Richard C. Allen

Synthesis and neuroleptic activity of 3-(1-substituted-4-piperidinyl)-1,2-benzisoxazoles.

The synthesis of a series of 3-(1-substituted-4-piperidinyl)-1,2-benzisoxazoles is described. The neuroleptic activity of the series was evaluated by utilizing the climbing mice assay and inhibition of [3H]spiroperidol binding. Structure-activity relationships were studied by variation of the substituent on the benzisoxazole ring with concomitant variation of four different 1-piperidinyl substituents. Maximum neuroleptic activity was realized when there was a 6-fluoro substituent on the benzisoxazole ring. The 1-piperidinyl substituent appeared less significant, although in most cases, the (1,3-dihydro-2-oxo-2H-benzimidazol-1-yl)propyl group imparted maximum potency. The most potent compound in both assays was 6-fluoro-3-[1-[3-(1,3-dihydro-2-oxo-2H-benzimidazol-1-yl) propyl]-4-piperidinyl]-1,2-benzisoxazole (11b).

SYNTHESIS AND NEUROLEPTIC ACTIVITY OF 3‐(1‐SUBSTITUTED‐4‐PIPERIDINYL)‐1,2‐BENZISOXAZOLES

Die nach zwei Methoden dargestellten Benzoylpiperidine (III) werden zu den Benzisoxazolen (VI) cyclisiert, aus denen wie angegeben die sekundaren Amine (VII) entstehen.

Chapter 33. To Market, To Market – 1987

Publisher Summary The new chemical entities (NCEs) recently introduced into the US marketplace are by no means an accurate and timely reflection of these milestones. As a continuation of the recent trends, anti-infectives and cardiovascular agents dominated the field. More so in 1987 than any previous years, a significant number of NCEs from these two categories could be considered as possessing major therapeutic gains. This list includes APSAC, alteplase, lovastatin, and zidovudine. It is worth noting that more than 50% of the NCEs originated in two countries: 18 in Japan and 15 in the United States followed by Italy, West Germany, France, and Denmark. It was during 1987 when a record number of new NCEs were approved in the United States and 17 reached the marketplace. Five of these, encainide hydrochloride, esmolol hydrochloride, lovastatin, mometasone furoate, and recombinant human growth hormone were also first worldwide launches. This chapter discusses a short summary, the profile, advantages/uniqueness, and utility of each compound. In all cases, this market introduction represents an accomplishment of some magnitude in the face of formidable odds. Some of the products discussed in the chapter include AF-2259, amsacrine, benexate hydrochloride, cefixime, cefuzonam sodium, enalaprila, goserelin, lenampicillin hydrochloride, lisinopril, nilutamide, ornoprosti, pinacidil, repirinast, roxithromycin, and zuclopenthixol acetate. These marketable products have been made informative by providing certain data that include trade name, originator of the product, country of origin, first introduction, introduced by, and originator. Such classification has made all these products marketable in a finer way. Categories of product vary from being anti-psychotic, antibiotic, anti-asthmatic, calcium metabolism regulator, anti-fungal, anti-inflammatory, anti-hypertensive, anti-arrhythmic, analgesic, anti-ulcer, anti-neoplastic, anti-glaucoma, and others.