Structure of 86324-51-8
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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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*For Research Use Only! Not for Human Use. We Do Not Sell to Patients.
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Chapter Eighteen: Synthesis and characterization of abscisic acid receptor modulators
Aditya S. Vaidya ; Sang-Youl Park ; Zenan Xing ; Sean R. Cutler ;
Abstract: The apocarotenoid phytohormone abscisic acid (ABA) regulates several aspects of plant development and stress responses. ABA is synthesized in response to multiple stressors and indirectly activates subfamily 2 Snf1-related kinases (SnRK2s) by receptor-mediated inhibition of clade A type IIC protein phosphatases (PP2Cs), which normally repress SnRK2 activity. The binding of ABA to its receptors triggers a change in receptor conformation that directs the formation of a receptor-ligand-PP2C complex that inhibits the activity of PP2C; this core mechanism can be harnessed for phosphatase activity-based measurements of receptor activation. In this chapter, we describe general methods for determining the effects of small molecules on ABA receptor function and supplement these with methods describing the synthesis of the high-affinity ligands opabactin (OP), which activates subfamily III and II ABA receptors, and the pan-receptor antagonist antabactin (ANT), and TAMRA-ANT fluorescent derivative of ANT. We present simple methods for quantifying receptor-ligand interactions using both PP2C inhibition and fluorescence polarization (FP) assays. Controls for determining the quality of recombinant receptors are provided, which are required for both quantitative analyses and for experimental consistency. Collectively, these methods will facilitate consistent biochemical measurements of the effects of ligand binding on ABA receptor function in vitro. Although the chapter describes ABA-specific methods, they illustrate and address a common need across receptor systems—reproducible assays that enable high throughput discovery and subsequent optimization of receptor modulators.
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| CAS No. : | 86324-51-8 |
| Formula : | C10H6FNO2 |
| M.W : | 191.16 |
| SMILES Code : | OC(=O)C1=NC2=C(C=C1)C=C(F)C=C2 |
| English Name : | 6-Fluoroquinoline-2-carboxylic acid |
| MDL No. : | MFCD09837268 |
| InChI Key : | LNRMNYOWYGXFBK-UHFFFAOYSA-N |
| Pubchem ID : | 22169810 |
| Num. heavy atoms | 14 |
| Num. arom. heavy atoms | 10 |
| Fraction Csp3 | 0.0 |
| Num. rotatable bonds | 1 |
| Num. H-bond acceptors | 4.0 |
| Num. H-bond donors | 1.0 |
| Molar Refractivity | 48.66 |
| TPSA ? Topological Polar Surface Area: Calculated from |
50.19 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.37 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.15 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.49 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.65 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.21 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.77 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-2.84 |
| Solubility | 0.275 mg/ml ; 0.00144 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-2.84 |
| Solubility | 0.279 mg/ml ; 0.00146 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.36 |
| Solubility | 0.0842 mg/ml ; 0.000441 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) |
No |
| Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.94 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 |
0.56 |
| 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<1.0 |
| Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.37 |
* 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 |
|---|---|---|
| 85% | With hydrogenchloride Heating; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With thionyl chloride In toluene for 4h; Heating; | ||
| With thionyl chloride for 4h; Reflux; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| In methanol; hexane; dichloromethane |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 85% | With sodium chlorite; sodium dihydrogenphosphate; 2-methyl-but-2-ene In water; <i>tert</i>-butyl alcohol at 20℃; | |
| With sodium chlorite; sodium dihydrogenphosphate; 2-methyl-but-2-ene In <i>tert</i>-butyl alcohol at 25℃; for 4h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Stage #1: 6-fluoroquinoline-2-carboxylic acid With hydrogen In methanol Stage #2: methanol With thionyl chloride |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1.1: H2 / PtO2 / methanol 1.2: SOCl2 2.1: LAH / tetrahydrofuran |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1.1: H2 / PtO2 / methanol 1.2: SOCl2 2.1: LAH / tetrahydrofuran 3.1: Et3N / CH2Cl2 / 0 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 5 steps 1.1: H2 / PtO2 / methanol 1.2: SOCl2 2.1: LAH / tetrahydrofuran 3.1: Et3N / CH2Cl2 / 0 °C 4.1: Et3N / tetrahydrofuran / Heating 5.1: K2CO3; MeOH / 0 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 4 steps 1.1: H2 / PtO2 / methanol 1.2: SOCl2 2.1: LAH / tetrahydrofuran 3.1: Et3N / CH2Cl2 / 0 °C 4.1: Et3N / tetrahydrofuran / Heating |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 6 steps 1.1: H2 / PtO2 / methanol 1.2: SOCl2 2.1: LAH / tetrahydrofuran 3.1: Et3N / CH2Cl2 / 0 °C 4.1: Et3N / tetrahydrofuran / Heating 5.1: K2CO3; MeOH / 0 °C 6.1: pyridine / acetonitrile |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 7 steps 1.1: H2 / PtO2 / methanol 1.2: SOCl2 2.1: LAH / tetrahydrofuran 3.1: Et3N / CH2Cl2 / 0 °C 4.1: Et3N / tetrahydrofuran / Heating 5.1: K2CO3; MeOH / 0 °C 6.1: pyridine / acetonitrile 7.1: methanol |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: SeO2 / dioxane / 3 h / 90 °C 2: aq. NaClO2; NaH2PO4; 2-methylbut-2-ene / 2-methyl-propan-2-ol / 4 h / 25 °C | ||
| Stage #1: 6-fluoro-2-methyl-quinoline With potassium <i>tert</i>-butylate; oxygen In dimethyl sulfoxide; <i>tert</i>-butyl alcohol Stage #2: With hydrogenchloride; water | Preparation of Quinoline Acid via Oxidation of Methyl Group: [CHEMMOL-00068] [0345] Typical procedure to prepare quinoline carboxylic acid via oxidation: Preparation of 6-fluoro-2-quinoline carboxylic acid: Air was bubbled into a solution of 6-fluoro-2-methylquinoline (1 g) with an excess of t-BuOK (20 ml, 1.0M in t-BuOH) in DMSO. When solvents were almost all evaporated, water (20 ml) was added to the residue and pH was adjusted to 7 by adding 10N HCl solution. The aqueous solution was then extracted with EtOAc (3×20 ml). And the combined organic layer was dried over anhydrous MgSO4, filtered and concentrated to afford a crude product which purified by silica gel column chromatography to provide 1.18 g of 6-fluoro-2-quinoline carboxylic acid. MS m/z: (M+H)+ calcd for C10H7FNO2 192.05, found 192.04. HPLC retention time: 1.04 minutes (column I). | |
| With pyridine; selenium(IV) oxide Reflux; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: hexane; CH2Cl2; methanol 2: aq. NH2NH2 / methanol / 60 h / 25 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 4 steps 1: hexane; CH2Cl2; methanol 2: aq. NH2NH2 / methanol / 60 h / 25 °C 3: CH2Cl2 / 18 h / 25 °C 4: aq. NaOH / ethanol; dioxane / 4 h / 85 °C |

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