David Cameron will tell world leaders that Syrian president Bashar al-Assad must eventually be replaced if there is to be a peaceful solution to the country's bloody civil war.
The Prime Minister flies out to the United Nations in New York on Sunday hoping to inject new momentum into the stalled Syrian peace process.
However, British officials warned that finding a resolution to the four-year conflict had been made more complicated by the unexpected Russian military build-up in support of the Assad regime, the Press Association reported.
President Vladimir Putin will be among the leaders attending the 70th anniversary meeting of the UN General Assembly along with US president Barack Obama and China's president Xi Jinping.
In recent weeks Russia has moved warplanes, helicopters, tanks, drones, artillery and troops into a military airbase near Latakia and the seaport of Tartus in an attempt to shore up Assad's beleaguered forces.
Putin argues that support for the regime is the best way of defeating the militant jihadis of Islamic State (IS) - also referred to as Isil - who have seized control of a large swathe of the country.
However, Mr Cameron will use a series of one-to-one meetings with other leaders - including Mr Obama - to make the case that a peaceful solution will ultimately require a different leadership which the whole country can unite around.
"Our view is very clear, Isil and Assad are both the enemies of the Syrian people," said one senior British official.
"The Prime Minister's view is still very clearly that in the endgame you need a different leader to build a peaceful and inclusive Syria."
While Russia, together with Iran, remains Assad's main international backer, some reports have suggested that Putin could be open to a change of leadership at some point in the future.
British ministers in turn have been careful not to call for a specific time frame for Assad to go, and officials acknowledged that they would need to work with Moscow if there was to be a diplomatic resolution.
"There has always been the idea that there will be a political transition and there are differing views between members of the international community ... what the steps are in the process. That is where there is more discussion ongoing," one senior official said.
Mr Cameron, who is not expected to meet Mr Putin in New York, nevertheless believes the migrant crisis - driven largely by Syrian refugees fleeing the region - could provide the impetus for a new push to the end the fighting.
"Events over the last few months have shifted the dynamic and added to the urgency of finding a political solution. We want to seize that opportunity to inject some momentum into the process," the official said.
The official said the discussions were at an early stage and that the shape of any final settlement was still unclear.
"There does need to be more thinking in capitals on what it would be," the official said. "This is complex and challenging and at the moment we are still trying to work out and agree what that solution might be."
Mr Cameron, who will address a sustainable development summit ahead of the main General Assembly meeting, will also urge other leaders to do more to support the millions of refugees still in the region.
Following his visit to the camps in neighbouring Jordan and Lebanon, he is particularly keen to promote employment opportunities for the refugees to provide an incentive for them to remain.
After the UN, Mr Cameron will travel on to visit Jamaica and Grenada before returning to the UK.