A compound of the following general formula which is useful in treating hypocholesterolemia and atherosclerosis: ##STR1## wherein X is oxygen or sulfur; R is hydrogen, alkyl having from 1 to 8 carbon atoms, or benzyl; R.sub.1 is phenyl, substituted phenyl, naphthyl, substituted naphthyl, an aralkyl group, a heterocyclic group, or a hydrocarbon chain of from 1 to 20 carbon atoms which is saturated or contains 1 to 3 double bonds and each of R.sub.2 and R.sub.3 is selected from hydrogen, provided both are not hydrogen, an aralkyl group, a hydrocarbon chain of from 1 to 20 carbon atoms which is saturated or contains 1 to 3 double bonds, an w-substituted alkylC.sub.1-6, a heterocyclic group, phenyl, substituted phenyl or NR.sub.2 R.sub.3 taken together form a monocyclic heterocyclic group.

BACKGROUND OF INVENTION 
This invention relates to chemical compounds having pharmacological 
activity, to pharmaceutical compositions which include these compounds, 
and to a pharmaceutical method of treatment. More particularly, this 
invention concerns certain aminosulfonyl carbamates which inhibit the 
enzyme acyl-coenzyme A:cholesterol acyltransferase (ACAT), pharmaceutical 
compositions containing these compounds, and a method of treating 
hypercholesterolemia and atherosclerosis. 
In recent years the role which elevated blood plasma levels of cholesterol 
plays in pathological conditions in man has received much attention. 
Deposits of cholesterol in the vascular system have been indicated as 
causative of a variety of pathological conditions including coronary heart 
disease. 
Initially, studies of this problem were directed toward finding therapeutic 
agents which would be effective in lowering total serum cholesterol 
levels. It is now known that cholesterol is transported in the blood in 
the form of complex particles consisting of a core of cholesteryl esters 
plus triglycerides and an exterior consisting primarily of phospholipids 
and a variety of types of protein which are recognized by specific 
receptors. For example, cholesterol is carried to the sites of deposit in 
blood vessels in the form of low density lipoprotein cholesterol (LDL 
cholesterol) and away from such sites of deposit by high density 
lipoprotein cholesterol (HDL cholesterol). 
Following these discoveries, the search for therapeutic agents which are 
more selective in their action: that is, agents which are effective in 
elevating the blood serum levels of HDL cholesterol and/or lowering the 
levels of LDL cholesterol. While such agents are effective in moderating 
the levels of serum cholesterol, they have little or no effect on 
controlling the initial absorption of dietary cholesterol in the body 
through the intestinal wall. 
In intestinal mucosal cells, dietary cholesterol is absorbed as free 
cholesterol which must be esterified by the action of the enzyme 
acyl-CoA:cholesterol acyltransferase (ACAT) before it can be packaged into 
the chylomicrons which are then released into the blood stream. Thus, 
therapeutic agents which effectively inhibit the action of ACAT prevent 
the intestinal absorption of dietary cholesterol into the blood stream or 
the reabsorption of cholesterol which has been previously released into 
the intestine through the body's own regulatory action. 
INFORMATION DISCLOSURE 
Phosphorus and Sulfur 19(2), 167-172 (1984) describes the following 
compounds as fungicides and bactericides. 
##STR2## 
Ar= 2,6-dimethylphenyl 
2,6-dimethoxyphenyl 
2,6-diisopropylmethyl 
2-methyl-6-isopropylphenyl 
2,6-di-tert-butylphenyl 
2,6-di-tert-butyl-4-methylphenyl 
2,4,6-tri-tert-butylphenyl 
German patent 940,292 dated Mar. 15, 1956 to Farbwerke Hoechst, Ag 
describes the folloiwng compounds which are said to be useful as textile 
assistants, pharmaceuticals and pesticides. No specific pharmaceutical 
utility is described. 
______________________________________ 
##STR3## 
R' R" 
______________________________________ 
C.sub.12 H.sub.25 H 
C.sub.2 H.sub.5 4-(OC.sub.2 H.sub.5)Ph 
C.sub.2 H.sub.5 Ph 
C.sub.2 H.sub.5 
##STR4## 
C.sub.18 H.sub.35 
##STR5## 
CH.sub.3 Ph 
C.sub.2 H.sub.5 C.sub.6 H.sub.11 
ClCH.sub.2 CH.sub.2 
Ph 
ClCH.sub.2 CH.sub.2 
4-CH.sub.3 Ph 
C.sub.3 H.sub.7 C.sub.3 H.sub.7 
i-C.sub.3 H.sub.7 C.sub.6 H.sub.11 
CH.sub.2 CHCH.sub.2 
Ph 
CH.sub.2 CHCH.sub.2 
CH.sub.2 CHCH.sub.2 
C.sub.4 H.sub.9 Ph 
C.sub.4 H.sub.9 C.sub.6 H.sub.11 
C.sub.4 H.sub.9 H 
(Et).sub.2 CHCH.sub.2 
H 
(C.sub.4 H.sub.9)(C.sub.2 H.sub.5)CHCH.sub.2 
H 
C.sub.6 H.sub.11 Ph 
PhCH.sub.2 C.sub.3 H.sub.7 
Ph H 
4-ClPh CH.sub.2 CHCH.sub.2 
CH.sub.3 OCH.sub.2 
CH.sub.2 CHCH.sub.2 
PhCH.sub.2 
##STR6## 
C.sub.12 H.sub.25 
##STR7## 
C.sub.18 H.sub.35 CH.sub.2 CH.sub.2 NEt.sub.2 
______________________________________ 
Chem. Ber. 96,56-67 (1963) describes compounds of the following formula. No 
utility for these compounds is disclosed. 
______________________________________ 
##STR8## 
R R' R" 
______________________________________ 
CH.sub.3 H Ph 
CH.sub.3 H C.sub.6 H.sub.11 
C.sub.2 H.sub.5 H C.sub.6 H.sub.11 
C.sub.2 H.sub.5 H Ph 
C.sub.2 H.sub.5 H 
##STR9## 
C.sub.2 H.sub.5 H 4-(COC.sub.2 H.sub.5)Ph 
ClCH.sub.2 CH.sub.2 
CH.sub.3 CH.sub.3 
ClCH.sub.2 CH.sub.2 
H 4-CH.sub.3 Ph 
-n-C.sub.3 H.sub.7 
H - n-C.sub.3 H.sub.7 
.sub.- i-C.sub.3 H.sub.7 
H Ph 
C.sub.12 H.sub.25 
CH.sub.3 CH.sub.3 
C.sub.18 H.sub.37 
CH.sub.3 CH.sub.3 
CH.sub.2 CHCH.sub.2 
H CH.sub.2 CHCH.sub.2 
CH.sub.2 CHCH.sub.2 
H Ph 
C.sub.6 H.sub.11 CH.sub.3 CH.sub.3 
C.sub.6 H.sub.11 H Ph 
Ph CH.sub.3 CH.sub.3 
Ph H Ph 
Ph H - n-C.sub.3 H.sub.7 
Ph H - n-C.sub.4 H.sub.9 
Ph H 
##STR10## 
______________________________________ 
J. Med. Chem. 8,781-784 (1965) describes the following compounds which are 
useful as hypoglycemic agents. 
##STR11## 
Tetrahedron Letters 24, (30) 3091-3094 (1983) describes the following 
compounds. No use is described for these compounds. 
______________________________________ 
##STR12## 
X R 
______________________________________ 
Cl Ph 
Br Ph 
Cl CH.sub.2 Ph 
Cl (C.sub.2 H.sub.5).sub.2 
Cl C.sub.6 H.sub.11 
Cl (CH.sub.2).sub.4 CH.sub.3 
______________________________________ 
SUMMARY OF INVENTION 
The present invention provides compounds of the following general Formula 
I, methods of using said compounds, pharmaceutical compositions and 
process for preparing the compounds of Formula I 
##STR13## 
wherein X is sulfur or oxygen; wherein R is hydrogen, a straight or 
branched alkyl having from 1 to 8 carbon atoms, or benzyl; 
wherein R.sub.1 is 
(a) phenyl which is unsubstituted or is substituted with from one to three 
substituents selected from: 
phenyl, 
alkyl having from one to six carbon atoms and which is straight or 
branched, 
alkoxy having from one to six carbon atoms and which is straight or 
branched, 
phenoxy, 
hydroxy, 
fluorine, 
chlorine, 
bromine, 
nitro, 
trifluoromethyl, 
--COOH, 
--COOalkyl wherein alkyl has from one to four carbon atoms and which is 
straight or branched, 
--(CH.sub.2).sub.p NR.sub.4 R.sub.5 wherein p is zero or one, and each of 
R.sub.4 and R.sub.5 is hydrogen or a straight or branched alkyl group 
having one to four carbon atoms; 
(b) 1- or 2-naphthyl which is unsubstituted or substituted with one to 
three substituents selected from 
phenyl, 
alkyl having from one to six carbon atoms and which is straight or 
branched, 
alkoxy having from one to six carbon atoms and which is straight or 
branched, 
hydroxy, 
phenoxy, 
fluorine, 
chlorine, 
bromine, 
nitro, 
trifluoromethyl, 
--COOH, 
--COOalkyl wherein alkyl has from one to four carbon atoms and is straight 
or branched, 
--(CH.sub.2).sub.p NR.sub.4 R.sub.5 wherein p, R.sub.4, and R.sub.5 have 
the meanings defined above; 
(c) the group 
##STR14## 
wherein t is zero or one to four; w is zero or one to four with the 
proviso that the sum of t and w is not greater than five; R.sub.6 and 
R.sub.7 are independently selected from hydrogen or alkyl having for one 
to six carbon atoms, or when R.sub.6 is hydrogen, R.sub.7 can be selected 
from the groups defined for R.sub.8 ; and R.sub.8 is phenyl or phenyl 
substituted with from one to three substituents selected from straight or 
branched alkyl having from one to six carbon atoms, straight or branched 
alkoxy having from one to six carbon atoms, phenoxy, hydroxy, fluorine, 
chlorine, bromine, nitro, trifluoromethyl, --COOH, COOalkyl wherein alkyl 
has from one to four carbon atoms and is straight or branched, or 
--(CH.sub.2).sub.p NR.sub.4 R.sub.5 wherein p, R.sub.4 and R.sub.5 have 
the meanings defined above; 
(d) --(CH.sub.2).sub.s --Q wherein s is a number of from zero to three and 
Q is a 5- or 6-membered monocyclic or fused bicyclic heterocycle 
containing at least one to four nitrogen, oxygen or sulfur atoms in at 
least one ring member; or 
(e) a straight or branched hydrocarbon chain having from 1 to 20 carbon 
atoms and which is saturated or contains from one to three double bonds; 
wherein each of R.sub.2 and R.sub.3 is 
(a) hydrogen; 
(b) the group 
##STR15## 
wherein t, w, R.sub.6, R.sub.7 and R.sub.8 have the meanings defined 
above; 
(c) a straight or branched hydrocarbon chain having from 1 to 20 carbon 
atoms and which is saturated or contains from one to three double bonds; 
(d) an alkyl group having from one to six carbon atoms wherein the terminal 
carbon is substituted with hydroxy or --NR.sub.6 R.sub.7 wherein R.sub.6 
and R.sub.7 have the meanings defined hereinabove; 
(e) --(CH.sub.2).sub.s Q wherein s and Q have the meanings defined above; 
(f) phenyl or phenyl substituted with from one to three substituents 
selected from 
phenyl, 
alkyl having from one to six carbon atoms and which is straight or 
branched, 
alkoxy having from one to six carbon atoms and which is straight or 
branched, 
phenoxy, 
hydroxy, 
fluorine, 
chlorine, 
bromine, 
nitro, 
trifluoromethyl, 
--COOH, 
--COOalkyl wherein the alkyl moiety has from one to four carbon atoms and 
is straight or branched, or 
--(CH.sub.2).sub.p NR.sub.4 R.sub.5 wherein p, R.sub.4, and R.sub.5 have 
the meanings defined above; or 
(g) NR.sub.1 R.sub.2 taken together form a monocyclic heterocyclic group 
selected from pyrrolidino, piperidino, morpholino, or piperazino, each of 
which is unsubstituted or substituted with one substituent selected from 
phenyl, straight or branched alkyl having from one to six carbon atoms; 
and pharmaceutically acceptable salts thereof; with the provisos: 
(i) when each of R.sub.2 and R.sub.3 is the group 
##STR16## 
R.sub.7 is hydrogen or alkyl having from one to six carbon atoms; (ii) at 
least one of R.sub.1, R.sub.2, and R.sub.3 is phenyl or substituted 
phenyl; 
(iii) both R.sub.2 and R.sub.3 are not hydrogen at the same time; 
(iv) when R.sub.1 is phenyl disubstituted on the 2,6-positions or 
trisubstituted on the 2,4,6-positions with alkyl having from one to four 
carbon atoms, or when R.sub.1 is phenyl disubstituted on the 2,6-positions 
with methoxy, neither of R.sub.2 or R.sub.3 is phenyl; and 
(v) the following compounds wherein Ph means phenyl are excluded: 
______________________________________ 
R.sub.1 R.sub.2 R.sub.3 
______________________________________ 
C.sub.2 H.sub.5 
H 4-(OC.sub.2 H.sub.5)Ph 
C.sub.2 H.sub.5 
H 
##STR17## 
C.sub.2 H.sub.5 
H Ph 
CH.sub.3 H Ph 
CH.sub.2 CHCH.sub.2 
H Ph 
C.sub.4 H.sub.9 
H Ph 
PhCH.sub.2 H C.sub.3 H.sub.7 
4(Cl)Ph H CH.sub.2 CHCH.sub.2 
.sub.- i-C.sub.3 H.sub.7 
H Ph 
Ph CH.sub.3 CH.sub.3 
Ph H Ph 
Ph H n-C.sub.3 H.sub.7 
Ph H n-C.sub.4 H.sub.9 
Ph H 
##STR18## 
______________________________________ 
The present invention also provides pharmaceutical compositions containing 
compounds of the following general Formula II and the method of treating 
hypercholesterolemia and atherosclerosis using the compounds of the 
following Formula II: 
##STR19## 
wherein X is sulfur or oxygen; wherein R is hydrogen, a straight or 
branched alkyl having from 1 to 8 carbon atoms, or benzyl; 
wherein R.sub.1 is 
(a) phenyl which is unsubstituted or is substituted with from one to three 
substituents selected from: 
phenoxy, 
hydroxy, 
fluorine, 
chlorine, 
bromine, 
nitro, 
trifluoromethyl, 
--COOH, 
--COOalkyl wherein alkyl has from one to four carbon atoms and which is 
straight or branched, 
--(CH.sub.2).sub.p NR.sub.4 R.sub.5 wherein p is zero or one, and each of 
R.sub.4 and R.sub.5 is hydrogen or a straight or branched alkyl group 
having one to four carbon atoms; 
(b) 1- or 2-naphthyl which is unsubstituted or substituted with one to 
three substituents selected from 
phenyl, 
alkyl having from one to six carbon atoms and which is straight or 
branched, alkoxy having from one to six carbon atoms and which is straight 
or branched, 
hydroxy, 
phenoxy, 
fluorine, 
chlorine, 
bromine, 
nitro, 
trifluoromethyl, 
--COOH, 
--COOalkyl wherein alkyl has from one to four carbon atoms and is straight 
or branched, 
--(CH.sub.2).sub.p NR.sub.4 R.sub.5 wherein p, R.sub.4, and R.sub.5 have 
the meanings defined above; 
(c) the group 
##STR20## 
wherein t is zero or one to four; w is zero or one to four with the 
proviso that the sum of t and w is not greater than five; R.sub.6 and 
R.sub.7 are independently selected from hydrogen or alkyl having for one 
to six carbon atoms, or when R.sub.6 is hydrogen, R.sub.7 can be selected 
from the groups defined for R.sub.8 ; and R.sub.8 is phenyl or phenyl 
substituted with from one to three substituents selected from straight or 
branched alkyl having from one to six carbon atoms, straight or branched 
alkoxy having from one to six carbon atoms, phenoxy, hydroxy, fluorine, 
chlorine, bromine, nitro, trifluoromethyl, --COOH, COOalkyl wherein alkyl 
has from one to four carbon atoms and is straight or branched, or 
--(CH.sub.2).sub.p NR.sub.4 R.sub.5 wherein p, R.sub.4 and R.sub.5 have 
the meanings defined above; 
(d) --(CH.sub.2).sub.s -Q wherein s is a number of from zero to three and Q 
is a 5- or 6-membered monocyclic or fused bicyclic heterocycle containing 
at least one to four nitrogen, oxygen or sulfur atoms in at least one ring 
member; or 
(e) a straight or branched hydrocarbon chain having from 1 to 20 carbon 
atoms and which is saturated or contains from one to three double bonds; 
wherein each of R.sub.2 and R.sub.3 is 
(a) hydrogen; 
(b) the group 
##STR21## 
wherein t, w, R.sub.6, R.sub.7 and R.sub.8 have the meanings defined 
above; 
(c) a straight or branched hydrocarbon chain having from 1 to 20 carbon 
atoms and which is saturated or contains from one to three double bonds; 
(d) an alkyl group having from one to six carbon atoms wherein the terminal 
carbon is substituted with hydroxy or --NR.sub.6 R.sub.7 wherein R.sub.6 
and R.sub.7 have the meanings defined hereinabove; 
(e) --(CH.sub.2).sub.s Q wherein s and Q have the meanings defined above; 
(f) phenyl or phenyl substituted with from one to three substituents 
selected from 
phenyl, 
alkyl having from one to six carbon atoms and which is straight or 
branched, 
alkoxy having from one to six carbon atoms and which is straight or 
branched, 
phenoxy, 
hydroxy, 
fluorine, 
chlorine, 
bromine, 
nitro, 
trifluoromethyl, 
--COOH, 
--COOalkyl wherein the alkyl moiety has from one to four carbon atoms and 
is straight or branched, or 
--(CH.sub.2).sub.p NR.sub.4 R.sub.5 wherein p, R.sub.4, and R.sub.5 have 
the meanings defined above; or 
(g) NR.sub.1 R.sub.2 taken together form a monocycl heterocyclic group 
selected from pyrrolidino, piperidino, morpholino, or piperazino, each of 
which is unsubstituted or substituted with one substituent selected from 
phenyl, straight or branched alkyl having from one to six carbon atoms; 
and pharmaceutically acceptable salts thereof; with the provisos: 
(i) when each of R.sub.2 and R.sub.3 is the group 
##STR22## 
R.sub.7 is hydrogen or alkyl having from one to six carbon atoms; (ii) at 
least one of R.sub.1, R.sub.2, and R.sub.3 is phenyl or substituted 
phenyl; 
(iii) both R.sub.2 and R.sub.3 are not hydrogen at the same time. 
DETAILED DESCRIPTION OF INVENTION 
The compounds of the present invention provide a novel class of 
aminosulfonyl carbamates which are ACAT inhibitors rendering them useful 
in treating hypercholesterolemia and atherosclerosis. 
Illustrative examples of straight or branched saturated hydrocarbon chains 
having from 1 to 20 carbon atoms include methyl, ethyl, n-propyl, 
isopropyl, n-butyl, iso-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, 
n-heptyl, n-octyl, n-undecyl, n-dodecyl, n-hexadecyl, 2,2-dimethyldodecyl, 
2-tetradecyl, and n-octadecyl groups. 
Illustrative examples of straight or branched hydrocarbon chains having 
from 1 to 20 carbon atoms and having from 1 to 3 double bonds include 
ethenyl, 2-propenyl, 2-butenyl, 3-pentenyl, 2-octenyl, 5-nonenyl, 
4-undecenyl, 5-heptadecenyl, 3-octadecenyl, 9-octadecenyl, 
2,2-dimethyl-11-eicosenyl, 9,12-octadecadienyl, and hexadecenyl. 
Straight or branched alkoxy groups having one to six carbon atoms include, 
for example, methoxy, ethoxy, n-propoxy, t-butoxy, and pentyloxy. 
Straight or branched alkyl groups having from one to six carbon atoms 
include, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, 
n-pentyl, n-hexyl, and tert-butyl. 
A 5- or 6-membered monocyclic or fused bicyclic heterocycle is a monocyclic 
or fused bicyclic aromatic ring containing at least one to four 
heteroatoms in at least one ring, such as nitrogen, oxygen, or sulfur or a 
combination thereof. Such a heterocyclic group includes, for example, 
thienyl, benzothienyl, furanyl, benzofuranyl, pyridyl, pyrimidinyl, 
pyridazinyl, pyrazinyl, pyrrolyl, pyrazolyl, isothiazolyl, thiazolyl, 
oxazolyl, isoxazolyl, triazolyl, tetrazolyl, imidazolyl, benzothiazolyl, 
indolyl, quinolinyl, isoquinolinyl, or N-oxides of heterocycle containing 
a nitrogen atom. 
More specifically, such a heterocycle may be a 2- or 3-thienyl; 2- or 
3-furanyl; 2-, or 3-, or 4-pyridyl or 2-, or 3-, or 4-pyridyl-N-oxide; 2-, 
4-, or 5-pyrimidinyl; 3- or 4-pyridazinyl; 2-pyrazinyl; 
2-pyrazinyl-N-oxide; 2- or 3-pyrrolyl; 3-, 4-, or 5-pyrazolyl; 2-, 4-, or 
5-thiazolyl; 3-, 4-, or 5-isoxazolyl; 2-, 4-, or 5-oxazolyl; 3-, 4-, or 
5-isothiazolyl; 5-tetrazolyl; 3- or 5-(1,2,4,-)triazolyl; 4- or 
5-(1,2,3-)triazolyl; 2-, 4-, or 5-imidazolyl; 2-, 3-, 4-, 5-, 6-, or 
7-indolyl; 2-, 3-, 4-, 5-, 6-, 7-, or 8-quinolinyl; 1 -, 3-, 4-, 5-, 6-, 
7-, or 8-isoquinolinyl; 2-, 4-, 5-, 6-, or 7-benzothiazolyl; or 2-, 3-, 
4-, 5-, 6-, or 7-benzothienyl. 
Preferred compounds of general Formulas I and II are those wherein one of 
R.sub.1, R.sub.2, and R.sub.3 is phenyl disubstituted in the 
2,6-positions. More preferably R.sub.1 and R.sub.2 are 2,6-disubstituted 
phenyl and R.sub.3 is hydrogen. Compounds wherein R.sub.1 is 
2,6-disubstituted phenyl and R.sub.2 and R.sub.3 are a straight or 
branched hydrocarbon chain having from 1 to 20 carbon atoms, and more 
preferably, 6 to 18 carbon atoms, and which is saturated or contains from 
1 to 3 double bonds are also preferred. 
Pharmaceutically acceptable salts of the compounds of Formula I are also 
included as a part of the present invention. 
The base salts may be generated from compounds of Formula I and Formula II 
by reaction of the latter with one equivalent of a suitable nontoxic, 
pharmaceutically acceptable base followed by evaporation of the solvent 
employed for the reaction and recrystallization of the salt, if required. 
The compounds of Formula I may be recovered from the base salt by reaction 
of the salt with an aqueous solution of a suitable acid such as 
hydrobromic, hydrochloric, or acetic acid, or by reaction with a suitable 
alkylating agent such as an alkyl halide, e.g., methyl iodide or benzyl 
bromide. 
Suitable bases for forming base salts of the compounds of this invention 
include amines such as triethylamine or dibutylamine, or alkali metal 
bases and alkaline earth metal bases. Preferred alkali metal hydroxides 
and alkaline earth metal hydroxides as salt formers are the hydroxides of 
lithium, sodium, potassium, or calcium. The class of bases suitable for 
the formation of nontoxic, pharmaceutically acceptable salts is well known 
to practitioners of the pharmaceutical formulation arts. See, for example, 
Stephen N. Berge, et al, J Pharm Sciences 66:1-19 (1977). 
Suitable acids for forming acid salts of the compounds of Formulas I and II 
containing a basic group include, but are not necessarily limited to 
acetic, benzoic, benzenesulfonic, tartaric, hydrobromic, hydrochloric, 
citric, fumaric, gluconic, glucuronic, glutamic, lactic, malic, maleic, 
methanesulfonic, pamoic, salicylic, stearic, succinic, sulfuric, and 
tartaric acids. The acid addition salts are formed by procedures well 
known in the art. 
Certain compounds of the present invention may also exist in different 
stereoisomeric forms by virtue of the presence of asymmetric centers in 
the compound. The present invention contemplates all stereoisomers may be 
obtained, if desired, by methods known in the art as, for example, the 
separation of stereoisomers in chiral chromatographic columns. 
Further, the compounds of this invention may exist in unsolvated as well as 
solvated forms with pharmaceutically acceptable solvents such as water, 
ethanol, and the like. In general, the solvated forms are considered 
equivalent to the unsolvated forms for the purposes of this invention. 
As shown by the data presented below in Table 1, the compounds of the 
present invention are potent inhibitors of the enzyme acyl-CoA: 
cholesterol acyltransferase (ACAT), and are thus effective in inhibiting 
the esterification and transport of cholesterol across the intestinal cell 
wall. The compounds of the present invention are thus useful in 
pharmaceutical formulations for the treatment of hypercholesterolemia or 
atherosclerosis. 
The ability of representative compounds of the present invention to inhibit 
ACAT was measured using an in vitro test more fully described in F. J. 
Field and R. G. Salone, Biochemica et Biophysica 712:557-570 (1982). The 
test assesses the ability of a test compound to inhibit the acylation of 
cholesterol by oleic acid by measuring the amount of radiolabeled 
cholesterol oleate formed from radiolabeled oleic acid in a tissue 
preparation containing rabbit intestinal microsomes. 
The data appear in Table 1 where they are expressed as IC50 values; i. e., 
the concentration of test compound required to inhibit the activity of the 
enzyme by 50%. 
TABLE 1 
______________________________________ 
IAI 
IC.sub.50 
Example No. (.mu.M) 
______________________________________ 
1 &gt;100 
2 33 
3 82 
4 15 
5 11.4 
6 16.8 
7 21.8 
8 19 
9 11 
10 58 
11 1.9 
12 20 
13 52 
14 38 
15 49 
16 25.8 
17 10.6 
18 11.5 
19 13.5 
20 24.4 
21 23.4 
22 3.2 
23 2.2 
24 3.2 
25 4.3 
26 19.4 
27 18.9 
28 164 
29 18 
30 21 
31 2.7 
32 31 
33 31 
34 89 
35 15 
36 12 
37 21 
38 58 
39 5.1 
40 22 
41 4.2 
42 1.3 
43 30.0 
50 &gt;100 
51 &gt;100 
52 53 
53 &gt;100 
54 43 
56 &gt;25 
57 1.9 
58 4.6 
______________________________________ 
In one in vivo screen designated APCC, male Sprague-Dawley rats (200 to 225 
g) were randomly divided into treatment groups and dosed at 4 PM with 
either vehicle (CMC/Tween) or suspensions of compounds in vehicle. The 
normal chow diet was then replaced with a high fat, high cholesterol diet 
with 0.5% cholic acid. The rats consumed this diet ad libitum during the 
night and were sacrificed at 8 AM to obtain blood samples for cholesterol 
analysis using standard procedures. Statistical differences between mean 
cholesterol values for the same vehicle were determined using analysis of 
variance followed by Fisher's least significant test. The results of this 
trial for representative compounds of the present invention appear in 
Table 2. The compounds were dosed at 30 mg/kg unless otherwise noted. 
TABLE 2 
______________________________________ 
Compound of Example 
% Change (mg/dl) 
______________________________________ 
1 -- 
2 0 
3 -55 
4 -77 
5* -35 
6* -57 
7* -32 
8* -26 
9* -3 
10 -67 
11 -57 
12 -43 
13 +8 
14* -55 
15* -29 
16* -65 
17* -46 
18* -42 
19* -56 
20* -54 
21* -33 
22 -4 
23 -42 
24 -19 
25 -40 
26 -52 
27 -29 
28 -13 
29 -55 
30 +2 
31 0 
32 -10 
33 -22 
34 -4 
35 -76 
36 -70 
37 -58 
38 -70 
39 -60 
40 -60 
41 -62 
42 -74 
43 -8 
50 -14 
51 -11 
52 -53 
53 -21 
54 -77 
56 -39 
57 -66 
58 +4 
______________________________________ 
*Indicates dosed at 50 mg/kg 
In therapeutic use as agents for treating hypercholesterolemia or 
atherosclerosis, the compounds of Formula I or pharmaceutically acceptable 
salts thereof are administered to the patient at dosage levels of from 250 
to 3000 mg per day. For a normal human adult of approximately 70 kg of 
body weight, this translates into a dosage of from 5 to 40 mg/kg of body 
weight per day. The specific dosages employed, however, may be varied 
depending upon the requirements of the patient, the severity of the 
condition being treated, and the activity of the compound being employed. 
The determination of optimum dosages for a particular situation is within 
the skill of the art. 
For preparing the pharmaceutical compositions from the compounds of this 
invention, inert, pharmaceutically acceptable carriers can be either solid 
or liquid. Solid form preparations include powders, tablets, dispersible 
granules, capsules, and cachets. 
A solid carrier can be one or more substances which may also act as 
diluents, flavoring agents, solubilizers, lubricants, suspending agents, 
binders, or tablet disintegrating agents; it can also be an encapsulating 
material. 
In powders, the carrier is a finely divided solid which is in a mixture 
with the finely divided active component. In tablets, the active component 
is mixed with the carrier having the necessary binding properties in 
suitable proportions and compacted in the shape and size desired. 
Powders and tablets preferably contain between about 5% to about 70% by 
weight of the active ingredient. Suitable carriers are magnesium 
dicarbonate, magnesium stearate, talc, lactose, sugar, pectin, dextrin, 
starch, tragacanth, methyl cellulose, sodium carboxymethyl cellulose, a 
low-melting wax, cocoa butter, and the like. 
The term "preparation" is intended to include the formulation of the active 
compound with encapsulating material as a carrier providing a capsule in 
which the active component (with or without carriers) is surrounded by a 
carrier, which is thus in association with it. In a similar manner cachets 
are also included. 
Tablets, powders, cachets, and capsules can be used as solid dosage forms 
suitable for oral administration. 
Liquid form preparations include solutions, suspensions, or emulsions 
suitable for oral administration. Aqueous solutions for oral 
administration can be prepared by dissolving the active compound in water 
and adding suitable flavorants, coloring agents, stabilizers, and 
thickening agents as desired. Aqueous suspensions for oral use can be made 
by dispersing the finely divided active component in water together with a 
viscous material such as natural or synthetic gums, resins, methyl 
cellulose, sodium carboxymethylcellulose, and other suspending agents 
known to the pharmaceutical formulation art. 
Preferably, the pharmaceutical preparation is in unit dosage form. In such 
form, the preparation is divided into unit doses containing appropriate 
quantities of the active component. The unit dosage form can be a packaged 
preparation containing discrete quantities of the preparation, for 
example, packeted tablets, capsules, and powders in vials or ampoules. The 
unit dosage form can also be a capsule, cachet, or tablet itself, or it 
can be the appropriate number of these packaged forms. 
The compounds of general Formulas I and II are prepared as generally 
described in Chart I hereof. 
An alcohol or thiol of the formula R.sub.1 XH is reacted with 
chlorosulfonyl isocyanate in an inert organic solvent such as THF, 
Et.sub.2 O, CH.sub.2 Cl.sub.2 at room temperature or preferably colder 
(.ltoreq.0.degree. C.). The resulting chlorosulfonyl (thio) carbamate may 
precipitate out of solution or it can be triturated with a non polar 
solvent such as hexanes. The chlorosulfonyl (thio) carbamate can be 
isolated or it can be used as is and reacted with an amine of the formula 
NHR.sub.2 R.sub.3 in an inert organic solvent such as those mentioned 
above at ambient temperature in the presence of an acid scavenger such as 
triethylamine. The oxysulfonyl (thio) carbamate thus formed can be 
converted to its base salt by reacting with an appropriate metal or amine 
base. The base salt can then be reacted with an appropriate alkylating 
agent such as methyl iodide or benzyl bromide. 
The alcohols R.sub.1 OH, thiols, R.sub.1 SH, and amines NHR.sub.2 R.sub.3 
used in preparing the compounds of this invention are known in the art or 
are prepared by procedures generally known in the art.

The specific examples set forth below further illustrate the preparation of 
compounds of general Formula I and Formula II. 
EXAMPLE 1 
Methyl[[2,6-bis(1-methylethyl)phenylamino]sulfonyl]carbamate 
A solution of methyl(chlorosulfonyl) carbamate (5.0 g, 28.8 mmol) in 60 mL 
THF was added dropwise to a solution of 2,6-diisopropylaniline (5.11 g, 
28.8 mmol) and excess triethylamine (.about.5 mL) in 100 mL THF at room 
temperature under an atmosphere of N.sub.2. The mixture was stirred for 72 
hrs, concentrated in vacuo and the residue was partitioned between 1N HCl 
and EtOAc. The organic layer was dried with MgSO.sub.4, filtered and 
evaporated to give an orange oil which was triturated with 10% 
EtOAc/hexanes to give 5.93 g (65%) of an off-white solid, mp 
152-155.degree. C. 
EXAMPLE 2 
Dodecyl[[2,6-bis(1-methylethyl)phenyl]amino]sulfonyl]carbamate 
A solution of dodecyl(chlorosulfonyl) carbamate (5.0 g, 15.2 mmol) in 70 mL 
THF was added dropwise to a solution of 2,6-diisopropylaniline (2.70 g, 
15.2 mmol) and excess triethylamine (.about.5 mL) in 100 mL THF at room 
temperature under an atmosphere of N.sub.2. The mixture was stirred for 16 
hrs, concentrated in vacuo and partitioned between 1N HCl and EtOAc. The 
organic layer was dried with MgSO.sub.4, filtered and concentrated to give 
an orange oil. Chromatography (SiO.sub.2, 5% EtOAc/hex) gave 5.86 g (82%) 
of an off-white solid, mp 82.degree.-84.degree. C. (hexanes). 
EXAMPLE 3 
2,6-bis(1,1-dimethylethyl)-4-methoxyphenyl[[(2,2-diphenylethyl)amino]sulfon 
yl]carbamate 
A solution of 2,6-bis(1,1-dimethylethyl)-4-methoxyphenyl(chlorosulfonyl) 
carbamate (5.0 g, 13.2 mmol) in 80 mL THF was added dropwise to a solution 
of 2,2-diphenylethylamine (2.61 g, 13.2 mmol) and excess triethylamine 
(.about.3 mL) in 100 mL THF at room temperature under an atmosphere of 
N.sub.2. The mixture was stirred for 72 hrs and then concentrated in 
vacuo. The residue was partitioned between 1N HCl and EtOAc. The organic 
layer was dried with MgSO.sub.4, filtered and evaporated to give a clear 
oil which was triturated with hexanes to give 5.36 g (75%) of an off-white 
solid, mp 132.degree.-138.degree. C. 
EXAMPLE 4 
2,6-bis(1,1-dimethylethyl)-4-methoxy 
phenyl[[[2,6-bis(1-methylethyl)phenyl]amino]sulfonyl]carbamate 
When in the general procedure of Example 3, an appropriate amount of 
2,6-diisopropylaniline was substituted for 2,2-diphenylethylamine, the 
title compound was obtained, mp 155.degree.-158.degree. C. 
EXAMPLE 5 
2,6-bis(1,1-dimethylethyl)phenyl[[(diphenylmethyl)amino]sulfonyl]carbamate 
A solution of 2,6-bis(1,1-dimethylethyl)phenyl (chlorosulfonyl) carbamate 
(2.85 g, 8.2 mmol) in 70 mL Et.sub.2 O was added dropwise to a solution of 
diphenylmethylamine (1.50 g, 8.2 mmol) and triethylamine (1.25 mL, 9.0 
mmol) in 80 mL Et.sub.2 O at -15.degree. C. under an atmosphere of 
N.sub.2. The mixture was warmed to room temperature and stirred for 6 hrs 
and then washed with 1N HCl and water. The organic layer was dried with 
MgSO.sub.4, filtered and evaporated to give 3.60 g (89%) of an off-white 
solid, mp 162.degree.-166.degree. C. 
EXAMPLE 6 
2,6-bis(1,1-dimethylethyl)phenyl[[[2,6-bis(1-methylethyl)phenyl]amino]sulfo 
nyl]carbamate 
When in the general procedure of Example 5, an appropriate amount of 
2,6-diisopropylaniline was substituted for diphenylmethylamine, the title 
compound was obtained, mp 180.degree.-181.degree. C. 
EXAMPLE 7 
2,6-bis(1,1-dimethylethyl)phenyl[[(2,2-diphenylethyl)amino]sulfonyl]carbama 
te 
When in the general procedure of Example 5, an appropriate amount of 
2,2-diphenylethylamine was substituted for diphenylmethylamine, the title 
compound was obtained, mp 147.degree.-150.degree. C. 
EXAMPLE 8 
2,6-bis(1,1-dimethylethyl)phenyl[(phenylamino)sulfonyl]carbamate 
When in general procedure of Example 5, an appropriate amount of aniline 
was substituted for diphenylmethylamine, the title compound was obtained, 
mp 169.degree.-172.degree. C. 
EXAMPLE 9 
2,6-bis(1,1-dimethylethyl)phenyl[[bis(phenylmethyl)amino]sulfonylcarbamate 
When in general procedure of Example 5, an appropriate amount of 
dibenzylamine was substituted for diphenylamine, the title compound was 
obtained, mp 182.degree.-183.degree. C. 
EXAMPLE 10 
2,6-bis(1-methylethyl)phenyl[(diphenylamino)sulfonyl]carbamate 
Solid NaH (0.68 g, 17.1 mmol) was added in portions to a solution of 
diphenylamine (2.41 g, 14.2 mmol) in 75 mL THF at room temperature under 
an atmosphere of N.sub.2. The mixture was stirred for 16 hrs and then a 
solution of 2,6-bis(1-methylethyl)phenyl (chlorosulfonyl) carbamate (5.0 
g, 15.6 mmol) in 50 mL THF was added dropwise. The reaction mixture was 
stirred for an additional 4 hrs and then quenched with 10 mL 1N HCl, and 
partitioned between 1N HCl and EtOAc. The organic layer was dried with 
MgSO.sub.4, filtered, and evaporated to give a green oil which was 
triturated and recrystallized from hexane to give 3.21 g (50%) of the 
title compound as an off-white solid, mp 149.degree.-151.degree. C. 
EXAMPLE 11 
Synthesis of 2,6-Bis(1-methylethyl)phenyl[(dibutylamino)sulfonyl]carbamate 
A solution of 2,6-bis(1-methylethyl)phenyl(chlorosulfonyl)carbamate (5.0 g, 
15.66 mmoles) in 75 mL THF was added dropwise to a solution of 
di-n-butylamine (1.84 g, 14.2 mmoles) and excess triethylamine (.about.2 
mL) in 75 mL THF. This was then stirred for 16 hours and then partitioned 
between 1N HCl and EtOAc. The organic layer was dried with MgSO.sub.4, 
filtered, and evaporated to give a pale orange oil Chromatography 
(SiO.sub.2, 5% EtOAc/hexane) gave 1.64 g (25%) of the title compound as a 
white solid, mp 94.degree.-97.degree. C. 
EXAMPLE 12 
Synthesis of 
2,6-Bis(1-methylethyl)phenyl[[bis(phenylmethyl)amino]sulfonyl]carbamate 
When in the general procedure of Example 11, an appropriate amount of 
dibenzylamine was substituted for di-n-butylamine, the title compound was 
obtained, mp 143.degree.-146.degree. C. 
EXAMPLE 13 
Synthesis of 2,6-Bis(1-methylethyl)phenyl(1H- 
benzimidazol-2-ylamino)sulfonyl]carbamate 
When in the general procedure of Example 11, an appropriate amount of 
2-aminobenzimidazole was substituted for di-n-butylamine, the title 
compound was obtained, mp 159.degree.-162.degree. C. 
EXAMPLE 14 
Synthesis of 2,6-Bis(1-methylethyl)phenyl[(phenylamino)sulfonyl]carbamate 
When in the general procedure of Example 11, an appropriate amount of 
aniline was substituted for di-n-butylamine, the title compound was 
obtained, mp 165.degree.-168.degree. C. 
EXAMPLE 15 
Synthesis of 
2,6-Bis(1-methylethyl)phenyl[2,2-diphenylethyl)amino]sulfonyl]carbamate 
When in the general procedure of Example 11, an appropriate amount of 
2,2-diphenylethylamine was substituted for di-n-butylamine, the title 
compound was obtained, mp 103.degree.-105.degree. C. 
EXAMPLE 16 
Synthesis of 
2,6-Bis(1-methylethyl)phenyl[[2,6-bis(1methylethyl)phenyl]amino]sulfonyl]c 
arbamate 
When in the general procedure of Example 11, an appropriate amount of 
2,6-diisopropylaniline was substituted for di-n-butylamine, the title 
compound was obtained, mp 172.degree.-174.degree. C. 
EXAMPLE 17 
Synthesis of 
2,6-Bis(1-methylethyl)phenyl[(diphenylmethyl)amino]sulfonyl]carbamate 
When in the general procedure of Example 11, an appropriate amount of 
diphenylmethylamine was substituted for di-n-butylamine, the title 
compound was obtained, mp 185.degree.-187.degree. C. 
EXAMPLE 18 
Synthesis of 
2,6-Bis(1,1-dimethylethyl)-4-methylphenyl[[(diphenylmethyl)amino1sulfonyl 
carbamate 
A solution of 
2,6-bis(1,1-dimethylethyl)-4-methylphenyl(chlorosulfonyl)carbamate (2.96 
g, 8.2 mmoles) in 70 mL Et.sub.2 O was added dropwise to a solution of 
diphenylmethylamine (1.5 g, 8.2 mmoles) and 1.25 mL (10.0 mmoles) of 
triethylamine in 80 mL Et.sub.2 O at -15.degree. C. under an atmosphere of 
N.sub.2. The mixture was allowed to warm to room temperature over 2 hours 
and then washed with 1N HCl and H.sub.2 O. The Et.sub.2 O layer was dried 
with MgSO.sub.4, filtered, and evaporated to give a pale yellow foam which 
was triturated with hexanes to give a white solid, mp 
150.degree.-152.degree. C. 
EXAMPLE 19 
Synthesis of 
2,6-Bis(1,1-dimethylethyl)-4-methylphenyl[[[bis(2,6-bis(1-methylethyl)phen 
yl]amino]sulfonyl]carbamate 
When in the procedure of Example 18, an appropriate amount of 
2,6-diisopropylaniline was substituted for diphenylmethylamine, the title 
compound was obtained, mp 176.degree.-178.degree. C. 
EXAMPLE 20 
Synthesis of 
2,6-Bis(1,1-dimethylethyl)-4-methylphenyl[[[(2,2-diphenylethyl)amino]sulfo 
nyl]carbamate 
When in the general procedure of Example 18, an appropriate amount of 
2,2-diphenylethylamine was substituted for diphenylmethylamine, the title 
compound was obtained. mp 139.degree.-141.degree. C. 
EXAMPLE 21 
Synthesis of 
2,6-Bis(1,1-dimethylethyl)-4-methylphenyl[(phenylamino)sulfonyl]carbamate 
When in the general procedure of Example 18, an appropriate amount of 
aniline was substituted for diphenylmethylamine, the title compound was 
obtained, mp 186.degree.-188.degree. C. 
EXAMPLE 22 
Synthesis of 
2,6-Bis(1,1-dimethylethyl)-4-methylphenyl[(dibutylamino)sulfonyl]carbamate 
When in the general procedure of Example 18, an appropriate amount of 
di-n-butylamine was substituted for diphenylmethylamine, the title 
compound was obtained, mp 134.degree.-135.degree. C. 
EXAMPLE 23 
Synthesis of 
2,6-Bis(1,1-dimethylethyl)-4-methylphenyl[(dipentylamino)sulfonyl]carbamat 
When in the general procedure of Example 18, an appropriate amount of 
di-n-pentylamine was substituted for diphenylmethylamine, the title 
compound was obtained, mp 107.degree.-108.degree. C. 
EXAMPLE 24 
Synthesis of 
2,6-Bis(1,1-dimethylethyl)-4-methylphenyl[[bis(1-methylethyl)amino]sulfony 
l]carbamate 
When in the general procedure of Example 18, an appropriate amount of 
diisopropylamine was substituted for diphenylmethylamine, the title 
compound was obtained, mp 198.degree.-199.degree. C. 
EXAMPLE 25 
Synthesis of 
2,6-Bis(1,1-dimethylethyl)-4-methylphenyl(dihexylamino)sulfonyl]carbamate 
When in the general procedure of Example 18, an appropriate amount of 
di-n-hexylamine was substituted for diphenylmethylamine, the title 
compound was obtained, mp 66.degree.-68.degree. C. 
EXAMPLE 26 
Synthesis of 
2,6-Bis(1,1-dimethylethyl)-4-methylphenyl[(hexylamino)sulfonyl]carbamate 
When in the general procedure of Example 18, an appropriate amount of 
hexylamine was substituted for diphenylmethylamine, the title compound was 
obtained, mp 123.degree.-128.degree. C. 
EXAMPLE 27 
Synthesis of 
2,6-Bis(1,1-dimethylethyl)-4-methylphenyl[[methyl(2-phenylethyl)amino]sulf 
onyl]carbamate 
When in the general procedure of Example 18, an appropriate amount of 
N-methyl-2-phenylethylamine was substituted for diphenylmethylamine, the 
title compound was obtained, mp 140.degree.-142.degree. C. 
EXAMPLE 28 
Synthesis of 
2,6-Bis(1,1-dimethylethyl)-4-methylphenyl[[[bis-3-(di-methylamino)propyl]a 
mino]sulfonyl]carbamate 
When in the general procedure of Example 18, an appropriate amount of 
bis-3-(dimethylamino)propyl amine was substituted for diphenylmethylamine, 
the title compound was obtained. .sup.1 H NMR (CDCl.sub.3) .delta. 8.05 
(bs, 1H), 7.05 (s, 2H), 3.29 (m, 4H), 2.87 (m, 4H), 2.56 (s, 12H), 2.29 
(s, 3H), 1.91 (m, 4H), 1.37 (s, 18H) ppm. 
EXAMPLE 29 
Synthesis of 2,6-Bis(1,1-dimethylethyl)-4-methylphenyl[(methyl octyl 
amino)sulfonyl]carbamate 
When in the general procedure of Example 18, an appropriate amount of 
N-methyl octylamine was substituted for diphenylmethylamine, the title 
compound was obtained, mp 65.degree.-68.degree. C. 
EXAMPLE 30 
Synthesis of 
2,6-Bis(1,1-dimethylethyl)-4-methyl[[bis[(tetrahydro-2-furanyl)methyl]amin 
o]sulfonyl]carbamate 
When in the general procedure of Example 18, an appropriate amount of 
bis-[(tetrahydro-2-furanyl)methyl] amine was substituted for 
diphenylmethylamine, the title compound was obtained, mp 
108.degree.-111.degree. C. 
EXAMPLE 31 
Synthesis of 
2,6-Bis(1,1-dimethylethyl)-4-methylphenyl[(dioctylamino)sulfonyl]carbamate 
When in the general procedure of Example 18, an appropriate amount of 
di-n-octylamine was substituted for diphenylmethylamine, the title 
compound was obtained, mp 53.degree.-55.degree. C. 
EXAMPLE 32 
Synthesis of 2,6-Bis(1,1-dimethylethyl)-4-methylphenyl[[[methyl 
2-(2-pyridinyl)ethyl]amino]sulfonyl]carbamate, hydrochloride salt 
A solution of 
2,6-bis(1,1-dimethylethyl)-4-methylphenyl(chlorosulfonyl)carbamate (5.0 g, 
13.8 mmoles) in 70 mL THF was added dropwise to a solution of 
2-(.beta.-methylaminoethyl)pyridine (1.88 g, 13.8 mmoles) and excess 
triethylamine (.about.2 mL) in 80 mL THF at room temperature under an 
atmosphere of N.sub.2. The solution was stirred for 16 hours and then 
concentrated in vacuo. The residue was partitioned between 1N HCl and 
EtOAc, the EtOAc layer dried with MgSO.sub.4, filtered, and evaporated to 
give a white solid which was then triturated with hexanes to give 5.00 g 
of the title compound, mp 178.degree.-181.degree. C. 
EXAMPLE 33 
Synthesis of 2,6-Bis(1,1-dimethylethyl)-4-methylphenyl[[[methyl 
2-(2-pyridinyl)ethyl]amino]sulfonyl]carbamate, sodium salt 
Excess 1N NaOH (30 mL) was added to a suspension of 
2,6-bis(1,1-dimethylethyl)-4-methylphenyl[[[methyl 
2-(2-pyridinyl)ethyl]amino]sulfonyl]carbamate hydrochloride (2.75 g, 5.5 
mmoles) in 50 mL EtOAc. The mixture was stirred for 16 hours, the organic 
layer separated, dried with MgSO.sub.4, filtered, and evaporated to give a 
clear oil which was triturated with hexanes to give the title compound as 
a white solid, mp 133.degree.-136.degree. C. 
EXAMPLE 34 
Synthesis of 
2,6-Bis(1,1-dimethylethyl)-4-methylphenyl[(dodecylamino)sulfonyl]carbamate 
When in the general procedure of Example 18, an appropriate amount of 
di-n-decylamine was substituted for diphenylmethylamine, the title 
compound was obtained as a waxy white solid, mp 63.degree.-65.degree. C. 
EXAMPLE 35 
Synthesis of 
2,6-Bis(1-methylethyl)phenyl[bis(1methylethyl)amino]sulfonyl]carbamate 
When in the general procedure of Example 11, an appropriate amount of 
diisopropylamine was substituted for di-n-butylamine, the title compound 
was obtained, mp 126.degree.-131.degree. C. 
EXAMPLE 36 
Synthesis of 
2,6-Bis(1-methylethyl)phenyl[(1methylethyl)phenylmethyl)amino]sulfonyl]car 
bamate 
When in the general procedure of Example 11, an appropriate amount of 
N-isopropyl benzylamine was substituted for di-n-butylamine, the title 
compound was obtained, mp 156.degree.-159.degree. C. 
EXAMPLE 37 
Synthesis of 2,6-Bis(1-methylethyl)phenyl(hexylamino)sulfonyl]carbamate 
When in the general procedure of Example 11, an appropriate amount of 
n-hexylamine was substituted for di-n-butylamine, the title compound was 
obtained, mp 105.degree.-106.5.degree. C. 
EXAMPLE 38 
Synthesis of 2,6-Bis(1-methylethyl)phenyl[(dioctylamino)sulfonyl]carbamate 
When in the general procedure of Example 11, an appropriate amount of 
di-n-octylamine was substituted for di-n-butylamine, the title compound 
was obtained, mp 64.degree.-67.degree. C. 
EXAMPLE 39 
Synthesis of 
2,6-Bis(1-methylethyl)phenyl[[cyclohexyl(1-methylethyl)amino]sulfonyl]carb 
amate 
When in the general procedure of Example 11, an appropriate amount of 
N-isopropylcyclohexylamine was substituted for di-n-butylamine, the title 
compound was obtained, mp 133.degree.-135.degree. C. 
EXAMPLE 40 
Synthesis of 
2,6-Bis(1-methylethyl)phenyl(methyloctylamino)sulfonyl]carbamate 
When in the general procedure of Example 11, an appropriate amount of 
N-methyloctylamine was substituted for di-n-butylamine, the title compound 
was obtained, mp 32.degree.-35.degree. C. 
EXAMPLE 41 
Synthesis of 2,6-Bis(1-methylethyl)phenyl[(dihexylamino)sulfonyl]carbamate 
When in the general procedure of Example 11, an appropriate amount of 
di-n-hexylamine was substituted for di-n-butylamine, the title compound 
was obtained, mp 57.degree.-61.degree. C. 
EXAMPLE 42 
Synthesis of 2,6-Bis(1-methylethyl)phenyl[(dipentylamino)sulfonyl]carbamate 
When in the general procedure of Example 11, an appropriate amount of 
di-n-pentylamine was substituted for di-n-butylamine, the title compound 
was obtained, mp 69.degree.-70.degree. C. 
EXAMPLE 43 
Synthesis of Dodecyl[[(2,4,6-trimethoxyphenyl)amino]sulfonyl]carbamate 
When in the general procedure of Example 2, an appropriate amount of 
2,4,6-trimethoxyaniline was substituted for 2,6-diisopropylaniline, the 
title compound was obtained, mp 133.degree.-136.degree. C. 
The following Example 44 through 49 teach the preparation of intermediates 
useful in preparing final products of the present invention. 
EXAMPLE 44 
Synthesis of Methyl(chlorosulfonyl)carbamate (Ref: Org. Synth. 56 40 
(1977)) 
A solution of methanol (10.2 mL, 252 mmoles) in 15 mL toluene was added 
dropwise to a solution of chlorosulfonyl isocyanate (22.0 mL, 252 mmoles) 
in 75 mL toluene at 0.degree. C. The cooling bath was removed and stirred 
for one-half hour at room temperature. This was then cooled to 0.degree. 
C. and 65 mL ice cold hexanes was added. The white precipitate was 
collected by filtration and washed 2 times with a small amount of cold 
hexane to give 33.0 g of a white solid, mp 72.degree.-74.degree. C. 
EXAMPLE 45 
Synthesis of Dodecyl(chlorosulfonyl)carbamate (Ref: R. Graf, Chem. Ber. 96 
56 (1963)) 
A solution of n-dodecyl alcohol (107 g, 52.4 mmoles) in 100 mL Et.sub.2 O 
was added dropwise to a solution of chlorosulfonyl isocyanate (5.0 mL, 
57.4 mmoles) in 100 mL Et.sub.2 O at -15.degree. C. under an atmosphere of 
N.sub.2. The resulting mixture was stirred for 2 hours and concentrated in 
vacuo. The residue was triturated with cold hexanes to give a white solid 
which was collected by filtration to give 19.12 g of a white solid, mp 
62.degree.-63.degree. C. 
EXAMPLE 46 
Synthesis of 2,6-Bis(1-methylethyl)phenyl(chlorosulfonyl)carbamate (Ref: 
Phos & Sulf 19 167 (1984)) 
A solution of 2,6-diisopropylphenol (37.1 mL, 0.2 moles) in 200 mL Et.sub.2 
O was added dropwise to a solution of chlorosulfonyl isocyanate (17.4 mL, 
0.2 moles)) in 200 mL Et.sub.2 O at -15.degree. C. This was then stored at 
-15.degree. C. under an atmosphere of N.sub.2 for 16 hours. Concentration 
gave an orange oil which was triturated with hexanes and quickly collected 
by filtration to give 55.64 g (87%) of product as a white solid. 
EXAMPLE 47 
Synthesis of 2,6-Bis(1,1-dimethylethyl)phenyl(chlorosulfonyl)carbamate 
(Ref: Phos & Sulf 19 167 (1984)) 
A solution of 2,6-di-t-butylphenol (20.63 g, 0.1 mol) in 100 mL Et.sub.2 O 
was added dropwise to a solution of chlorosulfonyl isocyanate (8.7 mL, 0.1 
moles) in 100 mL Et.sub.2 O at -15.degree. C. (acetone/ice bath) under an 
atmosphere of N.sub.2. This was stirred for 1 hour and then concentrated 
in vacuo to leave a thick gel which was triturated with hexanes and 
filtered to give 28.60 g (82%) of the title compound as a white solid, mp 
135.degree.-137.degree. C. 
EXAMPLE 48 
Synthesis of 
2,6-Bis(1,1-dimethylethyl)-4-methylphenyl(chlorosulfonyl)carbamate (Ref: 
phos & Sulf 19 167 (1984)) 
A solution of 2,6-di-t-butyl-4-methylphenol (22.04 g, 0.1 moles) in 100 mL 
Et.sub.2 O was added dropwise to a solution of chlorosulfonyl isocyanate 
(8.7 mL, 0.1 moles) in 100 mL Et.sub.2 O at -15.degree. C. under an 
atmosphere of N.sub.2. This was stirred for 2 hours, concentrated and 
trituration of the resulting gel with hexanes gave 26.82 g (74%) of the 
title compound as a white solid. 
EXAMPLE 49 
Synthesis of 
2,6-Bis(1,1-dimethylethyl)-4-methoxyphenyl(chlorosulfonyl)carbamate 
A solution of 3,5-di-t-butyl-4-hydroxyanisole (30.0 g, 0.127 moles) in 200 
mL Et.sub.2 O was added dropwise to a solution of chlorosulfonyl 
isocyanate (12.2 mL, 0.14 moles) in 250 mL Et.sub.2 O at -15.degree. C. 
under an atmosphere of N.sub.2. This was stirred for 1 hour and then 
concentrated in vacuo to give 41.0 g of product as a thick gel which was 
used without further purification. 
The examples set forth hereinbelow further illustrate the preparation of 
final products of the compounds of the present invention. 
When in the procedure of Example 11 an appropriate amount of the amine 
listed below was substituted for di-n-butylamine the respective product 
listed below was obtained: 
______________________________________ 
Example 
No. Amine Product 
______________________________________ 
50 Morpholine 2,6-Bis(1-methylethyl)- 
phenyl ester(4- 
morpholinylsulfonyl)- 
carbamic acid; 
.sup.1 H NMR (CDCl.sub.3) .delta. 7.9 
(bs, 1H), 7.1(m, 3H), 
3.7(t, 4H), 3.5(5, 
4H), 3.0(m, 2H), 1.2 
(d, 12H)ppm. 
51 Piperidine 2,6-Bis(1-methylethyl)- 
phenyl ester(1- 
piperidinylsulfonyl)- 
carbamic acid; 
.sup.1 H NMR (CDCl.sub.3) .delta. 8.1 
(bs, 1H), 7.1(m, 3H), 
3.4(t, 4H), 3.0(m, 
2H), 1.7(m, 4H), 1.6 
(m, 2H), 1.2(d, 
12H)ppm 
52 Pyrrolidine 2,6-Bis(1-methylethyl)- 
phenyl ester(1- 
pyrrolidinylsulfonyl)- 
carbamic acid; 
.sup.1 H NMR (CDCl.sub.3) .delta. 7.8 
(bs, 1H), 7.1(m, 3H), 
3.6(t, 4H), 3.0(m, 
2H), 1.9(t, 4H), 1.2 
(d, 12H)ppm. 
53 4-Methylpipera- 
2,6-Bis(1-methylethyl)- 
zine phenyl ester, 
monohydrochloride[(4- 
methyl-1-piperazinyl)- 
sulfonyl]carbamic acid; 
1H NMR (DMSO D.sub.6) .delta. 8.0 
(s, 1H), 7.0(d, 3H), 
3.3(m, 2H), 3.1(bs, 
4H), 2.8(bs, 4H), 2.5 
(s, 3H), 1.1(d, 
12H)ppm. 
54 2,3-Dihydroindole 
2,6-Bis(1-methylethyl)- 
phenyl ester[(2,3- 
dihydro-1H-indol-1- 
yl)sulfonyl[carbamic 
acid; .sup.1 H NMR (CDCl.sub.3) .delta. 
8.0(bs, 1H), 7.4(d, 
1H), 7.2(m, 3H), 7.1 
(m, 3H), 4.4(t, 2H), 
3.1(t, 2H), 2.5(m, 
2H), 1.0(d, 12H)ppm. 
______________________________________ 
EXAMPLE 55 
Synthesis of [1,1':3',1"-terphenyl]-2,-yl(chlorosulfonyl)carbamate 
A solution of 2,6-diphenyl phenol (25.0 g, 101 mmol) in 250 mL ethyl ether 
was added dropwise to a solution of chlorosulfonyl isocyanate (9.7 mL, 112 
.mu.mol) in 100 mL hexane at -15.degree. C. under an atmosphere of 
nitrogen. The resulting white suspension was allowed to warm to room 
temperature over 2 hours. Concentrated in vacuo and triturated with ice 
cold hexane. Vacuum filtration afforded the title compound as a white 
solid, mp 159.degree.-162.degree. C. 
EXAMPLE 56 
Synthesis of 1,1, 
3',1"-terphenyl]-2,-yl[[2,6-bis(1methylethyl)phenyl]amino]sulfonyl]carbama 
te 
A solution of [1,1':3',1"-terphenyl]-2,-yl(chlorosulfonyl)carbamate (5.0 g, 
12.9 mmol) in 75 mL tetrahydrofuran was added dropwise to a solution of 
2,6-diisopropyl aniline (2.29 g, 12.9 mmol) and triethylamine (1.3 g, 12.9 
mmol) in 100 mL tetrahydrofuran at -15.degree. C. under an atmosphere of 
nitrogen. The resulting mixture was warmed to room temperature and stirred 
for 16 hours. Concentrated in vacuo and partitioned the residue between 
water and ethyl acetate. Dried the organic layer over MgSO.sub.4 and 
evaporated to give an off-white solid. Chromatography on silica gel gave 
the title compound, mp 166.degree.-168.degree. C. 
EXAMPLE 57 
Synthesis of 2,6-bis(1-methylethyl)phenyl[(dibutylamino)sulfonyl]carbamate 
monosodium salt 
A solution of the 
2,6-bis(1-methylethyl)phenyl[(dibutylamino)sulfonyl]carbamate (5.5 g, 13.3 
mmol) in 75 mL tetrahydrofuran was added dropwise to a suspension of 
sodium hydride (0.4 g, 80% dispersion in mineral oil, 13.3 mmol) in 50 mL 
tetrahydrofuran at 0.degree. C. under an atmosphere of nitrogen. Stirred 
for 3 hours, gradually warming to room temperature. Concentrated in vacuo 
and triturated with hexanes to give the title compound, mp 
162.degree.-166.degree. C. 
EXAMPLE 58 
Synthesis of 
2,6-bis(1,1-dimethylethyl)phenyl[[(diphenylmethyl)amino]sulfonyl]methyl 
carbamate 
1,8-Diazabicyclo[5.4.0]undec-7-ene (1.0 mL, 6.7 mmol) was added in one 
portion to a solution of 
2,6-bis(1,1-dimethylethyl)phenyl[[(diphenylmethyl)amino]sulfonyl]carbamate 
(3.0 g, 6.1 mmol) and methyl iodide (0.95 g, 6.7 mmol) in 50 mL 
acetonitrile at room temperature and the resulting mixture was stirred for 
16 hours. Partitioned between 1N HCl and ethyl acetate. Dried the organic 
layer over MgSO.sub.4, filtered, and evaporated to give an orange oil. 
Chromatography on silica gel gave the title compound, mp 
175.degree.-178.degree. C.