PF-04457845

PF-04457845
PF-04457845
PF-04457845 Structure.svg
임상 데이터
ATC 코드
  • 없음.
법적 상태
법적 상태
식별자
  • N-피리다진-3-일-4-[(3-[5-(트리플루오로메틸)피리딘-2-일]옥시페닐)피페리딘-1-카르복사미드
CAS 번호
PubChem CID
켐스파이더
유니
첸블
CompTox 대시보드 (EPA )
화학 및 물리 데이터
공식C23H20F3N5O2
몰 질량455.441 g/120−1
3D 모델(JSmol)
  • n4ncc4NC(=O)N(CC3)CC\C3=C/c2cc(cc2)Oc(cc1)ncc1C(F)(F)f
  • InChI=1S/C23H20F3N5O2/c24-23(25,26)18-6-7-21(27-15-18)33-19-4-1-3-17(14-19)13-16-8-11-31(12-9-16)22-2-5-28-28-28
  • 키 : BATCTBJIJJEPHM-UHFFFAOYSA-N

PF-04457845는 IC가50 7.2nM인 효소 지방산아미드 가수분해효소(FAAH)의 강력하고 정교한 선택적 억제제이며, 동물 연구에서 [1]나프록센에 필적하는 진통제 및 항염증 효과도 있다.

인지기능 장애의 증거가 없는 높은 용량 범위에서도 인체 실험에서는 잘 견뎌졌으며, [1][2][3][4]골관절염 치료를 위한 2상 임상 시험을 완료했지만 효과가 [5]없는 것으로 밝혀졌다.

2021년 현재, 여러 연구에서 이 새로운 FAAH 억제제가 남성의 대마 금단 증상과 대마 사용을 감소시킬 수 있으며 대마 사용 [6][7][8]장애 치료에 효과적이고 안전한 접근방식을 나타낼 수 있다는 것이 밝혀졌다.

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레퍼런스

  1. ^ a b Johnson DS, Stiff C, Lazerwith SE, Kesten SR, Fay LK, Morris M, et al. (February 2011). "Discovery of PF-04457845: A Highly Potent, Orally Bioavailable, and Selective Urea FAAH Inhibitor". ACS Medicinal Chemistry Letters. 2 (2): 91–96. doi:10.1021/ml100190t. PMC 3109749. PMID 21666860.
  2. ^ Ahn K, Smith SE, Liimatta MB, Beidler D, Sadagopan N, Dudley DT, et al. (July 2011). "Mechanistic and pharmacological characterization of PF-04457845: a highly potent and selective fatty acid amide hydrolase inhibitor that reduces inflammatory and noninflammatory pain". The Journal of Pharmacology and Experimental Therapeutics. 338 (1): 114–24. doi:10.1124/jpet.111.180257. PMC 3126636. PMID 21505060.
  3. ^ Li GL, Winter H, Arends R, Jay GW, Le V, Young T, Huggins JP (May 2012). "Assessment of the pharmacology and tolerability of PF-04457845, an irreversible inhibitor of fatty acid amide hydrolase-1, in healthy subjects". British Journal of Clinical Pharmacology. 73 (5): 706–16. doi:10.1111/j.1365-2125.2011.04137.x. PMC 3403198. PMID 22044402.
  4. ^ 임상시험번호 NCT00981357 "무릎 골관절염 환자에게 PF-04457845가 통증 치료에 효과가 있는지, 안전하고 허용 가능한지를 조사하기 위한 연구" (ClinicalTrials.gov )
  5. ^ Huggins JP, Smart TS, Langman S, Taylor L, Young T (September 2012). "An efficient randomised, placebo-controlled clinical trial with the irreversible fatty acid amide hydrolase-1 inhibitor PF-04457845, which modulates endocannabinoids but fails to induce effective analgesia in patients with pain due to osteoarthritis of the knee". Pain. 153 (9): 1837–46. doi:10.1016/j.pain.2012.04.020. PMID 22727500. S2CID 25179328.
  6. ^ d'Souza, Deepak Cyril; Cortes-Briones, Jose; Creatura, Gina; Bluez, Grai; Thurnauer, Halle; Deaso, Emma; Bielen, Kim; Surti, Toral; Radhakrishnan, Rajiv; Gupta, Aarti; Gupta, Swapnil; Cahill, John; Sherif, Mohamed A.; Makriyannis, Alexandros; Morgan, Peter T.; Ranganathan, Mohini; Skosnik, Patrick D. (2019-01-01). "Efficacy and safety of a fatty acid amide hydrolase inhibitor (PF-04457845) in the treatment of cannabis withdrawal and dependence in men: a double-blind, placebo-controlled, parallel group, phase 2a single-site randomised controlled trial". The Lancet. 6 (1): 35–45. doi:10.1016/S2215-0366(18)30427-9. ISSN 2215-0366. PMID 30528676. S2CID 54471855.
  7. ^ Bonifacio, Maria Joao; Sousa, Filipa; Aires, Catia; Loureiro, Ana I.; Fernandes-Lopes, Carlos; Palma, Nuno; Moser, Paul; Soares-da-Silva, Patricio (2018). "Evaluation of the Potency and Selectivity of the Novel Faah Inhibitor Bia 10-2474 in Comparison with Pf-04457845 and Jnj-42165279". The FASEB Journal. 32 (S1): 692.14. doi:10.1096/fasebj.2018.32.1_supplement.692.14. ISSN 1530-6860.
  8. ^ Nielsen, Suzanne; Sabioni, Pamela; Gowing, Linda; Le Foll, Bernard (2020), Nader, Michael A.; Hurd, Yasmin L. (eds.), "Pharmacotherapies for Cannabis Use Disorders: Clinical Challenges and Promising Therapeutic Agents", Substance Use Disorders: From Etiology to Treatment, Handbook of Experimental Pharmacology, Cham: Springer International Publishing, vol. 258, pp. 355–372, doi:10.1007/164_2019_258, ISBN 978-3-030-33679-0, PMID 31375922, S2CID 199388107, retrieved 2021-08-22