Molecular structure of enalaprilatMolecular structure of enalaprilat
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Enalaprilat

Enalapril is an angiotensin converting enzyme (ACE) inhibitor used in the treatment of hypertension and some types of chronic heart failure. Enalapril was the first member of the group of ACE inhibitors known as the dicarboxylate-containing ACE inhibitors. It is marketed by Merck & Co. (Merck, Sharp & Dohme) under the trade names, RenitecĀ® and VasotecĀ®. more...

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Development

Enalapril was developed by researchers at Merck & Co. as part of their efforts to develop novel treatments for hypertension by modulating the renin-angiotensin-aldosterone (RAS) system.

The success of Squibb in developing the first inhibitor, captopril, provided a major impetus for Merck's research laboratories to develop a competing product. Captopril was not without its problems, however, as it was believed (and shown to be true) that the sulfhydryl-moeity of captoril was responsible for such adverse effects as metallic taste.

Enalaprilat

Enalaprilat, the first dicarboxylate-containing ACE inhibitor, was developed partly to overcome these limitations of captopril. The sulfhydryl-moeity was replaced by a carboxylate-moeity, but additional modifications were required in its structure-based design to achieve a similar potency to captopril.

Enalaprilat itself, however, was not without its problems. The consequence of the structural modifications was that it proved to be have unfavourable ionisation characteristics to allow sufficient potency for oral administration (in tablets). Thus enalaprilat was only suitable for intravenous administration. This was overcome by the researchers at Merck by the esterification of enalaprilat with ethanol to produce enalapril. As a prodrug, enalapril is metabolised in vivo to the active form enalaprilat by various esterases.

A prototype for others

Most importantly, perhaps, the QSAR-based modifications in structure serendipitously led to an improved understanding of the structure of ACE which aided in the development of subsequent carboxylate-containing ACE inhibitors.

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Professional neglience
From Law Reporter, 11/1/02

ATLA's Professional Negligence Law Reporter includes a broad range of professional liability cases. Here are examples of the kinds of cases appearing in each issue of PNLR

CLERGY

Sexual abuse of minors

Settlements for 32 people who were allegedly sexually abused during childhood by several priests and a nun. Plaintiffs claimed significant psychological problems such as substance abuse as a result of their molestation. Plaintiffs were represented by Carl DeLuca, Warwick, R.I.; Richard A. Cappalli, Woonsocket, R.I.; and Timothy J. Conlon, Providence, R.I.

White v. Roman Catholic Bishop of Providence, R.I., Newport County Super. Ct., No. 93-0089, Sept. 6, 2002.

Church not liable for negligent supervision of clergy member who allegedly assaulted congregant

The Maine Supreme Court held that a church was not liable for negligently supervising a clergy member who allegedly sexually assaulted a congregant during a meeting the two were having at the clergy member's home.

Napieralski v. Unity Church of Greater Portland, 802 A.2d 391 (Me. 2002).

FUNERAL HOME

Placement of wrong body in casket

Verdict, including punitive damages, for several family members who suffered emotional distress at the funeral of a deceased relative when it was revealed that an unknown person's body was mistakenly placed in her casket.

Members of the relative's family and her estate sued a funeral home owner, alleging outrage, breach of contract, and negligence, among other things. Leah Oldacre Taylor and Ted Taylor, both of Birmingham, Ala., represented plaintiffs.

Beauchamp v. SCI Alabama, Ala., Jefferson County Cir. Ct., No. CV 99 4788, May 19,2002.

LAW

Attorney who negligently drafts will may be liable to intended beneficiaries

The Supreme Court of Oklahoma held that an attorney who negligently fails to identify all of a client's heirs when drafting the client's will may be liable in either tort or contract to intended will beneficiaries. The court also held, however, that an attorney hired to draft a will for a client is not obligated to independently investigate the existence of the client's heirs, absent a specific request to do so. Timothy A. Heefner and Kirk Olson, both of Oklahoma City, Okla., represented plaintiffs.

Leak-Gilbert v. Fable, - P.2d -, No. 97,540, 2002 WL 1753198 (Okla. July 16, 2002).

NURSING HOME

Home operators could not enforce arbitration agreements signed by deceased resident's children

A California appellate court held that nursing home operators sued over the death of a resident could not enforce arbitration agreements signed by the resident's children a week after her admission to the home. Russell S. Balisok and Steven C. Wilheim, both of Glendale, Cal.; and Carol S. Jimenez, Los Alamitos, Cal., represented plaintiffs.

Pagarigan v. Libby Care Ctr, Inc., 120 Cal. Rptr. 2d 892 (Ct. App. 2002).

PHARMACY

Failure to dilute Enalaprilat

Verdict on behalf of a child who suffered brain damage in a neonatal intensive care unit after receiving a dose of Enalaprilat that was 125 times stronger than what his doctor had prescribed. His parents, individually and on his behalf, sued a hospital pharmacy technician, her supervisor, and the pharmacy director, alleging (1) failure to dilute the medicine and (2) improper supervision. Kenneth N. Margolin and Charles Capace, both of Boston, Mass., represented plaintiffs.

Rice v. Pagan, Mass., Suffolk County Super. Ct., No. 98-5379-H, Aug. 30, 2002.

PSYCHOTHERAPY

Failure to restrain self-injurious patient

Verdict for a psychiatric hospital patient who suffered paralyzing injuries after diving off a bed and breaking his neck.

He sued the hospital, alleging it was liable for failing to place him in adequate restraints, among other things.

Stephen J. Eisenberg and Pam Baumgartner, both of Madison, Wis., represented plaintiff.

Dickinson v. St. Marys Hosp., Wis., Dane County Cir. Ct., No. 00-CV-1715, June 5,2002.

Copyright Association of Trial Lawyers of America Nov 2002
Provided by ProQuest Information and Learning Company. All rights Reserved

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