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Type | HazMat fee for 500 gram (Estimated) |
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Structure of 583-61-9
*Storage: {[sel_prStorage]}
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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
*For Research Use Only !
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Development of reactive oxygen species (ROS) inhibitors and prodrugs for multiple applications
Senevirathne, Priyangika Prasadini ;
Abstract: Reactive oxygen species are a group of highly reactive oxygen-containing entities that are important at a cellular level for multiple biological processes. Low concentrations of ROS can be beneficial as powerful signaling molecules in those biological processes, although excessive concentrations can promote high levels of DNA damage and a variety of diseases such as skin cancer. A newly identified intracellular ROS production source in skin cells is NADPH oxidases. Out of the NOX enzyme family, the NOX1 holoenzyme is most abundantly expressed in the human keratinocyte cells. UV radiation can trigger the activation of NOX1 isoforms which stimulate the assembling of member CYBA and the cytoplasmic protein NOXO1. Inhibition of these enzymes represents a catalytic approach toward reducing ROS for the prevention of ROS inducible diseases. Key disease states include melanoma induced by UV exposure. The first half of the dissertation focuses on investigating new small molecule inhibitors of a key NOX1 holoenzyme to address these challenges. We designed a series of molecules by optimizing the structure of diapocynin and evaluated by in-silico docking methods to determine the binding affinity with NOXO1 cytoplasmic protein (1WLP crystal structure). And have synthesized the series of target molecules for the structure-activity relationship studies. In the first section of the project, we discovered that inhibitor NOX_inh_5 was not cytotoxic, but instead improved the viability of human primary cells from UV exposure, decreased the cellular stress in human skin through the p53 pathway, and reduced the UV-induced DNA damage as monitored by quantification of cyclobutane dimer formation after UV exposure. Then, we characterized the inhibition potential of NOX_inh_5 by using an Isothermal calorimetric (ITC) binding assay and heteronuclear single quantum coherence (HSQC) technique and revealed that the candidate iii molecule can prevent the complex formation of NOXO1 and CYBA membrane protein. In the second section of the project, we did a structure-activity relationship study for the NOX_inh_5 small molecule to optimize the biological characteristics. The last section of the dissertation discussed the development of ROS sensible prodrug to combat the opioid overdose crisis. Here we used oxidative stress conditions caused by opioid overdose to activate the prodrug. Even though opioid antagonist naloxone has a high affinity to bind with opioid receptors to block opioid-induced activation, it is metabolically unstable and has a short half-life of around 33 min. We developed a peroxide-induced prodrug to overcome this issue that can release a steady stream of naloxone. This allows the concentration of naloxone to remain high for longer periods.
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Purchased from AmBeed: 1007-16-5 ; 111-24-0 ; 14221-01-3 ; 99769-19-4 ; 351422-73-6 ; 158407-04-6 ; 1462-37-9 ; 583-61-9 ; 13965-03-2 ; 455-85-6 ; 148893-10-1
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CAS No. : | 583-61-9 |
Formula : | C7H9N |
M.W : | 107.15 |
SMILES Code : | CC1=NC=CC=C1C |
MDL No. : | MFCD00009605 |
InChI Key : | HPYNZHMRTTWQTB-UHFFFAOYSA-N |
Pubchem ID : | 11420 |
GHS Pictogram: |
![]() ![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H225-H302-H315-H318-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Class: | 3(8) |
UN#: | 2924 |
Packing Group: | Ⅲ |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.29 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 34.17 |
TPSA ? Topological Polar Surface Area: Calculated from |
12.89 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.7 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.62 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.7 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.15 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.31 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.69 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.08 |
Solubility | 0.891 mg/ml ; 0.00832 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.5 |
Solubility | 3.37 mg/ml ; 0.0314 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.73 |
Solubility | 0.199 mg/ml ; 0.00186 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 |
-5.8 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 |
2.0 |
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<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.03 |
* 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 |
---|---|---|
8.3 g | Stage #1: at 150℃; Stage #2: at 20℃; |
Step 1. Synthesis of 5-bromo-2,3-dimethyl-pyridine To a stirred solution of 2,3-dimethyl-pyridine (6.79 mL, 60 mmol) in fuming sulfuric acid (80 mL) held at 150° C. in a round bottom flask fitted with a water cooled reflux condenser and a calcium chloride filled drying tube, was added, dropwise, bromine (3.1 mL, 60 mmol) over 2 hr. The resulting dark red solution was stirred for 16 hr then cooled to room temperature and allowed to stand overnight. This mixture was poured into approximately 400 g of ice. This mixture was brought to pH 12 with cooling in an ice bath. The resulting mixture was extracted with ether and the ether extract washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica chromatography (50 g silica, eluted with 2-20percent ethyl acetate in hexanes) to give the title compound (8.3 g) as a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bromine; | EXAMPLE 25 2,3-Dimethylpyridine is treated with bromine in oleum to give a 3-bromo-5,6-dimethylpyridine which is converted into a Grignard reagent, and this is treated with ethyl orthoformate and the product hydrolyzed to give 5,6-dimethylpyridine-3-carboxaldehyde. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
8.3 g | Step 1. Synthesis of 5-bromo-2,3-dimethyl-pyridine To a stirred solution of 2,3-dimethyl-pyridine (6.79 mL, 60 mmol) in fuming sulfuric acid (80 mL) held at 150 C. in a round bottom flask fitted with a water cooled reflux condenser and a calcium chloride filled drying tube, was added, dropwise, bromine (3.1 mL, 60 mmol) over 2 hr. The resulting dark red solution was stirred for 16 hr then cooled to room temperature and allowed to stand overnight. This mixture was poured into approximately 400 g of ice. This mixture was brought to pH 12 with cooling in an ice bath. The resulting mixture was extracted with ether and the ether extract washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica chromatography (50 g silica, eluted with 2-20% ethyl acetate in hexanes) to give the title compound (8.3 g) as a colorless oil. | |
With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; disulfuric acid; at 10 - 105℃; for 2h; | To a stirred solution of 2,3-dimethylpyridine (1 Og, 0.09mol) in oleum 65% (30ml_) at 10C DBDMH (14.5g, 0,05mol) was added. There after the exothermic reactions started. The reaction mixture was then heated at 105C for 2h. After cooling to room temperature, the mixture was poured onto ice (150g) and the ph adjusted to 12 with aqueous sodium hydroxide solution. The product was extractedinto MTBE (3x100ml_), the organic phases were dried with MgS04 and evaporated under reduced pressure to give 5-bromo-2,3-dimethylpyridine as yellow oil (. Purity acc. to GC 87.3%; yield: 83.3%. | |
With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; fuming sulphuric acid; at 10 - 105℃; for 2h; | To a stirred solution of 2,3-dimethylpyridine (20g, 0.185mol) in oleum 65% (60ml_) at 10C DBDMH (31.7g, 0,11 mol) was added. There after the exothermic reactions started. The reaction mixture was then heated at 105C for 2h. After cooling to room temperature, the mixture was poured onto ice (250g) and the ph adjusted to 12 with aqueous sodium hydroxide solution. The product was extracted into MTBE (3x100ml_), the organic phases were dried with MgS04 and evaporated under reduced pressure to give 5-bromo-2,3-dimethylpyridine as yellow oil (34.3g). Purity acc. to GC 87.0%; yield: 86.7%. |
With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; fuming sulfuric acid; at 10 - 105℃; for 2h; | To a stirred solution of 2,3-dimethylpyridine (1 Og, 0.09mol) in oleum 65% (30mL) at 10C DBDMH (14.5g, 0,05mol) was added. There after the exothermic reactions started. The reaction mixture was then heated at 105C for 2h. After cooling to room temperature, the mixture was poured onto ice (150g) and the ph adjusted to 12 with aqueous sodium hydroxide solution. The product was extracted into MTBE (3x100mL), the organic phases were dried with MgS04 and evaporated under reduced pressure to give 5-bromo-2,3-dimethylpyridine as yellow oil (. Purity acc. to GC 87.3%; yield: 83.3%. | |
With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; fuming sulphuric acid; at 10 - 105℃; for 2h; | To a stirred solution of 2,3-dimethylpyridine (1 Og, 0.09mol) in oleum 65% (30ml_) at 10C DBDMH (14.5g, 0,05mol) was added. There after the exothermic reactions started. The reaction mixture was then heated at 105C for 2h. After cooling to room temperature, the mixture was poured onto ice (150g) and the ph adjusted to 12 with aqueous sodium hydroxide solution. The product was extracted into MTBE (3x100ml_), the organic phases were dried with MgS04 and evaporated under reduced pressure to give 5-bromo-2,3-dimethylpyridine as yellow oil (. Purity acc. to GC 87.3%; yield: 83.3%. |
Tags: 583-61-9 synthesis path| 583-61-9 SDS| 583-61-9 COA| 583-61-9 purity| 583-61-9 application| 583-61-9 NMR| 583-61-9 COA| 583-61-9 structure
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P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
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P231 | Handle under inert gas. |
P232 | Protect from moisture. |
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P234 | Keep only in original container. |
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P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
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P320 | |
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P321 | |
P322 | |
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P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
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P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
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P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
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P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
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P370 + P376 | In case of fire: Stop leak if safe to Do so. |
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H200 | Unstable explosive |
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H202 | Explosive; severe projection hazard |
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H205 | May mass explode in fire |
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H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
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H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
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H271 | May cause fire or explosion; strong oxidizer |
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H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
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H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
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H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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