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REC-2615 (HCl) is a novel and potent α1B-adrenoceptor antagonist
Physicochemical Properties
| Molecular Formula | C26H34CLN5O5 |
| Molecular Weight | 532.04 |
| Exact Mass | 567.202 |
| Elemental Analysis | C, 58.70; H, 6.44; Cl, 6.66; N, 13.16; O, 15.04 |
| CAS # | 173059-17-1 |
| PubChem CID | 56972225 |
| Appearance | Typically exists as solid at room temperature |
| LogP | 5.276 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 38 |
| Complexity | 706 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | Cl[H].Cl[H].O(C1C(=C([H])C([H])=C([H])C=1C([H])(C([H])([H])[H])C([H])([H])[H])OC([H])([H])[H])C([H])([H])C(N1C([H])([H])C([H])([H])N(C2N=C(C3=C([H])C(=C(C([H])=C3N=2)OC([H])([H])[H])OC([H])([H])[H])N([H])[H])C([H])([H])C1([H])[H])=O |
| InChi Key | XZGSTPYGKYGQLD-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C26H33N5O5.2ClH/c1-16(2)17-7-6-8-20(33-3)24(17)36-15-23(32)30-9-11-31(12-10-30)26-28-19-14-22(35-5)21(34-4)13-18(19)25(27)29-26;;/h6-8,13-14,16H,9-12,15H2,1-5H3,(H2,27,28,29);2*1H |
| Chemical Name | 1-[4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-2-(2-methoxy-6-propan-2-ylphenoxy)ethanone;dihydrochloride |
| Synonyms | REC-2615 2615; Rec-15; Rec15; REC 15/2615 DIHYDROCHLORIDE; 173059-17-1; 1782573-48-1; Rec 15/2615 hydrochloride; 1-[4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-2-(2-methoxy-6-propan-2-ylphenoxy)ethanone;dihydrochloride; 1-(4-Amino-6,7-dimethoxy-2-quinazolinyl)-4-[[2-methoxy-6-(1-methylethyl)phenoxy]acetyl]piperazinedihydrochloride; 1-[4-(4-amino-6,7-dimethoxy-2-quinazolinyl)-1-piperazinyl]-2-[2-methoxy-6-(1-methylethyl)phenoxy]-ethanone, dihydrochloride; CHEMBL5090661; REC 2615; REC2615 |
| 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 | α1A-adrenergic receptor (Ki = 1.9 nM); α1B-adrenergic receptor (Ki = 0.3 nM); Alpha-1D adrenergic receptor (Ki = 2.6 nM) |
| ln Vivo |
In anesthetized rabbits, intravaginal injection of the alpha-1 AR selective antagonist REC 15/2615 (50 and 100 microg/kg) caused a 2 to 3-fold increase in genital tissue oxyhemoglobin (OHb) concentration. Similar increases in tissue OHb were observed with intravaginal injection of phentolamine (500 microg/kg) or a tri-mixture of vasodilators (PGE1, papaverine, phentolamine). REC 15/2615, phentolamine or the tri-mixture also enhanced the amplitude and/or duration of change in genital tissue OHb after pelvic nerve stimulation. Thus, vaginal tissue expresses functional alpha-1 and alpha-2 AR, which modulate vaginal smooth muscle contractility and genital engorgement [2]. Effect of alpha-AR inhibition on genital tissue engorgement in the absence of pelvic nerve stimulation (PNS)[2] We examined the effects of the non-selective alpha-AR antagonist phentolamine and increasing doses (10–100 μg/kg) of the novel alpha-1b AR selective antagonist REC 15/2615 on genital tissue oxyhemoglobin (OHb) concentrations in the absence of PNS. On average, the baseline values of total hemoglobin and OHb were 108.3 ± 2.6 μM and 72.2 ± 1.8 μM, respectively. As shown in Fig. 4, administration of the vehicle (10% N,N-dimethylformamide) alone caused a slight increase in tissue OHb concentration (3.5 ± 1.2 μM). Intravaginal administration of 500 μg/kg of phentolamine mesylate caused a 2.1-fold increase in oxyhemoglobin concentration compared to vehicle, although this change did not reach statistical significance. Intravaginal injection of REC 15/2615 caused an increase in tissue OHb that was significantly greater than vehicle at the 50 and 100 μg/kg doses. Changes in genital blood flow were noted within 60 sec after drug injection and peaked within 5–10 min after administration of drugs. As a positive control, we used a tri-mixture (Tmx) of vasodilators (papaverine, phentolamine and prostaglandin E1). Intravaginal injection of Tmx resulted in a significant change in OHb concentration that was comparable to administration of 50–100 μg/kg of REC 15/2615 (Fig. 4). For all treatments, changes in total tissue hemoglobin concentration paralleled those of OHb [2]. |
| Animal Protocol | Intravaginal administration of vasoactive agents Animals were administered vehicle [10% (v/v) N,N-dimethylformamide in sterile, deionized water; n = 6], phentolamine mesylate (500 μg/kg; n = 6), REC 15/2615 (10, 50 or 100 μg/kg; n = 6 for each concentration) or a tri-mixture (Tmx; n = 3) of papaverine HCl (1.5 mg/kg), phentolamine mesylate (50 μg/kg) and prostaglandin E1 (0.5 μg/kg) by direct infusion into the muscularis layer of the lower vagina. Prior to the application of the laser oximeter probe, vehicle, alpha-AR antagonist or Tmx was loaded into two 23 gauge infusion sets connected to 1 ml syringes. Needles were inserted into the vaginal wall at the 3 and 9 o'clock positions. Stock solutions of vasoactive agents were made to the appropriate concentrations such that the total volume of infusion did not exceed 0.1 ml per syringe. [2] |
| References |
[1]. Ligand design for alpha1 adrenoceptor subtype selective antagonists. Bioorg Med Chem. 2000 Jan;8(1):201-14. [2]. Biochemical and functional characterization of alpha-adrenergic receptors in the rabbit vagina. Life Sci. 2002 Nov 1;71(24):2909-20. |
| Additional Infomation |
Alpha1 adrenoceptors have three subtypes and drugs interacting selectively with these subtypes could be useful in the treatment of a variety of diseases. In order to gain an insight into the structural principles governing subtype selectivity, ligand based drug design (pharmacophore development) methods have been used to design a novel 1,2,3-thiadiazole ring D analogue of the aporphine system. Synthesis and testing of this compound as a ligand on cloned and expressed human alpha1 adrenoceptors is described. Low binding affinity was found, possibly due to an unfavourable electrostatic potential distribution. Pharmacophore models for antagonists at the three adrenoceptor sites (alpha1A, alpha1B, alpha1D) were generated from a number of different training sets and their value for the design of new selective antagonists discussed. The first preliminary antagonist pharmacophore model for the alpha1D adrenoceptor subtype is also reported. [1] Vascular and non-vascular smooth muscle within the vagina mediate important physiological changes during sexual arousal in women. In this study, we have characterized alpha-adrenergic receptors (AR) in rabbit vagina by assessment of radioligand binding, contractility of isolated tissue strips and genital hemodynamics. [3H]Prazosin and [3H]RX821002 (alpha-1 and alpha-2 AR selective antagonists) bound to rabbit vaginal membrane preparations with high affinity and limited capacity. Competition binding assays using both non-selective and subtype selective ligands for AR (phentolamine, prazosin, delequamine, rauwolscine and UK14304) further confirmed the presence of alpha-1 and alpha-2 AR in vaginal tissue. In organ bath preparations of vaginal tissue strips, norepinephrine-induced contraction was attenuated by alpha-1 and alpha-2 AR antagonists (prazosin, tamsulosin, delequamine and phentolamine). [2] |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| 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 | 1.8796 mL | 9.3978 mL | 18.7956 mL | |
| 5 mM | 0.3759 mL | 1.8796 mL | 3.7591 mL | |
| 10 mM | 0.1880 mL | 0.9398 mL | 1.8796 mL |