Ramatroban
Ramatroban is a thromboxane receptor antagonist. It is also a DP2 receptor antagonist.
Ramatroban is indicated for the treatment of coronary artery disease. It has also been used for the treatment of asthma.
It has been suggested that ramatroban, by modulating DP2 receptor, can reverse viremia-associated proinflammatory and prothrombotic processes which are similar to those induced by SARS-Cov-2. Hence, ramatroban, that has been used for the treatment of allergic rhinitis in Japan for the past two decades with a well established safety profile, merits investigation as a novel immunotherapy for the treatment of COVID-19 disease, although no clinical trial has yet been conducted.
Ramatroban was developed by the German pharmaceutical company Bayer AG and is co-marketed in Japan by Bayer Yakuhin then marketed by Kyorin Pharmaceutical and Nippon Shinyaku Co., Ltd. under the trade name Baynas.
It is a tetrahydrocarbazolamine derivative and cyclized tryptamine.
Synthesis
The synthesis has been described: Cmp#4 Patent:The starting material is called 1,4-cyclohexanedione monoethylene glycol ketal aka 1,4-Dioxaspirodecan-8-one . The Borsche–Drechsel cyclization between and Phenylhydrazine gives 5-Oxo-tetrahydrocarbazole ethylene ketal . Hydrolysis of the ketal protecting group gives 1,2,4,9-tetrahydrocarbazol-3-one . Reduction of the ketone with sodium borohydride gives 2,3,4,9-tetrahydro-1H-carbazol-3-ol . Acetylation by treatment with vinyl acetate gives -3beta-Acetoxy-1,2,3,4-tetrahydro-9H-carbazole, PC59051734 & -1,2,3,4-Tetrahydro-9H-carbazole-3-ol, PC8142712. These can be separated at this stage into pure for the next step. A Mitsunobu reaction in the presence of DPPA leads to an Azide with pure Walden inversion kinetics w/o racemization. The Staudinger reduction of the azide in situ gives -3-Amino-1,2,3,4-tetrahydrocarbazole .