Piperidines

Clebopride is a dopamine antagonist drug with antiemetic and prokinetic properties used to treat functional gastrointestinal disorders. Chemically, it is a substituted benzamide, closely related to metoclopramide.

Diphenylpyraline (DPP; sold as Allergen, Arbid, Belfene, Diafen, Hispril, Histyn, Lergobine, Lyssipol, Mepiben, Neargal) is a first-generation antihistamine with anticholinergic effects of the diphenylpiperidine class. It is marketed in Europe for the treatment of allergies. DPP has also been found to act as a dopamine reuptake inhibitor and produces hyperactivity in rodents. It has been shown to be useful in the treatment of Parkinsonism.

Vandetanib, sold under the brand name Caprelsa, is an anti-cancer medication that is used for the treatment of certain tumors of the thyroid gland. It acts as a kinase inhibitor of a number of cell receptors, mainly the vascular endothelial growth factor receptor, the epidermal growth factor receptor, and the RET-tyrosine kinase. The drug was developed by AstraZeneca who sold the rights to Sanofi in 2015.

2,6-Dimethylpiperidines are chemical compounds with the formula C5H8(CH3)2NH. Three stereoisomers exist: the achiral (R,S)-isomer and the chiral (R,R)/(S,S) enantiomeric pair. Dimethylpiperidines are derivatives of the heterocycle piperidine, wherein two hydrogen atoms are replaced by methyl groups.

Brigatinib, sold under the brand name Alunbrig among others, is a small-molecule targeted cancer therapy being developed by Ariad Pharmaceuticals, Inc. Brigatinib acts as an inhibitor of the receptor tyrosine kinase anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR), as well as several nonreceptor tyrosine kinases such as FAK, FAK2, and FER. It shows activity against ALK-positive non–small cell lung cancer, ALK-positive anaplastic large cell lymphoma (ALCL), and NF2-related schwannomatosis.

Propiverine is an anticholinergic drug used for the treatment of urinary urgency, frequency and urge incontinence, all symptoms of overactive bladder syndrome. It is a muscarinic antagonist.

Indoramin (trade names Baratol and Doralese) is a piperidine antiadrenergic agent.

4-Hydroxy-TEMPO or TEMPOL, formally 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl, is a heterocyclic compound. Like the related TEMPO, it is used as a catalyst and chemical oxidant by virtue of being a stable aminoxyl radical. Its major appeal over TEMPO is that it is less expensive, being produced from triacetone amine, which is itself made via the condensation of acetone and ammonia. This makes it economically viable on an industrial scale.

Atogepant, sold under the brand name Qulipta among others, is a medication used to prevent migraines. It is a gepant, a calcitonin gene-related peptide receptor antagonist administered orally.

Ohmefentanyl (also known as β-hydroxy-3-methylfentanyl, OMF and RTI-4614-4) is an extremely potent opioid analgesic drug which selectively binds to the μ-opioid receptor.

Balofloxacin (INN) is a fluoroquinolone antibiotic. It is sold under the brand name Q-Roxin in Korea, and under various names in India. It is not approved by the FDA for use in the United States.

Zavegepant, sold under the brand name Zavzpret, is a medication used for the treatment of migraine. Zavegepant is a calcitonin gene-related peptide receptor antagonist. It is sprayed into the nose. It is sold by Pfizer.

Triacetonamine is an organic compound with the formula OC(CH2CMe2)2NH (where Me = CH3). It is a colorless or white solid that melts near room temperature. The compound is an intermediate in the preparation of 2,2,6,6-tetramethylpiperidine, a sterically hindered base and precursor to the reagent called TEMPO. Triacetonamine is formed by the poly-aldol condensation of acetone in the presence of ammonia and calcium chloride: 3 (CH3)2CO + NH3 → OC(CH2CMe2)2NH + 2 H2O

Revefenacin, sold under the brand name Yupelri, is a medication for the treatment of chronic obstructive pulmonary disease (COPD). It was approved for use in the United States in 2018. It was developed by Theravance Biopharma and is marketed by Mylan. Revefenacin is formulated as a solution that is nebulized and inhaled.

Pizotifen, also known as pizotyline and sold under the brand names Sandomigran and Mosegor among others, is an antimigraine agent of the tricyclic group which is used primarily as a preventative to reduce the frequency of recurrent migraine headaches.

Carpipramine (Prazinil, Defekton) is an atypical antipsychotic used for the treatment of schizophrenia and anxiety in France and Japan. In addition to its neuroleptic and anxiolytic effects, carpipramine also has hypnotic properties. It is structurally related to both tricyclics like imipramine and butyrophenones like haloperidol.

Piminodine (Alvodine) is an opioid analgesic that is an analogue of pethidine (meperidine). It was used in medicine briefly during the 1960s and 70s, but has largely fallen out of clinical use. It was used particularly for obstetric analgesia and in dental procedures and, like pethidine, could be combined with hydroxyzine to intensify the effects. The duration of action is 2–4 hours; 7.5–10 mg via the subcutaneous route is the most common starting dose, being equal to 80–100 mg of pethidine, 40–60 mg of alphaprodine and 10 mg of morphine. Oral formulations were also availab

Benidipine is a dihydropyridine calcium channel blocker for the treatment of high blood pressure (hypertension). It is a triple L-, T-, and N-type calcium channel blocker. It is reno- and cardioprotective.

Avacopan, sold under the brand name Tavneos, is a medication used to treat anti-neutrophil cytoplasmic autoantibody-associated vasculitis. Avacopan is a complement 5a receptor antagonist and a cytochrome P450 3A4 inhibitor.

Cinitapride (trade names Cintapro, Pemix, Gapulsid) is a gastroprokinetic agent and antiemetic agent of the benzamide class which is marketed in India, Mexico, Pakistan, Spain, Croatia and the Czech Republic. It acts as an agonist of the 5-HT1 and 5-HT4 receptors and as an antagonist of the 5-HT2 receptors.

1-(1-Phenylcyclohexyl)-4-hydroxypiperidine (PCHP) is a metabolite of phencyclidine (PCP). PCHP can be detected in the hair, urine, stool, sweat, and saliva of PCP users.

Gilteritinib, sold under the brand name Xospata, is an anti-cancer drug.

Mesoridazine (Serentil) is a phenothiazine class drug that is used in the treatment of schizophrenia. It is one of the active metabolites of thioridazine. The drug's name is derived from the methylsulfoxy and piperidine functional groups in its chemical structure.

Metopimazine (, , ), sold under the brand names Vogalen and Vogalene, is an antiemetic of the phenothiazine group which is used to treat nausea and vomiting. It is marketed in Europe, Canada, and South America. As of August 2020, metopimazine has been repurposed and is additionally under development for use in the United States for the treatment of gastroparesis.

Encainide (trade name Enkaid) is a class Ic antiarrhythmic agent. It is no longer used because of its frequent proarrhythmic side effects.

α-Methylthiofentanyl is an opioid analgesic that is an analogue of fentanyl.

Enzastaurin is a synthetic bisindolylmaleimide with potential antineoplastic activity. Binding to the ATP-binding site, enzastaurin selectively inhibits protein kinase C beta, an enzyme involved in the induction of vascular endothelial growth factor (VEGF)-stimulated neo-angiogenesis. This agent may decrease tumor blood supply, preventing growth.

Pempidine is a nicotinic antagonist drug, first reported in 1958 by two research groups working independently, and introduced as an oral treatment for hypertension.

Rolapitant (INN, trade name Varubi in the US and Varuby in the European Union) is a drug originally developed by Schering-Plough and licensed for clinical development by Tesaro, which acts as a selective NK1 receptor antagonist (antagonist for the NK1 receptor). It has been approved as a medication for the treatment of chemotherapy-induced nausea and vomiting (CINV) after clinical trials showed it to have similar or improved efficacy and some improvement in safety over existing drugs for this application.

Cyclomethycaine is a local anesthetic. It was first approved for use by the United States Food and Drug Administration in 1948.

Gepotidacin, sold under the brand name Blujepa, is an antibiotic medication used for the treatment of urinary tract infection or uncomplicated urogenital gonorrhea. Gepotidacin is a triazaacenaphthylene bacterial type II topoisomerase inhibitor. It is used as the salt gepotidacin mesylate, and is taken by mouth.

Zanubrutinib, sold under the brand name Brukinsa, is an anticancer medication used for the treatment of mantle cell lymphoma (MCL), Waldenström's macroglobulinemia (WM), marginal zone lymphoma (MZL), and chronic lymphocytic leukemia (CLL). Zanubrutinib is classified as a Bruton's tyrosine kinase (BTK) inhibitor. It is given by mouth.

Mosapramine (Cremin) is an atypical antipsychotic used in Japan for the treatment of schizophrenia. It is a potent dopamine antagonist with high affinity to the D2, D3, and D4 receptors, and with moderate affinity for the 5-HT2 receptors.

Fagopyrin is a phototoxic substance found in the flowers of buckwheat (Fagopyrum esculentum). Their chemical structure contains a naphthodianthrone skeleton similar to that of hypericin. After exposure, fagopyrin can cause sensitivity to light, also called fagopyrism, an itchy skin rash.

Clocapramine (Clofekton, Padrasen), also known as 3-chlorocarpipramine, is an atypical antipsychotic of the class which was introduced in Japan in 1974 by Yoshitomi for the treatment of schizophrenia. In addition to psychosis, clocapramine has also been used to augment antidepressants in the treatment of anxiety and panic.

Telcagepant (INN; development code MK-0974) is a calcitonin gene-related peptide receptor antagonist which was an investigational drug for the acute treatment and prevention of migraine, developed by Merck & Co.

Thenalidine is an antihistamine with anticholinergic properties used as an antipruritic drug. It was withdrawn from the US, Canadian, and UK markets in 1963 due to a risk of neutropenia.

Nemonoxacin is a non-fluorinated quinolone antibiotic undergoing clinical trials. It has the same mechanism of action as fluouroquinolones; it inhibits DNA gyrase, preventing DNA synthesis, gene duplication, and cell division. At the end of 2016, it had reached market in Taiwan, Russia, the Commonwealth Independent States, Turkey, mainland China, and Latin America under the brand name Taigexyn. Nemonoxacin has completed phase 2 trials in the US and has moved on to phase 3 trials. The U.S. Food and Drug Administration (FDA) has granted nemonoxacin qualified infectious disease product (QIDP) and

Difelikefalin, sold under the brand name Korsuva, is an opioid peptide used for the treatment of moderate to severe itch. It acts as a peripherally-restricted, highly selective agonist of the κ-opioid receptor (KOR).

3-Methylthiofentanyl is an opioid analgesic and analogue of fentanyl.

Pimethixene is an antihistamine and anticholinergic of the thioxanthene chemical class originally developed to treat hyperactivity, anxiety, sleep disorders, and allergy. It is also used for anesthesia and as a bronchodilator (to dilate the bronchi and bronchioles for more airflow).

Methimepip is a histamine agonist which is highly selective for the H3 subtype. It is the N-methyl derivative of immepip.

Ritanserin, also known by its developmental code name R-55667, is a serotonin receptor antagonist which was under development for the treatment of anxiety disorders and major depressive disorder but was never marketed. It was also investigated for treatment of insomnia, especially to enhance sleep quality by significantly increasing slow wave sleep by virtue of potent and concomitant serotonin 5-HT2A and 5-HT2C receptor antagonism. The drug is taken orally.

Sulforidazine (Imagotan, Psychoson, Inofal) a typical antipsychotic and a metabolite of thioridazine; it and mesoridazine are more potent than the parent compound, whose pharmacological effects are believed by some to be largely due to its metabolism into sulforidazine and mesoridazine.

Acetylfentanyl (acetyl fentanyl) is an opioid analgesic drug that is an analog of fentanyl. Studies have estimated acetylfentanyl to be 15 times more potent than morphine, which would mean that despite being somewhat weaker than fentanyl, it is nevertheless still several times stronger than pure heroin. It has never been licensed for medical use and instead has only been sold on the illicit drug market. Acetylfentanyl was discovered at the same time as fentanyl itself and had only rarely been encountered on the illicit market in the late 1980s. However, in 2013, Canadian police seized 3 kilogr

β-Hydroxyfentanyl is an opioid analgesic that is an analogue of fentanyl.

Viqualine (INN; developmental code PK-5078) is an antidepressant and anxiolytic drug that was never marketed. It acts as a potent and selective serotonin releasing agent (SRA) and serotonin reuptake inhibitor (SRI) similarly to para-chloroamphetamine (PCA). In addition, viqualine displaces diazepam from the GABAA receptor and produces benzodiazepine-like effects, indicating that it is also a positive allosteric modulator of the benzodiazepine site of the GABAA receptor. The drug has mainly been researched as a potential treatment for alcoholism.

Thiofentanyl is an opioid analgesic that is an analogue of fentanyl.

Dexetimide (brand name Tremblex) is a piperidine anticholinergic. It is a muscarinic antagonist that is used to treat drug induced parkinsonism. Dexetimide was discovered at Janssen Pharmaceutica in 1968.

Tipepidine (INN; also known as tipepidine hibenzate (JAN); brand names Asverin, Antupex, Asvelik, Asvex, Bitiodin, Cofdenin A, Hustel, Nodal, and Sotal) is a synthetic, non-opioid antitussive and expectorant of the thiambutene class. It acts as an inhibitor of G protein-coupled inwardly-rectifying potassium channels (GIRKs). The drug was discovered in the 1950s, and was developed in Japan in 1959. It is used as the hibenzate and citrate salts.

Bamipine (trade name Soventol) is a pharmaceutical drug acting as an H1 antihistamine with anticholinergic properties. It is used as an antipruritic ointment. No oral use is known.

Perhexiline (Pexsig) is a prophylactic antianginal agent used primarily in Australia and New Zealand. Perhexiline is thought to act by inhibiting mitochondrial carnitine palmitoyltransferase-1. This shifts myocardial metabolism from fatty acid to glucose utilisation which results in increased ATP production for the same O2 consumption and consequently increases myocardial efficiency. Its clinical use has been limited by its narrow therapeutic index and high inter- and intra-individual pharmacokinetic variability. It was outlawed in many countries due to its adverse effects on poor metabolisers

Mirfentanil is a fentanyl derivative with strong selectivity for the μ opioid receptor. At lower doses, it antagonizes the analgesic effects of alfentanil and substitutes for naloxone in morphine-treated monkeys; however, it also reverses naloxone-precipitated withdrawal in pigeons trained to discriminate morphine from naloxone.

Lapaquistat (TAK-475) is a cholesterol-lowering drug candidate that was abandoned before being marketed.

Muldamine is a phytosterol alkaloid isolated from Veratrum californicum. It is the acetate ester of the piperidine steroid teinemine.

Mepenzolate is an antimuscarinic medication primarily used to treat peptic ulcers by reducing stomach acid secretion. It is the methylated version of N-methyl-3-piperidyl benzilate.

Casopitant (), former tentative trade names Rezonic (U.S.) and Zunrisa (Europe), is an NK1 receptor antagonist which was undergoing research for the treatment of chemotherapy-induced nausea and vomiting. It was under development by GlaxoSmithKline. In July 2008, the company filed a marketing authorisation application with the European Medicines Agency. The application was withdrawn and development was discontinued in September 2009 because GlaxoSmithKline decided that further safety assessment was necessary. However, a 2022 review listed casopitant as under development as a potential novel ant

α-Methylacetylfentanyl (or alphamethylacetylfentanyl) is an opioid analgesic and an analog of fentanyl. It is classified as a Schedule I controlled substance in many jurisdictions.

Piperocaine is a local anesthetic drug developed in the 1920s and used as its hydrochloride salt for infiltration and nerve blocks. ==Synthesis== thumb|center|500px|Synthesis: Patent: