Structure of 75090-52-7
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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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Discovery of Inhibitory Fragments That Selectively Target Spire2-FMN2 Interaction
Kitel, Radoslaw ; Surmiak, Ewa ; Borggrafe, Jan ; Kalinowska-Tluscik, Justyna ; Golik, Przemyslaw ; Czub, Miroslawa , et al.
Abstract: Here, we report the fragment-based drug discovery of potent and selective fragments that disrupt the Spire2-FMN2 but not the Spire1-FMN2 interaction. Hit fragments were identified in a differential scanning fluorimetry-based screen of an inhouse library of 755 compounds and subsequently validated in multiple orthogonal biophys. assays, including fluorescence polarization, microscale thermophoresis, and 1H-15N HSQC NMR. Extensive structure-activity relationships combined with mol. docking followed by chem. optimization led to the discovery of compound 13, which exhibits micromolar potency and high ligand efficiency (LE = 0.38). Therefore, this fragment represents a validated starting point for the future development of selective chem. probes targeting the Spire2-FMN2 interaction.
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Purchased from AmBeed: 63010-72-0 ; 391-82-2 ; 188111-79-7 ; 23432-40-8 ; 75090-52-7 ; 178984-56-0 ; 57260-73-8 ; 21617-12-9 ; 611-35-8 ; 68500-37-8 ; 346-55-4 ; 181950-57-2 ; 216854-23-8 ; 86-98-6 ; 309956-78-3 ; 5407-57-8 ; 625471-18-3 ; 63136-61-8 ; 82121-05-9 ; 259731-83-4 ; 82121-08-2 ; 1557337-03-7 ; 41460-18-8 ; 766544-91-6 ; 256923-25-8 ; 91066-18-1
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CAS No. : | 75090-52-7 |
Formula : | C9H5BrClN |
M.W : | 242.50 |
SMILES Code : | BrC1=CC=C2C(=C1)N=CC=C2Cl |
MDL No. : | MFCD02684221 |
InChI Key : | JJUTYYVZDKDLBC-UHFFFAOYSA-N |
Pubchem ID : | 10800239 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P301+P312-P302+P352-P304+P340-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 54.45 |
TPSA ? Topological Polar Surface Area: Calculated from |
12.89 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.34 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.63 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.65 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.12 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.76 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.3 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.25 |
Solubility | 0.0137 mg/ml ; 0.0000566 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.59 |
Solubility | 0.0625 mg/ml ; 0.000258 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.17 |
Solubility | 0.00162 mg/ml ; 0.00000668 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) |
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 |
-5.2 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 |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 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) |
1.64 |
* 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.
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