Azaprocin Explained

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.

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.

Notes and References

  1. Cignarella G, Occelli E, Cristiani G, Paduano L, Testa E . 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 . November 1963 . 14184943 . 10.1021/jm00342a030 .
  2. Cignarella G, Occelli E, Testa E . 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 . May 1965 . 14323140 . 10.1021/jm00327a010 .
  3. Rosselli del Turco B, Maffii G . [Effect of analgesic drugs on the conditioned behavior of rats] . Bollettino Chimico Farmaceutico . 107 . 2 . 120–6 . February 1968 . 5730115 .
  4. Cignarella G, Barlocco D, Tranquillini ME, Volterra A, Brunello N, Racagni G . Interaction of 3,8-diazabicyclo (3.2.1) octanes with mu and delta opioid receptors . Pharmacological Research Communications . 20 . 5 . 383–94 . May 1988 . 2843931 . 10.1016/s0031-6989(88)80014-6 .
  5. Cignarella G, Testa E . 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 . May 1968 . 5656502 . 10.1021/jm00309a039 .
  6. Cignarella G, Barlocco D, Tranquillini ME, Volterra A, Brunello N, Racagni G . Interaction of 3,8-diazabicyclo (3.2.1) octanes with mu and delta opioid receptors . Pharmacological Research Communications . 20 . 5 . 383–94 . May 1988 . 2843931 . 10.1016/s0031-6989(88)80014-6 .
  7. Barlocco D, Cignarella G, Greco G, Novellino E . 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 . October 1993 . 8294946 . 10.1007/bf00124362 . 1993JCAMD...7..557B . 23360530 .
  8. Fadda P, Barlocco D, Tronci S, Cignarella G, Fratta W . 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 . November 1997 . 9402039 . 10.1007/pl00005095 . 40655683 .
  9. Barlocco D, Cignarella G, Vianello P, Villa S, Pinna GA, Fadda P, Fratta W . 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 . 1998 . 10081818 . 10.1016/s0014-827x(98)00065-2 .
  10. Cignarella G, Barlocco D, Vianello P, Villa S, Pinna GA, Fadda P, Fratta W, Toma L, Gessi S . 6 . 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 . 1998 . 10205853 . 10.1016/s0014-827x(98)00084-6 .
  11. Vianello P, Albinati A, Pinna GA, Lavecchia A, Marinelli L, Borea PA, Gessi S, Fadda P, Tronci S, Cignarella G . 6 . 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 . June 2000 . 10841790 . 10.1021/jm991140q .
  12. Pinna GA, Murineddu G, Curzu MM, Villa S, Vianello P, Borea PA, Gessi S, Toma L, Colombo D, Cignarella G . 6 . Synthesis, modelling, and mu-opioid receptor affinity of N-3(9)-arylpropenyl-N-9(3)-propionyl-3,9-diazabicycl . Farmaco . 55 . 8 . 553–62 . August 2000 . 11132733 . 10.1016/s0014-827x(00)00036-7 .
  13. Pinna GA, Cignarella G, Loriga G, Murineddu G, Mussinu JM, Ruiu S, Fadda P, Fratta W . 6 . 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 . June 2002 . 11937351 . 10.1016/s0968-0896(01)00436-9 .
  14. Pinna GA, Cignarella G, Ruiu S, Loriga G, Murineddu G, Villa S, Grella GE, Cossu G, Fratta W . 6 . 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 . September 2003 . 12927864 . 10.1016/s0968-0896(03)00373-0 .
  15. Loriga G, Manca I, Murineddu G, Chelucci G, Villa S, Gessi S, Toma L, Cignarella G, Pinna GA . 6 . Synthesis of 3,6-diazabicyclo[3.1.1]heptanes as novel ligands for the opioid receptors . Bioorganic & Medicinal Chemistry . 14 . 3 . 676–91 . February 2006 . 16243530 . 10.1016/j.bmc.2005.09.045 .

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