Bashar Assad must not escape prosecution even if he is allowed to play an interim role in any political solution in Syria, David Cameron insisted as he arrived in the US.
Injecting new momentum into the stalled peace process is top of the agenda for world leaders gathered in New York for the 70th anniversary meeting of the United Nations General Assembly.
Vladimir Putin is among those attending amid concerns over an unexpected build-up of Russian troops in support of the Moscow-backed Assad regime, which the Kremlin says is the best way to take on Islamic State fighters there.
The Prime Minister will use one-to-one talks with a number of key figures - though not Mr Putin - to press his case that the Syrian president "can't be part" of a peaceful solution to the civil war.
But with Europe increasingly overwhelmed by the upsurge of refugees fleeing the conflict and IS - also known as Isil - in control of large swathes of the country, he joined Western allies such as the US and France in signalling a willingness to discuss whether Assad could play a transitional role.
Speaking to reporters accompanying him on the flight to the UN meeting - which will also focus on climate change and new development goals - Mr Cameron said it was about "stepping up" international efforts to take on the militant threat.
"Assad can't be part of Syria's future. He has butchered his own people. He has helped create this conflict and this migration crisis. He is one of the great recruiting sergeants for Isil," he said.
"He can't play a part in the future of Syria and that position hasn't changed.
"Obviously conversations about how we bring about transition are very important and that's what we need to see greater emphasis on."
Asked if he believed Assad should face prosecution at the International Criminal Court, he said: "People who break international law should be subject to international law."
Mr Cameron said Russia and other powers had to be persuaded that it was "in everyone's interests" to co-operate in the fight against IS. The president of Iran - which also backs Assad - is among other leaders at the UN.
"What we have to discuss with Russia, what we have to reach agreement about, is that at the end of the day it is in everyone's interests that this part of the world has stability, that it is not fomenting terrorism," Mr Cameron said.
"My argument with Russia is always that Russia will suffer from Islamist extremist violence as much as anyone and so we need to defeat the extremism and its causes."
Mr Cameron said there had been no change in the position on the possible extension of RAF air strikes against IS positions from Iraq into Syria - despite the election of the anti-war left-winger Jeremy Corbyn as Labour leader.
"I have always said that it is important that Isil is defeated in Syria as in Iraq. We play a role in that already, helping countries that are doing the active work.
"To go further we would need parliamentary backing."