Azaprocin

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

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width=180
CAS_number=448-34-0
ATC_prefix=
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ATC_supplemental=
PubChem=6433185
DrugBank=
C=18 | H=24 | N=2 | O=1
molecular_weight = 284.396
smiles = CCC(=O)N1C2CCC1CN(C2)CC=CC3=CC=CC=C3
melting_point = 170
melting_high = 175
bioavailability=
metabolism =
elimination_half-life=
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legal_status = Legal
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Azaprocin is a drug which is an opioid analgesic with approximately 10x the potency of morphine, and a fast onset and short duration of action. [Cignarella G, Occelli E, Cristiani G, Paduano L, Testa E. Bicyclic Homologs of Piperazine. VI. Synthesis and Analgesic Activity of 3-Substituted 8-Propionyl-3,8-diazabicyclo [3.2.1] octanes. "Journal of Medicinal Chemistry" 1963; 6(6):764-766. PMID 14184943] [Cignarella G, Occelli E, Testa E. Bicyclic Homologs of Piperazine. VII. Synthesis and Analgesic Activity of 3-Aralkenyl-8-Propionyl-3,8-diazabicyclo [3.2.1] octanes. "Journal of Medicinal Chemistry" 1965 May;8:326-31. PMID 14323140] [Rosselli del Turco B, Maffii G. Effect of analgesic drugs on the conditioned behavior of rats. (Italian) "Bollettino Chimico Farmaceutico". 1968 Feb;107(2):120-6. 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 25x the potency of morphine. [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". 1988, 20(5):383-394. PMID 2843931] The ring-opened 2,6-dimethylpiperazine analogues are also active, [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". 1968 May;11(3):592-4. PMID 5656502] and a large family of opioid analgesic compounds derived from this parent structure have been developed over the last 40 years. [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. "Pharmacology Research Communications". 1988 May;20(5):383-94. PMID 2843931] [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". 1993 Oct;7(5):557-71. PMID 8294946] [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". 1997 Nov;356(5):596-602. PMID 9402039] [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". 1998 Aug-Sep;53(8-9):557-62. PMID 10081818] [Cignarella G, Barlocco D, Vianello P, Villa S, Pinna GA, Fadda P, Fratta W, Toma L, Gessi S. 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". 1998 Oct-Nov;53(10-11):667-74. PMID 10205853] [Vianello P, Albinati A, Pinna GA, Lavecchia A, Marinelli L, Borea PA, Gessi S, Fadda P, Tronci S, Cignarella G. 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". 2000 Jun 1;43(11):2115-23. PMID 10841790] [Pinna GA, Murineddu G, Curzu MM, Villa S, Vianello P, Borea PA, Gessi S, Toma L, Colombo D, Cignarella G. Synthesis, modelling, and mu-opioid receptor affinity of N-3(9)-arylpropenyl-N-9(3)-propionyl-3,9-diazabicycl. "Farmaco". 2000 Aug;55(8):553-62. PMID 11132733] [Pinna GA, Cignarella G, Loriga G, Murineddu G, Mussinu JM, Ruiu S, Fadda P, Fratta W. 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 and Medicinal Chemistry". 2002 Jun;10(6):1929-37. PMID 11937351] [Pinna GA, Cignarella G, Ruiu S, Loriga G, Murineddu G, Villa S, Grella GE, Cossu G, Fratta W. 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 and Medicinal Chemistry". 2003 Sep 1;11(18):4015-26. PMID 12927864] [Loriga G, Manca I, Murineddu G, Chelucci G, Villa S, Gessi S, Toma L, Cignarella G, Pinna GA. Synthesis of 3,6-diazabicyclo [3.1.1] heptanes as novel ligands for the opioid receptors. "Bioorganic and Medicinal Chemistry". 2006 Feb 1;14(3):676-91. PMID 16243530]

References