Certain thiazole-5-carboxamide compounds

Processes and intermediates for preparing 1-alkylamino-3-(5-substitutedaminocarbonylthiazol-2-yloxy)-2-propanols and 5-(5-substitutedaminocarbonylthiazol-2-yloxymethylene)-N-alkyloxazolidine and 2-substituted oxazolidine derivatives thereof and intermediates therefore. The present processes, and intermediates, reduce the number of transformations necessary to produce these products as compared with the prior processes. The products are useful to treat abnormal heart conditions and/or hypertension in mammals. The intermediates are 2-alkylsulfinyl-5-substitutedaminocarbonylthiazoles and 2-alkylsulfonyl-5-substitutedaminocarbonylthiazoles.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
This invention relates to processes for preparing 
1-alkylamino-3-(5-substitutedaminocarbonylthiazol-2-yloxy)-propan-2-ols 
and 3-(5-substitutedaminocarbonylthiazol-2-yloxy)-1,2-epoxypropanes; 
5-(5-substitutedaminocarbonylthiazol-2-yloxymethylene)-N-alkyloxazolidines 
and derivatives thereof. In a further aspect this invention relates to 
2-alkylsulfinyl-5-substituted aminocarbonylthiazoles and 
2-alkylsulfonyl-5-substitutedaminocarbonylthiazoles and to processes for 
preparing such compounds. 
2. The Prior Art 
The present invention relates to improved processes and intermediates for 
preparing certain 
1-alkylamino-3-(5-substitutedaminocarbonylthiazol-2-yloxy)-propan-2-ol 
.beta.-blocking cardiovascular agents. These cardiovascular agents are 
typically prepared by a multistep process (note U.S. Pat. Nos. 3,896,139 
and 3,897,441) requiring the conversion of the appropriate 2-halothiazole 
(or 5-substituted 2-halothiazole) to the corresponding thiazol-2-yloxy 
propanediol acetonide; thence to the diol; then to the mesylate and then 
finally to the corresponding 
3-(5-substitutedaminocarbonylthiazol-2-yloxy)-1,2-epoxypropane which is 
then easily converted to the final product via treatment with the desired 
alkylamine. In contrast to this, the 1,2-epoxypropane intermediate is 
prepared in the present process, in a single step either directly from the 
corresponding 2-halothiazole or from the corresponding 2-sulfinyl or 
2-sulfonylthiazole. The present invention also relates to improved 
processes for preparing certain 
5-(thiazol-2-yloxymethylene)-N-alkyloxazolidines and derivatives thereof, 
which can be conducted at lower temperatures and afford purer products 
than the prior art processes described in the aforementioned U.S. patents. 
SUMMARY OF THE INVENTION 
In summary the compounds of the invention can be represented by the 
following generic formula: 
##STR1## 
wherein X is the group --SOR.sup.1 or --SO.sub.2 R.sup.1 wherein R.sup.1 
is lower alkyl, phenyl, or benzyl and Z is selected from the group of 
alkyl having from one through 12 carbon atoms, and groups having the 
formulas: 
EQU R.sup.2 --(CH.sub.2).sub.m --; 
EQU R.sup.3 (CH.sub.2).sub.n --; 
EQU R.sup.4 --CH.dbd.CH--(CH.sub.2).sub.n --; 
EQU R.sup.5 --C.tbd.C--(CH.sub.2).sub.n -- 
wherein m is 1, 2, 3, or 4; n is 2, 3, or 4; R.sup.2 is cycloalkyl having 
from three through eight carbon atoms; R.sup.3 is selected from the group 
of bicyclo [3.1.0]hexyl; bicyclo [2.2.1]heptyl; adamantyl; and 
4-methylbicyclo [2.2.2]oct-1-yl and wherein attachment to the 
(CH.sub.2).sub.n linking group can be at any ring atom of bicyclo 
[3.1.0]hexyl; bicyclo [2.2.1]heptyl and adamantyl group and is at the 
1-position of the 4-methylbicyclo [2.2.2]octyl group; and R.sup.4 and 
R.sup.5 are hydrogen or alkyl having from one through four carbon atoms 
and wherein the groups R.sup.4 --CH.dbd.CH--(CH.sub.2).sub.n -- and 
R.sup.5 --C.tbd.C--(CH.sub.2).sub.n -- each have from four through eight 
carbon atoms. 
In summary the processes of the invention for preparing the compounds, of 
the invention, comprises oxidizing the corresponding 
5-substitutedaminocarbonyl-2-alkylthiothiazole to the corresponding 
2-sulfinyl or 2-sulfonyl compound of formula I. 
In summary the processes of the invention for preparing 
5-substitutedaminocarbonylthiazol-2-yloxy 1,2-epoxypropanes comprise 
reacting the corresponding compound of formula I with glycidol anion. In 
summary the processes for preparing the 
1-alkylamino-5-substitutedaminocarbonylthiazol-2-oxy propan-2-ol, comprise 
the additional step of reacting the 1,2-epoxy-propane intermediate with 
the desired alkylamine. 
In summary the processes for preparing 
5-(5-substituted-aminocarbonylthiazol-2-yloxymethylene)-N-alkyloxazolidine 
and derivatives thereof comprise condensing the corresponding compound of 
formula I with the desired 5-hydroxymethyl-3-lower alkyloxazolidine or 
2-mono or 2,2-dialkyl derivative thereof 
The invention will be further described hereinbelow. 
FURTHER DESCRIPTION OF THE INVENTION AND PREFERRED EMBODIMENTS 
The compounds of the invention can be represented by the following 
subgeneric formulas: 
##STR2## 
wherein R.sup.1 is lower alkyl, phenyl, or benzyl and Z is selected from 
the group of alkyl having from one through 12 carbon atoms, and groups 
having the formula 
EQU R.sup.2 --(CH.sub.2).sub.m --; 
EQU R.sup.3 (CH.sub.2).sub.n --; 
EQU R.sup.4 --CH.dbd.CH--(CH.sub.2).sub.n --; 
EQU R.sup.5 --C.tbd.C--(CH.sub.2).sub.n -- 
wherein m is 1, 2, 3, or 4; n is 2, 3, or 4; R.sup.2 is cycloalkyl having 
from three through eight carbon atoms; R.sup.3 is selected from the group 
of bicyclo [3.1.0]hexyl; bicyclo[2.2.1]heptyl; adamantyl; and 
4-methylbicyclo[2.2.2]oct-1-yl and wherein attachment to the 
(CH.sub.2).sub.n linking group can be at any ring atom of bicyclo 
[3.1.0]hexyl; bicyclo [2.2.21]heptyl and adamantyl group and is at the 
1-position of the 4-methylbicyclo [2.2.2]octyl group; and R.sup.4 and 
R.sup.5 are hydrogen or alkyl having from one through four carbon atoms 
and wherein the groups R.sup.4 --CH.dbd.CH--(CH.sub.2).sub.n -- and 
R.sup.5 --C.tbd.C--(CH.sub.2).sub.n -- each have from four through eight 
carbon atoms. 
Where the Z substituent contains asymmetric carbon, the compounds exist as 
optical isomers. The endo and exo forms of R.sup.3 are geometric isomers 
as are also the cis and trans forms of the group R.sup.4 
--CH.dbd.CH--(CH.sub.2).sub.n --. Correspondingly the above formulas are 
intended to represent both the individual enantiomers and diastereomers as 
well as mixtures thereof and both the respective individual isomers as 
well as mixtures thereof are encompassed within the invention. 
DEFINITIONS 
As used hereinabove and below, the following terms have the following 
meanings unless expressly stated to the contrary. The term alkyl refers to 
both straight and branched chain alkyl groups. The term lower alkyl refers 
to both straight and branched chain alkyl groups having a total of from 
one through six carbon atoms and thus includes primary, secondary, and 
tertiary alkyl groups. Typical lower alkyls include, for example, methyl, 
ethyl, n-propyl, isopropyl, n-butyl, t-butyl, n-hexyl and the like. 
The term alkenyl refers to unsaturated alkyl groups having a double bond 
(e.g. CH.sub.3 CH.dbd.CH(CH.sub.2).sub.2 --) and includes both straight 
and branched chain alkenyl groups. Typical alkenyl groups include, for 
example, but-3-enyl (i.e. H.sub.2 C.dbd.CH(CH.sub.2).sub.2 --); hex-4-enyl 
(i.e. CH.sub.3 CH.dbd.CH(CH.sub.2).sub.3 --); 5,5-dimethylhex-3-enyl 
##STR3## 
oct-5-enyl (i.e. C.sub.2 H.sub.5 CH.dbd.CH(CH.sub.2).sub.4 --) and the 
like. The terms cis and trans refer to the following orientations: 
##STR4## 
The term alkynyl refers to unsaturated alkyl groups having a triple bond 
(e.g. CH.sub.3 C.tbd.C(CH.sub.2).sub.2 --) and includes both straight and 
branched chain alkynyl groups. Typical alkynyl groups include, for 
example, but-3-ynyl (i.e. HC.tbd.C(CH.sub.2).sub.2 --); hex-4-ynyl (i.e. 
CH.sub.3 C.tbd.C(CH.sub.2).sub.3 --); 5,5-dimethylhex-3-ynyl 
##STR5## 
oct-5-ynyl (i.e. C.sub.2 H.sub.5 C.tbd.C(CH.sub.2).sub.4 --) and the like. 
The term alkylamino refers to the group having the formula R'HN-- wherein 
R' is alkyl and the term lower alkylamino refers to such groups wherein R' 
is lower alkyl. 
The term aminocarbonyl or carbamoyl refers to the group having the formula 
##STR6## 
The term substituted aminocarbonyl or substituted carbamoyl refers to the 
group having the formula 
##STR7## 
Typical substituted aminocarbonyl or substituted carbamoyl groups include, 
for example, 2-(endobicyclo[3.1.0]hex-6-yl)ethylaminocarbonyl or 
2-(endobicyclo[3.1.0]hex-6-yl)ethylcarbamoyl; 
4-(adamant-1-yl)-n-butylaminocarbonyl or 4-(adamant-1-yl)n-butylcarbamoyl; 
5-methylhexylaminocarbonyl, cyclopentylethylaminocarbonyl, 
hex-5-ynylaminocarbonyl, 5-methylhex-3-ynylaminocarbonyl, 
hex-5-ynylaminocarbonyl, oct-5-cis-enylaminocarbonyl, 
5,5-dimethylhex-cis-3-enylaminocarbonyl, oct-5-trans-enylaminocarbonyl and 
the like. 
The term bicyclo [3.1.0]hexyl refers to, and encompasses, the following 
structural formulas, and the radicals represented thereby, and wherein the 
open substituent represents the point of attachment to the 
##STR8## 
substituent of formula I: 
##STR9## 
The term bicyclo [2.2.1]heptyl, refers to, and encompasses, the following 
structural formulas, and the radicals represented thereby, and wherein the 
open substituent represents the point of attachment to the 
##STR10## 
substituent of formula I. 
##STR11## 
The term 4-methylbicyclo [2.2.2]oct-1-yl refers to the following structural 
formula and the radical represented thereby, wherein the open substituent 
represents the point of attachment to the 
##STR12## 
The term adamantyl refers to, and encompasses, the following structural 
formulas, and the radicals represented thereby, and wherein the open 
substituent represents the point of attachment to the 
##STR13## 
Typical illustrations of the compounds of formula I can be had, for 
example, hereinbelow by reference to Examples 1, 2, and 2A. The preferred 
Z substituents are 2-(endobicyclo[3.1.0]hex-6-yl)ethyl, 2-cyclohexylethyl, 
5-methylhex-3-ynyl and 5-methylhexyl. The preferred R.sup.1 substitutents 
are methyl, ethyl, benzyl or phenyl and especially ethyl and benzyl. 
The process of the invention for preparing the compounds of formula I can 
be represented by the following schematic overall reaction sequence. 
##STR14## 
wherein R.sup.1 and Z are as defined hereinabove. 
Steps 1 and 2 are both oxidation steps and generally can be conducted as a 
single step. The oxidation can, for example, be conducted by treating the 
compound of formula (A) with hydrogen peroxide using acetic acid as a 
solvent. Where the compound of formula II is desired, the treatment is 
typically conducted at temperatures in the range of about from 20.degree. 
to 60.degree. C, preferably about from 40.degree. to 50.degree. C, for 
about from 10 minutes to 6 hours, preferably about from 2 to 3 hours, 
using a mole ratio of hydrogen peroxide to starting material of formula A 
of about from one to 10, preferably about from one to two. Other suitable 
solvents which can be used include, for example, acetone, chloroform, 
methylene, chloride and the like. Where the compounds of formula III are 
desired, the treatment is typically conducted at temperatures in the range 
of about from 20.degree. to 70.degree. C, preferably about from 30.degree. 
to 55.degree. C, for about from 5 to 20 hours, preferably about from six 
to 12 hours, using a mole ratio of hydrogen peroxide to starting material 
of formula A of about from two to 10, preferably from six to eight. Also 
in place of acetic acid, the following solvents can, for example, be used, 
acetone, chloroform, methylene chloride and the like. The compounds of 
formula II can be similarly conveniently oxidized to the compounds of 
formula III by treatment with hydrogen peroxide in acetic acid. In this 
case, the treatment is typically conducted at temperatures in the range of 
about from 40.degree. to 70.degree. C, preferably about from 50.degree. to 
60.degree. C for about from 1 to 4 hours, using mole ratios of hydrogen 
peroxide to formula II of from bout two to 10, preferably from six to 
eight. Also other conventional oxidation systems could be used in place of 
the hydrogen peroxide system, for example, perbenzoic acid, peracetic 
acid, m-chloroperbenzoic acid, sodium periodate, and the like. In the case 
of the compounds of formula III wherein Z is R.sup.4 
--CH.dbd.CH--(CH.sub.2).sub.n -- poor results are generally obtained using 
the hydrogen peroxide treatment described above, hence these compounds are 
best prepared via oxidation of the corresponding compound of formula A 
with sodium periodate in a suitable solvent-system. Typically this 
oxidation is conducted at temperatures in the range of about from 
45.degree. to 75.degree. C, preferably about from 55.degree. to 65.degree. 
C, for about from 8 to 40 hours, preferably about from 15 to 20 hours 
using mole ratios of sodium periodate to compound of formula A in the 
range of about from two to ten, preferably about from two to three. 
Suitable solvents for the compounds of formula A which can be used 
include, for example, acetic acid, lower alkanols, e.g. methanol, ethanol, 
etc., and the like. Conveniently, water is used as the solvent for the 
sodium periodate. Hence, the solvent system will be water plus the 
particular inert organic solvent used for the compound of formula A. 
Typically the product of this oxidation is a major-minor mixture of both 
the compounds of formulas II and III, respectively, which can be used, 
without separation, as starting material to prepare the corresponding 
1,2-epoxypropane compound of formula B in the process described 
hereinbelow. If desired, however, the respective products can be separated 
by column chromatography (e.g. silica gel) or on a laboratory scale by 
thin layer chromatography such as, for example, described in Example 2A 
hereinbelow. 
The compound of formula II can be produced as the major product of the 
sodium periodate oxidation by reducing the reaction temperature (e.g. 
25.degree.-35.degree. C). 
The starting materials of formula A can be prepared by treating the 
2-alkylthiothiazole or 2-benzylthiazole with butyl lithium followed by 
carbon dioxide to yield the corresponding lithium salt of 2-alkylthio- or 
2-benzylthio-5-carboxythiazole. This lithium salt is allowed to react, for 
example, with ethylchloroformate or oxalyl chloride. The mixed anhydride 
or acid chloride is then heated with the appropriate monoamine (see 
Preparations 2 and 3 hereinbelow). The monoamines are known compounds or 
can be prepared by obvious adaptations of known procedures. Note, for 
example, the amine preparations described in U.S. application Ser. No. 
706,342, pages 22-44 by Lewis, Unger and Untch and U.S. applications Ser. 
Nos. 706,341 and 706,413, pages 20-22 and 21-23, respectively by Berkoz, 
Lewis and Unger, all filed on even date herewith and hereby incorporated 
by reference. The 2-alkyl-thiazole or 2-benzylthiazole starting materials 
can be prepared by treating 2-bromothiazole or 2-chlorothiazole with the 
desired alkanethiol or benzylthiol and sodium hydride (see Preparation 1 
hereinbelow). 
Where desired the individual geometric isomers of formula I can be obtained 
by conventional separation and purification procedures. 
The process, of the invention, for preparing the 1,2-epoxypropane thiazole 
intermediates and the process of the invention for preparing the 
1-alkylamino-3-(5-substituted-aminocarbonylthiazol-2-yloxy)-2-propanol 
cardiovascular agents can be schematically represented by the following 
overall reaction sequence: 
##STR15## 
wherein X' is bromo, chloro, --SOR.sup.1 or --SO.sub.2 R.sup.1, wherein 
R.sup.1 is lower alkyl, phenyl or benzyl; R.sup.6 is lower alkyl; and Z is 
as defined hereinabove. 
Step 1 can be effected by treating the compound of formula I' with glycidol 
anion in an inert organic solvent. This treatment is conveniently 
conducted by first treating glycidol with an alkali metal hydride to 
generate the glycidol anion. This initial treatment is typically conducted 
at temperatures in the range of about from -30.degree. to 30.degree. C, 
preferably about from -10.degree. to 5.degree. C for about 1 minute to 1 
hour, preferably about from 5 minutes to 20 minutes. The compound of 
formula I', typically dissolved in an inert organic solvent, can then be 
treated with the preceding glycidol anion mixture. Typically, this 
treatment is conducted at temperatures in the range of about from 
-30.degree. to 25.degree. C, preferably about from -10.degree. to 
0.degree. C, for about from 1 minute to 1 hour, preferably about from 10 
to 30 minutes. Typically, mole ratios of glycidol to alkali metal hydride 
of about from 1-5:1 are used, preferably about from 1.0 to 1.3:1, and mole 
ratios of glycidol to compound of formula I' in the range of about from 1 
to 5, preferably about from 1.0 to 1.3 are used. Suitable alkali metal 
hydrides which can be used include, for example, sodium hydride, potassium 
hydride, lithium hydride, and the like. Suitable inert organic solvents 
which can be used include, for example, tetrahydrofuran, diethyl ether, 
dioxane, dimethoxyethane, dimethylformamide and the like, and mixtures 
thereof. Both procedures of the treatment are conducted under anhydrous 
conditions, and preferably under an inert atmosphere (e.g. nitrogen). The 
resulting product of formula B is preferably isolated before being used as 
starting material for the next step. Such isolation can be effected by 
conventional separation procedures such as, for example, precipitation 
with water, extraction, crystallization or chromatography. Illustrations 
of typical separation and isolation procedures can be had by reference to 
Examples 3 and 4, hereinbelow. 
The 2-bromo- or 2-chloro-5-substituted aminocarbonylthiazole starting 
material of formula I' can be prepared by treating 2-bromo- or 
2-chloro-5-carboxythiazole with ethylchloroformate or oxalyl chloride 
followed by treatment with the desired primary amine. 
The products of formula C can be conveniently prepared by treating the 
compound of formula B with a monoalkylamine having the desired alkyl 
substituent. Typically, this treatment is conducted in an inert organic 
solvent and is typically conducted at temperatures in the range of about 
from -10.degree. to 100.degree. C, preferably about from 10.degree. to 
25.degree. C, for about from 1 hour to 48 hours, preferably about from 5 
to 18 hours. Typically about from one to 30 moles, preferably about from 1 
to 10 moles of alkylamine to compound of formula B is used. Suitable 
alkylamines which can be used include, for example, methylamine, 
ethylamine, isopropylamine, t-butylamine, n-pentylamine, 
4-methylpentylamine and the like. Suitable inert organic solvents which 
can be used include, for example, methanol, ethanol, monoglyme, acetone 
and the like and mixtures thereof. The resulting products of formula C can 
then be separated and isolated according to conventional procedures such 
as, for example, evaporation, crystallization, chromatography, thin-layer 
chromatography, etc. Specific illustrations of typical separation and 
isolation procedures can be had by reference to the corresponding 
examples, set forth hereinbelow. 
A further embodiment of the invention comprises an improved process for 
preparing the cardiovascular agents represented by formula (E) below. This 
process can be schematically represented by the following overall reaction 
equation. 
##STR16## 
wherein R.sup.9 is lower alkyl; R.sup.7 and R.sup.8 are independently 
hydrogen or lower alkyl; and X and Z are as defined hereinabove. 
This process is preferably conducted in two steps. In the initial step the 
5-hydroxymethyl-3-lower alkyl-oxazolidone or 2-mono or 2,2-dialkyl 
derivative thereof (formula D) is treated with an alkaline metal hydride, 
e.g. sodium hydride, in a suitable inert organic solvent. Typically, this 
treatment is conducted at temperatures in the range of about from 
-5.degree. to 100.degree. C, preferably about from 25.degree. to 
60.degree. C, for about 10 minutes to 6 hours, preferably about from 1 
hour to to 3 hours. Suitable inert organic solvents which can be used 
include, for example, tetrahydrofuran, dimethylformamide, monoglyme, 
diglyme, and the like. The second step can be effected by treating the 
initial product reaction mixture with the starting material of formula I 
having the 5-position substituent desired in the product. Typically, this 
treatment is conducted at temperatures in the range of about from 
-20.degree. to 80.degree. C, preferably about from 0.degree. to 30.degree. 
C, for about from 1 minute to 10 hours, preferably about from 5 minutes to 
2 hours. Typically, the compound of formula I is added to the reaction 
mixture in the form of a solution in a suitable inert organic solvent. 
Suitable inert organic solvents which can be used include, for example, 
tetrahydrofuran, dimethylformamide, monoglyme, diglyme, and the like. 
Also, in some instances, an excess of the oxazolidine reagent can be used 
as the solvent. Both steps of this procedure are conducted under anhydrous 
conditions and preferably are conducted in an inert gas such as, for 
example, nitrogen. 
The product of formula E can then be separated and purified according to 
conventional procedures such as, for example, illustrated in Example 7, 
hereinbelow. Care should be exercised during the purification procedure as 
the compounds of formula E are easily hydrolyzed to the compounds of 
1-alkylaminopropan-2-ol compounds of formula C, described hereinbelow, 
under both acid and basic conditions. Correspondingly, the alkylamino 
compounds of formula C can be readily prepared by simple acid or base 
hydrolysis of the corresponding compounds of formula E. Acid hydrolysis 
can be conveniently effected by treating the compound of formula E with a 
suitable organic acid such as, for example, acetic, formic, oxalic acid 
and the like or suitable inorganic acid such as, for example, 
hydrochloric, sulfuric, and the like. Preferably the hydrolysis is 
conducted under midly acidic conditions. Similarly, basic hydrolysis can 
be conducted by treating the compound of formula E with a suitable base 
such as, for example, dilute sodium hydroxide, potassium hydroxide and the 
like. Preferably the base hydrolysis is conducted under midly alkaline 
conditions. Alternatively, the hydrolysis can be conducted via exchange 
with a suitable ion exchange resin in either the H.sup.+ or OH.sup.- form. 
If desired the pharmaceutically acceptable acid addition salts of the 
products of formula C can be prepared from the parent compound, typically 
via neutralization of an amino moiety, with the desired acid. Other 
pharmaceutically acceptable addition salts can then be conveniently 
prepared from the addition salts via anion exchange with a suitable ion 
exchange resin in the desired anionic form. 
The compounds of formulas C and E, and their pharmaceutically acceptable 
salts (e.g. hydrochloride, maleate, etc.) are useful in the treatment and 
palliation of cardiovascular abnormalities in mammals. These compounds 
primarily achieve their therapeutic action by selectively blocking the 
cardiac .beta.-adrenergic receptor sites and, accordingly, because they 
are cardiac selective, they can also be applied to treat cardiac 
abnormalities in patients suffering from asthma or chronic obstructive 
lung disease. Further, based on the virtual identity of therapeutic 
activity, observed between the counterparts of formulas C and E, and the 
fact that the compounds of formula E are readily hydrolyzed to the 
compounds of formula C, it is believed that the compounds of formula E 
hydrolyze in vivo and hence function therapeutically as the compounds of 
formula C. The compounds are especially useful in the treatment or 
palliation of cardiac arrhythmias, angina pectoris, hypetrophic subaortic 
stenosis, pheochromocytoma, thyrotoxicosis, hyperkinetic syndromes, 
tetralogy of Fallot, mitral stenosis with tachycardia, general ischemic 
conditions, and hypertension founded on elevated cardiac outputs due to a 
hyperadrenergic state. The compounds are active, both in the treatment or 
palliation of acute attacks of such cardiac disorders, and further can be 
applied prophylactically to prevent or reduce the frequency of such 
attacks. This prophylactic action is particularly desirable in reducing 
the frequency of attacks of angina pectoris, since the medication (i.e. 
nitroglycerin) presently commonly used in the treatment of angina pectoris 
has no recognized prophylactic action. Additional information concerning 
the use, action and determination of .beta.-blockers can be obtained, by 
reference to the literature such as, for example, Dotlery et al, Clinical 
Pharmacology and Therapeutics, volume 10, no. 6, 765-797 and the 
references cited therein. 
These compounds are also useful in the treatment of hypertension in 
mammals. 
Whether administered for the treatment of cardiac disorders or 
hypertersion, the compounds are typically administered in dosages of about 
from 0.01 to 5 mg. per kg. of body weight. The precise effective dosage 
will, of course, vary depending upon the mode of administration, the 
condition being treated and the host. Where the compounds are used to 
treat cardiac conditions such as arrhythmias, the compounds are typically 
administered either orally or intravenously. Where the compounds are 
administered to treat hypertension or cardiac conditions such as angina 
pectoris, the compounds are, for the sake of convenience, typically 
administered orally. 
These compounds can be administered for the treatment of cardiac disorders 
and hypertension in a wide variety of dosage forms, either alone or in 
combination with other pharmaceutically compatible medicaments, in the 
form of pharmaceutical compositions suited for oral or parenteral 
administration. The compounds are typically administered as pharmaceutical 
compositions consisting essentially of the compounds of the invention and 
a pharmaceutical carrier. In the case of the compounds of formula C, the 
compounds are typically administered as pharmaceutically acceptable salts. 
The pharmaceutical carrier can be either a solid material or liquid, in 
which the compound is dissolved, dispersed or suspended, and can 
optionally contain small amounts of preservatives and/or pH-buffering 
agents. Suitable preservatives which can be used include, for example, 
benzyl alcohol and the like. Suitable buffering agents include, for 
example, sodium acetate and pharmaceutical phosphate salts and the like. 
The liquid compositions can, for example, be in the form of solutions, 
emulsions, suspensions, syrups or elixirs and optionally can contain small 
quantities of preservatives and/or buffering agents, and preferably 
contain the therapeutic agent in convenient unit dosage concentrations. 
The solid compositions can take the form of tablets, powders, capsules, 
pills or the like, preferably in unit dosage forms for simple 
administration or precise dosages. Suitable solid carriers include, for 
example, pharmaceutical grades of starch, lactose, sodium saccharin, 
sodium bisulfite and the like. 
A further understanding of the invention can be had from the following 
non-limiting Preparations and Examples. Also as used hereinabove and below 
unless expressly stated to the contrary, all temperatures and temperature 
ranges refer to the Centrigrade system and the terms ambient or room 
temperature refer to about 20.degree. C. The term percent or (%) refers to 
weight percent and the term mole or moles refers to gram moles. The term 
equivalent refers to a quantity of reagent equal in moles to the moles of 
the preceding or succeeding reactant recited in that Preparation or 
Example in terms of moles or finite weight or volume. Also unless 
expressly stated to the contrary, racemic mixtures and/or diastereomer 
mixtures are used as starting materials and correspondingly racemic 
mixtures and/or diastereomer mixtures are obtained as products and where 
necessary, preparations and examples are repeated to provide sufficient 
quantities of starting materials for subsequent preparations and examples. 
Where given proton magnetic resonance spectrum (n.m.r.) are determined at 
100 mHz (the signs of the coupling constants are not assigned) and signals 
are assigned as singlets (s), broad singlets (bs), doublets (d), double 
doublets (dd), triplets (t), double triplets (dt), quartets (q) and 
multiplets (m). 
PREATION 1 
2-Ethylthiothiazole 
In this preparation 0.15 mole of 50% sodium hydride in mineral oil is 
stirred in 100 ml. of dimethylformamide, under a nitrogen atmosphere, then 
cooled to -50.degree. C and 0.15 mole of ethanethiol (i.e. ethylmercaptan) 
is added dropwise. The resulting mixture is warmed to 0.degree. C and then 
recooled to -50.degree. C and 0.1 mole of 2-bromothiazole (K. Ganapathi et 
al, Proc. Indian Acad. Sci., A22, 362 (1945)) is added. The resulting 
mixture is warmed to room temperature (about 20.degree. C) and maintained 
at this temperature until the reaction is determined to be complete as 
shown by thin-layer chromatography; about two hours. The mixture is then 
poured into 500 ml. of hexane, then washed three times with water. The 
organic layer is dried with anhydrous magnesium sulfate, filtered, and the 
resulting filtrate evaporated under vacuum yielding 2-ethylthiothiazole as 
a colorless oil. 
Similarly by following the same procedure but respectively using methyl 
mercaptan, t-butylmercaptan, hexyl mercaptan and benzyl mercaptan in place 
of ethanethiol, 2-methylthiothiazole; 2-t-butylthiothiazole; 
2-hexylthiothiazone and 2-benzylthiothiazole are respectively prepared. 
PREATION 2 
2-Ethylthio-5-carboxythiazole 
In this preparation 0.2 mole of 2-ethylthiothiazole is dissolved in 300 ml. 
of anhydrous tetrahydrofuran, under a nitrogen atmosphere, then cooled to 
-80.degree. C. 0.2 Mole of butyl lithium in 125 ml. of hexane is then 
added dropwise with stirring. The mixture is stirred for five minutes and 
then anhydrous carbon dioxide bubbled through the mixture until reaction 
is completed (the reaction is monitored by thin-layer chromatography). The 
mixture is allowed to warm to 0.degree. C, 300 ml. of hexane added and 
then filtered. The filter cake is recovered and washed with ethyl ether, 
affording the lithium salt of 2-ethylthio-5-carboxythiazole, and then 
slurried with 300 ml. of ethyl acetate. The ethyl acetate slurry is then 
acidified with 2 Normal hydrochloric acid and washed with water. The 
organic layer is recovered, dried with anhydrous magnesium sulfate, and 
the resulting filtrate evaporated to dryness under vacuum yielding 
2-ethylthio-5-carboxythiazole. 
Similarly by following the same procedure, but using the remaining products 
prepared according to Preparation 1, the corresponding 2-alkyl and 
2-benzyl-5-carboxythiazoles are respectively prepared. 
PREATION 3 
2-Alkylthio-5-substituted aminocarbonylthiazole 
In this preparation 0.1 mole of 2-ethylthio-5-carboxythiazole is dissolved 
in 300 ml. of anhydrous tetrahydrofuran, under nitrogen, and 0.1 mole of 
triethylamine is added and the resulting mixture cooled to -30.degree. C. 
0.1 Mole of ethylchloroformate is then added dropwise with stirring and 
the resulting mixture allowed to warm to 0.degree. C. The mixture is then 
stirred for ten minutes, then cooled to -30.degree. C and 0.11 mole of 
2-(bicyclo[2.2.1]hept-7-yl)ethylamine in 50 ml. of tetrahydrofuran added 
dropwise. The mixture is allowed to warm to room temperature (about 
20.degree. C), poured into 500 ml. of ethyl acetate, washed with water, 
then washed with saturated aqueous sodium chloride solution, and dried 
over anhydrous magnesium sulfate. The mixture is then filtered and the 
resulting filtrate evaporated under vacuum yielding 
2-ethylthio-5-[2-(bicyclo[2.2.1]hept-7-yl)ethylaminocarbonyl]-thiazole as 
a solid, which is then further purified by recrystallization from ethyl 
acetate. 
Similarly by following the same procedure but respectively using the amines 
listed in Table A, hereinbelow, in place of 
2-(bicyclo[2.2.1]hept-7-yl)ethylamine, the corresponding 5-substituted 
aminocarbonylthiazole analogs are respectively prepared: 
TABLE A 
2-(bicyclo[2.2.1]hept-1-yl)ethylamine; 
2-(exobicyclo[2.2.1]hept-2-yl)ethylamine; 
2-(endobicyclo[2.2.1]hept-2-yl)ethylamine; 
2-(exobicyclo[3.1.0]hex-6-yl)ethylamine; 
2-(endobicyclo[3.1.0]hex-6-yl)ethylamine; 
2-(exobicyclo[3.1.0]hex-3-yl)ethylamine; 
2-(endobicyclo[3.1.0]hex-3-yl)ethylamine; 
2-(exobicyclo[3.1.0]hex-2 -yl)ethylamine; 
2-(endobicyclo[3.1.0]hex-2-yl)ethylamine; 
2-(bicyclo[3.1.0]hex-1-yl)ethylamine; 
2-(4-methylbicyclo[2.2.2]oct-1-yl)ethylamine; 
2-(adamant-2-yl)ethylamine; 
2-(adamant-1-yl)ethylamine; 
3-(bicyclo[2.2.1]hept-7-yl)n-propylamine; 
3-(exobicyclo[3.1.0]hex-6-yl)n-propylamine; 
3-(endobicyclo[3.1.0]hex-6-yl)n-propylamine; 
3-(endobicyclo[3.1.0]hex-3-yl)n-propylamine; 
3-(4-methylbicyclo[2.2.2]oct-1-yl)n-propylamine; 
3-(adamant-2-yl)n-propylamine; 
4-(bicyclo[2.2.1]hept-7-yl)n-butylamine; 
4-(exobicyclo[2.2.1]hept-2-yl)n-butylamine; 
4-endobicyclo[2.2.1]hept-2-yl)n-butylamine; 
4-(endobicyclo[3.1.0]hex-6-yl)n-butylamine; 
4-(endobicyclo[3.1.0]hex-3-yl)n-butylamine; 
4-(exobicyclo[3.1.0]hex-2-yl)n-butylamine; 
4-(4-methylbicyclo[2.2.2]oct-1-yl)n-butylamine; 
4-(adamant-2-yl)n-butylamine; 
4-(adamant-1-yl)n-butylamine; 
1-aminohex-5-ene; 
1-aminobut-3-ene; 
1-aminopent-cis-3-ene; 
1-aminohex-cis-3-ene; 
1-aminohept-cis-3-ene; 
1-amino-5-methylhex-cis-3-ene; 
1-aminooct-cis-3-ene; 
1-amino-6-methylhept-cis-3-ene; 
1-amino-5,5-dimethylhex-cis-3-ene; 
1-aminopent-4-ene; 
1-amino-6-methylhept-cis-4-ene; 
1-aminooct-cis-5-ene; 
1-aminopent-trans-3-ene; 
1-aminohex-trans-3-ene; 
1-aminohept-trans-3-ene; 
1-amino-5-methylhex-trans-3-ene; 
1-aminooct-trans-3-ene; 
1-amino-6-methylhept-trans-3-ene; 
1-amino-5,5-dimethylhex-trans-3-ene; 
1-aminohex-trans-4-ene; 
1-aminooct-trans-4-ene; 
1-aminohept-trans-5-ene; 
1-aminobut-3-yne; 
1-aminopent-3-yne; 
1-aminohex-3-yne; 
1-aminohept-3-yne; 
1-amino-5-methylhex-3-yne; 
1-aminooct-3-yne; 
1-amino-6-methylhept-3-yne; 
1-aminopent-4-yne; 
1-aminohex-4-yne; 
1-aminohept-4-yne; 
1-aminooct-4-yne; 
1-amino-6-methylhept-4-yne; 
1-aminohex-5-yne; 
1-aminohept-5-yne; 
1-aminooct-5-yne; 
1-amino-5,5-dimethylhex-3-yne; 
methylamine; 
t-butylamine; 
hexylamine; 
4-methylhexylamine; 
5-methylhexylamine; 
heptylamine; 
3-propylheptylamine; 
decylamine; 
dodecylamine; 
2-cyclopentylethylamine; 
2-cyclohexylethylamine; 
3-cyclopentylpropylamine; 
4-cyclohexylbutylamine; 
cycloheptylmethylamine; and 
4-cyclooctylbutylamine. 
Similarly, by following the same procedure but using the corresponding 
products of Preparation 2 as starting materials, the corresponding 
2-methylthio; 2-t-butylthio; 2-hexylthio and 2-benzylthio analogs and each 
of the above compounds are respectively prepared. 
PREATION 4 
By following the procedure of Preparation 3 but respectively using 
2-bromo-5-carboxythiazole and 2-chloro-5-carboxythiazole in place of 
2-ethylthio-5-carboxythiazole, the 2-bromo and 2-chloro analogs of the 
products of Preparation 3 are respectively prepared.

EXAMPLE 1 
This example illustrates the preparation of the compounds of formula I 
wherein X is --SOR.sup.1. In this example a mixture of 20 g. of 
2-ethylthio-5-[2-(bicyclo[2.2.1]hept-7-yl)ethylaminocarbonyl]thiazole 
(0.064 mole); 40 ml. of 30% aqueous hydrogen peroxide and 200 ml. of 
acetic acid is stirred at a temperature of from 40.degree. to 50.degree. C 
for 4 hours. The mixture is concentrated by evaporation of a large portion 
of the acetic acid, under vacuum, at room temperature (about 20.degree. C) 
and the resulting residue poured into 500 ml. of ethyl acetate and then 
washed with aqueous sodium bicarbonate solution until no acetic acid is 
present in the organic layer. The ethyl acetate layer is then separated, 
dried with anhydrous magnesium sulfate, filtered, and the resulting 
filtrate evaporated to dryness, under vacuum, affording 
2-ethylsulfinyl-5-[2-(bicyclo[2.2.1]hept-7-yl)ethylaminocarbonyl]thiazole. 
Similarly, by following the same procedure but respectively replacing 
2-ethylthio-5-[2-(bicyclo[2.2.1]hept-7-yl)ethyl aminocarbonyl]thiazole 
with the 2-ethylthio-5-substituted aminocarbonylthiazole products of 
Preparation 3, the following 2-ethylsulfinyl analogs are respectively 
prepared. 
2-ethylsulfinyl-5-[2-(bicyclo[2.2.1]hept-1-yl)ethylamino-carbonyl]thiazole; 
2-ethylsulfinyl-5-[2-(exobicyclo[2.2.1]hept-2-yl)ethylaminocarbonyl]thiazol 
e; 
2-ethylsulfinyl-5-[2-(endobicyclo[2.2.1]hept-2-yl)ethylaminocarbonyl]thiazo 
le; 
2-ethylsulfinyl-5-[2-(exobicyclo[3.1.0]hex-6-yl)ethylaminocarbonyl]thiazole 
; 
2-ethylsulfinyl-5-[2-(endobicyclo[3.1.0]hex-6-yl)ethylaminocarbonyl]thiazol 
e, nmr .delta.:1.29t, 3H; 1.65m, 11H; 
3.30m, 4H; 6.80bs, 1H; 8.30s, 1H; 
2-ethylsulfinyl-5-[2-(exobicyclo[3.1.0]hex-3-yl)ethylaminocarbonyl]thiazole 
; 
2-ethylsulfinyl-5-[2-(endobicyclo[3.1.0]hex-3-yl)ethylaminocarbonyl]thiazol 
e; 
2-ethylsulfinyl-5-[2-(exobicyclo[3.1.0]hex-2-yl)ethylaminocarbonyl]thiazole 
; 
2-ethylsulfinyl-5-[2-(endobicyclo[3.1.0]hex-2-yl)ethylaminocarbonyl]thiazol 
e; 
2-ethylsulfinyl-5-[2-(bicyclo[3.1.0]hex-1-yl)ethylaminocarbonyl]thiazole; 
2-ethylsulfinyl-5-[2-(4-methylbicyclo[2.2.2]oct-1-yl) 
ethylaminocarbonyl]thiazole; 
2-ethylsulfinyl-5-[2-(adamant-2-yl)ethylaminocarbonyl]thiazole, nmr 
(CDCl.sub.3) .delta.: 1.30t, 3H; 1.76bs, 17H; 3.30m, 4H; 6.50bs, 1H; 
8.27s, 1H; 
2-ethylsulfinyl-5-[2-(adamant-1-yl)ethylaminocarbonyl]thiazole; 
2-ethylsulfinyl-5-[3-(bicyclo[2.2.1]hept-7-yl)n-propylaminocarbonyl]thiazol 
e; 
2-ethylsulfinyl-5-[3-(exobicyclo[3.1.0]hex-6-yl)n-propylaminocarbonyl]thiaz 
ole; 
2-ethylsulfinyl-5-[3-(endobicyclo[3.1.0]hex-6-yl)n-propylaminocarbonyl]thia 
zole; 
2-ethylsulfinyl-5-[3-(endobicyclo[3.1.0]hex-3-yl)n-propylaminocarbonyl]thia 
zole; 
2-ethylsulfinyl-5-[3-(4-methylbicyclo[2.2.2]oct-1-yl)n-propylaminocarbonyl] 
thiazole; 
2-ethylsulfinyl-5-[3-(adamant-2-yl)n-propylaminocarbobnyl]thiazole; 
2-ethylsulfinyl-5-[4-(bicyclo[2.2.1]hept-7-yl)n-butylaminocarbonyl]thiazole 
; 
2-ethylsulfinyl-5-[4-(exobicyclo[2.2.1]hept-2-yl)n-butylaminocarbonyl]thiaz 
ole; 
2-ethylsulfinyl-5-[4-(endobicyclo[2.2.1]hept-2-yl)n-butylaminocarbonyl]thia 
zole; 
2-ethylsulfinyl-5-[4-(endobicyclo[3.1.0]hex-6-yl)n-butylaminocarbonyl]thiaz 
ole; 
2-ethylsulfinyl-5-[4-(endobicyclo[3.1.0]hex-3-yl)n-butylaminocarbonyl]thiaz 
ole; 
2-ethylsulfinyl-5-[4-(exobicyclo[3.1.0]hex-2-yl)n-butylaminocarbonyl]thiazo 
le; 
2-ethylsulfinyl-5-[4-(4-methylbicyclo[2.2.2]oct-1-yl)n-butylaminocarbonyl]t 
hiazole; 
2-ethylsulfinyl-5-[4-(adamant-2-yl)n-butylaminocarbonyl]thiazole; 
2-ethylsulfinyl-5-[4-(adamant-1-yl)n-butylaminocarbonyl]thiazole; 
2-ethylsulfinyl-5-(hex-5-enylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(but-3-enylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(pent-cis-3-enylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(hex-cis-3-enylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(hept-cis-3-enylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(5-methylhex-cis-3-enylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(oct-cis-3-enylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(6-methylhept-cis-3-enylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(5,5-dimethylhex-cis-3-enylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(pent-4-enylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(6-methylhept-cis-4-enylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(oct-cis-5-enylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(pent-trans-3-enylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(hex-trans-3-enylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(hept-trans-3-enylaminocarbonyl)thaizle; 
2-ethylsulfinyl-5-(5-methylhex-trans-3-enylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(oct-trans-3-enylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(6-methylhept-trans-3-enylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(5,5,-dimethylhex-trans-3-enylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(hex-trans-4-enylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(oct-trans-4-enylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(hept-trans-5-enylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(but-3-ynylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(pent-3-ynylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(hex-3-ynylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(hept-3-ynylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(5-methylhex-3-ynylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(oct-3-ynylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(6-methylhept-3-ynylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(pent-4-ynylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(hex-4-ynylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(hept-4-ynylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(oct-4-ynylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(6-methylhept-4-ynylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(hex-5-ynylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(hept-5-ynylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(oct-5-ynylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(5,5,-dimethylhex-3-ynylaminocarbonyl)thiazole nmr 
(CDCl.sub.3) .delta.:1.15d, 6H; 1.30t, 3H; 2.50t, 2H; 3.2m, 3H; 3.5t, 3H; 
6.82bs, 1H; 8.30s, 1H; 
2-ethylsulfinyl-5-(methylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(t-butylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(hexylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(4-methylhexylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(5-methylhexylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(heptylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(3-propylheptylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(decylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(dodecylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(cyclopentylethylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(2-cyclohexylethylaminocarbonyl)thiazole; 
2-ethylsulfinyl-5-(3-cyclopentylpropylaminocarbonyl)thiazole; 
-ethylsulfinyl-5-(4-cyclohexylbutylaminocarbonyl)thiazole; 
2-ethylsulfinl-5-(cycloheptylmethylaminocarbonyl)thiazole; and 
2-ethylsulfinyl-5-(4-cyclooctylbutylaminocarbonyl)thiazole. 
Similarly, by following the same procedure but using the corresponding 
products of Preparation 3 as starting materials, the corresponding 
2-methylsulfinyl; 2-t-butylsulfinyl; 2-hexylsulfinyl; and 2-benzylsulfinyl 
analogs of each of the above compounds are respectively prepared. 
EXAMPLE 2 
This example illustrated the preparation of the compounds of formula I 
wherein X is --SO.sub.2 R.sup.1. In this example a mixture of 10 g. (0.028 
mole) of 2-ethylthio-5-[2-(adamant-1-yl)ethylaminocarbonyl]thiazole; 20 
ml. of 30% hyrogen peroxide and 100 ml. of acetic acid are heated at 
75.degree. C for 2 hours, most of the acetic acid is then removed by 
evaporation under vacuum and the resulting residue dissolved in 250 ml. of 
ethyl acetate and then washed with aqueous sodium bicarbonate solution 
until all traces of acetic acid are removed. The ethyl acetate layer is 
separated and then dried with anhyrous magnesium sulfate, filtered, and 
the resulting filtrate evaporated under vacuum to dryness affording 
2-ethylsulfonyl-5-[2-(adamant-1-yl)ethylaminocarbonyl]thiazole, nmr 
(CDCl.sub.3) .delta.:1.38t, 3H; 1.60m, 17H; 3.46m, 4H; 6.50bs, 1H; 8.28S, 
1H; 
Similarly, by following the same procedure but respectively replacing 
2-ethylthio-5-[2-(adamant-1-yl)ethylaminocarbonyl]thiazole with the 
corresponding 2-ethylthio products of Preparation 3, the following 
2-ethylsulfonyl analogs are respectively prepared: 
2-ethylsulfonyl-5-[2-(bicyclo[2.2.1]hept-7yl)ethylaminocarbonyl]thiazole; 
2-ethylsulfonyl-5-[2-(bicyclo[2,2,1]hept-1-yl)ethylaminocarbonyl]thiazole; 
2-ethylsulfonyl-5-[2-(exobicyclo[2.2.1]hept-2-yl)ethylaminocarbonyl]thiazol 
e; 
2-ethylsulfonyl-5-[2-(endobicyclo[2.2.1]hept-2-yl)ethylaminocarbonyl]thiazo 
le; 
2-ethylsulfonyl-5-[2-(exobicyclo[3.1.0]hex-6-yl)ethylaminocarbonyl]thiazole 
; 
2-ethylsulfonyl-5-[2-(endobicyclo[3.1.0]hex-6-yl)ethylaminocarbonyl]thiazol 
e; 
2-ethylsulfonyl-5-[2-(exobicyclo[3.1.0]hex-3-yl)ethylaminocarbonyl]thiazole 
; 
2-ethylsulfonyl-5-[2-(endobicyclo[3.1.0]hex-3-yl)ethylaminocarbonyl]thiazol 
e; 
2-ethylsulfonyl-5-[2-(exobicyclo[3.1.0]hex-2-yl)ethylaminocarbonyl]thiazole 
; 
2-ethylsulfonyl-5-[2-(endobicyclo[3.1.0]hex-2-yl)ethylaminocarbonyl]thiazol 
e; 
2-ethylsulfonyl-5-[2-(bicyclo[3.1.0]hex-1-yl)ethylaminocarbonyl]thiazole; 
2-ethylsulfonyl-5-[2-(4-methylbicyclo[2.2.2]oct-1-yl)ethylaminocarbonyl]thi 
azole; 
2-ethylsulfonyl-5-[2-(adamant-2-yl)ethylaminocarbonyl]-thiazole; 
2-ethylsulfonyl-5-[3-(bicyclo[2.2.1]hept-7-yl)n-propylaminocarbonyl]thiazol 
e; 
2-ethylsulfonyl-5-[3-(exobicyclo[3.1.0]hex-6-yl)n-propylaminocarbonyl]thiaz 
ole; 
2-ethylsulfonyl-5-[3-(endobicyclo[3.1.0]hex-6-yl)n-propylaminocarbonyl]thia 
zole; 
2-ethylsulfonyl-5-[3-(endobicyclo[3.1.0]hex-3-yl)n-propylaminocarbonyl]thia 
zole; 
2-ethylsulfonyl-5-[3-(4-methylbicyclo[2.2.2]oct-1-yl)n-propylaminocarbonyl] 
thiazole; 
2-ethylsulfonyl-5-[3-(adamant-2-yl)n-propylaminocarbonyl] -thiazole; 
2-ethylsulfonyl-5-[4-(bicyclo[2.2.1]hept-7 
-yl)n-butylaminocarbonyl]thiazole; 
2-ethylsulfonyl-5-[4-(exobicyclo[2.2.1]hept-2-yl)n-butylaminocarbonyl]thiaz 
ole; 
2-ethylsulfonyl-5-[4-(endobicyclo[2.2.1]hept-2-yl)n-butylaminocarbonyl]thia 
zole; 
2-ethylsulfonyl-5-[4-(endobicyclo[3.1.0]-hex-6-yl)n-butylaminocarbonyl]thia 
zole; 
2-ethylsulfonyl-5-[4-(endobicyclo[3.1.0]hex-3-yl)n-butylaminocarbonyl]thiaz 
ole; 
2-ethylsulfonyl-5-[4-(exobicyclo[3.1.0]hex-2-yl)n-butylaminocarbonyl]thiazo 
le; 
2-ethylsulfonyl-5-[4-(4-methylbicyclo[2.2.2]oct-1-yl-n-butylaminocarbonyl]t 
hiazole; 
2-ethylsulfonyl-5-[4-adamant-2-yl)n-butylaminocarbonyl]-thiazole; 
2-ethylsulfonyl-5-[4-(4-adamant-1-yl)n-butylaminocarbonyl]-thiazole; 
2-ethylsulfonyl-5-(but-3-ynylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(pent-3-nynlaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(hex-3-ynylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(hept-3-ynylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(5-methylhex-3-ynylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(oct-3-ynylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(6-methylhept-3-ynylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(pent-4-ynylaminocabonyl)thiazole; 
2-ethylsulfonyl-5-(hex-4-ynylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(hept-4-ynylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(oct-4-ynylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(6-methylhept-4-ynylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(hex-5-ynylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(hept-5-ynylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(oct-5-ynylaminocarbonylthiazole; 
2-ethylsulfonyl-5(5,5,-dimethylhex-3-ynylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(methylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(t-butylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(hexylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(4-methylhexylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(5-methylhexylaminocarbonyl)thiazole, nmr (CLCl.sub.3) 
.delta.: 0.85d, 6H; 1.39;m, 9H, 3.47m, 4H; 6.90s, 1H; 8.34s, 1H; 
2-ethylsulfonyl-5-(heptylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(3-propylheptylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(decylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(dodecylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(2-cyclopentylethylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(2-cyclohexylethylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(3-cyclopentylpropylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(4-cyclohexylbutylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(cycloheptylmethylaminocarbonyl)thiazole; 
-enylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(4-cyclooctylbutylaminocarbonyl)thiazole; and 
Similarly, by following the same procedure but using the corresponding 
products of Preparation 3 as starting materials, the corresponding 
2-methylsulfonyl; 2-t-butylsulfonyl; 2-hexylsulfonyl; and 2-benzylsulfonyl 
analogs of each of the above compounds are respectively prepared. 
EXAMPLE 2A 
This example illustrates methods for preparing the compounds of formula I 
wherein X is --SO.sub.2 R.sup.1 and Z is R.sup.4 
--CH.dbd.CH--(CH.sub.2).sub.n --. In this example a solution of 14 mmoles 
of sodium periodate in 20 ml. of water is added to a solution of 1.85 
mmoles of 2-ethylthio-5-(hex-3-cis-enylaminocarbonyl)-thiazole in 50 ml. 
of acetic acid. The mixture is heated at 60.degree. C for 19 hours and 
then poured into water and extracted with methylene chloride (400 ml.). 
The methylene chloride solution is sequentially washed with water 10% 
aqueous sodium bicarbonate solution, water and then dried over magnesium 
sulfate and filtered. The filtrate is then evaporated under vacuum to 
remove the methylene chloride solvent affording a mixture of 
2-ethylsulfonyl-5-(hex-cis-3-enylaminocarbonyl)-thiazole and 
2-ethylsulfinyl-5-(hex-cis-3-enylaminocarbonyl)-thiazole as an oily 
residue. The respective products are then isolated from a sample of the 
oily residue by thin layer chromatography using ethyl acetate-hexane (1:1 
vol.) as the developing solvent. The sulfonyl product is obtained at about 
Rf 0.5 and the sulfinyl at about Rf 0.2. The remaining portion of the oily 
residue is used as starting material for Example 4. 
Similarly, by following the same procedure but respectively replacing 
2-ethylthio-5-(hex-cis-3-enylaminocarbonyl)-thiazole with the 
corresponding 2-ethylthio products of Preparation 3, the following 
2-ethylsulfonyl analogs (and the corresponding sulfinyl-sulfonyl mixtures) 
are respectively prepared: 
2-ethylsulfonyl-5-(hex-5-enylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(but-3-enylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(pent-cis-3-enylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(hept-cis-3-enylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(5-methylhex-cis-3-enylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(oct-cis-3-enylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(6-methylhept-cis-3-enylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(5,5-dimethylhex-cis-3-enylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(pent-4-enylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(6-methylhept-cis-4-enylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(oct-cis-5-enylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(pent-trans-3-enylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(hex-trans-3-enylaminocarbonyl) thiazole; 
2-ethylsulfonyl-5-(hept-trans-3-enylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(5-methylhex-3-enylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(oct-trans-3-enylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(6-methylhept-trans-3-enylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(5,5-dimethylhex-trans-3-enylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(hex-trans-4-enylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(oct-trans-4-enylaminocarbonyl)thiazole; 
2-ethylsulfonyl-5-(hept-trans-5-enylaminocarbonyl)thiazole; 
Similarly, by following the same procedure but using the corresponding 
products of Preparation 3 as starting materials, the corresponding 
2-methylsulfonyl; 2-t-butylsulfonyl; 2-hexylsulfonyl; and 2-benzylsulfonyl 
analogs of each of the above compounds are respectively prepared. 
EXAMPLE 3 
This example illustrates the process of the invention for preparing 
1,2-epoxy-3-(5-substituted aminocarbonylthiazole-2-yloxy)propane. In this 
example 0.0525 mole of sodium hydride in a 50% mineral oil mixture is 
stirred in 300 ml. of anhydrous tetrahydrofuran, under nitrogen, then 
cooled to -30.degree. C and 0.055 mole of glycidol is added dropwise. The 
mixture is allowed to warm to -5.degree. C and stirred for 10 minutes and 
then recooled to -30.degree. C. A solution of 0.05 mole of 
2-ethylsulfinyl-5-[2-(bicyclo[2.2.1]hept-7-yl)ethylaminocarbonyl]thiazole 
in 100 ml. of anhydrous tetrahydrofuran is added dropwise and the 
resulting mixture allowed to warm to 0.degree. C. Additional solvent is 
added as needed to facilitate stirring. The mixture is maintained for 30 
minutes at 0.degree. C and then poured into 500 ml. of ethyl acetate, 
extracted with 100 ml. of water, and then with 100 ml. of aqueous 
saturated sodium chloride and dried over anhydrous magnesium sulfate and 
filtered. The filtrate is evaporated under vacuum affording oily residue 
which is then further purified by chromatography on silica gel eluting 
with 40% ethyl acetate-60% hexane, by vol., affording 
1,2-epoxy-3-(5-[2-(bicyclo[2.2.1]hept-7-yl)ethylaminocarbonyl]thiazol-2-yl 
oxy)propane. 
Similarly, by following the same procedure, the products of Preparation 4 
and Example 1 are respectively converted into the corresponding 1,2-epoxy 
analogs. 
EXAMPLE 4 
This example illustrates further processes of the invention for preparing 
the 1,2-epoxypropane compounds of formula B. In this example 0.0525 mole 
of sodium hydride in a 50% mineral oil mixture is stirred in 300 ml. of 
anhydrous tetrahydrofuran, under nitrogen, then cooled to -30.degree. C 
and 0.055 mole of glycidol is added dropwise. The mixture is allowed to 
warm to -5.degree. C and stirred for 10 minutes and then recooled to 
-30.degree. C. A solution of 0.05 mole of 
2-ethylsulfonyl-5-[2-(adamant-1-yl)ethylaminocarbonyl]thiazole in 100 ml. 
of anhydrous tetrahydrofuran is added dropwise and the resulting mixture 
allowed to warm to 0.degree. C. Additional solvent is added as needed to 
facilitate stirring. The mixture is maintained at 30 minutes at 0.degree. 
C and then poured into 500 ml. of ethyl acetate, extracted with 100 ml. of 
water, and then with 100 ml. of aqueous saturated sodium chloride and 
dried over anhydrous magnesium sulfate and filtered. The filtrate is 
evaporated under dryness affording oily residue which is then further 
purified by chromatography on silica gel eluting with 40% ethyl acetate- 
60% hexane, by vol., affording 
1,2-epoxy-3-[5-(2-[adamant-1-yl]ethylaminocarbonyl)thiazol-2-yloxy]propane 
. 
Similarly, by following the same procedure, the products of Preparation 4 
and Examples 2 and 2A are respectively converted into the corresponding 
1,2-epoxy analogs. 
EXAMPLE 5 
This example illustrates the second step of the process of the invention 
for preparing the compounds of formula C. In this example a mixture 
containing 12 g. (0.037 mole) of 
1,2-epoxy-3-[5-(2-(bicyclo[2.2.1]hept-7-yl]ethylaminocarbonyl)thiazol-2-yl 
oxy]propane, 12 g. (0.164 mole) of t-butylamine and 20 ml. of ethanol is 
allowed to stand at room temperature for 12 hours. The mixture is then 
evaporated under vacuum to remove the ethanol solvent and the resulting 
residue dissolved in 50 ml. of ethyl acetate and cooled to -20.degree. C, 
and maintained at this temperature for 2 hours. The mixture is then 
filtered and the resulting filter cake washed with cold (about 0.degree. 
C) ethyl ether and then recrystallized from ethyl acetate affording 
1-t-butylamino-3-(5-[2-(bicyclo[2.2.1]hept-7-yl)ethylaminocarbonyl]thiazol 
-2-yloxy)propan-2-ol. 
Similarly, by following the same procedure but using the products of 
Examples 3 and 4 as starting materials, the corresponding 
1-t-butylamino-5-substituted products of formula C are respectively 
prepared, for example: 
1-t-butylamino-3-(5-[2-(4-methylbicyclo[2.2.2]oct-1-yl)ethylaminocarbonyl]t 
hiazol-2-yloxy)-propan-2-ol, m.p. 141.degree.-142.degree. C; 
1-t-butylamino-3-(5-[2-(adamant-2-yl)ethylaminocarbonyl]thiazol-2-yloxy)-pr 
opan-2-ol, m.p. 76.degree.-78.degree. C; 
1-t-butylamino-3-[5-(hex-5-ynylaminocarbonyl)thiazol-2-yloxy]-propan-2-ol, 
m.p. 147.degree.-148.degree. C; 
1-t-butylamino-3-[5-(hex-3-ynylaminocarbonyl)thiazol-2-yloxy]-propan-2-ol, 
m.p. 90.degree.-91.degree. C; and 
1-t-butylamino-3-[5-(hex-5-enylaminocarbonyl)thiazol-2-yloxy]-propan-2-ol, 
m.p. 80.degree.-81.degree. C. 
EXAMPLE 6 
This example illustrates processes of the invention for preparing the 
compounds of formula C. In this example a mixture containing 12 g. (0.0314 
mole) of 
1,2-epoxy-3-(5-[2-(adamant-2-yl)ethylaminocarbonyl]thiazol-2-yloxy)propane 
, 12 g. (0.203 mole) of isopropylamine and 20 ml. of ethanol is allowed to 
stand at room temperature for 12 hours. The mixture is then evaporated 
under vacuum to remove the solvent and the resulting residue dissolved in 
50 ml. of ethyl acetate and cooled to -20.degree. C, and maintained at 
this temperature for 2 hours. The mixture is then filtered and the 
resulting filter cake washed with cold (about 0.degree. C) ethyl ether and 
then recrystallized from ethyl acetate affording 
1-isopropylamino-3-(5-[2-(adamant-2-yl)ethylaminocarbonyl]thiazol-2-yloxy) 
-propan-2-ol. 
Similarly, by following the same procedure but using the products of 
Examples 3 and 4 as starting materials, the corresponding products of 
formula C are respectively prepared, for example: 
1-isopropylamino-3-(5-[2-(exobicyclo[3.1.0 
hex-6-yl)ethylaminocarbonyl]thiazol-2-yloxy)-propan-2-ol, m.p. 
128.degree.-130.degree. C; and 
1-isopropylamino-3-[5-(5-methylhex-cis-3-enylaminocarbonyl)thiazol-2-yloxy] 
-propan-2-ol, m.p. 158.degree.-160.degree. C. 
EXAMPLE 7 
In this example 0.012 mole of sodium hydride (50% mineral oil) is stirred 
in 50 ml. of tetrahydrofuran; under nitrogen, and 0.02 mole of 
5-hydroxymethyl-N-t-butyloxazolidine is added. The mixture is then warmed 
to 50.degree. C until reaction ceases (about 30 minutes) and then cooled 
to room temperature. 0.01 Mole of 
2-ethylsulfinyl-5-[2-(endobicyclo[3.1.0]hex-6-yl)ethylaminocarbonyl]thiazo 
le in 50 ml. of tetrahydrofuran is then added. The mixture is stirred for 
four hours at room temperature and then poured into 200 ml. of ethyl 
acetate, then washed with water; dried over anhydrous magnesium sulfate 
and filtered. The filtrate is evaporated under vacuum affording a crude 
residue of 
5-(5-[2-(endobicycl[3.1.0]hex-6-yl)ethylaminocarbonyl]thiazol-2-yloxy)meth 
ylene-N-5-butyloxazolidine, which is then dissolved in diethyl ether (100 
ml.) and hydrogen chloride gas passed over the surface with rapid stirring 
until no more precipitate is formed. The precipitate is filtered off, 
washed with ether, then recrystallized from propanol-diethyl ether 
mixture. The crystals are filtered off and dried under vacuum affording 
5-(5-[2-endobicyclo[3.1.0]hex-6-yl)ethylaminocarbonyl]thiazol-2-yloxy)meth 
ylene-N-5-butyloxazolidine hydrochoride. 
Similarly, by following the same procedure but using the products of 
Examples 1 and 2 as starting materials, the corresponding compounds of 
formula E, and their hydrochloride salts, are respectively prepared. 
EXAMPLE 8 
This example illustrates methods of converting the compounds of formula E 
into the compounds of formula C. In this example 1 g. of 
5-(5-[2-(bicyclo[2.2.1]hept-7-yl)ethylaminocarbonyl]thiazol-2-yloxy)-methy 
lene-N-t-butyl-2,2-dimethyloxazolidine is dissolved in 50 ml. of ethyl 
acetate and this solution is treated with aqueous 5% sodium hydroxide (20 
ml.) at 20.degree. C. The mixture is allowed to stand for 0.5 hours, 
washed three times with water, dried over magnesium sulfate and then 
evaporated to dryness affording 
1-t-butyl-3-(5-[2-(bicyclo[2.2.1]hept-7-yl)ethylaminocarbonyl]thiazol-2-yl 
oxy-propan-2-ol. 
Similarly, by following the same procedure, the products of Example 5 are 
respectively hydrolyzed to the corresponding compounds of formula C. 
EXAMPLE 9 
This example illustrates an alternate method for converting the compounds 
of formula E to the compounds of formula C. In this example 1 g. of 
5-(5-[2-(endobicyclo[3.1.0]hex-6-yl)ethylaminocarbonyl]thiazol-2-yloxy)-me 
thylen-N-t-butyloxazolidine is dissolved in 20 ml. of methanol containing 4 
cc of 5% aqueous hydrochloric acid at 20.degree. C. After 15 minutes, the 
mixture is neutralized with dilute aqueous sodium carbonate solution, 
poured into water and extracted with ethyl acetate. The ethyl acetate 
extract is evaporated to dryness yielding 
1-t-butylamino-3-(5-[2-(endobicyclo[3.1.0]hex-6-yl)ethylaminocarbonyl]thia 
zol-2-yloxy)-propan-2-ol. 
Similarly, by following the same procedure, the products of Example 5 are 
respectively hydrolyzed to the corresponding compounds of formula C. 
EXAMPLE 10 
This example illustrates methods of preparing hydrochloride addition salts 
of the compound of formula C. In this example 1 g. of 
1-t-butylamino-3-(5-[2-(bicyclo[2.2.1]hept-7-yl)ethylaminocarbonyl]thiazol 
-2-yloxy)propan-2-ol is dissolved in 10 ml. of ethyl ether at 20.degree. C. 
A stream of gaseous anhydrous hydrogen chloride is passed over the surface 
of the solution until the supernatent liquid becomes colorless. The 
resulting precipitate is collected by filtration, washed with ethyl ether 
and then crystallized from methanol/diethyl ether, affording crystalline 
1-t-butylamino-3-(5-[2-(bicyclo[2.2.1]hept-7-yl)ethylaminocarbonyl]thiazol 
-2-yloxy)-propan-2-ol hydrochloride, m.p. 161.degree.-166.degree. C. 
Similarly, by following the same procedure, the corresponding hydrochloride 
addition salts of each of the products of Examples 5 and 6 are 
respectively prepared, for example: 
1-isoproplyamino-3-[5-(2-[adamant-2-yl]ethylaminocarbonyl)thiazol-2-yloxy]- 
propan-2-ol hydrochloride, m.p. 159.degree.-161.degree. C. 
EXAMPLE 11 
This example illustrates methods of preparing the maleate addition salts of 
compounds of formula C. In this example one gram of 
1-t-butylamino-3-[5-(2-[adamant-1-yl]ethylaminocarbonyl)thiazol-2-yloxy]-p 
ropan-2-ol is dissolved in a solution of 5 ml. of ethyl ether and 5 ml. of 
ethanol at 20.degree. C. To this solution is added 10 ml. of a saturated 
solution of maleic acid in ethyl ether. The mixtutre is allowed to stand 
for one hour at room temperature. The resulting precipitate is recovered 
by filtration, washed three times with ethyl ether and then crystalized 
from a mixture of ethyl ether and ethanol (1:1) affording crystalline 
1-t-butylamino-3-[5-(2-[adamant-1-yl]ethylaminocarbonyl)thiazol-2-yloxy]-p 
ropan-2-ol maleate, m.p. 180.degree.-181.degree. C. 
Similarly, by following the same procedure, the corresponding maleate 
addition salts of each of the products of Examples 5 and 6 are 
respectively prepared, for example: 
1-isopropylamino-3-(5-[2-(endobicyclo[3.1.0]hex-6-yl)ethylaminocarbonyl]thi 
azol-2-yloxy)propan-2-ol maleate, m.p. 136.degree.-138.degree. C; 
1-t-butylamino-3-[5-(5-methylhex-3-ynylaminocarbonyl)thiazol-2-yloxy]-propa 
n-2-ol maleate, m.p. 174.degree.-175.degree. C; 
1-isopropylamino-3-[5-(methylhex-3-ynylaminocarbonyl)thiazol-2-yloxy]-propa 
n-2-ol maleate, m.p. 152.degree.-153.degree. C; 
1-isopropylamino-3-[5-(hex-cis-3-enylaminocarbonyl)-2-thiazolyloxy]-propan- 
2-ol maleate, m.p. 165.degree.-165.degree. C; and 
1-isopropylamino-3-[5-(hex-trans-3-enylaminocarbonyl)-2-thiazolyloxy]-propa 
n-2-ol maleate, m.p. 164.degree.-165.degree. C. 
Obviously many modifications and variations of the invention, described 
hereinabove and below in the claims, can be made without departing from 
the essence and scope thereof.