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(UPDATE 2: 5:05PM) The Associated Press reported that anti-Assad rebel commander Riyad al-Asaad claimed responsibility for the attack. He said the bomb was not a suicide attack, as previously reported, but rather his forces had planted a bomb inside the room where the senior government officials were meeting.
Meanwhile, the BBC said that Syria's state TV reported a new defence minister has already been appointed. He is Gen. Fahad Jassim al-Freij, previously the chief of staff of the armed forces.
(UPDATE 1: 4:40PM) President Bashar al-Assad's brother-in-law Gen. Assef Shawkat and the Deputy Defense Minister were among those killed in the suicide blast in Syria's capital, BBC reported.
Shawkat, who is married to Assad's elder sister Bushra, was among the most feared figures in Assad's inner circle.
Several other people are reported to have been injured, including the interior minister, BBC said.
A suicide bomber attacked a security building in the heart of Damascus, killing the country's defense minister and seriously wounding several other officials, Syria's state television reported on Wednesday.
"A suicide attack has targeted the National Security building." the channel said. "The terrorist explosion which targeted the national security building in Damascus occurred during a meeting of ministers and a number of heads of [security] agencies."
The BBC confirmed the death of the country's Minister of Defence Daoud Rajiha and said a number of officials were badly wounded.
The building is a heavily guarded headquarters headed by General Hisham Ikhtiyar, a key figure in the regime's repression of the 16-month revolt. On May 23 last year, the European Union added his name to the list of Syrian political figures targeted by sanctions.
The bombing comes on the fourth straight day of fighting in the capital city as activists protest the regime of President Bashar al-Assad.
Monitors say more than 14,100 people, mostly civilians, have died since a peaceful uprising began on March 15, 2011, prompting a bloody crackdown by Assad's forces that eventually prompted an armed reaction.
More than 2,302 have reportedly died in the past month alone.