Structure of 4018-65-9
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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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Clara Stuedemann ;
Abstract: Crystal engineering allows researchers to predict and modulate the behavior of molecules leading to improvement of physical properties without changing the intrinsic structure of the molecules. Recent methods of synthesis in the solid state use mechanochemistry to promote the self-assembly of cocrystals. Advantages of solid-state synthesis include meeting several of the 12 principles of green chemistry. Most notably, solid-state synthesis reduces derivatives, minimizes waste, and uses minimal solvent. This thesis work describes two sets of results. The first project involves three cocrystals of the anticancer agent 5-fluorouracil (5-fu): (5-fu)·(3,3’-bpe), (5-fu)·(4,4’-bpe), and a new polymorph of 2(5-fu)·(2,2’-bpe). We explored possible solvent effects on the two forms of 2(5-fu)·(2,2’-bpe) and report that methanol, 1:1 methanol:ethanol, acetonitrile and ethyl acetate yielded the previously reported form I while ethanol, hexane, isopropyl, and chloroform resulted in form II. Water is also reported as a unique solvent as it produced a mixture of both forms. In the second part of this thesis, we describe the discovery of three novel cocrystals, (3CC)·(2,2’-bpe) and 3(3CC)·2.5(2,2’-bpe) using 3-chlorocatechol (3CC); and 3-bromocatechol (3BC), (3BC)·(2,2’-bpe) as unsymmetrical templates for potential [2+2] photocycloadditions in the solid state. The products were analyzed using powder and single X-ray diffraction (PXRD and SCXRD)
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CAS No. : | 4018-65-9 |
Formula : | C6H5ClO2 |
M.W : | 144.56 |
SMILES Code : | OC1=C(O)C(Cl)=CC=C1 |
MDL No. : | MFCD00143111 |
InChI Key : | GQKDZDYQXPOXEM-UHFFFAOYSA-N |
Pubchem ID : | 19928 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 35.5 |
TPSA ? Topological Polar Surface Area: Calculated from |
40.46 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.27 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.86 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.75 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.41 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.55 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.57 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.4 |
Solubility | 0.574 mg/ml ; 0.00397 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.33 |
Solubility | 0.675 mg/ml ; 0.00467 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.84 |
Solubility | 2.09 mg/ml ; 0.0145 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) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.86 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 |
1.0 alert |
Brenk? Structural Alert: implemented from |
1.0 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) |
1.27 |
* 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.