The Viagra maker upped the price it was prepared to pay over the weekend to a deal worth £55 a share, 15% more than its previous proposal on May 2 which also represented its fourth and final approach.

AstraZeneca said the deal would bring “uncertainty and risk” for its shareholders and “undervalues the company and its attractive prospects”.

Chairman Leif Johansson said: “Pfizer’s approach throughout its pursuit of AstraZeneca appears to have been fundamentally driven by the corporate financial benefits to its shareholders of cost savings and tax minimisation.”

He said that from the time of initial talks in January, the US company had “failed to make a compelling strategic, business or value case”.

Pfizer chief executive Ian Read said: “We have tried repeatedly to engage in a constructive process with AstraZeneca to explore a combination of our two companies.

“Following a conversation with AstraZeneca earlier today, we do not believe that the AstraZeneca board is currently prepared to recommend a deal at a reasonable price.

“We remain ready to engage in a meaningful dialogue but time for constructive engagement is running out.

“We have said from the beginning that we will remain disciplined in the price we are willing to pay and we will not depart from that guiding principle.”

Viagra maker Pfizer wants to create a new pharmaceuticals giant that will be domiciled for tax purposes in the UK.

It has already pledged in a letter to Prime Minister David Cameron that any deal would not stop the building of Astra’s planned research and development (R&D) hub in Cambridge and that 20% of the combined company’s R&D workforce will be in the UK.

But Astra believes that Pfizer’s board is making an opportunistic attempt to acquire “a transformed AstraZeneca, without reflecting the value of its exciting pipeline”.

Chief executive Pascal Soriot said the mega-merger would prove a distraction from its scientific priorities.

And Pfizer’s pledges have also been criticised by the President of the Royal Society, who said they were “vague, come with caveats and have an inappropriate timescale”.

Additional reporting by PA