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| Formula | C19H28N2O3 |
| Molar mass | 332.444 g·mol−1 |
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AGN-2979 is a glutarimide tryptophan hydroxylase activation inhibitor. [1] [2] It shows antidepressant properties in rodent models of depression. [2]
Note that the starting benzylcyanide is a "dual use" agent, with application in ketobemidone and embutramide (Hoechst).
The halogenation of 3,3-Dimethylacrylic Acid [541-47-9] (1) with thionyl chloride gives 3,3-Dimethylacryloyl Chloride [3350-78-5] (2). Amide formation with morpholine gives 4-(3-methyl-1-oxo-2-butenyl)-Morpholine [53868-72-7] (3). Reaction with Triethyloxonium tetrafluoroborate [368-39-8] gives the enol ether quat salt CID:21425364 (4).
The base catalyzed alkylation between (3-Methoxyphenyl)acetonitrile [19924-43-7] (5) and (3-chloropropyl)dimethylamine [109-54-6] (6) gives alpha-[3-(Dimethylamino) propyl]-3-methoxybenzeneacetonitrile, CID:10998885 (7).
Base catalyzed alkylation between 4 and 7 gave Ethyl 4-cyano-7-(dimethylamino)-4-(3-methoxyphenyl)-3,3-dimethylheptanoate, CID:54204784 (8). Acid catalyzed ring closure completed the synthesis of AGN-2979 (9).
Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, especially for treatment-resistant depression and atypical depression. They are also used to treat panic disorder, social anxiety disorder, Parkinson's disease, and several other disorders.
In the chemical sciences, methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These terms are commonly used in chemistry, biochemistry, soil science, and the biological sciences.
Serotonin–norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant drugs used to treat major depressive disorder (MDD), anxiety disorders, obsessive–compulsive disorder (OCD), social phobia, attention-deficit hyperactivity disorder (ADHD), chronic neuropathic pain, fibromyalgia syndrome (FMS), and menopausal symptoms. SNRIs are monoamine reuptake inhibitors; specifically, they inhibit the reuptake of serotonin and norepinephrine. These neurotransmitters are thought to play an important role in mood regulation. SNRIs can be contrasted with the more widely used selective serotonin reuptake inhibitors (SSRIs), which act upon serotonin only.
Tyrosine hydroxylase or tyrosine 3-monooxygenase is the enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA). It does so using molecular oxygen (O2), as well as iron (Fe2+) and tetrahydrobiopterin as cofactors. L-DOPA is a precursor for dopamine, which, in turn, is a precursor for the important neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline). Tyrosine hydroxylase catalyzes the rate limiting step in this synthesis of catecholamines. In humans, tyrosine hydroxylase is encoded by the TH gene, and the enzyme is present in the central nervous system (CNS), peripheral sympathetic neurons and the adrenal medulla. Tyrosine hydroxylase, phenylalanine hydroxylase and tryptophan hydroxylase together make up the family of aromatic amino acid hydroxylases (AAAHs).
Rasagiline is an irreversible inhibitor of monoamine oxidase-B used as a monotherapy to treat symptoms in early Parkinson's disease or as an adjunct therapy in more advanced cases.
Aldosterone synthase, also called steroid 18-hydroxylase, corticosterone 18-monooxygenase or P450C18, is a steroid hydroxylase cytochrome P450 enzyme involved in the biosynthesis of the mineralocorticoid aldosterone and other steroids. The enzyme catalyzes sequential hydroxylations of the steroid angular methyl group at C18 after initial 11β-hydroxylation. It is encoded by the CYP11B2 gene in humans.
The Blanc chloromethylation is the chemical reaction of aromatic rings with formaldehyde and hydrogen chloride to form chloromethyl arenes. The reaction is catalyzed by Lewis acids such as zinc chloride. The reaction was discovered by Gustave Louis Blanc (1872-1927) in 1923
Ketobemidone, sold under the brand name Ketogan among others, is a powerful synthetic opioid painkiller. Its effectiveness against pain is in the same range as morphine, and it also has some NMDA-antagonist properties imparted, in part, by its metabolite norketobemidone. This may make it useful for some types of pain that do not respond well to other opioids. It is marketed in Denmark, Iceland, Norway and Sweden and is used for severe pain.
Tryptophan hydroxylase (TPH) is an enzyme (EC 1.14.16.4) involved in the synthesis of the neurotransmitter serotonin. Tyrosine hydroxylase, phenylalanine hydroxylase, and tryptophan hydroxylase together constitute the family of biopterin-dependent aromatic amino acid hydroxylases. TPH catalyzes the following chemical reaction
AlkB is a protein found in E. coli, induced during an adaptive response and involved in the direct reversal of alkylation damage. AlkB specifically removes alkylation damage to single stranded (SS) DNA caused by SN2 type of chemical agents. It efficiently removes methyl groups from 1-methyl adenines, 3-methyl cytosines in SS DNA. AlkB is an alpha-ketoglutarate-dependent hydroxylase, a superfamily non-haem iron-containing proteins. It oxidatively demethylates the DNA substrate. Demethylation by AlkB is accompanied with release of CO2, succinate, and formaldehyde.
In enzymology, a kynurenine 3-monooxygenase (EC 1.14.13.9) is an enzyme that catalyzes the chemical reaction
Diclofensine was developed by Hoffmann-La Roche in the 1970s in the search for a new antidepressant. It was found that the (S)-isomer was responsible for activity. Is a stimulant drug which acts as a triple monoamine reuptake inhibitor, primarily inhibiting the reuptake of dopamine and norepinephrine, with affinities (Ki) of 16.8 nM, 15.7 nM, and 51 nM for DAT, NET, and SERT, respectively. It was found to be an effective antidepressant in human trials, with relatively few side effects, but was ultimately dropped from clinical development, possibly due to concerns about its abuse potential.
Fenclonine, also known as para-chlorophenylalanine (PCPA), acts as a selective and irreversible inhibitor of tryptophan hydroxylase, which is a rate-limiting enzyme in the biosynthesis of serotonin.
Indeloxazine (INN) is an antidepressant and cerebral activator that was marketed in Japan and South Korea by Yamanouchi Pharmaceutical Co., Ltd for the treatment of psychiatric symptoms associated with cerebrovascular diseases, namely depression resulting from stroke, emotional disturbance, and avolition. It was marketed from 1988 to 1998, when it was removed from the market reportedly for lack of effectiveness.
Arylcyclohexylamines, also known as arylcyclohexamines or arylcyclohexanamines, are a chemical class of pharmaceutical, designer, and experimental drugs.
Igmesine (JO-1,784) is a sigma receptor agonist (IC50 = 39 nM (rat brain)). It has neuroprotective and antidepressant-like effects in animal studies, as well as nootropic effects in models of age-related cognitive decline. In two phase II clinical trials, igmesine was found to be effective in the treatment of depression and was as active as the comparator fluoxetine. However, in a large phase III clinical trial, igmesine failed to show significant effectiveness for depression. The drug has not been developed further.
Cyanodothiepin (developmental code name BTS-56424) is a tricyclic antidepressant (TCA) acting as a potent and highly selective (over norepinephrine and dopamine uptake) inhibitor of the reuptake of serotonin that was never marketed. It also has moderate affinity for the muscarinic acetylcholine receptors and weak/negligible affinity for the α1-adrenergic, 5-HT2A, D1, and D2 receptors; the H1 receptor has not been assayed, but cyanodothiepin is less sedating than the related drug cianopramine, suggesting that its antihistamine activity is not as pronounced as other TCAs. Cyanodothiepin is active in the forced swimming test (FST), implying that it may possess antidepressant properties in humans. However, it is only weakly active compared to cianopramine and imipramine in monoamine depletion-based tests of antidepressant potential.
Cericlamine is a potent and moderately selective serotonin reuptake inhibitor (SSRI) of the amphetamine family that was investigated as an antidepressant for the treatment of depression, anxiety disorders, and anorexia nervosa by Jouveinal but did not complete development and was never marketed. It reached phase III clinical trials in 1996 before development was discontinued in 1999.
Dimethylcarbamoyl chloride (DMCC) is a reagent for transferring a dimethylcarbamoyl group to alcoholic or phenolic hydroxyl groups forming dimethyl carbamates, usually having pharmacological or pesticidal activities. Because of its high toxicity and its carcinogenic properties shown in animal experiments and presumably also in humans, dimethylcarbamoyl chloride can only be used under stringent safety precautions.
P4-t-Bu is a readily accessible chemical from the group of neutral, peralkylated sterically hindered polyaminophosphazenes, which are extremely strong bases but very weak nucleophiles, with the formula (CH3)3C−N=P(−N=P(−N(CH3)2)3)3. "t-Bu" stands for tert-butyl(CH3)3C–. "P4" stands for the fact that this molecule has 4 phosphorus atoms. P4-t-Bu can also be regarded as tetrameric triaminoiminophosphorane of the basic structure H−N=P(−NH2)3. The homologous series of P1 to P7 polyaminophosphazenes of the general formula with preferably methyl groups as R1, a methyl group or tert-butyl group as and even-numbered x between 0 and 6 (P4-t-Bu: R1 = Me, R2 = t-Bu and x = 3) has been developed by Reinhard Schwesinger; the resulting phosphazene bases are therefore also referred to as Schwesinger superbases.
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