Azaprocin

{{Short description|Opioid analgesic drug}}

{{Drugbox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 458790006

| IUPAC_name = 1-(3-((E)-3-Phenylprop-2-enyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)propan-1-one

| image = Azaprocin v2.svg

| image_class = skin-invert-image

| width =

| tradename =

| legal_status =

| bioavailability =

| metabolism =

| elimination_half-life =

| excretion =

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

| CAS_number = 140844-23-1

| ATC_prefix = none

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C18H24N2O/c1-2-18(21)20-16-10-11-17(20)14-19(13-16)12-6-9-15-7-4-3-5-8-15/h3-9,16-17H,2,10-14H2,1H3/b9-6+/t16-,17+

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = RKNSPEOBXHFNTD-DQCUJPBYSA-N

| PubChem = 6433185

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 2105901

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 16736583

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

| UNII = D20F1K1BYP

| C=18 | H=24 | N=2 | O=1

| smiles = CCC(N1[C@@H]2CC[C@H]1CN(C2)C/C=C/C3=CC=CC=C3)=O

| melting_point = 170

| melting_high = 175

}}

Azaprocin is a drug which is an opioid analgesic with approximately ten times the potency of morphine, and a fast onset and short duration of action.{{cite journal | vauthors = Cignarella G, Occelli E, Cristiani G, Paduano L, Testa E | title = Bicyclic Homologs of Piperazine. VI.1Synthesis and Analgesic Activity of 3-Substituted 8-Propionyl-3,8-diazabicyclo[3.2.1]octanes | journal = Journal of Medicinal Chemistry | volume = 6 | issue = 6 | pages = 764–6 | date = November 1963 | pmid = 14184943 | doi = 10.1021/jm00342a030 }}{{cite journal | vauthors = Cignarella G, Occelli E, Testa E | title = Bicyclic Homologs of Piperazine. VII.1Synthesis and Analgesic Activity of 3-Aralkenyl-8-propionyl-3,8-diazabicyclo[3.2.1]octanes | journal = Journal of Medicinal Chemistry | volume = 8 | issue = 3 | pages = 326–31 | date = May 1965 | pmid = 14323140 | doi = 10.1021/jm00327a010 }}{{cite journal | vauthors = Rosselli del Turco B, Maffii G | title = [Effect of analgesic drugs on the conditioned behavior of rats] | journal = Bollettino Chimico Farmaceutico | volume = 107 | issue = 2 | pages = 120–6 | date = February 1968 | pmid = 5730115 }} It was discovered in 1963, but has never been marketed.

The derivative substituted on the phenyl ring with a p-nitro group is more potent than the parent compound, around 25× the potency of morphine.{{cite journal | vauthors = Cignarella G, Barlocco D, Tranquillini ME, Volterra A, Brunello N, Racagni G | title = Interaction of 3,8-diazabicyclo (3.2.1) octanes with mu and delta opioid receptors | journal = Pharmacological Research Communications | volume = 20 | issue = 5 | pages = 383–94 | date = May 1988 | pmid = 2843931 | doi = 10.1016/s0031-6989(88)80014-6 | hdl = 11380/1247742 | hdl-access = free }} The ring-opened 2,6-dimethylpiperazine analogues are also active,{{cite journal | vauthors = Cignarella G, Testa E | title = 2,6-Dialkylpiperazines. IV. 1-Propionyl-4-substituted cis-2,6-dimethylpiperazines structurally related to the analgetic 8-acyl-3,8-diazabicyclo[3.2.1]octanes | journal = Journal of Medicinal Chemistry | volume = 11 | issue = 3 | pages = 592–4 | date = May 1968 | pmid = 5656502 | doi = 10.1021/jm00309a039 }} and a large family of opioid analgesic compounds derived from this parent structure have been developed over the last 40 years.{{cite journal | vauthors = Cignarella G, Barlocco D, Tranquillini ME, Volterra A, Brunello N, Racagni G | title = Interaction of 3,8-diazabicyclo (3.2.1) octanes with mu and delta opioid receptors | journal = Pharmacological Research Communications | volume = 20 | issue = 5 | pages = 383–94 | date = May 1988 | pmid = 2843931 | doi = 10.1016/s0031-6989(88)80014-6 | hdl = 11380/1247742 | hdl-access = free }}{{cite journal | vauthors = Barlocco D, Cignarella G, Greco G, Novellino E | title = Computer-aided structure-affinity relationships in a set of piperazine and 3,8-diazabicyclo[3.2.1]octane derivatives binding to the mu-opioid receptor | journal = Journal of Computer-Aided Molecular Design | volume = 7 | issue = 5 | pages = 557–71 | date = October 1993 | pmid = 8294946 | doi = 10.1007/bf00124362 | bibcode = 1993JCAMD...7..557B | s2cid = 23360530 }}{{cite journal | vauthors = Fadda P, Barlocco D, Tronci S, Cignarella G, Fratta W | title = Antinociceptive action of DBO 17 and DBO 11 in mice: two 3,8 diazabicyclo (3.2.1.) octane derivates with selective mu opioid receptor affinity | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 356 | issue = 5 | pages = 596–602 | date = November 1997 | pmid = 9402039 | doi = 10.1007/pl00005095 | s2cid = 40655683 }}{{cite journal | vauthors = Barlocco D, Cignarella G, Vianello P, Villa S, Pinna GA, Fadda P, Fratta W | title = Synthesis and mu-opioid receptor affinity of a new series of nitro substituted 3,8-diazabicyclo[3.2.1]octane derivatives | journal = Farmaco | volume = 53 | issue = 8–9 | pages = 557–62 | year = 1998 | pmid = 10081818 | doi = 10.1016/s0014-827x(98)00065-2 }}{{cite journal | vauthors = Cignarella G, Barlocco D, Vianello P, Villa S, Pinna GA, Fadda P, Fratta W, Toma L, Gessi S | display-authors = 6 | title = Benzocondensed derivatives as rigid analogues of the mu-opioid agonist 3(8)-cinnamyl-8(3)-propionyl-3,8-diazabicyclo[3.2.1]octanes: synthesis, modeling, and affinity | journal = Farmaco | volume = 53 | issue = 10–11 | pages = 667–74 | year = 1998 | pmid = 10205853 | doi = 10.1016/s0014-827x(98)00084-6 }}{{cite journal | vauthors = Vianello P, Albinati A, Pinna GA, Lavecchia A, Marinelli L, Borea PA, Gessi S, Fadda P, Tronci S, Cignarella G | display-authors = 6 | title = Synthesis, molecular modeling, and opioid receptor affinity of 9, 10-diazatricyclo[4.2.1.1(2,5)]decanes and 2,7-diazatricyclo[4.4.0. 0(3,8)]decanes structurally related to 3,8-diazabicyclo[3.2. 1]octanes | journal = Journal of Medicinal Chemistry | volume = 43 | issue = 11 | pages = 2115–23 | date = June 2000 | pmid = 10841790 | doi = 10.1021/jm991140q }}{{cite journal | vauthors = Pinna GA, Murineddu G, Curzu MM, Villa S, Vianello P, Borea PA, Gessi S, Toma L, Colombo D, Cignarella G | display-authors = 6 | title = Synthesis, modelling, and mu-opioid receptor affinity of N-3(9)-arylpropenyl-N-9(3)-propionyl-3,9-diazabicycl | journal = Farmaco | volume = 55 | issue = 8 | pages = 553–62 | date = August 2000 | pmid = 11132733 | doi = 10.1016/s0014-827x(00)00036-7 }}{{cite journal | vauthors = Pinna GA, Cignarella G, Loriga G, Murineddu G, Mussinu JM, Ruiu S, Fadda P, Fratta W | display-authors = 6 | title = N-3(9)-arylpropenyl-N-9(3)-propionyl-3,9-diazabicyclo[3.3.1]nonanes as mu-opioid receptor agonists. Effects on mu-affinity of arylalkenyl chain modifications | journal = Bioorganic & Medicinal Chemistry | volume = 10 | issue = 6 | pages = 1929–37 | date = June 2002 | pmid = 11937351 | doi = 10.1016/s0968-0896(01)00436-9 }}{{cite journal | vauthors = Pinna GA, Cignarella G, Ruiu S, Loriga G, Murineddu G, Villa S, Grella GE, Cossu G, Fratta W | display-authors = 6 | title = Synthesis of novel diazatricyclodecanes (DTDs). Effects of structural variation at the C3' allyl end and at the phenyl ring of the cinnamyl chain on mu-receptor affinity and opioid antinociception | journal = Bioorganic & Medicinal Chemistry | volume = 11 | issue = 18 | pages = 4015–26 | date = September 2003 | pmid = 12927864 | doi = 10.1016/s0968-0896(03)00373-0 }}{{cite journal | vauthors = Loriga G, Manca I, Murineddu G, Chelucci G, Villa S, Gessi S, Toma L, Cignarella G, Pinna GA | display-authors = 6 | title = Synthesis of 3,6-diazabicyclo[3.1.1]heptanes as novel ligands for the opioid receptors | journal = Bioorganic & Medicinal Chemistry | volume = 14 | issue = 3 | pages = 676–91 | date = February 2006 | pmid = 16243530 | doi = 10.1016/j.bmc.2005.09.045 }} One analogue, AP-237, has been used in China to treat the pain caused by cancer.{{cn|date=October 2023}}