Isner was beaten 6-4, 6-3 by his Uzbekistani opponent, ranked number 63 in the world.
There were three American winners on the day to make up for Isner’s exit.
Fourth seed and 2010 champion Sam Querrey defeated Colombian Alejandro Falla 6-3 6-3, James Blake edged Florian Mayer 4-6 6-3 6-2 and Michael Russell was a 6-2 6-4 winner over Alex Bogomolov.
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