State television said Defense Minister Daoud Rajiha and Asef Shawkat, Assad's brother-in-law who was deputy chief of staff of the Syrian military, were killed when a suicide bomber attacked a building during a meeting of a group of senior ministers and security chiefs established to develop countermeasures to the 16-month uprising, The New York Times reported.
The White House said Wednesday President Barack Obama called Russian President Vladimir Putin to discuss the "developing situation" in Syria. The leaders agreed on the need to support a transition of power and have agreed to work toward a solution.
White House spokesman Jay Carney told reporters Assad "long ago gave up any opportunity to participate in a transition to democracy in Syria," adding he "has lost all credibility with his people by the simple fact that he has gone around the country killing innocent Syrian civilians."
"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. ... Assad is a spent force in terms of history. He will not be a part of Syria's future," Carney said.
Also Wednesday, the U.S. Treasury Department designated for sanctions 29 senior Syrian officials and five companies linked to the Syrian agency responsible for developing and producing non-conventional weapons and missiles.
"To date, we have imposed sanctions on more than 100 individuals and entities, as well as the entire Syrian government, including its Central Bank and oil companies," the Treasury Department said in a statement.
"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, treasury undersecretary for terrorism and financial intelligence. "As long as Assad stays in power, the bloodshed and instability in Syria will only mount, and we will continue working with our partners in the international community to ensure that the inevitable political transition occurs as rapidly as possible."
Syrian state media denied reports by activists that Interior Minister Mohammad Ibrahim al-Shaar had died, saying he was alive and in stable condition.
The Syrian Observatory for Human Rights in London said all members of the crisis group were either dead or injured, but the Times said there was no official confirmation.
The official Syrian Arab News Agency described the assault as a "suicide terrorist attack" while opponents called it a major victory. Analysts told the Times the incident marked a turning point in the crisis.
"The Syrian regime has started to collapse," the activist who heads the Syrian Observatory for Human Rights told the Times. "There was fighting for three days inside Damascus, it was not just a gun battle, and now someone has killed or injured all these important people."
In Damascus, speculation surfaced the bomber was a minister's bodyguard but the Times said that had yet to be confirmed.
"If a bodyguard blew himself up, then there [was] a major internal security breach," Elias Hanna, a former Lebanese military chief and military analyst, told the Times. "Who will replace these people? They are irreplaceable at this stage; it's hard to find loyal people now that doubt is sowed everywhere.
"Everyone, even those close to the inner circle, will now be under suspicion," he said.
Because of the confusion and the lack of an official tally of the dead and wounded, conflicting reports about who was killed and who survived were circulating, the Times said.
The Local Coordination Committees of Syria said regime forces "have intensified the shelling by using helicopter gunships, artillery and mortars" in Homs.
The Syrian Network for Human Rights and the Damascus Center for Human Rights Studies said 194 deaths were documented across Syria Wednesday -- 106 in Damascus and Rural Damascus; 18 in Aleppo; 16 in Idleb; 14 in Homs; and 11 in Deir Ezzor.
The SNHR and DCHRS said 85 Palestinians have been killed by Syrian forces since the uprising began, including five children and three women.
Israeli intelligence indicated Assad was shifting troops into Damascus from Syria's border with the disputed Golan Heights held by Israel, the Times said.
The U.N. Security Council put off a vote Wednesday on whether to extend the mission of 300 U.N. monitors on the ground in Syria as a Friday deadline loomed. The mission's work has been largely suspended because of surging violence since April, when U.N.-Arab League envoy Kofi Annan brokered a peace plan that included monitoring of a cease-fire.
The U.N. Security Council has two draft resolutions on the Syrian crisis before it. One threatens sanctions against Assad's regime if government forces don't stop attacks and also calls for renewing the U.N. observer mission for 45 days. Russia, a permanent Security Council member, has threatened to veto the measure.
Russia has opposed efforts seeking to blame, punish or change the Syrian government. Russia and China, trading partners with Syria, vetoed two other resolutions in the U.N. Security Council.
Russia has offered a draft resolution that "strongly urges all parties in Syria to cease immediately all armed violence in all its forms," CNN said. The Russian draft calls for renewing the observer mission for three months.
Two Syrian generals were among hundreds of refugees who crossed from Syria into Turkey overnight, bringing the total number of defecting generals to 20, the BBC reported.
The Syrian Network for Human Rights and the Damascus Center for Human Rights Studies said in its Tuesday report on rights violations several children were unable to receive proper care after they were injured by "indiscriminate bombardment carried out by the Syrian army."
The report said several Damascus neighborhoods and other villages were heavily damaged after being attacked by tanks and other weapons.
The United Nations estimates more than 10,000 people have been killed in the violence since the crisis began; opposition activists say more than 15,000 have died.