Semotiadil recemate fumarate is the racemate of Semotiadil fumarate. Semotiadil fumarate is a new vascular-selective Ca2+ channel antagonist.

Physicochemical Properties

Molecular Formula	C33H36N2O10S
Molecular Weight	652.7113
Exact Mass	652.209
CAS #	123388-25-0
PubChem CID	10078027
Appearance	Typically exists as solid at room temperature
LogP	4.79
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	12
Rotatable Bond Count	13
Heavy Atom Count	46
Complexity	880
Defined Atom Stereocenter Count	0
SMILES	S1C2=C([H])C([H])=C([H])C([H])=C2N(C([H])([H])[H])C(C1([H])C1C([H])=C(C([H])=C([H])C=1OC([H])([H])C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])OC1C([H])=C([H])C2=C(C=1[H])OC([H])([H])O2)OC([H])([H])[H])=O.O([H])C(C([H])=C([H])C(=O)O[H])=O
InChi Key	DIEJEELGDWGUCV-WLHGVMLRSA-N
InChi Code	InChI=1S/C29H32N2O6S.C4H4O4/c1-30(14-16-34-21-10-12-25-26(18-21)37-19-36-25)13-6-15-35-24-11-9-20(33-3)17-22(24)28-29(32)31(2)23-7-4-5-8-27(23)38-28;5-3(6)1-2-4(7)8/h4-5,7-12,17-18,28H,6,13-16,19H2,1-3H3;1-2H,(H,5,6)(H,7,8)/b;2-1+
Chemical Name	2-[2-[3-[2-(1,3-benzodioxol-5-yloxy)ethyl-methylamino]propoxy]-5-methoxyphenyl]-4-methyl-1,4-benzothiazin-3-one;(E)-but-2-enedioic acid
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

ln Vitro	Semotiadil produced 12.4±9.7% inhibition at a dose of 1 μM and 25±11.0% at a concentration of 10 μM [1]. The effect of Semotiadil on voltage-dependent Ca current (ICa) was examined in scattered smooth muscle cells of the rabbit portal vein. Semotiadil (> or =0.1 μM; dissolved in DMSO) reduces ICa in a concentration-dependent manner (IC50=2.0 μM) at a holding potential of -100 mV. At holding potentials of -80 mV or -60 mV, the concentration inhibition curve recorded in the presence of semotiadil is shifted to the left compared with that observed at -100 mV; semotiadil promotes voltage-dependent inactivation The curve advances to the left. The ICa decay curve is fitted by two time constants. Semotiadil (<1 μM) reduces slow time constants but not fast time constants. The recovery curve from ICa inactivation likewise consisted of two time constants, with Semotiadil (1 microM) prolonging the delayed recovery. Semotiadil dissolved in deionized water suppresses ICa more efficiently than Semotiadil dissolved in DMSO [2].
ln Vivo	For two weeks, conscious spontaneously hypertensive rats were given semotiadil fumarate, a new benzothiazine calcium antagonist, either alone or in combination with enalapril or clomethiazide. The antihypertensive effects of enalapril (5 mg/kg, po) and semotidil (10 mg/kg, po) when taken alone were first noticeable after the third dose and continued to grow every day, albeit they were less pronounced with the subsequent dose. These findings imply that regular coadministration of semotendil and enalapril, particularly at relatively moderate dosages of either, may be able to sustainably lower blood pressure [3].
References	[1]. Koidl B, et al. A novel benzothiazine Ca2+ channel antagonist, Semotiadil, inhibits cardiac L-type Ca2+ currents. Eur J Pharmacol. 1997 Mar 19;322(2-3):243-7. [2]. Teramoto N. Mechanisms of the inhibitory action of Semotiadil fumarate, a novel Ca antagonist, on the voltage-dependent Ca current in smooth muscle cells of the rabbit portal vein. Jpn J Pharmacol. 1993 Mar;61(3):183-95. [3]. Ichikawa M, et al. Antihypertensive effects of a novel calcium antagonist, Semotiadil fumarate (SD-3211), alone and in combination with Enalapril or trichlormethiazide in spontaneously hypertensive rats. Biol Pharm Bull. 1994 Nov;17(11):1513-5

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	1.5321 mL	7.6604 mL	15.3207 mL
	5 mM	0.3064 mL	1.5321 mL	3.0641 mL
	10 mM	0.1532 mL	0.7660 mL	1.5321 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.