Structure of 315203-39-5
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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. : | 315203-39-5 |
Formula : | C19H20Cl2N4 |
M.W : | 375.30 |
SMILES Code : | NC1=CC2=C(C=C1)C(CN3CCCC3)=NN2CC4=C(Cl)C=CC=C4Cl |
MDL No. : | MFCD03093364 |
InChI Key : | RPIVQHHCHQAMGO-UHFFFAOYSA-N |
Pubchem ID : | 10499688 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 25 |
Num. arom. heavy atoms | 15 |
Fraction Csp3 | 0.32 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 108.8 |
TPSA ? Topological Polar Surface Area: Calculated from |
47.08 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.02 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.1 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.04 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.69 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
4.05 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.78 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.93 |
Solubility | 0.00441 mg/ml ; 0.0000118 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.79 |
Solubility | 0.00602 mg/ml ; 0.0000161 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-6.67 |
Solubility | 0.0000797 mg/ml ; 0.000000212 mol/l |
Class? Solubility class: Log S scale |
Poorly 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) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
Yes |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
Yes |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
Yes |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.68 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 |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.73 |
* 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 |
---|---|---|
69% | With iron(III) chloride hexahydrate; pyrographite; hydrazine hydrate; In methanol; at 100℃; for 2h;Sealed tube; | To an oven dried pressure tube with stir bar was added indazole8 (18 mg, 0.044 mmol) and MeOH (5 mL). FeCl36H2O (25 mol%,2.6 mg), hydrazine monohydrate solution (65% active hydrazine,0.05 mL, 0.7 mmol), and activated charcoal (20 mg) were added,the tube was capped tightly, and the reaction was stirred at 100C for 2 h. A sample aliquot was taken from the reaction, concentratedunder reduced pressure, dissolved in a minimal amount ofHPLC grade MeCN, and analyzed with LCMS to confirm reactioncompletion. The reaction was filtered, the charcoal and filteredsolids were washed with MeOH (10 mL), and the filtrate was concentratedunder reduced pressure to give crude material that wasdry loaded using silica onto a 5 g silica column and purified withflash chromatography (0-20% MeOH/DCM) to give 9 (11.5 mg) asa white solid in 69% yield. LC-MS tR = 1.44 min (CharacterizationMethod A); m/z = 374.95 (M+H+); 1H NMR (300 MHz, CDCl3) d =7.57 (d, J = 8.5 Hz, 1H), 7.37 (d, J = 8.2 Hz, 2H), 7.31-7.20 (s, 1H),6.63 (d, J = 8.8 Hz, 1H), 6.58 (s, 1H), 5.63 (s, 2H), 4.29 (s, 2H), 3.96(br. s., 2H), 3.13 (br. s., 4H), 1.84 (br. s., 4H); 13C NMR (75 MHz,CDCl3) d = 146.5, 142.5, 137.0, 131.6, 130.3, 128.8, 121.0, 117.7,113.7, 92.2, 52.3, 48.5, 48.2, 23.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Part 1: Coupling reaction. Aniline 9 (40 mg, 0.11 mmol) wasadded to an oven-dried round bottom flask with stir bar and sealedunder nitrogen, then anhydrous THF (16 mL) was added. The solutionwas cooled in a NaCl/H2O bath (5 C) for 15 min., and thenboth DMAP (34.6 mg, 0.282 mmol) and triphosgene (12 mg, 0.04mmol) were added consecutively. Immediately the reactionbecame a light orange suspension. The reaction was stirred at -5C for 8 min., and then amine 4 (35 mg, 0.071 mmol) was addedand the reaction was stirred at 5 C for 1 h, then for an additional1 h while warming to room temperature. A sample aliquot wastaken from the reaction, concentrated under reduced pressure, dissolvedin a minimal amount of HPLC grade MeCN, and analyzedwith LC-MS to confirm reaction completion. The reaction was concentratedunder reduced pressure to give crude material 10 thatcould be either carried onto the next reaction without purification,or triturated with DCM/hexanes (1:1) to provide purer material. |