-Quinagolid_Structural_Formula_V1.svg) Structure without stereochemistry | |
| Clinical data | |
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| Trade names | Norprolac |
| AHFS/Drugs.com | International Drug Names |
| Routes of administration | Oral |
| Drug class | Dopamine receptor agonist |
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| CAS Number | |
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| Chemical and physical data | |
| Formula | C20H33N3O3S |
| Molar mass | 395.56 g·mol−1 |
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Quinagolide (INNTooltip International nonproprietary name,BANTooltip British Approved Name), sold under the brand nameNorprolac, is aselectivedopamineD2 receptoragonist which is used to managehyperprolactinemia.[1] It has also been found to be effective in the treatment ofbreast pain.[2] It is used in the UK, but it is not available in US.
Quinagolide is aracemate composed of the following two enantiomers:[3]
| Enantiomeres of Quinagolide | |
|---|---|
-Quinagolid_Structural_Formula_V1.svg) (+)-Quinagolid CAS number: 140630-79-1 | -Quinagolid_Structural_Formula_V1.svg) (-)-Quinagolid CAS number: 140630-80-4 |
The first synthesis of quinagolide was disclosed in patents filed bySandoz.[4]
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A sequence of nine steps is required to transform the starting material 5-methoxy-2-tetralone (1) into the octahydrobenzo[g]quinoline ring system with the correctstereochemistry required. This intermediate (11) is then converted in another five steps to the drug. Transformation of theester (13) into theamine (15) is accomplished by aCurtius rearrangement in which anacyl hydrazide is treated withnitrosyl chloride.[4][5][6]
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The laboratory route was not practical for the synthesis of quinagoline on a large scale. Therefore scientists atNovartis developed an improved process.[7]
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The starting material is 1,6-dimethoxynaphthalene (1). This is selectivelylithiated at the C-7 position and reacts with (2Z)-ethyl 2-cyano-3-ethoxyacrylate (2), to give the cyanoacrylate (3).Catalytic hydrogenation andhydrolysis produces (5).Birch reduction of (5) leads first to (6) which on acid work-up gives theimine (7), which is reduced withsodium borohydride to yield (8).Fischer esterification with methanol gives an ester that is nextalkylated with1-iodopropane to give (11). The required stereochemistry for quinagoline is set in the final steps.[7][8][9]
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