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While he’s best known for playing scary guys, Robert De Niro is negotiating to star in “Scared Guys,” a Columbia Pictures comedy in which he’ll play an obsessive-compulsive agoraphobic forced to leave home for the first time in six years to thwart a murder.

Dean Parisot (“GalaxyQuest”) is directing from a script by Jeff Nathanson, who wrote “Rush Hour 2” and “Catch Me If You Can.”

“Scared Guys” has been considered a plum project for Col since it was set up with producer John Baldecchi. The comedy nearly came together with Jim Carrey in the starring role before he chose the Frank Darabont-directed “Majestic.”

While the studio expected to land a major star, De Niro’s a surprise. Along with Tribeca Prods. partner Jane Rosenthal, he will come aboard to produce the project with Baldecchi.

In “Scared Guys,” De Niro will play a therapist who gives advice over the Internet in order to avoid having to leave his apartment. From afar, he falls in love with a female police dispatcher who works directly across the street. When the therapist discovers the woman has been targeted for murder, he and his agoraphobic roommate are compelled to exit the apartment, cross the street and try to save her life.

Winter start

Pic, being steered by Col exec Ange Gianetti, is pegged for a winter start. De Niro, who opens Friday opposite Edward Norton and Marlon Brando in the Frank Oz-directed “The Score,” has two other projects looming. Both are comic sequels. “Analyze That” will reteam him with “Analyze This” star Billy Crystal and director Harold Ramis, while the “Meet the Parents” sequel “Meet the Fockers” is in the development stage with director Jay Roach. But “Scared Guys” looms large as his next effort.

De Niro also has wrapped the Michael Caton-Jones directed drama “City by the Sea” as well as the Tom Dey-directed “Showtime” with Eddie Murphy. He’s repped by CAA.