Syria's defense minister and President Bashar Assad's brother-in-law were killed in a Damascus bomb attack on Wednesday, state television reported, the most serious blow to Assad's high command in the country's 16-month-old rebellion.

© SANA/ReutersSyrian Defence Minister Dawoud Rajha was the country's most senior Christian government official.
The bomber -- said by a Reuters security source to be a bodyguard assigned to Assad's inner circle -- struck during a meeting attended by ministers and senior security officials in the Syrian capital as battles raged within sight of the presidential palace.

Defense Minister Dawoud Rajha, 65, a former army general, was the country's most senior Christian government official. Assad appointed him to the post last year.

Within hours, Syrian State TV announced that Brig. Gen. Fahed Jassim el Friej would replace Rajha.

Assad's brother-in-law Assef Shawkat -- widely seen as a member of the president's inner circle -- was also reportedly killed in the attack.

A senior officer with the Free Syrian Army claimed responsibility for the high-level assassinations, a decisive moment in the conflict. The death of two of the regime's most senior operational commanders could seriously dent the effectiveness of Assad's army, as it fights battles across the capital.

The White House said on Wednesday that time is running out to find a peaceful solution to the violence in Syria and added it did not know the whereabouts of Assad, according to The Associated Press.

© AFP/Getty ImagesA file picture taken on June 13, 2000 shows General Assef Shawkat, the brother-in-law of Syrian President Bashar al-Assad, who was killed Wednesday.
"The window is closing, we need to take action in a unified way to help bring about the transition that the Syrian people so deserve," White House spokesman Jay Carney said at a news conference.

Both the U.S. Secretary of Defense Leon Panetta and his British counterpart, Phillip Hammond, said Assad's regime must ensure that the vast Syrian chemical weapons stockpiles remain secure.

"The situation in deteriorating," Panetta told reporters on Wednesday, NBC News reported.

A BBC News journalist reported that residents very close to the building where the attack took place said they had not heard the sound of explosion and gunfire, and had not seen injured being taken away.

Also on Wednesday, there were reports of explosions at the headquarters of the army's fourth division in Damascus, which is led by Assad's younger brother Maher, considered the second most powerful man in Syria.

It was not clear whether those forces were being targeted.

Syria's information minister denied on state television that any explosion had occurred at the base.

The capital has seen days of clashes pitting government troops against rebels. The fighting is an unprecedented challenge to government rule in the tightly controlled capital.

Activists in Damascus said by telephone that Republican Guards sealed off the Shami hospital in the capital after ambulances had brought casualties from the site of the explosion.

In addition to weakening the army command, Wednesday's killings are bound to heighten a sense of paranoia and mistrust among Assad's top ministers and officials.

The attack came as fighting erupted in major Damascus neighborhoods for a fourth day.

The Syrian Military has been using helicopters and firing rockets against Free Syrian Army rebels on the outskirts of the city. Loud explosions were heard and the streets of Damascus were virtually deserted.

An army barracks near the "palace of the people," a huge Soviet-style complex overlooking the city from the western district of Dummar, came under rebel fire around 7:30 a.m. (12:30 a.m. ET), activists and a resident said.

"I could hear the sound of small-arms fire and explosions are getting louder and louder from the direction of the barracks," Yasmine, who works as an architect, said by phone from Dummar.

Video footage broadcast by activists purportedly showed a fire in the barracks overnight as a result of an attack by mortar rounds, but residents who saw the fire said they had not heard explosions to indicate it was a result of an attack.

Dummar is a secure area containing many auxiliary installations for the presidential palace and the barracks is just hundreds of yards from the palace itself.

Fighting in Sunni areas

Fighting also erupted overnight in the southern neighborhoods of Asali and Qadam, and Hajar al-Aswad and Tadamun -- mainly Sunni Muslim districts housing Damascenes and Palestinian refugees.
© Syrian TV/AFP/Getty ImagesAn image taken from Syrian TV shows security forces during armed clashes with gunmen the TV called "terrorists" (unseen) in the Al-Midan district of Damascus on Wednesday.
Assad and the ruling elite belong to the minority Alawite sect, an offshoot of Shiite Islam that has dominated power in Syria since a 1963 coup.