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Type | HazMat fee for 500 gram (Estimated) |
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Structure of 206559-36-6
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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.
4.5
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CAS No. : | 206559-36-6 |
Formula : | C14H11NOS |
M.W : | 241.31 |
SMILES Code : | S=C=NC1=CC=CC(OCC2=CC=CC=C2)=C1 |
MDL No. : | MFCD00060374 |
InChI Key : | QJLFNDXMZQJMDL-UHFFFAOYSA-N |
Pubchem ID : | 561446 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H331-H302-H312-H314 |
Precautionary Statements: | P261-P273-P280-P305+P351+P338-P310 |
Class: | 8(6.1) |
UN#: | 2923 |
Packing Group: | Ⅲ |
Num. heavy atoms | 17 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.07 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 72.11 |
TPSA ? Topological Polar Surface Area: Calculated from |
53.68 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.05 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
5.19 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.85 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.37 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
5.03 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
4.3 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.86 |
Solubility | 0.0033 mg/ml ; 0.0000137 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-6.06 |
Solubility | 0.000208 mg/ml ; 0.000000863 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.26 |
Solubility | 0.00132 mg/ml ; 0.00000546 mol/l |
Class? Solubility class: Log S scale |
Moderately 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) |
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) |
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 |
-4.09 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
1.0 |
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 |
2.0 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) |
2.3 |
* 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 |
---|---|---|
80% | Intermediate 21 : Methyl fcralpha«s-4-(4-([(5-{f3-(benzyloxy)phenyI1amino|-l,3,4- oxadiazol-2-yl)carbonilamino}-3-nitrophenvi)cyclohexyllacetate; l-(Benzyloxy)-3-isothiocyanatobenzene (290 mg, 1.2 mmol) was added in one portion to a stirred solution of methyl [/ralpha«5-4-(4-[hydrazino(oxo)acetyl]amino}-3- nitrophenyl)cyclohexyl]acetate (Intermediate lvi, 378 mg, 1.0 mmol) in DMA (5 mL) and the reaction mixture was stirred at ambient temperature for 4 h. EDCI (288 mg, 1.5 mmol) was added in one portion and the reaction mixture was heated in a microwave at 80C for 10 mins. Water (15 mL) was added and the mixture was filtered to leave a solid, which was washed with water to give the title compound as a solid (470mg, 80%). 'H NMR deltal.Odelta-l^l (2H, m), 1.46-1.6 (2H, m), 1.73-1.9 (5H, m), 2.27 (2H, d), 2.6-2.7(IH, m), 3.61 (3H, s), 5.12 (2H, s), 6.76 (IH, dd), 7.17 (IH, dd), 7.25-7.5 (7H, m), 7.7 (IH, dd), 7.92-8.05 (2H, m), 11.05 (IH, s), 11.4 (IH, s); MS m/e MH+ SSO. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dichloromethane; at 20℃; | EXAMPLE 1. PREPARATION OF 1- (3-BENZYLOXY) PHENYLTHIOUREA (Compound 1); 1. I 02N X 1. 2. 1. TCD ., base >, I Compound 1 [0114] 3-Nitrophenol (X) is converted to ether (Y) by sequential treatment with sodium hydride and benzylbromide. Reduction of the aniline with tin chloride provides aniline (Z). In certain circumstances the reduction may be accomplished using a hydrogen/Pd catalyst system when the substituent on the aryl group does not include an aryl group. [0115] The final product, Compound 1 is obtained by treatment of Z with thiocarbonyl di- imidazole followed by ammonia. 3-Benzyloxyaniline (5 g, 25 mmol) is added dropwise over a one minute period to 4.94 g (27.6 mmol) thiocabonyl di-imidazole in methylene chloride (150 ml). The resulting mixture is stirred at room temperature overnight. An additional 400 mg thiocarbonyl di- imidazole (TCDI) is added and the reaction is continued for 2 hours more. The reaction is diluted with hexane and filtered through silica. Concentration provides 5.1 g of the desired 3- benzyloxyphenyl isothiocyanate. [0116] A portion of this isothiocyanate (50 mg, 0.21 mmol) in 1 ml methylene chloride is mixed with 0.5 ml of 2 M ammonia in methanol. After 30 minutes the reaction is concentrated to provide Compound 1 in quantitative yield. [0117] Alternatively thiocarbonyl di-imidazole (1.1 mmol, 196 mg) is added to a solution of 3-benzyloxyaniline (1 mmol, 199 mg) in dichloromethane (5 mL). The reaction is stirred at room temperature until the aniline is consumed, about 1 hour. A solution of methanolic ammonia (2 M, 2 mL) is added and the stirring continued for 2 hours. Solvent is evaporated and the residue purified by chromatography on silica gel to give 150 mg of (3-benzyloxyphenyl) thiourea. [0118] NMR (CDCI3) D : 5.08 (s, 2H), 6.03 (brs, 2H), 6.8 (M, 2H), 6.93 (m, 1H), 7. 3- 7. 47 (M, 6H), 7.82 (brs, 1H). MS (APCI) : M++1 = 259. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With ammonia; In methanol; dichloromethane; for 0.5h;Product distribution / selectivity; | EXAMPLE 1. PREPARATION OF 1- (3-BENZYLOXY) PHENYLTHIOUREA (Compound 1); 1. I 02N X 1. 2. 1. TCD ., base >, I Compound 1 [0114] 3-Nitrophenol (X) is converted to ether (Y) by sequential treatment with sodium hydride and benzylbromide. Reduction of the aniline with tin chloride provides aniline (Z). In certain circumstances the reduction may be accomplished using a hydrogen/Pd catalyst system when the substituent on the aryl group does not include an aryl group. [0115] The final product, Compound 1 is obtained by treatment of Z with thiocarbonyl di- imidazole followed by ammonia. 3-Benzyloxyaniline (5 g, 25 mmol) is added dropwise over a one minute period to 4.94 g (27.6 mmol) thiocabonyl di-imidazole in methylene chloride (150 ml). The resulting mixture is stirred at room temperature overnight. An additional 400 mg thiocarbonyl di- imidazole (TCDI) is added and the reaction is continued for 2 hours more. The reaction is diluted with hexane and filtered through silica. Concentration provides 5.1 g of the desired 3- benzyloxyphenyl isothiocyanate. [0116] A portion of this isothiocyanate (50 mg, 0.21 mmol) in 1 ml methylene chloride is mixed with 0.5 ml of 2 M ammonia in methanol. After 30 minutes the reaction is concentrated to provide Compound 1 in quantitative yield. [0117] Alternatively thiocarbonyl di-imidazole (1.1 mmol, 196 mg) is added to a solution of 3-benzyloxyaniline (1 mmol, 199 mg) in dichloromethane (5 mL). The reaction is stirred at room temperature until the aniline is consumed, about 1 hour. A solution of methanolic ammonia (2 M, 2 mL) is added and the stirring continued for 2 hours. Solvent is evaporated and the residue purified by chromatography on silica gel to give 150 mg of (3-benzyloxyphenyl) thiourea. [0118] NMR (CDCI3) D : 5.08 (s, 2H), 6.03 (brs, 2H), 6.8 (M, 2H), 6.93 (m, 1H), 7. 3- 7. 47 (M, 6H), 7.82 (brs, 1H). MS (APCI) : M++1 = 259. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dichloromethane; at 20℃; for 4h; | Step b): General procedure for the preparation of the N-(3-amino-propyl)-N'-(benzyloxyphenyl)thiourea resins; A 0.24 M solution of benzyloxyphenyl isothiocyanate in dichloromethane (4.5 ml; 6 eq.) is added to a reactor containing the 1,3-propane-diamine resin (180 umol; 1 eq.). The suspension is stirred for 4 hours at room temperature. The resin is then washed with dichloromethane (3x5 ml) and N-methylpyrrolidone (NMP; 3x5 ml). The resin is stored as a suspension in NMP (1 ml) and then used in the following reaction. |
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