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There were unconfirmed reports that the blast was caused by a remote-controlled rebel bomb.

The assassinations were the first of such high-ranking members of the elite in the revolt and could represent a turning point in the conflict, analysts said. The nature and target of the attack strengthened the opposition’s claims that its forces have been marshaling strength to strike at the close-knit centers of state power.

While President Assad was not believed to have been attending the meeting, his whereabouts was not immediately clear.

According to state television, the dead included the defense minister, Daoud Rajha; Asef Shawkat, the president’s brother-in-law who was the deputy chief of staff of the Syrian military; and Hassan Turkumani, a former minister of defense and military adviser to Vice President Farouk Sharaa, who died later from injuries.

But the television report rejected claims by activists that the minister of the interior also was killed, saying he was in stable condition.

General Rajha was appointed minister of defense in August. A Christian, he was one of the prominent minority figures used by the Assad government to put a face of pluralism on the military and security services dominated by the president’s Alawite sect.

The British-based Syrian Observatory for Human Rights, an anti-Assad activist organization, said all the members of the crisis group set up by President Assad to try to put down the revolt were are either dead or injured. But there was no official confirmation of that account.

The government moved rapidly to project an image of control, naming Gen. Fahed Jassem al-Freij, the military chief of staff and a man once assigned to subdue restive Idlib province in the north, as the new minister of defense. In a statement read by General Freij on state television, he said: "The armed forces will continue their duties to eliminate terrorism and defend the homeland.”At the Pentagon on Wednesday morning, Defense Secretary Leon E. Panetta said that situation in Syria "is rapidly spinning out of control" and warned Mr. Assad’s government to safeguard its large stockpile of chemical weapons. "It’s obvious what is happening in Syria is a real escalation of the fighting," he said at a joint news conference with the British defense minister, Philip Hammond.

The attack came as diplomatic maneuvers to seek a cease-fire remained deadlocked by differences between Syria’s international adversaries and its sponsors, principally Russia, ahead of a United Nations Security Council vote scheduled later on whether to extend the mission of 300United Nations monitors. The work of the unarmed observers has been suspended because of the violence, and they have basically been trapped in their hotel rooms since last month.

In Moscow, Deputy Foreign Minister Gennady Gatilov, offering Russia’s first official commentary on the bombing, said via his Twitter account that the attack had put consensus between members of the Security Council even farther out of reach.

“A dangerous logic: While discussions on settling the Syrian crisis are being held in the U.N. Security Council, militants intensify terrorist attacks, frustrating all attempts,” he wrote.

Kofi Annan, the Syria special envoy representing the United Nations and Arab League, asked the Security Council to delay the vote until Thursday, and diplomats said they were considering the request. With tensions already high in Damascus after three days of clashes between the Syrian Army and rebels near the city center, SANA, the official news agency, described the assault as a “suicide terrorist attack” without offering any explanation of how such an assault could have been carried out in such heavily secured location. Opponents claimed a major victory.

“The Syrian regime has started to collapse,” said the activist who heads the Syrian Observatory, who goes by the pseudonym Rami Abdul-Rahman for reasons of personal safety. “There was fighting for three days inside Damascus, it was not just a gun battle, and now someone has killed or injured all these important people.”

Rumors swirled around Damascus that the bomber was the minister’s bodyguard, but there was no confirmation of those reports. CNN quoted the deputy leader of the opposition Free Syrian Army, Col. Malek al-Kurdi, as saying the explosion was caused by a remote-controlled bomb, but he offered no further explanation of how such an attack could have been carried out.

The attack came despite a huge security presence to isolate embattled neighborhoods of the capital.

The casualties were from the core team trying to enforce a security solution to the uprising in Syria, and in such a tense, suspicious climate, it was not clear who Mr. Assad might find to replace them.

“If a bodyguard blew himself up, then there was a major internal security breach,” said Elias Hanna, a retired Lebanese military officer and a military analyst knowledgeable about Syria.

 “Who will replace these people?” Mr. Hanna said. “They are irreplaceable at this stage, it’s hard to find loyal people now that doubt is sowed everywhere. Whoever can get to Asef Shawkat can get to Assad.”

“Everyone, even those close to the inner circle, will now be under suspicion,” he said.

The government moved rapidly to project an image of control, naming Fahed Jassem al-Freij, the military chief of staff and a man once assigned to subdue restive Idlib province in the north, as the new minister of defense.

An Army statement quoted by state television said in part: “This terrorist act will only increase our insistence to purge this country from the criminal terrorist thugs and to protect the dignity of Syria and its sovereignty.”

The information minister, Omran al-Zoubi, also went on a talk show to reject claims by those calling it the beginning of the end.  

  “The morale of our people is very high and our armed forces are at their highest level,” he said.

Activists reached in Damascus said the city appeared deserted, aside from the security cordon thrown up around the leafy, well-to-do neighborhood where the explosion took place — just down the road from the American ambassador’s residence, which has been vacant for months. The area is dotted with embassies and government offices.

“All the stores and shops are closed,” said an activist in Damascus reached via Skype. “Some people are scared and some are happy, you can hear people firing off gunshots in many places.”

The injured from the explosion were evacuated to the Alshame hospital, an elite medical facility used to treat the Assad family, ministers and other senior officials. Security forces threw up a cordon around the facility.

In the confusion after the attack, and in the absence of an authoritative official account, there were conflicting reports about who was killed and who survived.

Activists and media reports spoke of fatalities among the most senior figures in the very inner circle of the Assad administration, a close group that includes the deputy chief of staff of the military, Mohamed Sha’ar, the minister of the interior and Hisham Ikthtiar, the head of the national security bureau.

Other members of the group include Gen. Ali Mamlouk, the chief of general intelligence; Abdel-Fattah Qudsiyeh, the head of military intelligence, and Mohammad Nassif Kheyrbek, a senior security adviser.

Since the uprising began in March, 2011, Syria has been run by an ever tighter circle of army and security officials close to the president. The killings represented as much a psychological blow as a physical one, emboldening the opposition, analysts said, and challenging Mr. Assad to demonstrate quickly that his forces can still confront the rebels.

“Can they demonstrate the ability to put down this challenge and show that they are on the way to survival?” said an analyst with long experience in Damascus, speaking in return for anonymity because he still works there. “The opposition cannot defeat the regime militarily but they can defeat it through psychology.”

Even as state media reported the attack, the country’s Russian-armed military was reported to have suffered further defections among its top ranks, with two brigadier generals among 600 Syrians who fled to Turkey overnight, Reuters reported.

Their action brought to 20 the number of such high-ranking figures, who include a onetime close associate of Mr. Assad, Gen. Manaf Tlass, the son of a former defense minister.

There was also new evidence, reported by Israel’s intelligence chief, that Mr. Assad was moving troops into Damascus from Syria’s border with the disputed Golan Heights territory held by Israel, a possible sign of the seriousness of the fighting shaking regions at Mr. Assad’s doorstep.

Before the bombing on Wednesday, the epicenter of the Damascus fighting remained an area in the capital’s southwest where street battles first erupted on Sunday, particularly the Midan neighborhood where rebel fighters concentrated after Mr. Assad’s forces chased them from surrounding quarters.

Activists also reported continued government attacks on the northern suburb of Qaboun overnight and spoke of a clash around a military base near the presidential palace. Those reports, however, were sketchy and difficult to confirm.

Opponents posted videos online showing what they said was the destruction of civilian homes by earlier artillery in Qaboun and Midan. Images said to be from Midan showed a series of traditional, arched stone buildings with the roofs collapsed.

Midan is one of the oldest, more traditional quarters, a labyrinthine patchwork of narrow streets and old stone houses that attracted the rebel fighters partly because the army’s heavy weaponry is difficult to maneuver in the neighborhood.

But it is best known for the bustling Jazmateyeh food market, packed with popular restaurants and food shops, and the go-to address for Damascenes seeking the city’s famous honey-pistachio pastries. With the holy month Ramadan looming, when such foods are popular for the sunset feast to break the daily fast, the fighting in Midan suddenly threw the quarter’s traditional role into question.

In fact, Damascenes, having seen residents of other cities where fighting raged over the past 16 months flee to the capital, were suddenly casting about, alarmed over where they could turn should the fighting spread. “People from other areas sought refuge in Damascus — where would the people of Damascus go now?” one activist said.