"Of course we are not fighting for specific leaders, we are defending our national interests, on the one hand," Medvedev said in an interview to air on state television.
"And secondly, we have a request from the lawful authorities (of Syria). That is the basis we are working on," he said, quoted on the government website.
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"The prime minister said this: it's obvious that if we don't destroy these terrorists there, they will come to Russia."
Medvedev said that it did not matter to Russia who heads Syria in the future, as long as it is not the Islamic State jihadist group.
"We don't want IS to head Syria... It should be civilised, legitimate authorities," he said.
"Who will lead Syria should be decided by the Syrian people," Medvedev said.
Nevertheless he added that currently Russia is "working on the basis that Assad is the legitimate president."
Moscow this week expressed outrage that the United States declined to host a Russian delegation on Syria led by Medvedev.
"I think this is stupid behaviour," Medvedev said. "As a result of such decisions or a refusal to hold talks, the Americans just demonstrate their weakness."
Medvedev said that the US operation in Syria had "practically zero" impact on IS and "only Russia's intervention changed the situation.
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