3-([1,4′-Bipiperidin]-1′-ylmethyl)-7-bromo-N-(1-phenylcyclopropyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxamide
- Product Name
- 3-([1,4′-Bipiperidin]-1′-ylmethyl)-7-bromo-N-(1-phenylcyclopropyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxamide
- CAS No.
- 1336960-13-4
- Chemical Name
- 3-([1,4′-Bipiperidin]-1′-ylmethyl)-7-bromo-N-(1-phenylcyclopropyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxamide
- Synonyms
- GSK2193874;GSK2193874 ，S8367;GSK 2193874; GSK2193874;GSK2193874 >=98% (HPLC);GSK2193874, 10 mM in DMSO;TRPV4 antagonist GS2193874;GSK2193874,inhibit,GSK 2193874,Transient receptor potential channels,GSK-2193874,Inhibitor,TRP Channel;3-([1,4′-Bipiperidin]-1′-ylmethyl)-7-bromo-N-(1-phenylcyclopropyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxamide;3-([1,4'-Bipiperidin]-1'-ylmethyl)-7-bromo-N-(1-phenylcyclopropyl)-2-(3-(trifluoromethyl)phenyl)quinoline-4-carboxamide;4-Quinolinecarboxamide, 3-([1,4'-bipiperidin]-1'-ylmethyl)-7-bromo-N-(1-phenylcyclopropyl)-2-[3-(trifluoromethyl)phenyl]-
- CBNumber
- CB62751087
- Molecular Formula
- C37H38BrF3N4O
- Formula Weight
- 691.62
- MOL File
- 1336960-13-4.mol
3-([1,4′-Bipiperidin]-1′-ylmethyl)-7-bromo-N-(1-phenylcyclopropyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxamide Property
- Boiling point:
- 737.8±60.0 °C(Predicted)
- Density
- 1.43±0.1 g/cm3(Predicted)
- storage temp.
- room temp
- solubility
- DMSO: soluble10mg/mL, clear
- pka
- 12.82±0.20(Predicted)
- form
- powder
- color
- white to beige
Safety
- Hazard Codes
- T
- Risk Statements
- 25-36/37/38
- Safety Statements
- 26-45
- RIDADR
- UN 2811 6.1 / PGIII
- WGK Germany
- 3
Hazard and Precautionary Statements (GHS)
- Symbol(GHS)
-
- Signal word
- Danger
- Hazard statements
-
H301Toxic if swalloed
H315Causes skin irritation
H319Causes serious eye irritation
H335May cause respiratory irritation
- Precautionary statements
-
P302+P352IF ON SKIN: wash with plenty of soap and water.
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
- SML0942
- Product name
- GSK2193874
- Purity
- ≥98% (HPLC)
- Packaging
- 5MG
- Price
- $114.95
- Updated
- 2025/07/31
- Product number
- SML0942
- Product name
- GSK2193874
- Purity
- ≥98% (HPLC)
- Packaging
- 25MG
- Price
- $343.7
- Updated
- 2025/07/31
- Product number
- 17715
- Product name
- GSK2193874
- Purity
- ≥95%
- Packaging
- 1mg
- Price
- $32
- Updated
- 2024/03/01
- Product number
- 17715
- Product name
- GSK2193874
- Purity
- ≥95%
- Packaging
- 5mg
- Price
- $100
- Updated
- 2024/03/01
- Product number
- 17715
- Product name
- GSK2193874
- Purity
- ≥95%
- Packaging
- 10mg
- Price
- $184
- Updated
- 2024/03/01
3-([1,4′-Bipiperidin]-1′-ylmethyl)-7-bromo-N-(1-phenylcyclopropyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxamide Chemical Properties,Usage,Production
Uses
GSK 2193874 is an orally active, potent and selective TRPV4 antagonist.
Uses
GSK2193874 has been used as a transient receptor potential vanilloid 4 (TRPV4) antagonist:
- to study its effects on GSK101-induced colon contractions in mice
- to study its effects on murine compact bone-derived osteoblasts(CB-OB)
- to study its effects on lung injury post-lipopolysaccharide (LPS) in mice
Biochem/physiol Actions
GSK2193874 is a very potent, specific antagonist of TRPV4 ion channels (IC50 = 50 nM). Lung edema caused by high pulmonary venous pressure (PVP) is driven by TRPV4 activity. GSK2193874 blocks TRPV4-mediated calcium influx in cells expressing native and recombinant TRPV4, and inhibits vascular permeability and lung edema in isolated rodent and canine lungs subjected to high PVP. The compound also resolves pulmonary edema in murine myocardial infarction model.
Synthesis
1336964-26-1
41049-53-0
1336960-13-4
3-(1,4'-Bipiperidin-1'-ylmethyl)-7-bromo-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (2.5 g, 4.34 mmol) and 1-phenylcyclopropanamine (0.900 g, 5.42 mmol) were added to a 500 mL flask with HOBT (0.664 g, 4.34 mmol), EDC ( 3.74 g, 19.52 mmol), dichloromethane (45 mL) and N,N-diisopropylethylamine (7.57 mL, 43.4 mmol). The reaction mixture was heated to 60 °C and kept for 5 hours. After the reaction was completed, it was cooled to room temperature and saturated aqueous sodium bicarbonate solution (50 mL), water (50 mL) and dichloromethane (50 mL) were added. After stirring for 30 minutes, the two phases were separated and the aqueous phase was extracted three times with dichloromethane. The organic phases were combined, filtered through a phase separator, concentrated and purified by reversed-phase HPLC (Biotage, 0-100% CH3CN/water with 0.1% TFA). The fraction containing the target product was collected, transferred to a partition funnel and saturated aqueous NaHCO3 and dichloromethane were added. The organic phase was separated and the aqueous phase was extracted three more times with dichloromethane. The organic phases were combined and concentrated to give 3-(1,4'-bipiperidin-1'-ylmethyl)-7-bromo-N-(1-phenylcyclopropyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxamide (2.5 g, 83% yield).1H NMR (400 MHz, DMSO-d6) δ 9.51 (s, 1H), 8.32 (d, J = 2.01 Hz , 1H), 7.95 (s, 1H), 7.80-7.90 (m, 3H), 7.69-7.76 (m, 1H), 7.67 (d, J = 8.78 Hz, 1H), 7.42-7.50 (m, 2H), 7.38 (t, J = 7.65 Hz, 2H), 7.24-7.30 (m, 1H), 3.43 (br.s. , 2H), 2.38 (d, J = 9.79 Hz, 2H), 2.24-2.35 (m, 3H), 1.94 (t, J = 10.92 Hz, 1H), 1.59 (t, J = 10.92 Hz, 2H), 1.37-1.47 (m, 5H), 1.33 (br.s., 6H), 0.89-1.03 (m, 2H). MS (m/z) 693.2 (M + H+).
in vivo
The pharmacokinetic (PK) properties for GSK2193874 are evaluated in both rat and dog and found to have half-lives and oral exposure suitable for oral dosing in chronic animal models (Rat PK: iv CL=7.3 mL/min/kg, po t1/2=10 h, %F=31. Dog PK: iv CL=6.9 mL/min/kg, po t1/2=31 h, %F=53). In addition, GSK2193874 shows no blood pressure or heart rate effect in rats when dose up to 30 mg/kg. GSK2193874 is the first-in-class orally bioavailable TRPV4 inhibitor that demonstrated ability to improve pulmonary functions in a number of heart failure models[1]. GSK2193874 shows low clearance (7.3 mL/min/kg) and good rat oral bioavailability (31%)[2].
storage
Store at +4°C
References
[1] Patent: WO2011/119704, 2011, A1. Location in patent: Page/Page column 49
[2] ACS Medicinal Chemistry Letters, 2017, vol. 8, # 5, p. 549 - 554
3-([1,4′-Bipiperidin]-1′-ylmethyl)-7-bromo-N-(1-phenylcyclopropyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxamide Preparation Products And Raw materials
Raw materials
Preparation Products
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