BEIRUT — A bomb ripped through a high-level security meeting Wednesday in Damascus, killing three top regime officials — including President Bashar Assad’s brother-in-law — in the harshest blow to Syria’s ruling family dynasty and the rebels’ boldest attack in the country’s civil war.

Syrian state-run TV said the blast came during a meeting of Cabinet ministers and senior security officials in Damascus, which has seen four straight days of clashes between rebels and government troops.

The high-level assassinations could signal a turning point in the civil war as the violence becomes increasingly chaotic.

U.S. Defense Secretary Leon Panetta said the bombing showed that the bloodshed in Syria was “rapidly spinning out of control,” and it was time for the international community to bring “maximum pressure” on Assad to step down and permit a stable transfer of power. The Obama administration also slapped new financial sanctions on Assad’s government.

It was not immediately clear where Assad was. He gave no immediate statements on the attacks.

The Assad family has ruled Syria for four decades, creating an ironclad and impenetrable regime. Wednesday’s attack was an unheard-of strike on the inner circle.

Syria’s rebel commander, Riad al-Asaad, claimed responsibility, saying his rebel forces planted a bomb in the room and detonated it. All those involved in carrying out the attack are safe, he said.

State-run TV initially said it was a suicide blast but later referred to the attack as a bomb.

“God willing, this is the beginning of the end of the regime,” al-Asaad told The Associated Press in a telephone interview from his base in neighboring Turkey.

“Hopefully Bashar will be next,” he added.

Syrian TV confirmed the deaths of Defense Minister Dawoud Rajha, 65, a former army general and the most senior government official to be killed in the rebels’ battle to oust Assad; Gen. Assef Shawkat, the deputy defense minister who is married to Assad’s elder sister, Bushra, and is one of the most feared figures in the inner circle; and Hassan Turkmani, a former defense minister who died of wounds suffered in the attack.   

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.

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

A member of the Syrian National Council opposition group, Omar Shawaf, said the 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.

Republican Guard troops surrounded the nearby al-Shami Hospital, where some officials were treated, witnesses said.

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

Police had cordoned off the area, and journalists were not allowed to approach the site.

Earlier, SANA said soldiers were chasing rebels in the Midan neighborhood, causing “great losses among them.” The Britain-based Syrian Observatory for Human Rights said army helicopters attacked the neighborhoods of Qaboun and Barzeh.

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 neighborhoods, he added.

“More than 80 percent of shops in Damascus are closed. People are rushing home,” he said.

“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 last major attacks on regime figures and government buildings date back to the early 1980s, when members of the Syrian Muslim Brotherhood were waging a guerrilla war to topple the regime of Assad’s father and predecessor, President 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.

The violence in Syria has spiked in recent 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-Qaida or other extremists are joining the fight.

Activists say more than 17,000 people have died since the uprising began in March 2011.

The Syrian army said in a statement that 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,” it said.

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 minority Christians, who make up about 10 percent of Syria’s population and have mostly stood by the regime.

Christians say they are particularly vulnerable to the violence sweeping the country of 22 million people, and they are fearful that Syria will become another Iraq, with Christians caught in the crossfire between rival Muslim groups.

At the United Nations, international envoy Kofi Annan urged the Security Council to delay a vote scheduled for later Wednesday on a new resolution on Syria in a last-minute effort to get Western nations and Russia to reach agreement on its wording.

Council diplomats, speaking on condition of anonymity because discussions have been private, said a delay is virtually certain.

The new resolution was aimed at pressuring the Assad regime to comply with a peace plan put forth by Annan.

Russia, a close ally of Syria, remains at odds with the U.S. and its European allies over any mention of sanctions and Chapter 7 of the U.N. charter, which could eventually allow the use of force to end the fighting.

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 on Wednesday.

Supporting the opposition “is a dead-end policy, because Assad is not leaving voluntarily,” he said.

Israeli Defense Minister Ehud Barak summoned his top security and intelligence advisers to discuss the situation in Syria. Israel fears that militant groups said to be operating in Syria, including al-Qaida, might try to take advantage of any power vacuum to stage attacks on Israel. On Tuesday, Israel’s military intelligence chief said Assad had diverted his troops away from the Israeli border area toward the center of the country, reflecting Assad’s worsening position. He said jihadist groups have moved into the border area and might try to exploit the situation.

The new financial sanctions imposed by the U.S. targets a huge swath of top members of Assad’s government, including the prime minister and 28 other Cabinet ministers and senior officials. The move freezes any assets they 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.

“Today’s actions reflect the unwavering commitment of the United States to pressure the Assad regime to end the carnage and relinquish power,” said David S. Cohen, the undersecretary for terrorism and financial intelligence at the Treasury Department.  “As long as Assad stays in power, the bloodshed and instability in Syria will only mount.”

As news of the assassinations broke, Syrians opposed to Assad’s regime 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 Saraqeb and other towns in the northern Idlib province. The AP could not immediately verify the authenticity of the video.

Residents of Hass 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.

In a dust-filled refugee processing center in Jordan, tens of refugees gathered to celebrate. 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.”