Fluperamide

Fluperamide
Identifiers
	IUPAC name 4-[4-[4-chloro-3-(trifluoromethyl)phenyl]-4-hydroxypiperidin-1-yl]-N,N-dimethyl-2,2-diphenylbutanamide;
CAS Number	53179-10-5;
PubChem CID	131534;
ChemSpider	116243;
UNII	6H13T09362;
ChEMBL	ChEMBL421665;
CompTox Dashboard (EPA)	DTXSID00866305 ;
Chemical and physical data
Formula	C30H32ClF3N2O2
Molar mass	545.04 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CN(C)C(=O)C(CCN1CCC(CC1)(C2=CC(=C(C=C2)Cl)C(F)(F)F)O)(C3=CC=CC=C3)C4=CC=CC=C4;
	InChI InChI=1S/C30H32ClF3N2O2/c1-35(2)27(37)29(22-9-5-3-6-10-22,23-11-7-4-8-12-23)17-20-36-18-15-28(38,16-19-36)24-13-14-26(31)25(21-24)30(32,33)34/h3-14,21,38H,15-20H2,1-2H3; Key:WPYGCZCMGMVGNO-UHFFFAOYSA-N;

Fluperamide is a synthetic opioid structurally related to loperamide, developed as a potent antidiarrheal agent.^[1]^[2] Like loperamide, it acts primarily as a peripherally selective μ-opioid receptor agonist, effectively reducing gastrointestinal motility and fluid secretion without significant central nervous system effects due to limited blood-brain barrier penetration.

Fluperamide’s pharmacological profile was designed to maximize antidiarrheal efficacy while minimizing the risk of opioid-related side effects and abuse potential, a strategy that has contributed to the development of related compounds in the phenylpiperidine class. Although fluperamide demonstrated strong antidiarrheal activity in preclinical and early clinical studies, it was ultimately not commercialized, with loperamide becoming the preferred agent in this therapeutic category due to its favorable safety and efficacy.^[3]

References

^ Stokbroekx RA, Vandenberk J, Van Heertum AH, Van Laar GM, Van der Aa MJ, Van Bever WF, et al. (July 1973). "Synthetic antidiarrheal agents. 2,2-Diphenyl-4-(4'-aryl-4'-hydroxypiperidino)butyramides". Journal of Medicinal Chemistry. 16 (7): 782–6. doi:10.1021/jm00265a009. PMID 4725924.
^ Chen Z, Davies E, Miller WS, Shan S, Valenzano KJ, Kyle DJ (November 2004). "Design and synthesis of 4-phenyl piperidine compounds targeting the mu receptor". Bioorganic & Medicinal Chemistry Letters. 14 (21): 5275–9. doi:10.1016/j.bmcl.2004.08.032. PMID 15454210.
^ Baker DE (2007). "Loperamide: a pharmacological review". Reviews in Gastroenterological Disorders. 7 (Suppl 3): S11 – S18. PMID 18192961.

[Stokbroekx_1973-1] Stokbroekx RA, Vandenberk J, Van Heertum AH, Van Laar GM, Van der Aa MJ, Van Bever WF, et al. (July 1973). "Synthetic antidiarrheal agents. 2,2-Diphenyl-4-(4'-aryl-4'-hydroxypiperidino)butyramides". Journal of Medicinal Chemistry. 16 (7): 782–6. doi:10.1021/jm00265a009. PMID 4725924.

[pmid15454210-2] Chen Z, Davies E, Miller WS, Shan S, Valenzano KJ, Kyle DJ (November 2004). "Design and synthesis of 4-phenyl piperidine compounds targeting the mu receptor". Bioorganic & Medicinal Chemistry Letters. 14 (21): 5275–9. doi:10.1016/j.bmcl.2004.08.032. PMID 15454210.

[pmid18192961-3] Baker DE (2007). "Loperamide: a pharmacological review". Reviews in Gastroenterological Disorders. 7 (Suppl 3): S11 – S18. PMID 18192961.

[1]

[2]

[3]

v t e Antidiarrheals, intestinal anti-inflammatory and anti-infective agents (A07)
Rehydration	Oral rehydration therapy
Intestinal anti-infectives	Antibiotics Amphotericin B Colistin Fidaxomicin Kanamycin Natamycin Neomycin Nystatin Paromomycin Polymyxin B Rifaximin Streptomycin Vancomycin Sulfonamides Phthalylsulfathiazole Succinylsulfathiazole Sulfaguanidine Nitrofuran Nifuroxazide Nifurzide Imidazole Miconazole Arsenical Acetarsol Oxyquinoline Broxyquinoline
Intestinal adsorbents	Charcoal Bismuth (including bismuth subsalicylate, known as Pepto-Bismol) Pectin Kaolin Crospovidone Attapulgite Diosmectite
Antipropulsives (opioids)	Opium tincture (laudanum) Codeine Morphine Camphorated opium tincture (paregoric) crosses BBB: Diphenoxylate (+atropine) Difenoxin does not cross BBB: Eluxadoline Loperamide^# (+simethicone)
Intestinal anti-inflammatory agents	corticosteroids acting locally Prednisolone^# Hydrocortisone Prednisone Betamethasone^# Tixocortol Budesonide Beclometasone antiallergic agents, excluding corticosteroids Cromoglicic acid Aminosalicylates Sulfasalazine Mesalazine Olsalazine Balsalazide
Antidiarrheal micro-organisms	Escherichia coli Saccharomyces boulardii
Other antidiarrheals	Albumin tannate Bismuth subsalicylate Ceratonia Crofelemer Octreotide Racecadotril Kaopectate
^#WHO-EM ^‡Withdrawn from market Clinical trials: ^†Phase III ^§Never to phase III

See also

References