TRPV1 antagonist 3 (Compound 7q) is a potent TRPV1 antagonist (inhibitor) with IC50 of 2.66 nM for capsaicin. TRPV1 antagonist 3 has mode selectivity, good oral bioavailability (F) (F = 60%), and crosses the BBB (blood-brain barrier).

Physicochemical Properties

Molecular Formula	C23H25N3OS
Molecular Weight	391.52910399437
Exact Mass	391.171
CAS #	2765294-54-8
PubChem CID	163322232
Appearance	Off-white to pale purple solid powder
LogP	5
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	4
Heavy Atom Count	28
Complexity	522
Defined Atom Stereocenter Count	1
SMILES	CC(C)C1=CC(=CC=C1)NC(=O)N2CCC[C@H]2C3=NC=C(S3)C4=CC=CC=C4
InChi Key	CZISSZWUQQBGMU-FQEVSTJZSA-N
InChi Code	InChI=1S/C23H25N3OS/c1-16(2)18-10-6-11-19(14-18)25-23(27)26-13-7-12-20(26)22-24-15-21(28-22)17-8-4-3-5-9-17/h3-6,8-11,14-16,20H,7,12-13H2,1-2H3,(H,25,27)/t20-/m0/s1
Chemical Name	(2S)-2-(5-phenyl-1,3-thiazol-2-yl)-N-(3-propan-2-ylphenyl)pyrrolidine-1-carboxamide
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	hTRPV1 2.66 nM (IC50) TRPM8 7.45 μM (IC50)
ln Vitro	Compared to other TRP channels, TRPV1 antagonist 3 (Compound 7q) has a high degree of selectivity for the TRPV1 receptor[1]. TRPV1 antagonist 3 exhibits a satisfactory solubility in water (26 μg/mL at pH 7.4) [1].
ln Vivo	The anti-nociceptive effect of TRPV1 antagonist 3 (Compound 7q) (0-30 mg/kg; ip; 30 min) is mostly mediated by inhibiting CAP-activated channel[1]. In rats, the TRPV1 antagonist 3 (0-100 mg/kg; ig) exhibited no discernible thermal effect[1]. TRPV1 antagonist 3 (10 mg/kg; iv) has good CNS penetration, with a brain/plasma ratio of 1.66, and a decent concentration in the brain at 0.5 hours, with a value of 2311 ng/g[1].
Animal Protocol	Animal/Disease Models: KM male mice (18-22 g), capsaicin, acetic acid, and thermal induced pain model[1] Doses: 3, 10, and 30 mg/kg. 20 μL of solution of capsaicin (16 mg/20 mL) was injected sc under the skin of the dorsal surface of the right hind paw, or injected with 0.6% acetic acid (0.1 mL/10 g/mouse ip). Route of Administration: intraperitoneally (ip) administration; 30 min Experimental Results: In capsaicin-induced nociception, licking time diminished Dramatically in a dose-dependent manner. In acid-induced nociception, no significant anti-nociceptive activities were found compared with the control (SB-705498 and BCTC) at all dosage. In thermal-induced nociception, the latency time of nociceptive responses was increased at the doses of 10 and 30 mg/kg. Animal/Disease Models: Spragur-Dawley male rats (220-250 g)[1] Doses: 10 mg/kg or 20 mg /kg Route of Administration: intravenous (iv) injection of 10 mg/kg or oral dose of 20 mg/kg (pharmacokinetic/PK Analysis) Experimental Results: In vivo pharmacokinetic/PK parameters of TRPV1 antagonist 3 in rats (n=3)[1
References	[1]. Discovery of (S)-N-(3-isopropylphenyl)-2-(5-phenylthiazol-2-yl)pyrrolidine-1-carboxamide as potent and brain-penetrant TRPV1 antagonist. Eur J Med Chem. 2022 Apr 5;233:114191.

Solubility Data

Solubility (In Vitro)

DMSO: ≥ 100 mg/mL (255.41 mM)

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.5541 mL	12.7704 mL	25.5408 mL
	5 mM	0.5108 mL	2.5541 mL	5.1082 mL
	10 mM	0.2554 mL	1.2770 mL	2.5541 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.