1221443-94-2
1221443-94-2 structure
- Name: A-1165442
- Chemical Name: A-1165442
- CAS Number: 1221443-94-2
- Molecular Formula: C22H20ClF2N3O2
- Molecular Weight: 431.863
- Catalog: Signaling Pathways Membrane Transporter/Ion Channel TRP Channel
- Create Date: 2018-04-03 17:15:10
- Modify Date: 2024-01-08 15:34:41
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A-1165442 is a potent, competitive and orally available TRPV1 antagonist with an IC50 of 9 nM for human TRPV1.
| Name | A-1165442 |
|---|---|
| Synonyms |
Urea, N-[(4R)-7-chloro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-1-benzopyran-4-yl]-N'-(3-methyl-5-isoquinolinyl)-
1-[(4R)-7-Chloro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-5-isoquinolinyl)urea |
| Description | A-1165442 is a potent, competitive and orally available TRPV1 antagonist with an IC50 of 9 nM for human TRPV1. |
|---|---|
| Related Catalog | |
| Target |
IC50: 9 nM (human TRPV1)[1] |
| In Vitro | A-1165442 displays potent, competitive antagonism at recombinant human TRPV1 activated by capsaicin (IC50=9 nM) and incomplete blockade of acid-evoked response (62% block at 30 μM). A-1165442 possesses excellent selectivity (>100-fold) versus other members of the TRP family (TRPA1, TRPM8, TRPV2, TRPV3) and other receptors expressed in peripheral sensory neurons including P2X2/3, Cav2.2, Nav channels, and KCNQ2/3. A-1165442 shows minimal cross-reactivity upon evaluation (10 μM) in a broad screening panel (n=74, CEREP) of cell-surface receptors, ion channels, and enzymes[1]. |
| In Vivo | A-1165442 exhibits excellent pharmacological selectivity, has a favorable pharmacokinetic profile, and demonstrates good efficacy against osteoarthritis pain in rodents. Oral administration of A-1165442 prevents capsaicin-induced nocifensive behaviors in rats, with an ED50 of 9.5 μmol/kg corresponding to plasma concentration of 420 ng/mL (970 nM). A single dose of A-1165442 produces a robust effect on grip force, with an ED50 of 35 μmol/kg measured 1 h postdosing. Repeated dosing of A-1165442 results in an increase in potency relative to acute analgesic efficacy. No significant changes in core body temperature is observed in conscious rats dosed with A-1165442 and this temperature-neutral profile is maintained in conscious dogs[1]. |
| Animal Admin | Dogs: Male beagle dogs are instrumented with telemetry transmitters capable of monitoring core body temperature and then allowed to recover. Dosing is initiated at time zero, with dogs receiving a single oral dose of vehicle, compound 1 at (30 μmol/kg), or A-1165442 (100 μmol/kg); n=4−6 per group. Measurements are recorded every 5 min for the duration of the study, then averaged to 15 min and 1 h intervals. Temperature signals are transmitted as radio signals by each implanted transmitter to a receiver placed on the cage and interfaced with a desktop personal computer[1]. |
| References |
| Density | 1.4±0.1 g/cm3 |
|---|---|
| Boiling Point | 574.4±50.0 °C at 760 mmHg |
| Molecular Formula | C22H20ClF2N3O2 |
| Molecular Weight | 431.863 |
| Flash Point | 301.2±30.1 °C |
| Exact Mass | 431.121216 |
| LogP | 4.36 |
| Vapour Pressure | 0.0±1.6 mmHg at 25°C |
| Index of Refraction | 1.635 |
| Storage condition | 2-8℃ |