Pyrazolam

Benzodiazepine
Pharmacokinetic dataElimination half-life17 hoursIdentifiers
  • 8-Bromo-1-methyl-6-(pyridin-2-yl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine
CAS Number
  • 39243-02-2
PubChem CID
  • 12562545
ChemSpider
  • 15417688
UNII
  • 8LH16383PK
ChEMBL
  • ChEMBL3246831
CompTox Dashboard (EPA)
  • DTXSID101043303 Edit this at Wikidata
Chemical and physical dataFormulaC16H12BrN5Molar mass354.211 g·mol−13D model (JSmol)
  • Interactive image
  • CC1=NN=C2CN=C(C3=NC=CC=C3)C3=CC(Br)=CC=C3N12
InChI
  • InChI=1S/C16H12BrN5/c1-10-20-21-15-9-19-16(13-4-2-3-7-18-13)12-8-11(17)5-6-14(12)22(10)15/h2-8H,9H2,1H3
  • Key:BGRWSFIQQPVEML-UHFFFAOYSA-N

Pyrazolam (SH-I-04)[2] is a benzodiazepine derivative originally developed by a team led by Leo Sternbach at Hoffman-La Roche in the 1970s.[3] It has since been "rediscovered" and sold as a designer drug since 2012.[4][5][6][7][8][9][excessive citations]

Pyrazolam has structural similarities to alprazolam[10] and bromazepam. Unlike other benzodiazepines, pyrazolam does not appear to undergo metabolism, instead being excreted unchanged in the urine.[4]

Legal status

United Kingdom

In the UK, pyrazolam has been classified as a Class C drug by section 5 of the May 2017 amendment to The Misuse of Drugs Act 1971 along with several other designer benzodiazepine drugs.[11]

Synthesis

The condensation of bromazepam (1) with methylamine and titanium tetrachloride gives the amidine (2). Treatment with nitrous acid gives the nitrosylation product (3). Further reaction with hydrazine gives (4), which is treated with triethyl orthoacetate to complete the synthesis of pyrazolam.[12]

See also

References

  1. ^ (customs (prohibited imports) regulations 1956 - schedule 4, 1956)
  2. ^ Clayton T, Poe MM, Rallapalli S, Biawat P, Savić MM, Rowlett JK, et al. (2015). "A Review of the Updated Pharmacophore for the Alpha 5 GABA(A) Benzodiazepine Receptor Model". International Journal of Medicinal Chemistry. 2015: 430248. doi:10.1155/2015/430248. PMC 4657098. PMID 26682068.
  3. ^ US 3954728, Sternbach LH, Walser A, "Preparation of triazolo benzodiazepines and novel compounds", issued 4 May 1976, assigned to Hoffmann La Roche Inc. 
  4. ^ a b Moosmann B, Hutter M, Huppertz LM, Ferlaino S, Redlingshöfer L, Auwärter V (July 2013). "Characterization of the designer benzodiazepine pyrazolam and its detectability in human serum and urine". Forensic Toxicology. 31 (2): 263–271. doi:10.1007/s11419-013-0187-4. S2CID 23273522.
  5. ^ Moosmann B, King LA, Auwärter V (June 2015). "Designer benzodiazepines: A new challenge". World Psychiatry. 14 (2): 248. doi:10.1002/wps.20236. PMC 4471986. PMID 26043347.
  6. ^ Pettersson Bergstrand M, Helander A, Hansson T, Beck O (April 2017). "Detectability of designer benzodiazepines in CEDIA, EMIT II Plus, HEIA, and KIMS II immunochemical screening assays". Drug Testing and Analysis. 9 (4): 640–645. doi:10.1002/dta.2003. PMID 27366870.
  7. ^ Høiseth G, Tuv SS, Karinen R (November 2016). "Blood concentrations of new designer benzodiazepines in forensic cases". Forensic Science International. 268: 35–38. doi:10.1016/j.forsciint.2016.09.006. PMID 27685473.
  8. ^ Manchester KR, Maskell PD, Waters L (March 2018). "Experimental versus theoretical log D7.4 , pKa and plasma protein binding values for benzodiazepines appearing as new psychoactive substances". Drug Testing and Analysis. 10 (8): 1258–1269. doi:10.1002/dta.2387. PMID 29582576.
  9. ^ Manchester KR, Waters L, Haider S, Maskell PD (July 2022). "The blood-to-plasma ratio and predicted GABAA-binding affinity of designer benzodiazepines". Forensic Toxicology. 40 (2): 349–356. doi:10.1007/s11419-022-00616-y. PMC 9715504. PMID 36454409. S2CID 247455284.
  10. ^ Hester JB, Rudzik AD, Kamdar BV (November 1971). "6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines which have central nervous system depressant activity". Journal of Medicinal Chemistry. 14 (11): 1078–1081. doi:10.1021/jm00293a015. PMID 5165540.
  11. ^ "The Misuse of Drugs Act 1971 (Amendment) Order 2017". legislation.gov.uk.
  12. ^ Leo Henryk Sternbach & Armin Walser, U.S. patent 3,954,728 (1976 to Hoffmann La Roche Inc).
  • v
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1,4-Benzodiazepines
1,5-Benzodiazepines2,3-Benzodiazepines*TriazolobenzodiazepinesImidazobenzodiazepinesOxazolobenzodiazepinesThienodiazepinesThienotriazolodiazepinesThienobenzodiazepines*PyridodiazepinesPyridotriazolodiazepinesPyrazolodiazepinesPyrrolodiazepinesTetrahydroisoquinobenzodiazepinesPyrrolobenzodiazepines*Benzodiazepine prodrugs
* atypical activity profile (not GABAA receptor ligands)
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