LY2955303
- Product Name
- LY2955303
- CAS No.
- 1433497-19-8
- Chemical Name
- LY2955303
- Synonyms
- CS-2631;LY2955303;LY2955303 >=98% (HPLC);LY2955303; LY-2955303; LY 2955303;inhibit,LY 2955303,Autophagy,LY-2955303,Retinoic acid receptors,RAR/RXR,Inhibitor,LY2955303,Retinoid X receptors;4-[5-[3,5-Bis(1,1-dimethylethyl)phenyl]-1-[4-[(4-methyl-1-piperazinyl)carbonyl]phenyl]-1H-pyrazol-3-yl]benzoic acid;Benzoic acid, 4-[5-[3,5-bis(1,1-dimethylethyl)phenyl]-1-[4-[(4-methyl-1-piperazinyl)carbonyl]phenyl]-1H-pyrazol-3-yl]-
- CBNumber
- CB03312276
- Molecular Formula
- C36H42N4O3
- Formula Weight
- 578.74
- MOL File
- 1433497-19-8.mol
LY2955303 Property
- Boiling point:
- 721.9±60.0 °C(Predicted)
- Density
- 1.15±0.1 g/cm3(Predicted)
- storage temp.
- 2-8°C
- solubility
- Chloroform: 25 mg/ml
- form
- A crystalline solid
- pka
- 3.84±0.10(Predicted)
- color
- White to off-white
Hazard and Precautionary Statements (GHS)
- Symbol(GHS)
-
- Signal word
- Warning
- Hazard statements
-
H315Causes skin irritation
H319Causes serious eye irritation
H335May cause respiratory irritation
- Precautionary statements
-
P261Avoid breathing dust/fume/gas/mist/vapours/spray.
P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.
N-Bromosuccinimide Price
- Product number
- 25833
- Product name
- LY2955303
- Packaging
- 1mg
- Price
- $32
- Updated
- 2024/03/01
- Product number
- 25833
- Product name
- LY2955303
- Packaging
- 5mg
- Price
- $93
- Updated
- 2024/03/01
- Product number
- 25833
- Product name
- LY2955303
- Packaging
- 10mg
- Price
- $169
- Updated
- 2024/03/01
- Product number
- 25833
- Product name
- LY2955303
- Packaging
- 25mg
- Price
- $381
- Updated
- 2024/03/01
- Product number
- 5984
- Product name
- LY2955303
- Purity
- ≥98%(HPLC)
- Packaging
- 25
- Price
- $284
- Updated
- 2021/12/16
LY2955303 Chemical Properties,Usage,Production
Uses
LY 2955303, is a potent and selective retinoic acid receptor gamma (RARγ) antagonist with a Ki of 1.09 nM.
Biological Activity
LY2955303 is a potent and selective RARγ antagonist (Ki = 1.09 nM/RARγ, >1.70 μM/RARα, >2.98 μM/RARβ) th at effectively inhibits RARγ-, but not RARα- or RARβ-, dependent reporter activity upon 15 nM all-trans retinoic acid stimulation in respective HEK293 transfectants (KB = 7.11 nM/RARγ, 1.51 μM/RARβ, 4.44 μM/RARα; 10 nM ATRA for RARβ transfectant). LY2955303 exhibits therapeutic efficacy in a r at model of osteoarthritis-like joint pain (ED50 = 0.72 mg/kg; single p.o. dosage 9 days post OA pain induction by MIA intra-articular injection) with good pharmacokinetic properties, aqueous solubility (>1.0 mg/mL in simulated intestinal fluid), oral availability (F = 26%; 10 mg/kg p.o. over 2 mg/kg i.v.), and no RARα antagonism-associated adverse effects (no testicular degeneration up to 10 mg/kg) seen with BMS-189453 treatment or in RARα-knockout mice.
Synthesis
1433497-65-4
1433497-19-8
1. THF (1790 L) was added to the reactor followed by methyl 4-[5-(3,5-di-tert-butylphenyl)-1-[4-(4-methylpiperazine-1-carbonyl)phenyl]pyrazol-3-yl]benzoate (358 g, 0.605 mol) and water (1140 mL), keeping the temperature at 8-12 °C. 2. lithium hydroxide monohydrate (38 g, 0.905 mol) was added one time and the reaction mixture was stirred at 8-12 °C for 16 hours. 3. After completion of the reaction, EtOAc (30 L) was added and the pH of the mixture was adjusted to 5 with 1N HCl. 4. The two phases were separated and the aqueous layer was extracted with EtOAc (2 x 10 L). The organic layers were combined, dried with sodium sulfate, filtered and the solvent was removed under reduced pressure to give a solid product. 5. The crude product was purified by column chromatography using DCM/MeOH (20/1) as eluent to give a light yellow solid. 6. The solid was ground in a solvent mixture of acetonitrile/MTBE (1/3, 4 L) for 1 h. The solid was collected by filtration. 7. The solid was dried under vacuum at 50 °C for 72 h to give 4-(5-(3,5-di-tert-butylphenyl)-1-(4-(4-methylpiperazine-1-carbonyl)phenyl)-1H-pyrazol-3-yl)benzoic acid (264.2 g, 75% yield) as a white solid. lc-es/ms m/z 579 [M + H]+.
in vivo
A single oral dose of LY2955303 demonstrates a dose responsive effect whereby the rat reduces differential weight bearing (ED50=0.72 mg/kg)[1].
storage
Store at -20°C
References
[1] Patent: WO2013/66640, 2013, A1. Location in patent: Page/Page column 39
[2] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 14, p. 3274 - 3277
LY2955303 Preparation Products And Raw materials
Raw materials
Preparation Products
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