Structure of 281655-34-3
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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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DIELS-ALDER METHOD DEVELOPMENT AND THE GENERATION OF A DRUG DELIVERY CELL PENETRATING PEPTIDE
Rumple, Joshua Keith ; ;
Abstract: The access of ring junction functionalized 5,6-hydrindanone systems has been elusive in the realm of synthetic methodology, and the functionalization of a pre-built ring system rarely explored. These 5,6-hydridanone systems are prevalent in a variety of terpenoid ring systems, especially that of steroidal molecules. Previous synthetic methods to reach these systems using a Diels-Alder cycloaddition proved to be difficult and lacked labile functional groups that would be useful for substitution after the cycloaddition. The design of the α-nitrile cyclopentenone dienophile allows for both post-cyclization adduct functionalization, as well as lowering the energy barrier of the cycloaddition itself. In this work, it is shown that the Lewis acid promoted Diels-Alder reaction with α-nitrile β-methyl cyclopentenone dienophile can be performed under standard temperatures and pressures unlike previously established methods.1 This reaction can generate four chiral centers in a single synthetic step when the starting materials are prochiral. After the generation of 5,6-hydrindanone systems, radical cleavage of the nitrile functionality also allowed for electrophile trapping at the ring junction. This radical cleavage and electrophile trapping pathway allows for functionalization of a quaternary carbon at the ring junction, a method that should be fruitful in the generation of difficult to synthesize steroidal and other terpenoid molecules. In the work on synthetic cell penetrating peptides, camptothecin whilst a notably effective topoisomerase I inhibitor, has never quite reached it’s potential as a therapeutic due to its poor solubility in living systems. Previously, cationic amphiphilic polyproline helices (CAPH) molecules from the Chmielewski lab have been hydrophobically functionalized through O-alkylation of hydroxyprolines at specific regions within the peptide to generate a hydrophobic face. The combination of the cationic faces and the hydrophobic face have made the CAPH molecules notably cell penetrant and tunable. With camptothecin’s notable insolubility in water, it may serve as valuable surrogate to the hydrophobic groups on CAPH molecules and allowing it to be delivered intracellularly. Using an endogenously cleavable linker, we have worked towards a CPP that acts as a drug delivery vehicle. Acting as a replacement of the hydrophobic residue of a CAPH molecule, camptothecin will be chaperoned into the cell and should be released through the action of intracellular esterases.
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CAS No. : | 281655-34-3 |
Formula : | C39H33NO4S |
M.W : | 611.75 |
SMILES Code : | O=C([C@H]1N(C(OCC2C3=C(C4=C2C=CC=C4)C=CC=C3)=O)C[C@H](SC(C5=CC=CC=C5)(C6=CC=CC=C6)C7=CC=CC=C7)C1)O |
MDL No. : | MFCD01860721 |
InChI Key : | CHBJBMXEGJSHBN-GERKYKROSA-N |
Pubchem ID : | 45024445 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Tags: 281655-34-3 synthesis path| 281655-34-3 SDS| 281655-34-3 COA| 281655-34-3 purity| 281655-34-3 application| 281655-34-3 NMR| 281655-34-3 COA| 281655-34-3 structure
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P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
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P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
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. |
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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. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
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P370 + P378 | In case of fire: |
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Storage | |
Code | Phrase |
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P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
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H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
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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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H272 | May intensify fire; oxidizer |
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Health hazards | |
Code | Phrase |
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H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
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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