SH-I-048A

{{Short description|Benzodiazepine drug}}

{{Drugbox

| IUPAC_name = (3S)-7-bromo-5-(2-fluorophenyl)-3-methyl-1H-benzo[e] [1,4]diazepin-2(3H)-one

| image = SH-I-048A.svg

| image_class = skin-invert-image

| width = 200

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| legal_CA = Schedule IV

| legal_UK = PSA

| legal_DE = NpSG

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| CAS_number_Ref = {{cascite|correct|CAS}}

| CAS_number = 872874-11-8

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = KN27P6CSU9

| ATC_prefix =

| ATC_suffix =

| PubChem = 49850464

| ChemSpiderID = 57381614

| C=16 | H=12 | Br=1 | F=1 | N=2 | O=1

| melting_point =

| smiles = Fc3ccccc3C2=N[C@@H](C)C(=O)Nc1ccc(Br)cc12

| StdInChI=1S/C16H12BrFN2O/c1-9-16(21)20-14-7-6-10(17)8-12(14)15(19-9)11-4-2-3-5-13(11)18/h2-9H,1H3,(H,20,21)/t9-/m0/s1

| StdInChIKey = QEFZCKUXGLDPPT-VIFPVBQESA-N

}}

SH-I-048A (SH-i-048A) is a benzodiazepine derivative related in structure to compounds such as flubromazepam and meclonazepam. SH-I-048A is described as a non subtype selective superagonist at the benzodiazepine site of GABA_A receptors,{{cite journal|author10-link=Bryan Roth | vauthors = Obradović AL, Joksimović S, Poe MM, Ramerstorfer J, Varagic Z, Namjoshi O, Batinić B, Radulović T, Marković B, Roth BL, Sieghart W, Cook JM, Savić MM | title = Sh-I-048A, an in vitro non-selective super-agonist at the benzodiazepine site of GABAA receptors: the approximated activation of receptor subtypes may explain behavioral effects | journal = Brain Research | year = 2014 | volume = 1554 | pages = 36–48 | doi = 10.1016/j.brainres.2014.01.036 | pmid = 24472579 | pmc = 3996760 }} with a binding affinity of 0.77 nM at the α₁ subtype, 0.17 nM at α₂, 0.38 nM at α₃ and 0.11 nM at α₅.{{cite journal | vauthors = Clayton T, Poe MM, Rallapalli S, Biawat P, Savić MM, Rowlett JK, Gallos G, Emala CW, Kaczorowski CC, Stafford DC, Arnold LA, Cook JM | display-authors = 6 | title = A Review of the Updated Pharmacophore for the Alpha 5 GABA(A) Benzodiazepine Receptor Model | journal = International Journal of Medicinal Chemistry | volume = 2015 | pages = 430248 | date = 2015 | pmid = 26682068 | pmc = 4657098 | doi = 10.1155/2015/430248 | doi-access = free }} It has been used to study the functional differences between the different subtypes of the GABA_A receptor.{{cite journal | vauthors = Obradović LA, Joksimović S, Poe MM, Timić T, Cook JM, Savić MM | title = Delayed Behavioral Effects of SH–I–048A, a Novel Nonselective Positive Modulator of Gabaa Receptors, After Peripheral Nerve Injury in Rats. | journal = Acta Veterinaria | date = June 2014 | volume = 64 | issue = 2 | pages = 189–99 | doi = 10.2478/acve-2014-0018 | doi-access = free }}{{cite journal | vauthors = Elgarf AA, Siebert DC, Steudle F, Draxler A, Li G, Huang S, Cook JM, Ernst M, Scholze P | display-authors = 6 | title = Different Benzodiazepines Bind With Distinct Binding Modes to GABAA Receptors | journal = ACS Chemical Biology | volume = 13 | issue = 8 | pages = 2033–2039 | date = August 2018 | pmid = 29767950 | pmc = 6102643 | doi = 10.1021/acschembio.8b00144 }}