Major shareholders in AstraZeneca are demanding that executives at the pharmaceuticals group plunder its $4 billion (£2.1 billion) cash pile to rebuild its weak pipeline of new drugs with new acquisitions, The Times has learnt.

David Brennan, the new chief executive, and other board members are to meet some of the company’s biggest shareholders this month to explain the group’s third-quarter figures.

“The obvious question to ask is, ‘What are you going to do about the pipeline?’ ” said Gareth Powell, fund manager at AXA Framlington, which owns 15 million shares or 1 per cent of AstraZeneca. “They are going to have to go out, be aggressive and buy smaller companies.”

John Wilson, investment director at Standard Life, which owns 17 million shares in the company, said: “It generates wads of cash but the question is what it does with it. It needs to find deals that are going to make it work.”

Shareholders have grown increasingly alarmed in recent months by the withdrawal from development of four key drugs once viewed as central to the company’s future revenues — Cerovive, an anti-stroke drug, Galida, a diabetes treatment, Exanta, a blood-clot drug, and Iressa, for lung-cancer sufferers.

The company’s current product range is performing well, but there is a yawning gap opening up as patents start to expire. Mr Brennan now faces calls to buy in new technology.

Anne-Marieke Ezendam, fund manager at Threadneedle Investments, which owns 13 million shares, said: “I think we will have a discussion about whether AstraZeneca should go out and buy products or companies.”

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