Merck + Co., Inc.

Janos Kollonitsch

Stephen Marburg

Arthur A Patchett

Philippe L Durette

Frederick M Kahan

Arsenio A Pessolano

George A Doldouras

Leroy M Perkins

New immunosuppressive cyclosporin analogs are disclosed having one or more fluorinated amino acids. These analogs may also have a 'C-9 amino acid' wherein the double bond is replaced by a heteroatom such as sulfur or oxygen.

Immunosuppressive fluorinated cyclosporin analogs

(S)-.alpha.-fluoromethylhistidine, a potent, selective, mechanism-based inhibitor of mammalian histidine carboxylase, the enzyme responsible for biosynthesis of histamine in mammals, is useful in the treatment of asthma.

Method of treating asthma using (S)-.alpha.-fluoromethyl-histidine and

Novel substituted .alpha.-fluoromethyl-.alpha.-amino alkanoic acids and esters thereof are disclosed. The novel compounds have biological activity including decarboxylase inhibition.

Fluorinated amino acids

Novel .alpha.-difluoromethyl tyrosines and esters thereof are disclosed. The novel compounds have useful pharmacological activity.

.alpha.-Difluoromethyl amino acids and hypertension treating

Novel 1-fluoromethyl-substituted alkyl amines are disclosed. The novel compounds have biological activity including decarboxylase inhibition.

Fluorinated imidazolyl alkylamines

Fluorinated tryptamines

A process for resolving a mixture of .alpha.-fluoromethylhistidine enantiomers is described. The process features use of an ester derivative of .alpha.-fluoromethylhistidine. Novel diastereoisomer salts of said derivative are also disclosed.

Acid addition salts of N-trityl-.alpha.-fluoromethylhistidine enantiomer

Alcohols are reacted with certain isocyanate compounds to produce the N-substituted carbamoyloxy derivatives which are cleaved to obtain the carbamate.

Cephalosporin compounds

A process for preparing .alpha.-fluoromethyl amino acids is disclosed. The process utilizes SF.sub.4 and BF.sub.3 or AlCl.sub.3 in HF to effect the fluorination.

Fluorination process

A process for preparing .alpha.-fluoromethyl amino acids from corresponding .alpha.-hydroxymethyl amino acids is disclosed. The process utilizes SF.sub.4 and BF.sub.3 or AlCl.sub.3 in HF to effect the fluorination.

Process for the preparation of 3-carbamoyl cephalosporins using

Organic compounds containing one or more alcoholic hydroxyl groups are transformed into fluorine compounds by reacting them with sulfur tetrafluoride in liquid hydrogen fluoride solution, at temperatures between around -80.degree. C. and +20.degree. C. The method can be descriptively termed 'fluorodehydroxylation', because it represents the reaction:

Fluorodehydroxylation of serine

Organic compounds containing a mercapto group or a dithiane moiety can be transformed into the analogous fluoro or difluoro compounds by reacting them with a halogenating reagent in liquid hydrogen fluoride, optionally containing boron trifluoride or antimony pentafluoride solution, at temperatures from about -80.degree. and 15.degree. C. The method may be descriptively termed 'fluorodesulfurization'.

Fluorodesulfurization of alkyl mercaptans or alkyl dithianes

Organic compounds having at least one replaceable hydrogen atom are fluorinated in the liquid or solid state by treatment with fluoroxyperfluoroalkanes or fluoroxypentafluorosulfur under the influence of a free radical initiator.

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Westfield, NJ, United States of America

Janos Kollonitsch