The chlorine group at the 6-position of the heterocyclic ring is more reactive than the chlorine at the 2-position, hence it can be selectively replaced by an amino group, which was then converted to an amide using nitrous acid. Finally, the remaining chlorine was replaced by the amino group of aciclovir using ammonia in methanol. This synthesis and other methods for preparing the compound have been reviewed. History
Aciclovir was seen as the start of a new era in antiviral therapy, as it is extremely selective and low in cytotoxicity. Since discovery in mid 1970s, it has been used as an effective drug for the treatment of infections caused by most known species of the herpesvirus family, including herpes simplex and varicella zoster viruses. Nucleosides isolated from a Caribbean sponge, Cryptotethya crypta, were the basis for the synthesis of aciclovir. It was codiscovered by Howard Schaeffer following his work with Robert Vince, S. Bittner and S. Gurwara on the adenosine analog acycloadenosine which showed promising antiviral activity. Later, Schaeffer joined Burroughs Wellcome and continued the development of aciclovir with pharmacologist Gertrude B. Elion. A U.S. patent on aciclovir listing Schaeffer as inventor was issued in 1979. Vince later invented abacavir, an nRTI drug for HIV patients. Elion was awarded the 1988 Nobel Prize in Medicine, partly for the development of aciclovir. A related prodrug form, valaciclovir came into medical use in 1995.
A cervical fracture, commonly called a broken neck, is a fracture of any of the seven cervical vertebrae in the neck. Examples of common causes in humans are traffic collisions and diving into shallow water. Abnormal movement of neck bones or pieces of bone can cause a spinal cord injury resulting in loss of sensation, paralysis, or usually instant death. Causes
Considerable force is needed to cause a cervical fracture. Vehicle collisions and falls are common causes. A severe, sudden twist to the neck or a severe blow to the head or neck area can cause a cervical fracture. Although high energy trauma is often associated with cervical fractures in the younger population, low energy trauma is more common in the geriatric population. In a study from Norway the most common cause was falls and the relative incidence of CS-fx increased significantly with age.Sports that involve violent physical contact carry a risk of cervical fracture, including American football, association football (especially the goalkeeper), ice hockey, rugby, and wrestling. Spearing an opponent in football or rugby, for instance, can cause a broken neck. Cervical fractures may also be seen in some non-contact sports, such as gymnastics, skiing, diving, surfing, powerlifting, equestrianism, mountain biking, and motor racing. Certain penetrating neck injuries can also cause cervical fracture which can also cause internal bleeding among other complications. Execution by hanging is intended to cause a fatal cervical fracture.