Structure of 5096-73-1
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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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Evaluation of Pyrazinamide and Pyrazinoic Acid Analogues for Control of Key Weeds in Multiple Crops
Gregory R. Armel ; James T. Brosnan ; Nilda R. Burgos ; Peter J. Porpiglia ; Jose J. Vargas ;
Abstract: Numerous similarities exist between the structure–activity relationships of pharmaceutical drugs and pesticides, creating the potential for finding new crop management tools with novel mechanisms of action. Analogues of pyrazinamide and its active metabolite pyrazinoic acid were evaluated on a variety of monocot and dicot species to assess their potential as commercial herbicides. Six analogues, applied postemergence at 3 kg ai/ha, controlled yellow nutsedge (Cyperus esculentus) ≥ the commercial standards bentazon or imazethapyr. The compound 5-fluoropyrazine-2-carboxylic acid provided between 71 and 95% control of barnyardgrass (Echinochloa crus-galli) and yellow nutsedge with only modest injury (8–25%) to soybean (Glycine max). A similar compound containing a bromine atom in the 5-position controlled yellow nutsedge greater than bentazon and affected soybean, sweet corn (Zea mays convar. saccharata var. rugosa), and rice (Oryza sativa) in a similar fashion to bentazon as well. The herbicidal sites of action targeted by these analogues of pyrazinamide and pyrazinoic acid are unknown, but it is hypothesized that they may be disrupting targets in the biosynthesis pathways of nicotinamide adenine dinucleotide (NAD) and/or ethylene.
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Keywords: herbicide ; rice ; pyrazinamide ; pharmaceutical ; prodrug ; soybean ; sweet corn
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Purchased from AmBeed: 23688-89-3 ; 86873-60-1 ; 54013-04-6 ; 374068-01-6 ; 40155-43-9 ; 36070-80-1 ; 40155-42-8 ; 312736-49-5 ; 356783-15-8 ; 34604-60-9 ; 27398-39-6 ; 21279-64-1 ; 38275-61-5 ; 1211533-09-3 ; 876161-05-6 ; 5326-23-8 ; 1174321-06-2 ; 5096-73-1 ; 1060814-50-7 ; 1211584-50-7
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CAS No. : | 5096-73-1 |
Formula : | C5H3ClN2O2 |
M.W : | 158.54 |
SMILES Code : | ClC1=CC=C(N=N1)C(=O)O |
MDL No. : | MFCD00160464 |
InChI Key : | HHGZQZULOHYEOH-UHFFFAOYSA-N |
Pubchem ID : | 6415762 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 34.0 |
TPSA ? Topological Polar Surface Area: Calculated from |
63.08 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.88 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.65 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.83 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.2 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.97 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.71 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.61 |
Solubility | 3.89 mg/ml ; 0.0245 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.55 |
Solubility | 4.46 mg/ml ; 0.0282 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.63 |
Solubility | 3.72 mg/ml ; 0.0234 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 |
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) |
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 |
-6.81 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) |
1.67 |
* 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 |
---|---|---|
72% | A solution of 6-chloro-pyridazine-3-carboxylic acid (700 mg, 4.53mmol) in thionyl chloride (15 ml) was refluxed for 3 h. The reaction was cooled to ambient temperature and evaporated to dryness. Sodium methoxide (244 mg, 4.53 mmol) in [MEOH] (20 ml) was added to the residue and the solution was stirred on at room temperature (rt). [H2O] was added and the mixture was extracted three times with DCM. The combined organic phases were dried and concentrated. Flashchromatography [(SI02,] Heptane/EtOAc 1: 1) afforded 560 mg (72percent) of the title compound. [1H] NMR [(CDC13),] 5 (ppm): 4.09 (s, 3 H), 7.69 (d, 1 H), 8. 18 (d, 1 H). [LC-MS] [(M++1)] : 173 and 175 (3: 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step 1: To a mixture of compound 7-1 (4.14 g, 26.1 mmol) in DCM (100 mL) was added oxalyl chloride (3.98 g, 31.3 mmol) dropwise. DMF (0.05 mL) was added and the resulting mixture was stirred at room temperature until the compound 7-1 was dissolved. Then MeOH (2 mL) was added dropwise and stirred for another 0.5 hr. After being washed with brine (100 mL), the mixture was dried over anhydrous Na2SC>4 and concentrated to give crude product. The crude product was purified by silica-gel column chromatography (eluting with PE/EA = 4/1) to yield the desired product 7-2 as white solid. LC-MS: m/z = 173.1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With dmap; In tetrahydrofuran; at 50.0℃; for 1.0h; | A suspension of (1) (2.0g, 12.7mmol) and 4-(dimethylamino)pyridine (776mg, 6.3mmol) in THF (50ml_) was treated with di-fe/f-butyl dicarbonate (3.6g, 16.5mmol). It was heated up to 50C for 1 h, then stirred at rt overnight. The reaction mixture was concentrated in vacuo, re-dissolved in EtOAc (20ml_), poured into HCI solution (1 M, 20ml_) and extracted with EtOAc (2 x 20ml_). The combined organics were washed with NaHC03 solution (50ml_) and brine (50ml_), dried over MgS04, filtered and concentrated in vacuo. Purification by silica gel column chromatography with hexane/EtOAc (1 :0-3: 1 ) yielded (2) as a white solid (2.2g, 81 %). (0878) LCMS (ES): Found 237.0 [M+Naf. (0879) 1H NMR (300 MHz, Chloroform-cf), d: 8.08 (d, J= 8.7 Hz, 1 H), 7.63 (d, J=8.9 Hz, 1 H), 1.67 (s, 9H). |
56% | With dmap; In dichloromethane; at 20.0℃; for 12.0h; | Dissolve 6-chloropyridazine-3-carboxylic acid (7a) (2g, 12.62mmol) in 20mL DCM, add DMAP (3.08g, 25.23mmol),(Boc)2O (5.51g, 25.23mmol) was added at room temperature, and the reaction was stirred at room temperature for 12h.The solvent was removed under reduced pressure, and the residue was separated and purified by silica gel column chromatography (ethyl acetate/petroleum ether (v/v)=10/1-3/1),The tert-butyl 6-chloropyridazine-3-carboxylate (7b) (1.5 g, yield: 56%) was obtained. |
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