Syria's state-run TV says President Bashar al-Assad's brother-in-law, also the country's deputy defence minister, as well as Defence Minister Dawoud Rajiha were killed today in a suicide blast in the capital of Damascus.
Gen. Assef Shawkat, among the most feared figures in Assad's inner circle, is married to Assad's elder sister, Bushra.
Rajha, 65, a former army general, is the most senior government official to be killed in the Syrian civil war as rebels battle to oust Assad. Interior Minister Mohammed Shaar was wounded and said to be in stable condition.
State-TV says the bomber struck the National Security building during a meeting of cabinet ministers and senior security officials
The capital has seen four straight days of clashes pitting government troops against rebels, who are trying to bring down the regime by force. The fighting is an unprecedented challenge to government rule in the tightly controlled capital.
The latest deaths will resonate with Syria's minority Christian population, who make up about 10 per cent of Syria's population and have generally 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.
Damascus-based activist Omar al-Dimashki said Republican Guard troops surrounded the nearby al-Shami Hospital where some officials were taken for treatment.
Facing increasingly chaotic violence, the UN Security Council was scheduled to vote later Wednesday on a new resolution aimed at pressuring the Syrian regime to comply with a peace plan.
But Russia remained at loggerheads with the U.S. and its European allies over any mention of sanctions and Chapter 7 of the UN charter, which could eventually allow the use of force to end the conflict in Syria.
More than 17,000 killed in uprising
Besides a government crackdown, rebel fighters are launching increasingly deadly attacks on regime targets, and several massive suicide attacks this year suggest al-Qaeda or other extremists are joining the fray.
Activists say more than 17,000 people have been killed since the uprising began last year.
The state-run news agency SANA reported that Wednesday's blast was aimed at the National Security building, a headquarters for one of Syria's intelligence branches and less than 500 metres from the U.S. Embassy.
Police had cordoned off the area, and journalists were banned from approaching the site.
Earlier Wednesday, 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 neighbourhoods of Qaboun and Barzeh.
Russia opposed to sanctions
Diplomacy so far has failed to stop the bloodshed, and there appeared to be little hope that the UN's most powerful body would unite behind a plan.
The key stumbling block is the Western demand for a resolution threatening non-military sanctions and tied to Chapter 7 of the UN charter, which could eventually allow the use of force to end the conflict in Syria.
Russia is adamantly opposed to any mention of sanctions or Chapter 7. After Security Council consultations late Tuesday on a revised draft resolution pushed by Moscow, Russia's deputy UN ambassador Alexander Pankin said these remain "red lines."
Russia has said it will veto any Chapter 7 resolution, but council diplomats said there is still a possibility of last-minute negotiations.