Rebels penetrated the heart of Syria's power elite Wednesday, detonating a bomb inside a high-level crisis meeting in Damascus that killed three leaders of the regime, including President Bashar Assad's brother-in-law and the defence minister.

The unprecedented blow to the ruling dynasty could mark a turning point in the civil war, suggesting that those once close to Assad are turning against him. The bombing follows some of the worst bloodshed in Damascus of the 16-month uprising, a growing list of high-ranking defections and mounting frustration by world leaders over their inability to find a diplomatic solution.

The White House said the bombing showed Assad was "losing control" of Syria.

Rebels claimed responsibility for the attack, saying they had been planning it for two months and finally decided to plant the bomb in the room where the top government security officials in charge of crushing the revolt were holding a crisis meeting.

"God willing, this is the beginning of the end of the regime," said Riad al-Asaad, a commander of the disparate rebel forces who operate across the country. Al-Asaad, who is not related to the president, spoke to The Associated Press by telephone from Turkey, where he is based.

"Hopefully Bashar will be next," Al-Asaad said in a chilling warning to the 46-year-old Syrian president, a tall, lanky leader who once felt so confident in his security that he was known to hate being surrounded by bodyguards.

The whereabouts of Assad, his wife and his three young children were not immediately clear. He gave no immediate statements on the attack, which state-run TV initially blamed on a suicide bomber but later called simply a bomb.

As news of the assassinations broke, Syrians opposed to Assad celebrated in several locations across the country.

Internet video showed people in convoys of cars and motorbikes honking their horns and firing weapons in the air in the northeastern Idlib province, along with Aleppo in the north, Daraa in the south and Homs in central Syria. In the village of Hass, residents distributed sweets as they gleefully shouted: "You are going to hell, shabihas" — a reference to the pro-regime militia that has been blamed for mass killings.

The AP could not immediately verify the authenticity of the video.

Syrian TV confirmed that those killed were:

• Defence Minister Dawoud Rajha, 65, a former army general and the most senior government official to die.
• Gen. Assef Shawkat, 62, the deputy defence minister who is married to Assad's elder sister, Bushra, and is one of the most feared figures in the inner circle.
• Hassan Turkmani, 77, a former defence minister who died of his wounds in the hospital.

Also wounded were Interior Minister Mohammed Shaar and Maj. Gen. Hisham Ikhtiar, who heads the National Security Department. State TV said both were in stable condition.

CBC's Sasa Petricic tweeted that reports from Damascus were indicating Shaar may have died in hospital.

Petricic also said on Twitter that there are unconfirmed reports of widespread defections from the Assad military in Damascus and other parts of Syria.

Christians feeling vulnerable

Rajha was the most senior Christian government official in Syria, appointed to the post by Assad last year. His death will resonate with Syria's Christians, who make up about 10 per cent of the population of 22 million and have mostly stood by the regime.

Christians say they are particularly vulnerable and they fear that Syria will become another Iraq, with Christians caught in the crossfire between rival Muslim groups.

The attack came at a time of great momentum for the forces trying to oust Assad, whose family has ruled Syria for four decades. Although the uprising began in March 2011, recent weeks have seen a spike in potentially transformative events, including high-level defections from the regime.

Four straight days of clashes between rebels and government troops this week in Damascus showed the rebels can now infiltrate the tightly controlled capital. On Tuesday, Israel's military intelligence chief said Assad had diverted his troops away from the Israeli border area toward the centre of Syria, reflecting the regime's worsening position.

The state-run news agency, SANA, reported the bombing was aimed at the National Security building, a headquarters for one of Syria's intelligence branches and less than 500 metres from the U.S. Embassy. The embassy has been closed since Washington withdrew its ambassador months ago.

Although there were no statements from Assad, Syrian TV said after the attack that a decree from him named Gen. Fahd Jassem al-Freij as the new defence minister. Al-Freij used to be the army chief of staff.

Wednesday's attack was the most brazen by the rebels. The last major attacks on regime figures and government buildings date back to the early 1980s, when the Syrian Muslim Brotherhood waged a guerrilla war to topple the regime of Assad's father and predecessor, Hafez Assad.

Hafez Assad himself survived an assassination attempt in 1980 when members of the Muslim Brotherhood threw grenades at him, wounding him in the leg.

Paul Salem, director of the Carnegie Middle East Center in Beirut, said the bombing could usher in the end of the Assad regime.

"I think this type of event has massive impact," he said. "A few weeks ago, we were counting the life span of this regime in months. Now after the last week and today, I think you'd have to say weeks. This is a very fast moving conflict."

'Regime losing its grip'

Salem said the key signs that the regime is losing its grip are that the fighting has reached Damascus and that a bomb has been planted inside a top-level meeting.

Defence Minister Gen. Dawoud Rajha, in an undated photo, was a former army general and the most senior Christian government official in Syria. He was among government officials killed in a blast Wednesday, according to state-run TV. (SANA/Associated Press)

"This is not something that can go on for months," Salem said. "It changes the timetable."

But there were no signs the regime was willing to back down.

Shortly after Wednesday's attack, the Syrian army said its forces will continue to fight.

"Whoever thinks that by targeting the country's leaders they will be able to twist Syria's arm is disillusioned because Syria's people, army and leadership are now more determined than ever to fight terrorism ... and cleanse the nation from the armed gangs," the army said.

Eager to show the government is still in control of Damascus, the Interior Ministry took journalists on a tour of its quiet neighbourhoods. But even there, traffic on the streets was thin and almost all shops were closed.

Troops hit streets after explosion

Damascus-based activist Omar al-Dimashki said large numbers of troops and plainclothes police were deployed in the streets after the explosion. Snipers took positions on high buildings in different neighbourhoods, he added.

"It's so empty, it reminds me of when Hafez Assad died in 2000," said a resident of Damascus, who declined to be identified for fear of retribution. "Everyone is really scared of the coming days, especially tonight, with the possibility that the regime will take revenge."

The attack came two days before the start of the Muslim holy month of Ramadan, when observant Muslims abstain from eating, drinking and sex from dawn to dusk. Last year, anti-government protests sharply increased during Ramadan.

The government characterizes the revolt as the work of terrorists and foreign extremists, and denies the conflict even began as a popular uprising, inspired by the movements sweeping the Arab World starting with Tunisia and Egypt.

Although the uprising began with mostly peaceful protests, a fierce government crackdown led many in the opposition to take up arms. Soon, an armed insurgency began to boil — and on Sunday the Red Cross formally declared the conflict to be a full-blown civil war. Activists say more than 17,000 people have died.

The violence has metastasized over the months. Besides a government crackdown, rebel fighters are launching increasingly deadly attacks on regime targets, and several big suicide attacks this year suggest that al-Qaeda or other extremists are joining the fight.

A member of the Syrian National Council opposition group, Omar Shawaf, said Wednesday's assassinations sent a clear message to the regime that no one is safe — including Assad himself.

"The hands of the Syrian people and the Free Syrian Army can reach anyone inside Damascus," he said from Turkey, where he is based.

Wednesday's attack raised alarm across the region. Syria is intertwined in alliances with Iran, Hezbollah and Palestinian militant groups, and borders Israel — making the fallout from the crisis unpredictable.

"The incident today makes clear that Assad is losing control, that violence is increasing rather than decreasing and that all of our partners internationally need to come together to support a transition," said White House spokesman Jay Carney.

U.K. Foreign Secretary William Hague, U.S. Defence Secretary Leon Panetta and a spokesman for Canadian Foreign Affairs Minister John Baird said ending the violence is long overdue.

Their comments came as the Obama administration said it is slapping financial sanctions on a huge swath of top members in Assad's government, targeting the prime minister and 28 other cabinet ministers and senior officials. The U.S. move freezes any assets the ministers may have in U.S. jurisdictions and bars Americans from doing business with them. The administration had already imposed similar penalties on security officials, but the latest step extends those sanctions to virtually the entire government.

Hague said there's an urgent need for a Chapter 7 resolution.

"The situation in Syria is clearly deteriorating," said Hague in a release Wednesday. "All the members of the UN Security Council have a responsibility to put their weight behind the enforcement of joint special envoy Kofi Annan's plan to end the violence."

Rick Roth, Baird's press secretary, said tough Security Council sanctions against Syria are long overdue.

"We are well over a year into the crisis in Syria whereby a brutal and desperate dictator has slaughtered thousands of his own people," said Roth from Ottawa.

Bombing victims called 'comrades' by Hezbollah

In a sign of Hezbollah's close ties to Syria, the group's leader, Sheik Hassan Nasrallah, said the bombing victims were "comrades" in the struggle against Israel. He said "the most important rockets" that Hezbollah fired on Israel in the 2006 war came from Syria.

"Israel has every right to be happy," Nasrallah said, saying the opposition to Assad serves Israel's interests. "Israel can be happy because pillars in the Syrian army today were targeted and killed."

Israeli Defence Minister Ehud Barak summoned his top security and intelligence advisers to discuss the situation. Israel fears that militant groups said to be operating in Syria, including al-Qaeda, might try to take advantage of any power vacuum to stage attacks on Israel.

At the United Nations, the Security Council delayed a vote scheduled for later in the day on a new resolution on Syria in a last-minute effort to get Western nations and Russia — a close Damascus ally — to reach agreement on measures to end the violence.

The key stumbling block to an agreement is the Western demand for a resolution threatening non-military sanctions. It is tied to Chapter 7 of the UN Charter, which could eventually allow the use of force to end the conflict. Russia, a close ally of Syria, is adamantly opposed to sanctions and any mention of Chapter 7.

Although Western nations appear to have little appetite for force, Russia fears a repeat of the NATO campaign in Libya and adamantly opposes any intervention.

Reacting to the bombing, Russian Foreign Minister Sergey Lavrov accused the West of inciting Syria's opposition.

"Instead of calming the opposition down, some of our partners are inciting it to go on," he was quoted as saying by the RIA Novosti news agency. Supporting the opposition is a "dead-end policy," Lavrov said, "because Assad is not leaving voluntarily."

Even if Assad did leave, the opposition is widely perceived to be far too disorganized to take over.

But in a dust-filled refugee processing centre in Jordan, crowds of refugees said they hoped the attack would spell the end of the regime. Women wearing the black Muslim veil and head-to-toe robes ululated as men danced under a scorching sun.

"It's great news," said a 43-year-old refugee from the restive southern town of Daraa, who identified himself only by his first name, Ahmad, for fear of retribution. "God willing, the criminal Bashar is next."

With files from CBC News