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Bryan Molloy

1939–2004 · Scottish-American · Eli Lilly and Company, Indianapolis (1966-2001)

Bryan Barnet Molloy (1939-2004) was a medicinal chemist born in Broughty Ferry, Dundee, who took his BSc and PhD at the University of St Andrews, did postdoctoral work at Imperial College London and Columbia University, and joined Eli Lilly in 1966. In 1970 he began a collaboration with the pharmacologist Robert Rathbun aimed at an antidepressant that kept the efficacy of the tricyclics without their cardiac and anticholinergic effects. With Klaus Schmiegel and Kenneth Hauser he made a large series of phenoxyphenylpropylamines derived from the antihistamine diphenhydramine; David Wong's synaptosome screen identified one of them, LY110140, as a highly selective inhibitor of serotonin reuptake. It was published in 1974, approved by the FDA on 29 December 1987 and launched as Prozac in January 1988. Molloy and Schmiegel hold the composition-of-matter patent. He became a Lilly Research Fellow in 1983 and was inducted into the National Inventors Hall of Fame in 1999.

Compounds credited overall: over 30 patents and more than 100 papers at Lilly; three compounds from one 1970s series are securely traceable to him, of which fluoxetine is the lasting one

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3 credited across 2 classes · 1 with a page here

  • SNRIs
  • Nisoxetine first synthesis, 1971 source

    LY94939, the o-methoxy member of the same diphenhydramine-derived series, turned out to be a selective noradrenaline reuptake inhibitor and is the compound whose structure-activity analysis pointed the way to fluoxetine. Wong, Perry & Bymaster (2005) attribute the series to 'Molloy, along with colleagues Schmiegel and Hauser' and place the identification of LY94939 in the 1971-72 window, but do not say who ran the specific bench prep, hence medium confidence. Never marketed; it survives as a research tool and as the ligand [3H]nisoxetine. Family is the closest fit in the site's vocabulary - it is a selective NRI rather than a dual-action SNRI.

  • Atomoxetine first synthesis, 1974 source

    Atomoxetine (originally tomoxetine, LY139603) is the o-methyl analogue in the same aryloxyphenylpropylamine series and was first disclosed in Molloy and Schmiegel's US 4,314,081, filed 10 January 1974 - the genus patent that also covers fluoxetine. It was developed first as an antidepressant, then approved for ADHD in 2002 as Strattera. Medium confidence because the attribution rests on inventorship of the genus patent and membership of Molloy's series; the Wikipedia article on atomoxetine names no individual chemist, and no source found here says Molloy made this specific compound. Family is the closest fit in the site's vocabulary - it is a selective NRI, not a dual-action SNRI.

  • SSRIs
  • Fluoxetine C17H18F3NO first synthesis, 1972 source

    Molloy, with Klaus Schmiegel and Kenneth Hauser, synthesised the phenoxyphenylpropylamine series from which fluoxetine came; the most potent serotonin-uptake inhibitor in David Wong's screen was the oxalate LY82816, and Molloy and Hauser then made the more soluble hydrochloride, LY110140, which is fluoxetine. Ray Fuller chaired the project team. First published in Life Sciences in 1974 (Wong, Horng, Bymaster, Hauser, Molloy); composition-of-matter patent US 4,314,081 to Molloy and Schmiegel, filed 10 January 1974. FDA approval 29 December 1987, launched as Prozac January 1988. It was the first SSRI marketed in the United States and the first commercially successful one, but not the first SSRI to market: Astra's zimelidine reached European markets in 1982 and was withdrawn.

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