Structure of PDEC-NB
CAS No.: 874302-76-8
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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. : | 874302-76-8 |
| Formula : | C14H12N2O5S2 |
| M.W : | 352.39 |
| SMILES Code : | O=C(OC1=CC=C([N+]([O-])=O)C=C1)OCCSSC2=NC=CC=C2 |
| English Name : | 4-nitrophenyl 2-(pyridin-2-yldisulfanyl)ethyl carbonate |
| MDL No. : | MFCD28556879 |
| InChI Key : | JHDROZPIXZYTMZ-UHFFFAOYSA-N |
| Pubchem ID : | 11638899 |
| Num. heavy atoms | 23 |
| Num. arom. heavy atoms | 12 |
| Fraction Csp3 | 0.14 |
| Num. rotatable bonds | 9 |
| Num. H-bond acceptors | 6.0 |
| Num. H-bond donors | 0.0 |
| Molar Refractivity | 89.67 |
| TPSA ? Topological Polar Surface Area: Calculated from |
144.84 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.64 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.41 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.95 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.0 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.69 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.34 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-3.97 |
| Solubility | 0.0382 mg/ml ; 0.000108 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-6.13 |
| Solubility | 0.00026 mg/ml ; 0.000000739 mol/l |
| Class? Solubility class: Log S scale |
Poorly soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.34 |
| Solubility | 0.0161 mg/ml ; 0.0000456 mol/l |
| Class? Solubility class: Log S scale |
Moderately soluble |
| GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
| 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) |
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 |
-6.03 cm/s |
| Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
| Ghose? Ghose filter: implemented from |
None |
| Veber? Veber (GSK) filter: implemented from |
1.0 |
| Egan? Egan (Pharmacia) filter: implemented from |
1.0 |
| 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 |
4.0 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) |
3.01 |
* 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 |
|---|---|---|
| 64% | With pyridine; benzotriazol-1-ol; In N,N-dimethyl-formamide; at 16℃; for 16h;Inert atmosphere; | To a solution of compound 1(60mg, 0.17 mmol), MMAE (110 mg, 0.123 mmol), HOBt (4.6 mg, 0.034 mmol) in dry DMF (3.0 mL) was added pyridine (134 mg, 1.7 mmol) at 20°C, and the mixture was allowed to stir at 16°C for 16 h under N2. The mixture was filtered and purified by prep-HPLC (FA conditions), to give compound A (99.7 mg, yield: 64percent) as a whitesolid. LCMS: (10-80, AB, 2 mm), 1.331 mm, MS = 932.5[M+2j; ?H NMR (400 MI-Tz, DMSOd 6) 5 8.46 (d, J= 4.4 Hz, 1 H), 7.80 -7.76 (m, 2 H), 7.56 (s, 1 H), 7.34 -7.18 (m, 7 H), 5.10 (s, 1H), 4.56 -4.51 (m, 2 H), 4.29 -4.16 (m, 3 H), 4.03 (s, 2 H), 3.77 (d, J 11.6Hz, 2 H), 3.37 (d, J= 9.6 Hz, 2 H), 3.28 - 3.23 (m, 8 H), 3.15 (s, 3 H), 2.84 (s, 3 H), 2.40 (s, 2 H), 2.18 (s, 2 H), 2.00(s, 1 H), 1.81 (s, 3 H), 1.62 - 1.56 (m, 2 H), 1.34 (d, J= 6.4 Hz, 1 H), 1.05 - 1.01 (m, 8 H), 0.88 -0.80 (m, 18 H). The molecular weight determined by NMR was 930.50. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 50.05% | With benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 25℃; for 16h; | 20.3 Procedure for preparation of compound 4 To a solution of compound 3 (230.52 mg, 654.17 umol) in DMF (2 mL) was added Motohmod (0.15 g, 327.09 umol), DIEA (126.82 mg, 981.26 umol, 170.92 uL) and HOBt (53.04 mg, 392.50 umol). The mixture was stirred at 25 °C for 16 hr. LC-MS indicated compound 3 was consumed completely and a peak with desired mass (m/z: 672.1([M+H+])) was detected. The reaction mixture was purified by prep-HPLC (A: H20, B: ACN). Compound 4 (0.11 g, 163.72 umol, 50.05% yield) was obtained as a white solid. Calculated MW: 671.8 observed m/z: 672.1([M+H+]) |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 90% | With triethylamine In dichloromethane | 3.3.3 3.3.3. Synthesis of the 2-(pyridin-2-yldisulfanyl)ethyl 4-(isoquinolin-5-ylsulfonyl)-1.4-diazepane- 1 -carboxylate To a solution of 4-nitrophenyl (2-(pyridin-2-yldisulfanyl)ethyl) carbonate (600 mg, 1.703 mmol) in CH2CI2 (75 ml) was added EbN (430 pi, 3.10 mmol) and Fasudil-HCI (508 mg, 1.55 mmol) at room temperature. The residue was subjected to column chromatography on silica gel (ethyl acetate (EtOAc) EtOAc: Methanol 95:5) to give a yellow viscous oil (702 mg, 90%).1H NMR (300 MHz, CDC ) d 9.37 (s, 1 H), 8.72 (d, J = 6.2 Hz, 1 H), 8.46 (t, J = 6.6 Hz, 2H), 8.26 - 8.10 (m, 3H), 7.84 - 7.54 (m, 3H), 7.18 - 7.08 (m, 1 H), 6.96 - 6.85 (m, 2H), 5.32 (s, 1 H), 4.35 (t, J = 6.2 Hz, 2H), 3.75 - 3.33 (m, 10H), 3.05 (t, J = 6.1 Hz, 2H), 2.02 (t, J = 1 1.7 Hz, 2H), 1.60 (s, 1 H), 1.27 (s, 1 H). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With dmap; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 50℃; | S1 Compound 9 (110 mg, 0.31 mmol) was added to a DMF solution of compound 8 (Duo5, the synthesis of which has been previously described in US Patent 10,590,165, which is incorporated herein in its entirety) (200 mg, 0.26 mmol), DIPEA (100 mg, 0.77 mmol), HOBt (81 mg, 0.6 mmol), and DMAP (50 mg) at room temperature. The resulting mixture was stirred at 50oC for 5 hours and LCMS showed a major desired product peak. The crude reaction mixture was purified directly on reverse phase HPLC and the desired product peak was combined and freeze dried. Compound 10 was isolated as a fluffy white powder. MS m/z 985.5 (M+H). |

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