Azaprocin

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.^[1]^[2]^[3] It was discovered in 1963, but has never been marketed.

ATC code

none

CAS Number

140844-23-1^Y

PubChem CID

6433185

ChemSpider

16736583^Y

Quick facts Clinical data, ATC code ...

Azaprocin
Clinical data

ATC code	none
Identifiers
IUPAC name 1-(3-((E)-3-Phenylprop-2-enyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)propan-1-one
CAS Number	140844-23-1^Y
PubChem CID	6433185
ChemSpider	16736583^Y
UNII	D20F1K1BYP
ChEMBL	ChEMBL2105901^N
CompTox Dashboard (EPA)	DTXSID20161480
Chemical and physical data
Formula	C₁₈H₂₄N₂O
Molar mass	284.403 g·mol⁻¹
3D model (JSmol)	Interactive image
Melting point	170 to 175 °C (338 to 347 °F)
SMILES CCC(N1[C@@H]2CC[C@H]1CN(C2)C/C=C/C3=CC=CC=C3)=O
InChI InChI=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+^Y Key:RKNSPEOBXHFNTD-DQCUJPBYSA-N^Y
^NY (what is this?) (verify)

Para-nitroazaprocin, 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.^[4] The ring-opened 2,6-dimethylpiperazine analogues are also active,^[5] and a large family of opioid analgesic compounds derived from this parent structure have been developed over the last 40 years.^[6]^[7]^[8]^[9]^[10]^[11]^[12]^[13]^[14]^[15] One analogue, AP-237, has been used in China to treat the pain caused by cancer.^{[citation needed]}

[1]
Cignarella G, Occelli E, Cristiani G, Paduano L, Testa E (November 1963). "Bicyclic Homologs of Piperazine. VI.1Synthesis and Analgesic Activity of 3-Substituted 8-Propionyl-3,8-diazabicyclo[3.2.1]octanes". Journal of Medicinal Chemistry. 6 (6): 764–6. doi:10.1021/jm00342a030. PMID 14184943.
[2]
Cignarella G, Occelli E, Testa E (May 1965). "Bicyclic Homologs of Piperazine. VII.1Synthesis and Analgesic Activity of 3-Aralkenyl-8-propionyl-3,8-diazabicyclo[3.2.1]octanes". Journal of Medicinal Chemistry. 8 (3): 326–31. doi:10.1021/jm00327a010. PMID 14323140.
[3]
Rosselli del Turco B, Maffii G (February 1968). "[Effect of analgesic drugs on the conditioned behavior of rats]". Bollettino Chimico Farmaceutico. 107 (2): 120–6. PMID 5730115.
[4]
Cignarella G, Barlocco D, Tranquillini ME, Volterra A, Brunello N, Racagni G (May 1988). "Interaction of 3,8-diazabicyclo (3.2.1) octanes with mu and delta opioid receptors". Pharmacological Research Communications. 20 (5): 383–94. doi:10.1016/s0031-6989(88)80014-6. hdl:11380/1247742. PMID 2843931.
[5]
Cignarella G, Testa E (May 1968). "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 of Medicinal Chemistry. 11 (3): 592–4. doi:10.1021/jm00309a039. PMID 5656502.
[6]
Cignarella G, Barlocco D, Tranquillini ME, Volterra A, Brunello N, Racagni G (May 1988). "Interaction of 3,8-diazabicyclo (3.2.1) octanes with mu and delta opioid receptors". Pharmacological Research Communications. 20 (5): 383–94. doi:10.1016/s0031-6989(88)80014-6. hdl:11380/1247742. PMID 2843931.
[7]
Barlocco D, Cignarella G, Greco G, Novellino E (October 1993). "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 of Computer-Aided Molecular Design. 7 (5): 557–71. Bibcode:1993JCAMD...7..557B. doi:10.1007/bf00124362. PMID 8294946. S2CID 23360530.
[8]
Fadda P, Barlocco D, Tronci S, Cignarella G, Fratta W (November 1997). "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". Naunyn-Schmiedeberg's Archives of Pharmacology. 356 (5): 596–602. doi:10.1007/pl00005095. PMID 9402039. S2CID 40655683.
[9]
Barlocco D, Cignarella G, Vianello P, Villa S, Pinna GA, Fadda P, Fratta W (1998). "Synthesis and mu-opioid receptor affinity of a new series of nitro substituted 3,8-diazabicyclo[3.2.1]octane derivatives". Farmaco. 53 (8–9): 557–62. doi:10.1016/s0014-827x(98)00065-2. PMID 10081818.
[10]
Cignarella G, Barlocco D, Vianello P, Villa S, Pinna GA, Fadda P, et al. (1998). "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". Farmaco. 53 (10–11): 667–74. doi:10.1016/s0014-827x(98)00084-6. PMID 10205853.
[11]
Vianello P, Albinati A, Pinna GA, Lavecchia A, Marinelli L, Borea PA, et al. (June 2000). "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 of Medicinal Chemistry. 43 (11): 2115–23. doi:10.1021/jm991140q. PMID 10841790.
[12]
Pinna GA, Murineddu G, Curzu MM, Villa S, Vianello P, Borea PA, et al. (August 2000). "Synthesis, modelling, and mu-opioid receptor affinity of N-3(9)-arylpropenyl-N-9(3)-propionyl-3,9-diazabicycl". Farmaco. 55 (8): 553–62. doi:10.1016/s0014-827x(00)00036-7. PMID 11132733.
[13]
Pinna GA, Cignarella G, Loriga G, Murineddu G, Mussinu JM, Ruiu S, et al. (June 2002). "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". Bioorganic & Medicinal Chemistry. 10 (6): 1929–37. doi:10.1016/s0968-0896(01)00436-9. PMID 11937351.
[14]
Pinna GA, Cignarella G, Ruiu S, Loriga G, Murineddu G, Villa S, et al. (September 2003). "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". Bioorganic & Medicinal Chemistry. 11 (18): 4015–26. doi:10.1016/s0968-0896(03)00373-0. PMID 12927864.
[15]
Loriga G, Manca I, Murineddu G, Chelucci G, Villa S, Gessi S, et al. (February 2006). "Synthesis of 3,6-diazabicyclo[3.1.1]heptanes as novel ligands for the opioid receptors". Bioorganic & Medicinal Chemistry. 14 (3): 676–91. doi:10.1016/j.bmc.2005.09.045. PMID 16243530.

References

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