Note that if the ring cylization step was missed you instead get Clocapramine.
Patents:
The Strecker like condensation between 1-Benzyl-4-piperidone [3612-20-2] (1), piperidine, and potasssium cyanide gives 1-benzyl-4-piperidin-1-ylpiperidine-4-carbonitrile [84254-97-7] (2). Partial hydrolysis of the nitrile to the amide gives 1-benzyl-4-piperidin-1-ylpiperidine-4-carboxamide [1762-50-1] (3). Catalytic hydrogenation then removes the benzyl protecting group to give 4-piperidin-1-ylpiperidine-4-carboxamide [39633-82-4] (4). Treatment with a palladium on carbon catalyt apparently forms spiro[1,5,6,7,8,8a-hexahydroimidazo[1,2-a]pyridine-3,4'-piperidine]-2-one, CID:13002712 (5).
Convergent synthesis with 3-(2-chloro-5,6-dihydrobenzo[b][1]benzazepin-11-yl)propyl methanesulfonate, CID:20533966 (6) completed the synthesis of Mosapramine (7).
The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs largely introduced after the 1970s and used to treat psychiatric conditions. Some atypical antipsychotics have received regulatory approval for schizophrenia, bipolar disorder, irritability in autism, and as an adjunct in major depressive disorder.
Ziprasidone, sold under the brand name Geodon among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It may be used by mouth and by injection into a muscle (IM). The IM form may be used for acute agitation in people with schizophrenia.
Aripiprazole, sold under the brand names Abilify and Aristada among others, is an atypical antipsychotic. It is primarily used in the treatment of schizophrenia and bipolar disorder. Other uses include as an add-on treatment in major depressive disorder, tic disorders and irritability associated with autism. It is taken by mouth or injection into a muscle. A Cochrane review found low-quality evidence of effectiveness in treating schizophrenia.
Azapirones are a class of drugs used as anxiolytics, antidepressants, and antipsychotics. They are commonly used as add-ons to other antidepressants, such as selective serotonin reuptake inhibitors (SSRIs).
A dopamine antagonist, also known as an anti-dopaminergic and a dopamine receptor antagonist (DRA), is a type of drug which blocks dopamine receptors by receptor antagonism. Most antipsychotics are dopamine antagonists, and as such they have found use in treating schizophrenia, bipolar disorder, and stimulant psychosis. Several other dopamine antagonists are antiemetics used in the treatment of nausea and vomiting.
Tiotixene, or thiothixene, sold under the brand name Navane among others, is a typical antipsychotic of the thioxanthene class which is related to chlorprothixene and is used in the treatment of psychoses like schizophrenia and bipolar mania. It was introduced in the United States in 1967 by Pfizer.
Amisulpride is an antiemetic and antipsychotic medication used at lower doses intravenously to prevent and treat postoperative nausea and vomiting; and at higher doses by mouth to treat schizophrenia and acute psychotic episodes. It is sold under the brand names Barhemsys and Solian, Socian, Deniban and others. It is also used to treat dysthymia.
Pipamperone, also known as carpiperone and floropipamide or fluoropipamide, and as floropipamide hydrochloride (JAN), is a typical antipsychotic of the butyrophenone family used in the treatment of schizophrenia and as a sleep aid for depression. It is or has been marketed under brand names including Dipiperon, Dipiperal, Piperonil, Piperonyl, and Propitan. Pipamperone was discovered at Janssen Pharmaceutica in 1961, and entered clinical trials in the United States in 1963.
Iloperidone, commonly known as Fanapt and previously known as Zomaril, is an oral atypical antipsychotic for the treatment of schizophrenia.
Bifeprunox (INN) (code name DU-127,090) is an atypical antipsychotic which, similarly to aripiprazole, combines minimal D2 receptor agonism with serotonin receptor agonism. It was under development for the treatment of schizophrenia but has since been abandoned.
Timiperone, sold under the brand name Tolopelon, is a typical antipsychotic of the butyrophenone class which is marketed in Japan for the treatment of schizophrenia. It is similar in chemical structure to benperidol, but has a thiourea group instead of a urea group. It acts as an antagonist for the D2 and 5-HT2A receptors.
Perospirone (Lullan) is an atypical antipsychotic of the azapirone family. It was introduced in Japan by Dainippon Sumitomo Pharma in 2001 for the treatment of schizophrenia and acute cases of bipolar mania.
Blonanserin, sold under the brand name Lonasen, is a relatively new atypical antipsychotic commercialized by Dainippon Sumitomo Pharma in Japan and Korea for the treatment of schizophrenia. Relative to many other antipsychotics, blonanserin has an improved tolerability profile, lacking side effects such as extrapyramidal symptoms, excessive sedation, or hypotension. As with many second-generation (atypical) antipsychotics it is significantly more efficacious in the treatment of the negative symptoms of schizophrenia compared to first-generation (typical) antipsychotics such as haloperidol.
Pimavanserin , sold under the brand name Nuplazid, is an atypical antipsychotic which is approved for the treatment of Parkinson's disease psychosis and is also being studied for the treatment of Alzheimer’s disease psychosis, schizophrenia, agitation, and major depressive disorder. Unlike other antipsychotics, pimavanserin is not a dopamine receptor antagonist.
Moperone (Luvatren, since discontinued) is a typical antipsychotic of the butyrophenone class which is marketed in Japan for the treatment of schizophrenia. It is an antagonist for the D2 (Ki 0.7–1.9 nM), D3 (Ki 0.1–1 nM), and 5-HT2A (Ki 52 nM) receptors. It also has a high binding affinity for the sigma receptors.
Tiospirone (BMY-13,859), also sometimes called tiaspirone or tiosperone, is an atypical antipsychotic of the azapirone class. It was investigated as a treatment for schizophrenia in the late 1980s and was found to have an effectiveness equivalent to those of typical antipsychotics in clinical trials but without causing extrapyramidal side effects. However, development was halted and it was not marketed. Perospirone, another azapirone derivative with antipsychotic properties, was synthesized and assayed several years after tiospirone. It was found to be both more potent and more selective in comparison and was commercialized instead.
Clocapramine, also known as 3-chlorocarpipramine, is an atypical antipsychotic of the iminodibenzyl 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.
Cariprazine, sold under the brand names Vraylar and Reagila among others, is an on oral atypical antipsychotic originated by Gedeon Richter, which is used in the treatment of schizophrenia, bipolar mania, and bipolar depression. It acts primarily as a D3 and D2 receptor partial agonist, with a preference for the D3 receptor. Cariprazine is also a partial agonist at the serotonin 5-HT1A receptor and acts as an antagonist at 5-HT2B and 5-HT2A receptors, with high selectivity for the D3 receptor. Positive Phase III study results were published for schizophrenia and mania in early 2012, and for bipolar disorder I depression from a Phase II trial in 2015.
Brilaroxazine, also known as oxaripiprazole, is an investigational atypical antipsychotic which is under development by Reviva Pharmaceuticals for the treatment of schizophrenia and schizoaffective disorder. Reviva Pharmaceuticals also intends to investigate brilaroxazine for the treatment of bipolar disorder, major depressive disorder, psychosis/agitation associated with Alzheimer's disease, Parkinson's disease psychosis, attention deficit hyperactivity disorder (ADD/ADHD), and autism. As of August 2022, it is in phase III clinical trials for schizophrenia.
Aripiprazole lauroxil, sold under the brand name Aristada, is a long-acting injectable atypical antipsychotic that was developed by Alkermes. It is an N-acyloxymethyl prodrug of aripiprazole that is administered via intramuscular injection once every four to eight weeks for the treatment of schizophrenia. Aripiprazole lauroxil was approved by the U.S. Food and Drug Administration (FDA) on 5 October 2015.
References
↑ Takahashi N, Terao T, Oga T, Okada M (1999). "Comparison of risperidone and mosapramine addition to neuroleptic treatment in chronic schizophrenia". Neuropsychobiology. 39 (2): 81–5. doi:10.1159/000026565. PMID10072664. S2CID6554048.
↑ Sumiyoshi T, Suzuki K, Sakamoto H, Yamaguchi N, Mori H, Shiba K, Yokogawa K (February 1995). "Atypicality of several antipsychotics on the basis of in vivo dopamine-D2 and serotonin-5HT2 receptor occupancy". Neuropsychopharmacology. 12 (1): 57–64. doi:10.1016/0893-133X(94)00064-7. PMID7766287.
↑ Chiaki Tashiro & Ichiro Horii, EP 0073845 (1985 to Welfide Corp).
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