3.43 |
* 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 |
---|---|---|
75% | In dichloromethane; for 52h;Heating / reflux; | Example 8; (2E)-3-{4-[({1-[({3-cycIohexyI-1-[2-(4-methylpiperazin-1-yI)-2- oxoethyl]-2-phenyl-1H-indol-6-yl}carbonyl)amino]cyclopentyl }carbonyl) amino]rhohenyI}acryli acid; Step 1; tert-butyl 3-cycIohexyl-1H-indole-6-carboxylate; A solution of 3-cycIohexenyl-1H -indole-6-carboxylic acid (1 eq., prepared as described in Example 1, Step 1) in dry DCM (0,19 M) was treated with tert-butyl N,N'-diisopropylimidocarbamate (2 eq.). The resulting clear solution was heated at reflux for 36 h. Addition of a further equivalent of isourea was required after 16 h to drive the reaction to completion. After cooling down the solvent was evaporated giving a residue that was purified by silica gel chromatography (Flashmaster Personal, PE: EtOAc, 30:1) affording tert-butyl 3-cyclohexyl-1H-indole-6-carboxylate (75percent) |
58% | In dichloromethane; for 19h;Heating / reflux; | Step 4: tert-butyl S-cvclohexyl-lH-indole--carboxylate; 2 eq of tert-buty\\ N,N-diisopropylimidocarbamate (prepared according to literature precedent: Synthesis1979, 561) were added to a solution of 3-cyclohexyl-l//-indole-6-carboxylic acid (prepared as described in published International patent application WO2004087714) in CH2Cl2 (0.4 M) and the mixture heated at reflux under N2 for 16 h. A further 2.5 eq of tert-butyl N,N-diisopropylimidocarbamate were then added portionwise over 3 h, with heating being resumed after each addition. The reaction mixture was then filtered whilst hot through a pad of celite and the filtrate concentrated in vacuo. The residue was purified by flash chromatography (5percent EtOAc/PE) to afford the title compound (58 percent); MS (ES") m/z 298 (M-H)". |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
7.2 g | In tetrahydrofuran; at 20℃; for 2h;Inert atmosphere; | DIC (12.1 mL, 77.8 mmol) was added to a mixture of CuCl (140 mg, 1.4 mmol) and tert-butanol (29.9 mL, 312.6 mmol) and the mixture was stirred at room temperature for 12 h. The volatile components were removed under reduced pressure. The solid was dissolved in THF (25 mL) and 5-methoxy-2-methyl-1H-indole-3-acetic acid (2) (7.0 g, 31.9 mmol) was added and the mixture stirred at room temperature for 2 h. The solvent was evaporated and the solid was purified by column chromatography with a mixture of hexanes (80-100 C) and ethyl acetate (3:1). The solvent was removed under reduced pressure to yield a white solid. Yield: 7.2 g (82%); elemental Anal. Calcd for C16H21NO3: C, 69.80; H, 7.69. Found: C, 69.57; H, 7.67; mp: 110-111 C; ESI MS (-) (CH3COCH3): m/z: 274.0 (100%, [M-H]-); 1H NMR (CDCl3, ppm): 7.75 (s, vbr, NHindole), 7.14 (d, 3JHH = 8 Hz, 1H, CHindole), 7.00 (d, 4JHH = 2 Hz, 1H, CHindole), 6.76 (dd, 3JHH = 8 Hz, 4JHH = 2 Hz, 1H, CHindole), 3.85 (s, 3H, OCH3), 3.54 (s, 2H, CH2), 2.39 (s, 3H, CH3), 1.43 (s, 9H, C(CH3)3); 13C{1H} NMR (CDCl3, ppm): 171.4 (COO), 154.0 (CindoleO), 133.5 (Cindole), 130.2 (Cindole), 129.1 (Cindole), 110.9 (CindoleH), 110.9 (CindoleH), 105.0 (Cindole), 100.6 (CindoleH), 80.5 (C(CH3)3), 55.9 (OCH3), 31.9 (CH2), 28.1 (C(CH3)3), 11.9 (CH3); IR (selected, KBr, cm-1): = 3342 (s, nu(N-H)), 3005 (w), 2980 (w), 2965 (w), 2914 (w), 2837 (w), 2047 (w), 1722 (s, nu(CO)). |
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