| Iupac Name: | 1-methyl-4-(8-methylsulfanyl-5,6-dihydrobenzo[b][1]benzothiepin-6-yl)piperazine |
| Width: | 225px |
| Cas Number: | 20229-30-5 |
| Cas Supplemental: | 19728-88-2 (maleate) |
| Pubchem: | 4106 |
| Iuphar Ligand: | 89 |
| Chemspiderid: | 3963 |
| Chebi: | 64203 |
| Unii: | 55D94103HL |
| Synonyms: | Methiothepin; Methiothepine; Ro 8-6837 (maleate); VUFB-6276 (mesylate) |
| C: | 20 |
| H: | 24 |
| N: | 2 |
| S: | 2 |
| Smiles: | CN1CCN(CC1)C2Cc3ccccc3Sc4c2cc(cc4)SC |
| Stdinchi: | 1S/C20H24N2S2/c1-21-9-11-22(12-10-21)18-13-15-5-3-4-6-19(15)24-20-8-7-16(23-2)14-17(18)20/h3-8,14,18H,9-13H2,1-2H3 |
| Stdinchikey: | RLJFTICUTYVZDG-UHFFFAOYSA-N |
Metitepine (; developmental code names Ro 8-6837 (maleate), VUFB-6276 (mesylate)), also known as methiothepin, is a drug described as a "psychotropic agent" of the tricyclic or tetracyclic group which was never marketed.[1]
It acts as a non-selective antagonist of serotonin, dopamine, and adrenergic receptors, including of the serotonin 5-HT1, 5-HT2, 5-HT5, 5-HT6, and 5-HT7 receptors.[2] [3] [4] [5] [6] The drug has antipsychotic properties.[7]
| Affinity (Ki, nM) | Species | ||
|---|---|---|---|
| 2.2–631 | Human | ||
| 0.2–40 | Human | ||
| 5.8–170 | Human | ||
| 120–209 | Human | ||
| 646–652 | Human | ||
| 0.1–3.2 | Human | ||
| 0.58–2.1 | Human | ||
| 0.34–4.5 | Human | ||
| ≥3,000 | Rat | ||
| 1.0–32 100–126 29–146 | Human Mouse Rat | ||
| 16 29–145 | Mouse Rat | ||
| 0.30–4.1 | Human | ||
| 0.4–4.0 | Human | ||
| 0.06–7.9 | Guinea pig | ||
| 0.5 | Pig | ||
| 2.0 | Rat | ||
| 0.40 | Rat | ||
| Notes: The lower the affinity value, the more avidly the drug binds to the site. Refs: | |||
Metitepine is closely structurally related to certain other tetracyclic compounds including amoxapine, batelapine, clorotepine, clotiapine, clozapine, flumezapine, fluperlapine, loxapine, metiapine, olanzapine, oxyprothepin, perathiepin, perlapine, quetiapine, tampramine, and tenilapine.
The reduction of 2-(4-methylsulfanylphenyl)sulfanylbenzoic acid, CID:2733664 (1) gives [2-(4-methylsulfanylphenyl)sulfanylphenyl]methanol, CID:12853582 (2). Halogenating with thionyl chloride gives 1-(chloromethyl)-2-(4-methylsulfanylphenyl)sulfanylbenzene, CID:12853583 (3). FGI with cyanide gives 2-[2-(4-methylsulfanylphenyl)sulfanylphenyl]acetonitrile, CID:12853584 (4). Alkali hydrolysis of the nitrile to 2-[2-(4-methylsulfanylphenyl)sulfanylphenyl]acetic acid, CID:12383832 (5). PPA cyclization to 3-methylsulfanyl-6H-benzo[b][1]benzothiepin-5-one, CID:827052 (6). The reduction with sodium borohydride gives 3-methylsulfanyl-5,6-dihydrobenzo[b][1]benzothiepin-5-ol, CID:13597048 (7). Halogenating with a second round of thionyl chloride gives 5-chloro-3-methylsulfanyl-5,6-dihydrobenzo[b][1]benzothiepine, CID:12404411. Alkylation with 1-methylpiperazine [109-01-3] completed the synthesis of Metitepine (9).