Merck + Co., Inc.

Regina M Black

James M Balkovec

Harold B Wood

Frances A Bouffard

John J Acton, Iii

Peter T Meinke

Kun Liu

Sheryl Davis Debenham

Kevin Michael Belyk

David L Hughes

Dean R Bender

William R Leonard

Anthony Brian Jones

Indoles having aryloxyalkanoic acid substituents or arylalkanoic acid substituents are agonists or partial agonists of PPAR gamma and are useful in the treatment and control of hyperglycemia that is symptomatic of type II diabetes, as well as dyslipidemia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, and obesity that are often associated with type 2 diabetes.

Indoles having anti-diabetic activity

Certain N-substituted indoles having aryloxyacetic acid, substituents are agonists or partial agonists of PPAR gamma, and are useful in the treatment, control or prevention of non-insulin dependent diabetes mellitus (NIDDM), hyperglycemia, dyslipidemia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, atherosclerosis, obesity, vascular restenosis, inflammation, and other PPAR mediated diseases, disorders and conditions.

N-substituted indoles useful in the treatment of diabetes

Ceretain aza cyclohexapeptide compounds have been found to have superior antibiotic properties. Novel processes for their preparation are also described.

Aza cyclohexapeptide compounds

There is disclosed a novel process for preparing aza cyclohexapeptides of the formula ##STR1## where all variables are defined herein.

Process for preparing certain aza cyclohexapeptides

Compounds represented by the formula I (SEQ ID NO. 1) are disclosed: ##STR1## as well as pharmaceutically acceptable salts and hydrates thereof. R.sup.I represents C.sub.9 to C.sub.19 alkyl, C.sub.9 to C.sub.19 alkenyl, an aryl group which includes phenyl, biphenyl, naphthyl and terphenyl or a C.sub.1 to C.sub.12 alkyl, alkylamino, dialkylamino or alkoxyaryl group. R.sup.1, R.sup.2 and R.sup.4 independently represent H or --OH. R.sup.3 represents H, --OH, --O(CH.sub.2).sub.n NR.sup.V R.sup.VI, where R.sup.V and R.sup.VI independently represent H or C.sub.1-4 alkyl, or --O(CH.sub.2).sub.n NR.sup.V R.sup.VI R.sup.VII+ Y.sup.-, wherein R.sup.V and R.sup.VI are as defined above, R.sup.VII represents H or C.sub.1-4 alkyl, n is an integer of from 2-6 inclusive, and Y represents a counterion. R.sup.5 represents H, --CH.sub.3 or --OH; R.sup.6 represents H or --CH.sub.3 ; R.sup.7 represents H, --CH.sub.3, --CH.sub.2 C(.dbd.O)NH.sub.2, --(CH.sub.2).sub.2 NR.sup.V R.sup.VI or --(CH.sub.2).sub.2 NR.sup.V R.sup.VI R.sup.VII+ Y.sup.- with n, R.sup.V, R.sup.VI R.sup.VII and Y as defined above; and R.sup.8 represents --Cl, --Br, --I, --NO.sub.2, --N.sub.3, --(CH.sub.2).sub.0-4 NH.sub.2, --(CH.sub.2).sub.0-4 NH(C.sub.1-4 alkyl), --(CH.sub.2).sub.0-4 N(C.sub.1-4 alkyl).sub.2, --(CH.sub.2).sub.0-3 CH(.dbd.NOH), --NHC(.dbd.O)(CH.sub.2).sub.1-6 NH.sub.2 or --NHC(.dbd.O)(CH.sub.2).sub.1-6 NHC(.dbd.NH)(CH.sub.2).sub.0-3 H. Pharmaceutical compositions and methods of use are also disclosed.

Antifungal and anti-pneumocystis compounds, compositions containing such

Aza cyclohexapeptide compounds are disclosed with a nitrogen attached to the cyclohexapeptide ring at the 5-carbon of the 4-hydroxyornithine component. Such compounds are represented by the formula: ##STR1## The compounds are disclosed as having antifungal, antiprotozoal and anti-Pneumocystis carinii activity.

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Cranford, NJ, United States of America

Regina M Black