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In this June 13, 2000, file photo, Syrian President Bashar al-Assad, right, his brother Maher, middle, and brother-in-law Major-General Assef Shawkat, left, stand during the funeral of late president Hafez Assad in Damascus.STR/The Associated Press

For the three senior security officials killed in Wednesday's brazen bombing in Damascus, it was just a matter of time before they would become fallen victim to someone's hit man.

Defence Minister General Daoud Rajiha, Deputy Defence Minister General Assef Shawkat, and Deputy Vice-President General Hassan Turkmani all were responsible for elements of the lethal crackdown against opposition protesters, a crackdown that would eventually lead to the full-fledged civil war that has killed thousands.

And each man in his own way also was a controversial figure inside President Bashar al-Assad's closest circle of aides.

There were many people who wanted to see these men dead.

Indeed, it was widely rumoured that all three had been murdered in May, victims of poison administered by rebels. Also among those reportedly assassinated this way was Interior Minister Mohammed al-Shaar, a man who was badly wounded in Wednesday's blast.

For more than four decades, Hafez al-Assad and his son, Bashar, ruled Syria with an iron fist and never before suffered an attack on their inner circle such as Wednesday's bombing.

"This type of event has massive impact," said Paul Salem, director of the Carnegie Middle East Center in Beirut.

The fact that a deadly bomb was brought into a top-level meeting not far from the President's palace shatters the notion that Mr. al-Assad and his regime still have firm control of the capital.

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

For its part, the regime quickly appointed a new Defence Minister, General Fahad Jassim al-Freij, who had been serving as the military chief of staff.

In a statement on state television, Gen. al-Freij, a Sunni Muslim, told Syrians he regards those killed in Wednesday's bombing as martyrs.

"This terrorist bombing," he said, "will not stop our armed forces from their duty to find the culprits and cut every hand that threatens the security of this nation and its civilians. Glory and eternity for the righteous martyrs."

Given the tight security that surrounded Wednesday's high-level meeting, it also is possible that the device was planted by a member of Mr. al-Assad's own regime.

"This would suggest a growing opposition movement comprised of disenchanted regime members," wrote Strategic Forecasting (Stratfor), a Texas-based global intelligence firm, in an analysis published Wednesday.

Perhaps most interestingly, some of the inner-circle members killed or wounded in the blast were men whose loyalty to the regime had been questioned at one time or another. Gen. Shawkat was a personal enemy of Maher al-Assad, the President's younger brother; Gen. Rajiha, the Christian, was viewed as not strictly loyal; and the seriously wounded Interior Minister Mr. al-Shaar, a Sunni Muslim who reportedly maintains a good relationship with the Alawites, also has contacts with members of the Sunni-led rebel insurgency.

"Al-Shaar topped the list of inner-circle regime members who would be suspected of carrying out a palace coup," wrote Stratfor in its report.