Antibiotic compounds derived from cephalosporins, process for their production and pharmaceutical compositions

The present invention relates to derivatives of the cephalosporin family, the process for their preparation and their therapeutic use.
The compounds according to the invention correspond to the formula: ##STR2## in which: The COOA group at the 4 position is an acid radical, or an alkaline or alkaline-earth salt, or an amino acid or amine salt, for example triethylamine or ethanolamines, or an easily hydrolyzable or metabolically labile and pharmaceutically acceptable ester radical.
X denotes an oxygen atom or a sulfur atom
n is zero or 1
R.sub.1 and R.sub.2 each denote independently hydrogen or a lower alkyl group, preferably a methyl group, or
R.sub.1 and R.sub.2 taken together with the carbon atom to which they are linked form a cyclobutyl or cyclopentyl nucleus.
B is the residue of a primary or secondary amine selected by the following groups:
Z--NH--R where Z is an alkylene group with a straight or branched chain having from 2 to 7 carbon atoms, possibly interrupted by a sulfur atom and possible substituted by a hydroxyl, thiol, methylthio, amino, acetamido, carbamoyl, phenyl, hydroxyphenyl or imidazolyl group.
Z can also be a cyclopentylidene or cyclohexylidene group. R represents a hydrogen atom or an alkyl group having from 1 to 3 carbon atoms.
Z'--Alk--NH--R where Z' represents a 1,2-phenylene or 1,3-phenylene or 1,4-phenylene group possibly substituted by a halogen atom or by 1 or 2 methoxy groups or by 1, 2 or 3 methyl groups or Z' represents a 1,2-cyclohexylene, 1,3-cyclohexylene or 1,4-cyclohexylene group.
Alk represents a straight or branched alkyl group having from 1 to 3 carbon atoms.
R is as defined above. ##STR3## where Z' is as defined above.
Y denotes an alkyl group (CH.sub.2).sub.m in which m=0, 1, 2, 3 or 4, a branched alkyl group having 2 or 3 carbon atoms or also Y with NH--R" constitutes a ring ##STR4## R' and R", identical or different, have the same meaning as that given for R above.
Z"--NH--R where Z" is a 1,3-cyclohexylene or 1,4-cyclohexylene and R is as previously defined. ##STR5## where R.sub.3 represents a hydrogen atom or a methyl group. n=0 or 1 and Alk and R are as previously defined.
A 2-piperidyl, 3-piperidyl or 4-piperidyl group possibly substituted on the nitrogen atom by a --CO--Alk--NH.sub.2 group ##STR6## where Alk is as previously defined.
The salts that the compounds of Formula 1 can give with pharmaceutically acceptable acids form an integral part of the invention.
As a result of the presence in the formula of an oxime group, the compounds (I) exist in two isomeric forms syn and anti. The syn isomers whose therapeutic activity is higher are the preferred compounds.
It is understood that the compounds (I) indicated above can exist:
either in the form indicated in Formula (I),
or in tautomeric form (I'): ##STR7## in which A, X, R.sub.1, R.sub.2, B and n have the previously indicated meanings.
The invention also relates to a process for the preparation of compounds of Formula (I).
According to the reaction diagram below, this process consists of first of all acylating 4-tertiobutyl-1-S-oxide 7-amino-3-bromomethyl-3-cepheme carboxylate (II) with the acid (III) to obtain the compound (IV) described in European patent application No. 60,745. To the compound TV, is then added the acid B--(CH.sub.2).sub.n --COOH or the thioacid B(CH.sub.2).sub.n COSH whose amine function must be previously protected, according to a known method, by a protective group like tertiobutoxycarbonyl or trichlorethoxycarbonyl, for example, B' then represents the group B in which the amine function is protected.
The addition of the sodium or potassium salt of the acid B'--(CH.sub.2).sub.n COOH to the compound (IV) is preferably done in an aprotic polar solvent, for example dimethylformamide, whilst the addition of the sodium or potassium salt of the thioacid B'--(CH.sub.2)HD nCOSH can be done in an apolar solvent like tetrahydrofuran. The compound (V) is obtained.
In the case of the thioacids, to prepare the compounds (V), it is possible to use the thioacid itself instead of an alkali salt. The operation is then in anhydrous acetone in the presence of potassium bicarbonate and sodium iodide.
Finally, to end with the compound (I), the protective groups on the amines and the tertiobutyl esters are removed by a known process, in particular by hydrolysis in an acid medium by using, for example, trifluoracetic acid or a mixture of formic acid and hydrochloric acid. ##STR8## T.sub.r represents trityl, tBu tertiobutyl, X, R.sub.1, R.sub.2, n, B' and B have the previously indicated meanings.
The compounds (I) of the invention in which A is other than H are obtained from compounds (I) in which A is H by reactions known in themselves.
Thus the inorganic salts are obtained by the action on compounds (I), in which A is H, of an inorganic base such as soda or potash or sodium bicarbonate in an equimolecular amount; the salification reaction is carried in a solvent such as water or ethanol and the salt obtained is isolated by evaporation of the solution.
The salts of organic bases are obtained by the action on a solution of the acid I (A=H), in a solvent or a mixture of suitable solvents, of an equimolecular amount of the organic base. The salt is isolated by precipitation with ether.
The esters are obtained by known esterification processes; for example there will advantageously be used the action of a halogen derivative on a salt such as the sodium salt of the acid; preferably the reaction will be carried out in a solvent capable of dissolving the starting acid derivative, for example in dimethylformamide.
The syn and anti form isomers are obtained by a suitable choice of reagents.
the following examples enable the scope of the invention to be further understood without however limiting it.
Thus as is usual in this family of compounds, the products according to the invention do not have a distinct melting point but only points of decomposition which do not permit them to be characterized.
The products will therefore be characterized by their nuclear magnetic resonance spectrum recorded at 60 MHz or at 250 MHz, the internal standard being hexamethyldisiloxane. The spectra are recorded in deuteriated dimethylsulfoxide with the exceptions indicated in the description of the spectrum: 50 mg of product in 0.5 ml of solvent at 60 MHz and 10 mg in 0.5 ml at 250 MHz. The chemical displacements are measured at .+-.0.01 ppm and the coupling constants at .+-.0.5 Hz.
The following abbreviations will be used:
S: singlet
D: doublet
D of D: doublet of doublet
S.e.: widened singlet
M: multiplet
Q: quadruplet
AB: AB system
J: represents the coupling constant.
In addition elementary microanalyses were carried out in each case and are in agreement with the formulae indicated.
The infra-red spectra also serve to characterize the products obtained. They were recorded between 4,000 cm.sup.-1 and 600 cm.sup.-1 from a preparation constituted by a potassium bromide tablet containing the product at a concentration of about 2%; when the spectrum is recorded in solution at 1% in a chlorinated solvent, the nature of the latter is mentioned. The elongation vibration frequency of the carbonyl groups of the molecule is noted (.nu.CO).

EXAMPLE 1
7-[2-(2-Amino 4-thiazolyl)2-(2-carboxy 2-propyl oxyimino)acetamido]3-(4-piperidinyl)carbonyl oxymethyl 3-cepheme 4-carboxylic1.beta.-S-oxide acid trifluoroacetate syn isomer. SR 41 862
(a) 7-[2-(2-tritylamino-4-thiazolyl)2-(2-tertiobutoxycarbonyl 2-propyl oxyimino)acetamido]3-(1-tertiobutoxycarbonyl 4-piperidinyl carbonyl oxymethyl)3-cepheme 1-.beta.-S-oxide carboxylate of Tertiobutyl; syn isomer ##STR9## tBu and T have the previously indicated meanings, Boc denotes the tertiobutoxycarbonyl group.
To a solution of 1.38 g of 4-tertiobutyl 1-.beta.-S-oxide 7-[2-(2-tritylamino 4-thiazolyl)2-(2-tertiobutoxycarbonyl 2-propyl oxyimino)acetamido]3-bromomethyl 3-cepheme carboxylate syn isomer, in 20 ml of anhydrous dimethylformamide, are added 1 g of 1-tertiobutyloxycarbonyl 4-piperidinyl carboxylic acid and 1.5 g of potassium bicarbonate.
After 17 hours of stirring at ambiant temperature (20.degree.-25.degree. C.) the reaction mixture is poured on to 200 ml of ice water. After vigorous stirring, the crystals were filtered and washed with water. They are then taken up with 70 ml of dichloromethane. The organic phase is then washed with a saturated solution of sodium chloride, dried over magnesium sulfate and evaporated. The lacquer obtained is chromatographed on a column of 50 g of silica. It is eluted with a dichloromethane-ethyl acetate mixture 90-10 (vol/vol). After evaporation of the fractions containing the compound and trituration in hexane, 1.3 g of the expected compound is obtained.
IR Spectrum: .differential. CO 1805 cm.sup.-1 : C.dbd.O at 8 of the .beta. lactame; 1735 cm.sup.-1 : C.dbd.O of the tertiobutyl esters and of the ester at the 3 position; 1695 cm.sup.-1 : C.dbd.O of the tertiobutoxycarbonyl protecting group of the piperidine.
NMR Spectrum at 250 MHz. 1H at 8.75 ppm (S, NHTr)--1H at 8.10 ppm (D, J=9 Hz, CONH)--15H at 7.25 ppm (M, H aromatics)--1H at 6.73 ppm (S, H thiazole)--1H at 5.81 ppm (M, H.sub.7)--1H at 5.25 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.94 ppm (D, J=4 Hz, H.sub.6)--1H at 4.55 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.90 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.79 ppm (D, J=12 Hz, HCN Boc equatorials)--1H at 3.53 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 2.75 ppm (M, HCH Boc arials)--1H at 2.50 ppm (M, HCCO.sub.2)-- 2H at 1.75 ppm (D, J=12 Hz, HCHCO.sub.2 equatorials)--9H at 1.46 ppm (S, CO.sub.2, tBU)--2H at 1.40 ppm (M, HCCHCO.sub.2 axials)--6H at 1.39 ppm (S, (CH.sub.3).sub.2 C)--9H at 1.36 ppm (S, CO.sub.2 tBU)--9H at 1.29 ppm (S, Boc N).
(b) SR 41 862
0.8 g of the compound obtained above was dissolved in 10 ml of trifluoroacetic acid. After 45 minutes at 23.degree. C. the acid was evaporated under vacuum without heating and the oily residue was crystallized by the addition of 50 ml of isopropyl ether. The crystals were filtered and washed with isopropyl ether and then with hexane. They were then dried under vacuum over phosphoric anhydride. 0.66 g of the expected products was obtained.
IR Spectrum: .differential. CO 1795 cm.sup.-1 : C.dbd.O at 8 of the .beta. lactam; 1735 cm.sup.-1 : C.dbd.O of the ester at 3; 1680 cm.sup.-1 wide band: C.dbd.O of the acids of the molecule, of the amide at 7, of the ions CF.sub.3 CO.sub.2.sup.-.
NMR Spectrum at 250 MHz. 2H at 8.60 ppm (S.e., NH.sub.2.sup.+)--1H at 8.50 ppm (D, J+9 Hz, CONH)--3H at 8.40 ppm (S.e., NH.sub.3.sup.+)--1H at 6.68 ppm (S, H thiazole)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.16 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.60 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.90 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.25 ppm (M, CH.sub.2 NH)--2H at 2.90 ppm (M, CH.sub.2 NH)--1H at 2.66 ppm (M, CHCO.sub.2)--2H at 1.90 ppm (M, CH.sub.2 CH)--2H at 1.70 ppm (M, CH.sub.2 CH)--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C).
EXAMPLE 2
7-[2-(2-amino 4-thiazolyl)2-(2-carboxy 2-propyl oxyimino)acetamido](3-amino propionyl)3-thiomethyl 3-cepheme 4-carboxylic .beta.1-S-oxide acid trifluoracetate syn isomer SR 41884
(a) Tertiobutoxycarbonyl 3-amino thiopropionic acid
1.8 g of tertiobutoxycarbonyl 3-amino propionic acid was solubilized in 50 ml of anhydrous dichloromethane. The triple-neck flask was provided with a calcium chloride trap and cooled in a bath of water and ice. In order, there were added 1.4 ml of triethylamine and 1.3 ml of isobutyl chloroformate. After 20 minutes stirring in the cold, 1.5 ml of triethylamine was added and a light current of hydrogen sulfide was bubbled through for 15 minutes. then the mixture was stirred in the cold for 45 minutes before being evaporated to dryness. 150 ml of sulfate buffer (pH 2) were added and the thioacid was extracted twice with 70 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate and evaporated.
The oily product obtained was used as such.
(b) 7-[2-(2-tritylamino 4-thiazolyl)2-(2-tertiobutoxycarbonyl 2-propyl oxyimino)acetamido](3-tertiobutoxycarboxylamino propionyl)3-thiomethyl 3-cepheme 1.beta.-S-oxide carboxylate of 4-Tertiobutyl; syn isomer
To a solution of 0.46 g of 4-Tertiobutyl 1.beta.-S-oxide 7-[2-(2-tritylamino 4-thiazolyl)2-(2-tertiobutyoxycarbonyl 2-propyl oxyimino)acetamido]3-bromomethyl 3-cepheme carboxylate syn isomer, in 10 ml of tetrahydrofurane, were added 0.4 g of the thioacid described above as well as 0.6 g of potassium bicarbonate. After 4 hours stirring at ambiant temperature the solvent was evaporated and the residue taken up again with 100 ml of water and 50 ml of dichloromethane. After decantation the aqueous phase was extracted with 50 ml of dichloromethane. The organic phases were combined, dried over magnesium sulfate and evaporated.
The lacquer so obtained was chromatographed on a column of silica (40 g), it was eluted with a mixture of dichloromethane-ethyl acetate 90-10 (vol/vol).
IR Spectrum: .differential. CO 1805 cm: C.dbd.O at 8 of the .beta. lactame; 1720 cm: C.dbd.O of the tertiobutylic esters; 1690 cm: C.dbd.O of the amide at 7, of the thioester at 3 and of the tertiobutoxy carbonyl protecting the amine.
NMR Spectrum at 250 MHz (CDCL.sub.3). 1H at 7.75 ppm (D, J=9 Hz, CONH)--15H at 7.27 ppm (M, H ar Trit)--1H at 6.95 ppm (S.e., NH--Trit)--1H at 6.63 ppm (S, H thiazole)--1H at 6.21 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.85 ppm (S.e., NH--Boc)--1H at 4.50 ppm (D, J=4 Hz, H.sub.6)--1H at 4.29 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.75 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.58 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--2H at 3.36 ppm (M, CH.sub.2 NH Boc)--1H at 3.22 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--2H at 2.75 ppm (T, J=6 Hz, CH.sub.2 --CS)--15H at 1.52 ppm (S, Boc NH and (CH.sub.3).sub.2 C)--18H at 1.39 ppm (2S, CO.sub.2 tBu).
(c) SR 41 884
The whole of the compound obtained above was solubilized in 10 ml of trifluoroacetic acid. After 45 minutes at 23.degree. C. the acid was evaporated under vacuum without heating, and the oily residue was crystallized by the addition of 50 ml of isopropyl ether. The crystals were filtered and washed with isopropyl ether and then with hexane. They were then dried under vacuum over phosphoric anhydride.
0.37 g of the expected product was obtained.
IR Spectrum: .differential. CO 1785 cm.sup.-1 : C.dbd.O at 8 of the .beta. lactam 1680 cm.sup.-1 wide band: C.dbd.O of the acids of the molecule, of the amide at 7, of the thioester, of the CF.sub.3 CO.sub.2.sup.- ions.
NMR Spectrum at 250 MHz. 1H at 8.40 ppm (D, J=9 Hz, CONH)--3H at 7.80 ppm (S.e., NH.sub.3.sup.+)--3H at 7.30 ppm (S.e., NH.sub.3.sup.+)--1H at 6.78 ppm (S, H, thiazole)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.92 ppm (D, J=4 Hz, H.sub.6)--1H at 4.18 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.79 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.66 ppm (S, CH.sub.2 SO)--2H at 3.0 ppm (M, CH.sub.2 NH)--2H at 2.92 ppm (M, CH.sub.2 COS)--6H at 1.44 ppm (S, (CH.sub.3).sub.2 C).
EXAMPLE 3
Trifluoroacetate of 7 -[2-(2-amino 4-thiazoyl)2-(2-carboxy 2-propyl oxyimino)acetamido](3-amino propionyl)3-thiomethyl 3-cepheme 4-carboxylic 1.beta.-S-oxide acid; syn isomer, SR 41884
(a) 7-[2-(2-tritylamino 4-thiazolyl)2-tertiobutoxy 2-(carbonyl 2-propyl oxyimino)acetamido](3-tertiobutoxy carbonylamino)3-thiomethyl 3-cepheme 1.beta.-S-oxide carboxylate of 4-Tertiobutyl; syn isomer
To 0.46 g of 4-Tertiobutyl 1.beta.-S-oxide 7-[2-(2-tritylamino 4-thiazolyl)2-(2-tertiobutoxy carboxylamino 2-propyl oxyimino)acetamido]3-bromomethyl 3-cepheme carboxylate syn isomer in 10 ml of anhydrous acetone, were added 0.4 g of 3-tertiobutoxycarvonylamino thiopropionic acid, 0.6 g of potassium bicarbonate and 0.25 g of sodium iodide.
After 2 hours stirring at room temperature, the solvent was evaporated to dryness. The residue was taken up again in 100 ml of water and extracted with 50 ml of dichloromethane. The organic phase is separated and the aqueous phase reextracted with 50 ml of dichloromethane. The organic extracts were combined, dried over magnesium sulfate and evaporated to dryness.
The product obtained was chromatographed on a silica column by eluting with a dichloromethane-ethyl acetate mixture 90-10 (vol/vol).
An identical product (IR spectrum and NMR spectrum) to the product of Example 2(b) was obtained.
(b) SR 41 884
The deprotection was carried out as indicated in Example 2(c).
By operating as in Example 1, the compounds according to the invention were prepared in the form of trifluoroacetate, described in Table I below. ##STR10##
These compounds are identified by a reference number. For each among them the values of R.sub.1, R.sub.2, B and n and the NMR spectrum are given.
The acid B'--(CH.sub.2).sub.n --COOH which reacts on (IV) to give (V) is an aminoacid of the L series or of the D series or racemic; the corresponding indication appears in Table I, at column B.
The chromatographic eluant is also given which serves to isolate (V): the last intermediate product before deblocking the acid and amine functions of the molecule. This intermediate V is characterized by its infra-red spectrum, the wavelengths indicated in cm.sup.-1 correspond in order to the elongation vibration frequencies of the carbonyl at the 8 position of the beta lactam, the tertiobutylic esters and the ester at the 3 position, the amide at the 7 position and the carbamate protecting the amine. When 2 wavelengths only are indicated, the second corresponds to a wide band which covers the elongation vibration frequencies both of the esters, of the amide and of the protective carbamate of the amine.
The list of NMR spectra of the compounds mentioned in Table I is given following this table.
TABLEAU I__________________________________________________________________________ SR no. n ##STR11## B vol/volintermediate Veluant fromChromatography Vintermediate.delta.CO cm.sup.-1R NMR no.__________________________________________________________________________41 730 0 ##STR12## (CH.sub.2).sub.2 NH.sub.2 CH.sub.2 Cl.sub.2 AcOEt 85 15 1805 1725 1690 141 731 " " ##STR13## CH.sub.2 Cl.sub.2 AcOEt 92.5 7.5 1805 1720 241 732 " " ##STR14## CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1725 341 733 " " ##STR15## CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1725 441 806 " " ##STR16## CH.sub.2 Cl.sub.2 AcOEt 95 5 1805 1730 541 807 " " ##STR17## CH.sub.2 Cl.sub.2 AcOEt 50 50 1805 1735 1680 641 810 " " ##STR18## CH.sub.2 Cl.sub.2 AcOEt 80 20 1805 1725 741 854 " " (CH.sub. 2).sub.3 NH.sub.2 CH.sub.2 Cl.sub.2 90 1805 8 AcOEt 10 172541 855 " " (CH.sub.2).sub.5 NH.sub.2 CH.sub.2 Cl.sub.2 90 1805 9 1725 AcOEt 10 169041 856 " " (CH.sub.2).sub.7 NH.sub.2 CH.sub.2 Cl.sub.2 90 1805 10 1725 AcOEt 10 169541 857 " " ##STR19## CH.sub.2 Cl.sub.2 MeOH 100 1.5 1805 1725 1680 1141 858 " " ##STR20## CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1725 1241 859 " " ##STR21## CH.sub.2 Cl.sub.2 AcOEt 92.5 7.5 1810 1725 1341 860 " " ##STR22## CH.sub.2 Cl.sub.2 AcOEt 92.5 7.5 1805 1725 1441 885 " " ##STR23## CH.sub.2 Cl.sub.2 AcOEt 85 15 1805 1720 1541 886 " " ##STR24## CH.sub.2 Cl.sub.2 MeOH 100 1.5 1805 1720 1680 1641 887 " " ##STR25## CH.sub.2 Cl.sub.2 AcOEt 95 5 1805 1725 1741 888 " " ##STR26## CH.sub.2 Cl.sub.2 MeOH 100 1 1805 1720 1841 889 " " ##STR27## CH.sub.2 Cl.sub.2 AcOEt 80 20 1805 1755 1720 1941 891 " " ##STR28## CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1725 2041 967 " " (CH.sub.2).sub.4 NH.sub.2 CH.sub.2 Cl.sub.2 90 1805 21 1725 AcOEt 10 169041 975 " " ##STR29## CH.sub.2 Cl.sub.2 AcOEt 92.5 7.5 1805 1725 2241 976 " " ##STR30## CH.sub.2 Cl.sub.2 AcOEt 92.5 7.5 1805 1730 2341 977 " " ##STR31## CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1720 2441 987 " " ##STR32## CH.sub.2 Cl.sub.2 AcOEt 85 15 1805 1720 2542 022 " " ##STR33## CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1730 1690 2642 023 " " ##STR34## CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1720 2742 024 " " ##STR35## CH.sub.2 Cl.sub.2 AcOEt 85 15 1805 1730 1690 2842 025 " " ##STR36## CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1725 1690 2942 026 " " ##STR37## CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1725 3042 027 " " ##STR38## CH.sub.2 Cl.sub.2 AcOEt 92 8 1805 1730 1690 3142 028 " " (CH.sub. 2).sub.3 NHCH.sub.3 CH.sub.2 Cl.sub.2 90 1805 32 1730 AcOEt 10 169042 029 " " (CH.sub.2).sub.4 NHCH.sub.3 CH.sub.2 Cl.sub.2 90 1805 33 1730 AcOEt 10 169042 031 " " ##STR39## CH.sub.2 Cl.sub.2 AcOEt 85 15 1805 1725 1675 3442 042 " " ##STR40## CH.sub.2 Cl.sub.2 AcOEt 90 10 1810 1730 1690 CCl.sub.4 3542 073 " " ##STR41## CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1725 1690 3642 117 " " ##STR42## CH.sub.2 Cl.sub.2 MeOH 100 1 1810 1725 1685 CCl.sub.4 3742 120 " " ##STR43## CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1725 3842 121 " " ##STR44## CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1725 1690 3942 139 " " ##STR45## CH.sub.2 Cl.sub.2 AcOEt 95 5 1805 1725 1690 4042 140 " " CH.sub.2 CH.sub.2 NHCH.sub.3 CH.sub.2 Cl.sub.2 90 1805 41 1730 AcOEt 10 169042 181 " " (CH.sub.2).sub.3 NHCH.sub.2 CH.sub.3 CH.sub.2 Cl.sub.2 100 1805 42 1730 MeOH 1 1685 CH.sub.2 Cl.sub.242 182 " " ##STR46## CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1735 1685 4342 183 " " (CH.sub.2).sub.5 NHCH.sub.3 CH.sub.2 Cl.sub.2 100 1810 44 1735 MeOH 1 1690 CCl.sub.442 191 " CH.sub.2 ##STR47## CH.sub.2 Cl.sub.2 AcOEt 85 15 1805 1730 1690 4542 192 " ##STR48## ##STR49## CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1730 1690 4642 193 " CH.sub.2 ##STR50## CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1720 4742 194 " ##STR51## ##STR52## CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1725 4842 195 " CH.sub.2 (CH.sub.2).sub.3 NH.sub.2 CH.sub.2 Cl.sub.2 85 1805 49 1730 AcOEt 15 169042 196 " ##STR53## " CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1725 1695 5042 197 " CH.sub.2 (CH.sub.2).sub.4 NH.sub.2 CH.sub.2 Cl.sub.2 85 1805 51 1725 AcOEt 15 169042 198 " ##STR54## " CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1725 1695 5242 200 " " ##STR55## CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1725 5342 201 " " ##STR56## CH.sub.2 Cl.sub.2 AcOEt 90 1805 1725 1690 5442 208 " " ##STR57## CH.sub.2 Cl.sub.2 AcOEt 92.5 7.5 1805 1725 5542 209 " " ##STR58## CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1725 1690 5642 210 " " ##STR59## CH.sub.2 Cl.sub.2 AcOEt 92.5 7.5 1805 1725 5742 211 " CH.sub.2 ##STR60## CH.sub.2 Cl.sub.2 AcOEt 85 1805 1725 1690 5842 212 " ##STR61## " CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1725 1690 5942 213 " ##STR62## (CH.sub.2).sub.3 NH.sub.2 CH.sub.2 Cl.sub.2 AcOEt 85 15 1805 1730 1690 6042 214 " " (CH.sub.2).sub.4 NH.sub.2 CH.sub.2 Cl.sub.2 85 1805 61 1730 AcOEt 15 169042 215 " " ##STR63## CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1735 1690 6242 216 " ##STR64## ##STR65## CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1725 CCl.sub.4 6342 217 " " ##STR66## CH.sub.2 Cl.sub.2 AcOEt 90 10 1810 1725 1690 6442 320 " ##STR67## ##STR68## CH.sub.2 Cl.sub.2 AcOEt 95 5 1805 1725 6542 321 " " ##STR69## CH.sub.2 Cl.sub.2 MeOH 100 1 1805 1730 1690 6642 371 1 " ##STR70## CH.sub.2 Cl.sub.2 MeOH 100 0.7 6742 372 " " ##STR71## CH.sub.2 Cl.sub.2 MeOH 100 0.7 6842 374 0 " ##STR72## CH.sub.2 Cl.sub.2 MeOH 100 1 1805 1725 1690 6942 379 " " ##STR73## CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1725 7042 380 " " ##STR74## CH.sub.2 Cl.sub.2 AcOEt 95 5 1805 1725 7142 395 " " ##STR75## CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1725 1685 7242 396 " " ##STR76## CH.sub.2 Cl.sub.2 MeOH 100 0.6 1805 1725 1685 7342 397 " " ##STR77## CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1725 1685 7442 456 " " ##STR78## CH.sub.2 Cl.sub.2 AcOEt 95 5 7542 457 " " ##STR79## CH.sub.2 Cl.sub.2 MeOH 100 1 1805 1725 7642 458 " " ##STR80## CH.sub.2 Cl.sub.2 AcOEt 95 5 1805 1725 7742 459 " " ##STR81## CH.sub.2 Cl.sub.2 AcOEt 85 15 7842 460 " " ##STR82## CH.sub.2 Cl.sub.2 MeOH 100 1 1805 1720 7942 461 " " ##STR83## CH.sub.2 Cl.sub.2 MeOH 100 1 1802 1720 8042 462 " ##STR84## ##STR85## CH.sub.2 Cl.sub.2 MeOH 100 1 1805 1720 8142 463 " " ##STR86## CH.sub.2 Cl.sub.2 MeOH 100 1 1805 1720 8242 464 " " ##STR87## CH.sub.2 Cl.sub.2 MeOH 100 1 1805 1720 1690 8342 465 " ##STR88## ##STR89## CH.sub.2 Cl.sub.2 MeOH 100 1.5 1805 1725 1690 8442 466 " " ##STR90## CH.sub.2 Cl.sub.2 MeOH 100 1.5 1805 1720 8542 467 " " ##STR91## CH.sub.2 Cl.sub.2 MeOH 100 2 1805 1720 8642 471 1 ##STR92## ##STR93## CH.sub.2 Cl.sub.2 MeOH 100 0.5 1805 1720 1675 CCl.sub.4 8742 472 " " ##STR94## CH.sub.2 Cl.sub.2 AcOEt 95 5 1805 1725 1675 CCl.sub.4 8842 473 " " ##STR95## CH.sub.2 Cl.sub.2 MeOH 100 0.5 1805 1725 1685 CCl.sub.4 8942 474 " ##STR96## ##STR97## CH.sub.2 Cl.sub.2 AcOEt 95 5 1805 1725 1685 CCl.sub.4 9042 537 0 " ##STR98## CH.sub.2 Cl.sub.2 MeOH 100 1 1805 1725 1690 9142 538 " " ##STR99## CH.sub.2 Cl.sub.2 MeOH 100 1 1805 1725 1690 9242 539 " " ##STR100## CH.sub.2 Cl.sub.2 MeOH 100 0.8 1805 1725 1685 9342 540 " ##STR101## ##STR102## CH.sub.2 Cl.sub.2 MeOH 100 0.7 1805 1720 9442 541 " " ##STR103## CH.sub.2 Cl.sub.2 MeOH 100 0.7 1805 1720 9542 542 " " ##STR104## CH.sub.2 Cl.sub.2 MeOH 100 0.5 1805 1720 9642 544 " ##STR105## ##STR106## CH.sub.2 Cl.sub.2 MeOH 100 1 1802 1720 9742 545 " " ##STR107## CH.sub.2 Cl.sub.2 MeOH 100 1 1803 1720 9842 546 " " ##STR108## CH.sub.2 Cl.sub.2 MeOH 100 1 1805 1720 9942 547 ##STR109## ##STR110## CH.sub.2 Cl.sub.2 MeOH 100 1.5 1805 1720 10042 548 " " ##STR111## CH.sub.2 Cl.sub.2 MeOH 100 2 1802 1720 10142 549 " ##STR112## ##STR113## CH.sub.2 Cl.sub.2 MeOH 100 1 1805 1720 10242 581 " " ##STR114## CH.sub.2 Cl.sub.2 MeOH 100 0.8 1805 1725 10342 582 " " ##STR115## CH.sub.2 Cl.sub.2 MeOH 100 0.8 1805 1725 1690 10442 583 " " ##STR116## CH.sub.2 Cl.sub.2 MeOH 100 0.5 1805 1720 1685 10542 584 " " ##STR117## CH.sub.2 Cl.sub.2 MeOH 100 1 1802 1720 10642 585 " " ##STR118## CH.sub.2 Cl.sub.2 MeOH 100 0.8 1805 1720 1690 10742 586 " " ##STR119## CH.sub.2 Cl.sub.2 MeOH 100 1 1805 1725 1690 10842 587 " " ##STR120## CH.sub.2 Cl.sub.2 MeOH 100 1.5 1805 1720 1690 10942 657 " " ##STR121## CH.sub.2 Cl.sub.2 MeOH 100 0.7 1805 1725 1675 11042 658 " ##STR122## ##STR123## CH.sub.2 Cl.sub.2 MeOH 100 1 1805 1720 11142 675 " " ##STR124## CH.sub.2 Cl.sub.2 AcOEt 90 10 1805 1725 11242 676 " ##STR125## ##STR126## CH.sub.2 Cl.sub.2 MeOH 100 0.5 1805 1720 11342 677 " " ##STR127## CH.sub.2 Cl.sub.2 MeOH 100 0.5 1805 1720 11442 687 " " ##STR128## CH.sub.2 Cl.sub.2 MeOH 100 0.9 1805 1725 1690 11542 688 " " ##STR129## CH.sub.2 Cl.sub.2 MeOH 100 0.8 1805 1720 11642 689 " " ##STR130## CH.sub.2 Cl.sub.2 MeOH 100 0.8 1805 1720 11742 690 " " ##STR131## CH.sub.2 Cl.sub.2 MeOH 100 1 1805 1715 11842 811 " " ##STR132## CH.sub.2 Cl.sub.2 MeOH 100 0.5 1805 1725 CH.sub.2 Cl.sub.2 11942 812 " " ##STR133## CH.sub.2 Cl.sub.2 AcOEt 92.5 7.5 1805 1725 12042 814 " " ##STR134## CH.sub.2 Cl.sub.2 MeOH 100 1 1805 1725 1690 12142 815 " " ##STR135## CH.sub.2 Cl.sub.2 MeOH 100 0.7 1805 1725 1690 12242 816 " " ##STR136## CH.sub.2 Cl.sub.2 MeOH 100 0.7 1805 1725 1690 12342 817 " " ##STR137## CH.sub.2 Cl.sub.2 MeOH 100 0.9 1805 1720 12442 818 " ##STR138## " CH.sub.2 Cl.sub.2 MeOH 100 0.9 1805 1720 12542 781 " ##STR139## ##STR140## CH.sub.2 Cl.sub.2 MeOH 100 1 1805 1725 1675 CH.sub.2 Cl.sub.2 12642 782 " " ##STR141## CH.sub.2 Cl.sub.2 MeOH 100 1.5 1805 1725 12742 783 " " ##STR142## CH.sub.2 Cl.sub.2 MeOH 100 1 12842 846 " " ##STR143## CH.sub.2 Cl.sub.2 MeOH 100 1 1805 1725 1680 CH.sub.2 Cl.sub.2 12942 848 " " ##STR144## CH.sub.2 Cl.sub.2 MeOH 100 0.7 1805 1720 13042 849 " ##STR145## ##STR146## CH.sub.2 Cl.sub.2 MeOH 100 0.7 1805 1720 13142 852 " ##STR147## ##STR148## CH.sub.2 Cl.sub.2 MeOH 100 0.5 1805 1725 13242 857 " " ##STR149## CH.sub.2 Cl.sub.2 MeOH 100 1.5 1805 1725 13342 862 " " ##STR150## CH.sub.2 Cl.sub.2 MeOH 100 1 1805 1725 13442 869 " " ##STR151## CH.sub.2 Cl.sub.2 AcOEt 85 15 1805 1725 13542 870 " ##STR152## ##STR153## CH.sub.2 Cl.sub.2 AcOEt 80 20 1805 1720 13642 901 " ##STR154## ##STR155## CH.sub.2 Cl.sub.2 MeOH 100 1 1805 1720 1680 137__________________________________________________________________________
NMR SPECTRA: The spectra are recorded at 60 MHz, indicated by (a) or at 250 MHz, indicated by (b); when there exist two diastereo-isomers in a molecule, the split signals are indicated by *.
NMR no. 1-(b): 1H at 8.44 ppm (D, J=9 Hz, CONH)--3H at 7.90 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.50 ppm N.sup.+ H.sub.3)--1H at 6.78 ppm (S, H thiazol)--1H at 5.97 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.18 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.94 ppm (D, J=4 Hz, H.sub.6)--1H at 4.64 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.90 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.58 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.00 ppm (M, CH.sub.2 NH.sub.2)--2H at 2.61 ppm (M, CH.sub.2 CO.sub.2)--6H at 1.44 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 2-(b): 4H at 8.45 ppm (M, N.sup.+ H.sub.3, CONH)--3H at 7.35 ppm (S.e., N.sup.+ H.sub.3)--5H at 7.25 ppm (M, H aromatics--1H at 6.82 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.20 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.92 ppm (D, J=4 Hz, H.sub.6)--1H at 4.81 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.31 ppm (S.e., CHNH.sub.2)--1H at 3.50 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.30 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.10 ppm (M, CH.sub.2 C.sub.6 H.sub.5 )--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 3-(b): 5H at 8.45 ppm (S.e., N.sup.+ H.sub.2, OH, CONH)--3H at 7.50 ppm (S.e., N.sup.+ H.sub.3)--2H at 6.95 ppm (D, J=8 Hz, H meta OH)--1H at 6.78 ppm (S, H thiazol)--2H at 6.68 ppm (D, J=8 Hz, H ortho OH)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.16 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.92 ppm (D, J=4 Hz, H.sub.6)--1H at 4.74 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.19 ppm (M, CHNH.sub.2)--1H at 3.66 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.34 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 2.93 ppm (M, CH.sub.2 --CH--NH.sub.2)--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 4-(b): 1H at 8.50 ppm (D, J=9 Hz, CONH)--3H at 8.40 ppm (S.e. N.sup.+ H.sub.3)--3H at 7.60 ppm (S.e. N.sup.+ H.sub.3)--1H at 6.79 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.80 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.08 ppm (M, CHNH.sub.2)--1H at 3.92 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.58 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.44 ppm (S, (CH.sub.3).sub. 2 C)--3H at 1.34 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 5-(b): 1H at 8.45 ppm (D, J=9 Hz, CONH)--3H at 8.40 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.60 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.78 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hzn H.sub.7)--1H at 5.25 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 3.92 ppm (M, CHNH.sub.2 and CH.sub.2 SO)--1H at 3.56 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 2.11 ppm (M, CH(CH.sub.3).sub.2)--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C)--6H at 0.9 ppm (D, J=7 Hz, (CH.sub.3).sub.2 CH).
NMR no. 6-(b): 1H at 8.45 ppm (D, J=9 Hz, CONH)--3H at 8.35 ppm (S.e., N.sup.+ H.sub.3)--4H at 7.40 ppm (S.e., CONH.sub.2, N.sup.+ H.sub.3)--1H at 6.92 ppm (S.e., CONH.sub.2)--1H at 6.76 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.25 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.00 ppm (M, CHNH.sub.2)--1H at 3.95 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.56 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 2.20 ppm (M, CH.sub.2 --CONH.sub.2)--2H at 1.95 ppm (M, CH.sub.2 --CH)--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 7-(b): 1H at 8.50 ppm (D, J=9 Hz, CONH)--3H at 8.40 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.40 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.76 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.25 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.92 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.16 ppm (M, CHNH.sub.2)--1H at 3.95 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.81 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 OH)--1H at 3.69 ppm (B of AB, J.sub.AB =13 Hz, CH.sub.2 OH)--1H at 3.55 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 8-(a): 8H between 5.5 and 8.5 ppm (widened signal, NH.sub.2, CO.sub.2 H, TRA)--1H at 8.40 ppm (D, J=9 Hz, CONH)--1H at 6.82 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.15 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.67 ppm (B of AB, J=13 Hz, CH.sub.2 OCO)--1H at 3.85 ppm (A of AB, J=17 Hz; CH.sub.2 SO)--1H at 3.62 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--2H at 2.80 ppm (M, CH.sub.2 NH.sub.2)--2H at 2.40 ppm (M, CH.sub.2 CO.sub.2)--2H at 1.80 (M, CH.sub.2 CH.sub.2 CH.sub.2)--6H at 1.43 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 9-(a): 8H between 5.5 and 8.7 ppm (wide signal, CO.sub.2 H, NH.sub.2, TFA)--1H at 8.40 ppm (D, J=9 Hz, CONH)--1H at 6.87 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.15 ppm (A of AB, J=13 Hz, CH.sub.2 OCO)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.60 ppm (B of AB, J=13 Hz, CH.sub.2 OCO)--1H at 3.85 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.60 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--2H at 2.80 ppm (M, CH.sub.2 NH.sub.2)--2H at 2.30 ppm (M, CH.sub.2 CO)--12H at 1.45 ppm (S.e., (CH.sub.3).sub.2 C and CH.sub.2 (CH.sub.2).sub.3 CH.sub.2).
NMR no. 10-(a): 8H between 5.5 and 8.0 ppm (wide signal, NH.sub.2, CO.sub.2 H, TFA)--1H at 8.45 ppm (D, J=9 Hz, CONH)--1H at 6.87 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.15 ppm (A of AB, J=13 Hz, CH.sub.2 OCO)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.65 ppm (B of AB, J=13 Hz, CH.sub.2 OCO)--1 H at 3.85 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.62 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--2H at 2.80 ppm (M, CH.sub.2 NH.sub.2)--2H at 2.30 ppm (M, CH.sub. 2 CO.sub.2)--6H at 1.45 ppm (S, (CH.sub.3).sub.2 C)--10H at 1.35 ppm (S.e., CH.sub.2 (CH.sub.2).sub.5 CH.sub.2).
NMR no. 11-(a): 2H at 8.40 ppm (M, CONH, CH.sub.3 CONH)--8H at 7.50 ppm (S.e., N.sup.+ H.sub.3, CO.sub.2 H)--1H at 6.90 ppm (S, H thiazol)--1H at 6.05 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.40 ppm (A of AB, J=13 Hz, CH.sub.2 OCO)--1H at 4.98 ppm (D, J=4 Hz, H.sub.6)--1H at 4.90 ppm (B of AB, J=13 Hz, CH.sub.2 OCO)--3H at 4.30 ppm (M, CH.sub.2 NHCOCH.sub.3, CHNH.sub.2)--1H at 4.00 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.65 ppm (B of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--2H at 3.00 ppm (M, CH.sub.2 S)--3H at 1.80 ppm (S, CH.sub.3 CONH)--6H at 1.45 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 12-(a): 8H between 6.5 and 9 ppm (wide signal, CO.sub.2 H, TFA, NH.sub.2)--1H at 8.5 ppm (D, J=9 Hz, CONH)--1H at 6.90 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.30 ppm (A of AB, J=13 Hz, CH.sub.2 OCO)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.80 ppm (B of AB, J=13 Hz, CH.sub.2 OCO)--1H at 3.92 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.67 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--12H at 1.45 ppm (S, (CH.sub.3).sub.2 C--CO.sub.2 H, (CH.sub.3).sub.2 CNH.sub.2).
NMR no. 13-(a): 8H between 6.5 and 9.5 ppm (wide signal, CO.sub.2 H, NH.sub.2, TFA)--1H 8.5 ppm (D, J=9 Hz, CONH)--1H at 6.90 ppm (S, H thiazol)--1H at 6.05 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.30 ppm (A of AB, J=13 Hz, CH.sub.2 OCO)--1H at 5.05 ppm (D, J=4 Hz, H.sub.6)--1H at 4.90 ppm (B of AB, J=13 Hz, CH.sub.2 OCO)--3H at 3.80 ppm (M, CHNH.sub.2 and CH.sub.2 SO)--3H at 1.50 ppm (M, CH.sub.2 --CH)--6H at 1.45 ppm (S, (CH.sub.3).sub.2 C)--6H at 0.85 ppm (D, J=7 Hz, (CH.sub.3).sub.2 CH).
NMR no. 14-(a): 8H between 7 and 9 ppm (wide signal, NH.sub.2, CO.sub.2 H, TFA)--1H at 8.50 ppm (D, J=9 Hz, CONH)--1H at 6.90 ppm (S, H thiazol)--1H 6.08 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.30 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 5.05 ppm (D, J=4 Hz, H.sub.6) 1H at 4.49 ppm (B of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--3H at 3.90 ppm (M, CH.sub.2 SO and CHCH.sub.2) 1H at 1.80 ppm (M, CHCH.sub.3)--6H at 1.45 ppm (S, (CH.sub.3).sub.2 C)--2H at 1.30 ppm (M, CH.sub.2 CH.sub.3)--6H at 0.88 ppm (M, CH.sub.3 CH.sub.2 and CH.sub.3 CH).
NMR no. 15-(b):
1H at 8.5 ppm (D, J=9 Hz, CONH)--3H at 8.30 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.40 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.76 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.24 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.92 ppm (D, J=4 Hz, H.sub.6)--1H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.10 ppm (M, CH--NH.sub.2)--1H at 3.97 ppm (M, CH--OH)--1H at 3.94 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.44 ppm (S, (CH.sub.3).sub.2 C)--3H at 1.14 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 16-(b): 1H at 8.5 ppm (D, J=9 Hz, CONH)--3H at 8.40 ppm (S.e., N.sup.+ H.sub.3)--1H at 7.66 ppm (S, CONH.sub.2)--3H at 7.50 ppm (S.e., N.sup.30 H.sub.3)--1H at 7.22 ppm (S, CONH.sub.2)--1H at 6.78 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.29 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.92 ppm (D, J=4 Hz, H.sub.6)--1H at 4.79 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.26 ppm (M, CHNH.sub.2)--1H at 3.92 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.52 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 2.71 ppm (M, CH.sub.2 CONH.sub.2)--6H at 1.44 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 17-(b): 1H at 8.50 ppm (D, J=9 Hz, CONH)--3H at 8.45 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.45 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.78 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.24 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.98 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.13 ppm (M, CHNH.sub.2)--1H at 3.92 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.10 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 2.50 ppm (M, CH.sub.2 S)-- 5H at 2.0 ppm (M, CH.sub.3 S et CH.sub.2 --CH.sub.2 --S)--6H at 1.44 ppm S, (CH.sub.3).sub.2 C).
NMR no. 18-(b): 4H at 8.50 ppm (M, CONH, N.sup.+ H.sub.3)--3H at 7.80 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.50 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.79 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.24 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.97 ppm (M, CHNH.sub.2)--1H at 3.92 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.60 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 2.75 ppm (M, CH.sub.2 NH.sub.2, --1H at 1.75 ppm (MCH.sub.2 CH)--11H at 1.40 ppm (S.e., (CH.sub.3).sub.2 C, (CH.sub.2).sub.3 CH.sub.2 NH.sub.2).
NMR no. 19-(b): 1H at 9 ppm (S, H.sub.2 imidazol)--3H at 8.6 ppm (S.e., N.sup.+ H at 8.5 ppm (D, J=9 Hz, CONH)--1H at 7.40 ppm (S, H.sub.4 imidazol)--3H 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.79 ppm (S, H thiazol)--1H 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.22 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.90 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.40 ppm (M, CHNH.sub.2)--1H at 3.89 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.52 ppm (D, J= 17 Hz, CH.sub.2 SO)--2H at 3.20 ppm (M, CH.sub.2 CH)--6H at 1.44 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 20-(b): 1H at 8.50 ppm (D, J=9 Hz, CONH)--3H at 8.40 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.40 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.77 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.76 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.81 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.06 ppm (M, CHNH.sub.2)--1H at 3.95 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.63 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.44 ppm (S, (CH.sub.3 ).sub.2 C)--3H at 1.36 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 21-(a): 8H between 6.5 and 9 ppm (widened signal, NH.sub.2, CO.sub.2 H, TFA)--1H at 8.35 ppm (D, J=9 Hz, CONH)--1H at 6.80 ppm (S, H thiazol)--1H 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.15 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.65 ppm (B of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H 3.95 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.65 ppm (B of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--2H at 2.80 ppm (M, CH.sub.2 NH.sub.2) 2H at 2.35 ppm (M, CH.sub.2 CO)--10H at 1.45 ppm (S.e., (CH.sub.3).sub.2 C+CH.sub.2 (CH.sub.2).sub.2 CH.sub.2).
NMR no. 22-(a): 8H between 6 and 9 ppm (wide signal, TFA, NH.sub.2, CO.sub.2 H)--1H at 8.42 ppm (D, J=9 Hz, CONH)--1H at 6.85 ppm (S, H thiazol)--1H 6.05 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.30 ppm (A of AB, J=13 Hz, CH.sub.2 OCO)--1H at 5.05 ppm (D, J=4 Hz, H.sub.6)--1H 4.68 ppm (B of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 4.0 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.65 ppm (B of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--8H at 1.75 ppm (M, H, cyclopentane)--6H at 1.45 ppm (S, (CH.sub.3).sub. 2 C).
NMR no. 23-(a): 8H between 7 and 10 ppm (wide signal, TFA, NH.sub.2, CO.sub.2 H)--1H at 8.50 ppm (D, J=9 Hz, CONH)--1H at 6.92 ppm (S, H thiazol)--1H 6.10 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.35 ppm (A of AB, J=13 Hz, CH.sub.2 OCO)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.75 ppm (B of AB, J=13 Hz, CH.sub.2 OCO)--1H at 4.0 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.70 ppm (B of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--16H between 1 and 2.3 ppm (M, (CH.sub.3).sub.2 C and cyclohexane).
NMR no. 24-(a): 9H between 8 and 10 ppm (wide signal, NH.sub.2, OH, CO.sub.2 H, TFA)--1H at 8.55 ppm (D, J=9 Hz, CONH)--2H at 7.10 ppm (D, J=8 Hz, H meta OH)--1H at 6.90 ppm (S, H thiazol)--2H at 6.80 ppm (D, J=8 Hz, H ortho, OH)--1H at 6.10 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.80 ppm (A of AB, J=13 Hz, CH.sub.2 OCO)--1H at 5.05 ppm (D, J=4 Hz, H.sub.6)--1H at 4.80 ppm (B of AB, J=13 Hz, CH.sub.2 OCO)--1H at 4.30 ppm (M, CHNH.sub.2)--2H at 3.70 ppm (M, CH.sub.2 SO)--2H at 3.0 ppm (M, CH.sub.2 --C.sub.6 H.sub.4 OH--6H at 1.46 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 25-(a): 10H between 6.5 and 9.5 ppm (wide signal, NH.sub.2, CO.sub.9 H, TFA)--1H at 8.40 ppm (D, J=9 Hz CONH)--1H at 6.85 ppm (S, H thiazol)--1H 6.05 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.30 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.85 ppm (B of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 4.20 ppm (M, CHNH.sub.2)--2H 3.80 ppm (M, CH.sub.2 SO)--2H at 2.95 ppm (M, CH.sub.2 NH.sub.2)--2H at 2.20 ppm (M, CH.sub.2 CH.sub.2 NH.sub.2)--6H at 1.45 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 26-(b): 3H at 8.60 ppm (S.e., N.sup.+ H.sub.3)--1H at 8.44 ppm (D, J=9 Hz, CONH)--1H at 6.78 ppm (S, H thiazol)--1H 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.16 ppm (2D, J=13 Hz, CH.sub.2 OCO)*--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.66 ppm (2D, J=13 Hz, CH.sub.2 OCO)*--1H at 3.92 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.56 ppm (D, J=17 Hz, CH.sub.2 SO)--5H between 2.5 and 3.5 ppm (M, CH.sub.2 N et CHCO.sub.2)--4H between 1.5 and 2.0 ppm (M, CH.sub.2).sub.2 CH.sub.2 N)--6H at 1.44 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 27-(b): 3H at 8.50 ppm (S.e., N.sup.+ H.sub.3)--1H at 8.44 ppm (D, J=9 Hz, CONH)--3H at 7.80 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.78 ppm (S, H thiazol)--1H 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.26 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.08 ppm (M, CHCO.sub.2)--1H at 3.94 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.56 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 2.80 ppm (M, CH.sub.2 NH.sub.2)--4H at 1.60 ppm (M, (CH.sub.2).sub.2 CH.sub.2 NH.sub.2)--6H at 1.44 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 28-(b): 1H at 8.37 ppm (D, J=9 Hz, CONH)--3H at 7.90 (S.e., N.sup.+ H.sub.3)--3H at 7.20 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.76 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.16 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.66 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.92 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.58 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.50 ppm (M, CHNH.sub.2)--2H at 2.56 ppm (M, CH.sub.2 CHNH.sub. 2) 6H at 1.44 ppm (S, (CH.sub.3).sub.2 C)--3H at 1.16 ppm (D, J=6 Hz, CH.sub.3 --CH).
NMR no. 29-(b): 1H at 8.44 ppm (D, J=9 Hz, CONH)--3H at 7.95 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.50 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.78 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7) 1H at 5.20 ppm (2D, J=13 Hz, CH.sub.2 OCO)*--1H at 4.95 ppm (M, H.sub.6)--1H at 4.62 ppm (2D, J=13 Hz, CH.sub.2 OCO)*--1H at 3.94 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.58 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.0 ppm (M, CHCO.sub.2)--2H at 2.75 ppm (M, CH.sub.2 NH.sub.2)-- 6H at 1.44 ppm (M, (CH.sub.3).sub.2 C)--3H at 1.10 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 30-(b): 4H at 8.45 ppm (M, N.sup.+ H.sub.3, CONH)--8H at 7.35 ppm (M, N.sup.+ H.sub.3, H aromatic)--1H at 6.78 ppm (S, H thiazol)--1H at 6.0 ppm (M, H.sub.7)--1H at 5.05 ppm (2D, J=13 Hz, CH.sub.2 OCO)* 1H at 4.94 ppm (2D, J=4 Hz, H.sub.6)*--1H at 4.60 ppm (M, CHNH.sub.2)--1H at 3.66 ppm (2D, J=17 Hz, CH.sub.2 SO)*--1H at 3.40 ppm (2D, J=17 Hz, CH.sub.2 SO)*--2H at 3.0 ppm (M, CH.sub.2 CO.sub.2) 6H at 1.44 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 31-(b): 1H at 8.40 ppm (D, J=9 Hz, CONH)--3H at 7.74 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.40 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.81 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7) 1H at 5.13 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.63 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.90 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.16 ppm (M, CHNH.sub.2)--2H at 2.40 ppm (M, CH.sub.2 CO)-- 1H 1.77 ppm (M, CH.sub.2 CHNH.sub.2)--1H at 1.61 ppm (M, CH.sub.2 CHNH.sub.2)--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C) 1H at 1.0 ppm (D, J=7 Hz, CH.sub.3 --CH).
NMR no. 32-(a): 7H between 7 and 9 ppm (NH, NH.sub.2, CO.sub.2 H, TFA)--1H at 8.50 ppm (D, J=9 Hz, CONH)--1H at 6.90 ppm (S, H thiazol)--1H at 6.05 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.15 ppm (A of AB, J=13 Hz, CH.sub.2 OCO)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.70 ppm (B of AB, J=13 Hz, CH.sub.2 OCO)--1H at 3.95 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.65 ppm (B of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--2H at 2.90 ppm (M, CH.sub.2 NH)--3H at 2.45 ppm (D, J= 6 Hz, CH.sub.3 NH)--2H at 2.4 ppm (M, CH.sub.2 CO)--2H at 1.70 ppm (M, CH.sub.2 CH.sub.2 CH.sub.2)--6H at 1.42 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 33-(a): 7H between 7 and 9.5 ppm (NH.sub.2, NH, CO.sub.2 H, TFA)--1H at 8.46 ppm (D, J=9 Hz, CONH)--1H at 6.90 ppm (S, H thiazol)--1H at 6.05 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.15 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.70 ppm (B of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 3.90 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO) 1H at 3.65 ppm (B of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--2H at 2.75 ppm (M, CH.sub.2 NHCH.sub.3)--5H 2.45 ppm (M, CH.sub.3 NH and CH.sub.2 CO)--10H at 1.45 ppm (S.e., (CH.sub.3).sub.2 C and CH.sub.2 (CH.sub.2).sub.2 CH.sub.2).
NMR no. 34-(a): 8H between 6 and 9 ppm (widened signal, NH.sub.2, TFA, OH, CO.sub.2 H)--1H at 8.47 ppm (D, J=9 Hz, CONH)--1H at 6.90 ppm (S, H thiazol)--1H at 6.15 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz--H.sub.7)--1H at 5.35 ppm (AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.85 ppm (B of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--4H at 3.95 ppm (M, CH.sub.2 SO and CHOHCHNH.sub.2)--6H at 1.45 ppm (S, (CH.sub.3).sub.2 C)--3H at 1.20 ppm (D, J=7 HZ, CH.sub.3 CHOH).
NMR no. 35-(b): 1H at 8.50 ppm (D, J=9 Hz, CONH)--3H at 8.35 ppm (S.e., N.sup.+ H.sub.3)--2H at 7.94 ppm (D, J=8 Hz, H ortho CO)--2H at 7.55 ppm (D, J=8 Hz, H meta CO)--1H at 6.84 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.44 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.99 ppm (D, J=4 Hz, H.sub.6)--1H at 4.86 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.1 ppm (M, CH.sub.2 NH.sub.2, CH.sub.2 SO)--1H at 3.72 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 36-(a): 3H at 9.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 8.55 ppm (D, J=9 Hz, CONH)--3H at 8.05 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.92 ppm (S, H thiazol)--1H 6.05 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.30 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 5.05 ppm (D, J=4 Hz, H.sub.6)--1H at 4.70 ppm (B of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 3.95 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.65 ppm (B of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--2H at 3.0 ppm (S.e., CH.sub.2 NH.sub.2)-- 6H at 1.45 ppm (S, (CH.sub.3).sub.2 C--ON)--6H at 1.17 ppm (S, (CH.sub.3).sub.2 CO.sub.2 CH.sub.2).
NMR no. 37-(b): 8H between 5 and 9 ppm (wide signal, CO.sub.2 H, TFA, NH.sub.2)--1H at 8.50 ppm (D, J=9 Hz, CONH)--1H at 6.90 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J=9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.15 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.58 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.9 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.54 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 2.6 ppm (M, CH.sub.2 NH.sub.2)--1H at 2.25 ppm (T, J=12 Hz, CHCO.sub.2)--4 H at 1.84 ppm (M, CH.sub.2 CHCO)--6H at 1.45 ppm (S, (CH.sub.3).sub.2 C)--3H at 1.25 ppm (M, CHCH.sub.2 NH.sub.2 and CH.sub.2 CHCH.sub.2 NH.sub.2)--2H at 0.95 ppm (M, CH.sub.2 CHCH.sub.2 NH.sub.2).
NMR no. 38-(b): 1H at 8.37 ppm (D, J=9 Hz, CONH)--3H at7.90 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.40 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.79 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.11 ppm (2D, J=13 Hz, CH.sub.2 OCO)*--1H at 4.98 ppm (D, J=4 Hz, H.sub.6)--1H at 4.61 ppm (2D, J=13 Hz, CH.sub.2 OCO)*--1H at 3.90 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.59 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.0 ppm (S.e., CHNH.sub.2)--1H at 2.40 ppm (M, CHCO.sub.2)--1H at 2.10 ppm (M, CH.sub.2 CHNH.sub.2)--3H at 1.80 ppm (M, CH.sub.2 CHNH.sub.2)--6H 1.44 ppm (2S, (CH.sub.3).sub.2 C)--4H between 1 and 1.5 ppm (M, CH.sub.2 --CH.sub.2 --CH--CO.sub.2).
NMR no. 39-(b): 1H at 8.5 ppm (D, J=9 He, CONH)--6H between 7 and 8 ppm (wide signal, NH.sub.2, TFA)--1H at 6.81 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J=9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.15 ppm (2D, J=13 Hz, CH.sub.2 OCO)*--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.63 ppm (2D, J=13 Hz, CH.sub.2 OCO)*--1H at 3.89 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.56 ppm D, J=17 Hz, CH.sub.2 SO)--2H at 2.77 ppm (M, CH.sub.2 NH.sub.2)--1H at 2.52 ppm (M, CHCO.sub.2)--1H at 1.84 ppm (M, CH.sub.2 CH)--1H at 1.56 ppm (M, CH.sub.2 CH)--6H at 1.44 ppm (S, (CH.sub.3).sub.2 C)--3H at 1.06 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 40-(a): 1H at 8.45 ppm (D, J=9 Hz, CONH)--8H at 7.30 ppm (S.e., N.sup.+ H.sub.3, CO.sub.2 H)--1H at 6.80 ppm S, H thiazol)--1H at 6.0 ppm (M, H.sub.7)--1H at 5.20 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 OCO) 1H at 4.90 ppm (B of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 4.90 ppm (D, J=4 Hz, H.sub.6)--3H at 3.80 ppm (M, CH.sub.2 SO, CHNH.sub.2)--1H at 2.00 ppm (M, CH(CH.sub.3).sub.2)--6H at 1.45 ppm (S, (CH.sub.3).sub.2 C)--6H at 0.95 ppm (2D, J=7 Hz, (CH.sub.3).sub.2 CH).
NMR no. 41-(a): 2H at 8.50 ppm (S.e., N.sup.+ H.sub.2)--1H at 8.45 ppm (D, J=9 Hz, CONH)--3H at 7.30 ppm S.e., N.sup.+ H.sub.3)--1H at 6.80 ppm (S, H thiazol)--1H at 6.0 ppm (M, H.sub.7)--1H at 5.15 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 4.96 ppm (D, J=4 Hz, H.sub.6)--1H at 4.65 ppm (B of AB, 13 Hz, CH.sub.2 OCO)--1H at 3.90 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.65 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--2H at 3.00 ppm (M, CH.sub.2 NH)--5H at 2.50 ppm (M, CH.sub.3 NH, CH.sub.2 CO.sub.2)-- 6H at 1.42 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 42-(a): 7H at 9.4 ppm (S.e., N.sup.+ H.sub.3, N.sup.+ H.sub.2, CO.sub.2 H)--1H at 8.45 ppm (D, J=9 Hz, CONH)--1H at 6.85 ppm (S, H thiazol)--1H at 6.00 ppm (M, H.sub.7)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at (A of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 4.65 ppm (B of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 3.85 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.60 ppm (B of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--4H at 2.85 ppm (M, CH.sub.2 NHCH.sub.2)--2H at 2.40 ppm (M, ##STR156## 2H at 1.80 ppm (M, CH.sub.2 CH.sub.2 CH.sub.2 NH)--6H at1.45 ppm (S, (CH.sub.3).sub.2 C)--3H at 1.10 ppm (T, J=7 Hz, CH.sub.3 CH.sub.2 NH).
NMR no. 43-(a): 2H at 8.50 ppm (S.e., N.sup.+ H.sub.2)--1H at 8.40 ppm (D, J=9 Hz, CONH)--3H at 7.00 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.76 pm (S, H thiazol)--1H at 5.95 ppm (M, H.sub.7)--1H at 5.10 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.65 ppm (B AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 3.85 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.50 ppm, B of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.30 ppm (M, CHNH)--5H at 2.45 ppm (M, CH.sub.3 NH and ##STR157## 2H at 1.80 ppm (M, ##STR158## 6H at 1.45 ppm (S, (CH.sub.3).sub.2 C)--3H at 1.10 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 44-(a): 1H at 8.40 ppm (D, J=9 Hz, CONH)--7H at 7.80 ppm (S.e., N.sup.+ H.sub.3, N.sup.+ H.sub.2, CO.sub.2 H)--1H at 6.80 ppm (S, H thiazol)--1H at 6.00 ppm (M, H.sub.7)--1H at 5.00 ppm (M, H.sub.6)--1H at 5.00 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 OCO)--1H at 4.65 ppm (B of AB, J.sub.AB =13 Hz), CH.sub.2 OCO)--1H at 3.85 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (B of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--2H at 2.80 ppm (M, CH.sub.2 NH)--5H at 2.40 ppm (M, CH.sub.3 NH, CH.sub.2 CO.sub.2)--12H at 1.45 ppm (S.e., (CH.sub.3).sub.2 C and CH.sub.2 (CH.sub.2).sub.3 CH.sub.2 NH).
NMR no. 45-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--1H at 8.60 ppm (S.e., N.sup.+ H.sub.2)--1H at 8.40 ppm (S.e., N.sup.+ H.sub.2)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.78 ppm (S, H thiazol)--1H at 5.91 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.13 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.61 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.55 ppm (S, CH.sub.2 ON)--1H at 3.84 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (B of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--2H at 3.20 ppm (M, CH.sub.2 NH)--2H at 2.90 ppm (M, CH.sub.2 NH)--1H at 2.64 ppm (M, CHCO.sub.2)--2H at 1.95 ppm (M, CH.sub.2 CH.sub.2 NH)--2H at 1.66 ppm (M, CH.sub.2 CH.sub.2 NH).
NMR no. 46-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--1H at 8.60 ppm (S.e., N.sup.+ H.sub.2)--1H at 8.40 ppm (S.e., N.sup.+ H.sub.2)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.78 ppm (S, H thiazol)--1H at 5.94 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.13 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.61 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.90 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--2H at 3.20 ppm (M, CH.sub.2 NH)--2H at 2.90 ppm (M, CH.sub.2 NH)--1H at 2.64 ppm (M, CHCO.sub.2)--4H at 2.40 ppm (M, ##STR159## 6H between 1.5 and 2 ppm ##STR160## CH.sub.2 --CH.sub.2 NH).
NMR no. 47-(b): 1H at 8.79 ppm (D, J=9 Hz, CONH)--3H at 8.30 ppm (S.e., N.sup.+ H.sub.3)--2H at 7.97 ppm (D, J=8 Hz, H ortho CO)--2H at 7.55 ppm (D, J=8 Hz, H meta CO)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.84 ppm (S, H thiazol)--1H at 5.92 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.40 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.56 ppm (S, CH.sub.2 ON)--1H at 4.08 ppm (M, CH.sub.2 NH.sub.2)--1H at 4.00 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.71 ppm (B of AB, J.sub.AB =17 Hz, CH.sub.2 SO).
NMR no. 48-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--3H at 8.30 ppm (S.e., N.sup.+ H.sub.3)--2H at 7.95 ppm (D, J=8 Hz, H ortho CO)--2H at 7.55 ppm (D, J=8 Hz, H meta CO)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.78 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.44 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.98 ppm (D, J=4 Hz, H.sub.6)--1H at 4.81 ppm (D, J=13 Hz)--CH.sub.2 OCO)--1H at 4.10 ppm (S.e., CH.sub.2 NH.sub.2)--1H at 4.05 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.71 ppm (B of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--4H 2.40 ppm (M, ##STR161## 2H at 1.85 ppm (M, ##STR162##
NMR no. 49-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--3H at 7.70 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.82 ppm (S, H thiazol)--1H at 5.90 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.10 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.56 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.53 ppm (S, CH.sub.2 ON)--1H 3.84 ppm (A of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (B of AB, J.sub.AB =17 Hz, CH.sub.2 SO)--2H at 2.76 ppm (M, CH.sub.2 NH.sub.2)--2H at 2.40 ppm (M, CH.sub.2 CO.sub.2)--2H at 1.72 ppm (M, CH.sub.2 CH.sub.2 CH.sub.2 NH.sub.2).
NMR no. 50-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--3H at 7.75 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.25 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.77 ppm (S, H thiazol)--1H at 5.94 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.11 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.63 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.89 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--2H at 2.78 ppm (M, CH.sub.2 NH.sub.2)--6H at 2.40 ppm (M, ##STR163## CH.sub.2 CO.sub.2)--4H at 1.85 ppm (M, CH.sub.2 CH.sub.2 NH.sub.2, ##STR164##
NMR no. 51-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--3H at 7.60 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.82 ppm (S, H thiazol)--1H at 5.87 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.61 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.92 ppm (D, J=4 Hz, H.sub.6)--1H at 4.58 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.57 ppm (S, CH.sub.2 ON)--1H at 3.81 ppm (A of AB, J=13 Hz, CH.sub.2 SO)--1H at 3.55 ppm (B of AB, J=13 Hz, CH.sub.2 SO)--2H at 2.75 ppm (M, CH.sub.2 NH.sub.2)--2H at 2.31 ppm (M, CH.sub.2 CO.sub.2)--4H at 1.50 ppm (M, CH.sub.2 (CH.sub.2).sub.2 CH.sub.2 N).
NMR no. 52-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--3H at 7.70 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.30 ppm (S.e. N.sup.+ H.sub.3)--1H at 6.78 ppm (S, H thiazol)--1H 5.92 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.13 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.58 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.86 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--2H at 2.74 ppm (M, CH.sub.2 NH.sub.2)--6H at 2.40 ppm (M, ##STR165## 2H at 1.85 ppm (M, ##STR166## 4H at 1.50 ppm (M, CH.sub.2 CH.sub.2 CH.sub.2 CO.sub.2).
NMR no. 53-(b): 1H at 8.80 ppm (D, J=9 Hz, CONH)--3H at 8.40 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.40 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.78 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.25 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.78 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.08 ppm (M, CHNH.sub.2)--1H at 3.95 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.60 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--4H at 2.40 ppm (M, ##STR167## 2H at 1.80 ppm (M, ##STR168## 3H at 1.36 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 54-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--3H at 7.87 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.78 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.19 ppm (2D, J=13 Hz, CH.sub.2 OCO)*--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.64 ppm (2D, J=13 Hz, CH.sub.2 OCO)*--1H at 3.92 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.0 ppm (M, CHCO.sub.2)--2H at 2.80 ppm (M, CH.sub.2 NH.sub.2)--4H at 2.40 ppm (M, ##STR169## 2H at 1.80 ppm (M, ##STR170## 3H at 1.08 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 55-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--3H at 7.80 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.80 ppm (S, H thiazol)--1H at 5.95 ppm (M, H.sub.7)--1H at 5.20 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (S.e., H.sub.6)--1H at 4.63 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.90 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.58 ppm (B of AB, J=17 Hz, CH.sub.2 SO) 2H at 2.93 ppm (M, CH.sub.2 NH.sub.2)--4H at 2.40 ppm (M, ##STR171## 2H at 1.90 ppm (M, ##STR172## 6H at 1.14 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 56-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--3H at 7.75 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.35 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.80 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.15 ppm (2D, J=13 Hz, CH.sub.2 OCO)*--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.60 ppm (2D, J=13 Hz, CH.sub.2 OCO)*--1H at 3.90 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.56 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--2H at 2.74 ppm (M, CH.sub.2 NH.sub.2)--1H at 2.50 (M, CHCO.sub.2)--4H at 2.40 ppm (M, ##STR173## 3H at 1.90 ppm (M, ##STR174## and CH.sub.2 CH.sub.2 NH.sub.2)--1H at 1.55 ppm (M, CH.sub.2 CH.sub.2 NH.sub.2)--3H at 1.08 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 57-(b): 1H at 8.80 ppm (D, H=9 Hz, CONH)--3H at 8.40 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.40 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.79 ppm (S H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.28 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.75 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.95 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.61 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--4H at 2.40 ppm (M, ##STR175## 2H at 2.10 ppm (M, CH.sub.2 cyclopentane)--2H at 1.90 (M, ##STR176## 6H at 1.80 ppm (M, CH.sub.2 cyclopentane).
NMR no. 58-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--3H at 2.70 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.84 ppm (S, H thiazol)--1H at 5.89 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.13 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--3H at 4.55 ppm (M, CH.sub.2 ON and CH.sub.2 OCO)--1H at 3.82 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--2H at 2.60 ppm (M, CH.sub.2 NH.sub.2)--1H at 2.21 ppm (M, CHCO.sub.2)--4H at 1.80 ppm, (M, CH.sub.2 cyclohexane)--1H at 1.45 ppm (M, CHCH.sub.2 NH.sub.2)--2H at 1.25 ppm (M, CH.sub.2 cyclohexane)--2H at 0.90 ppm (M, CH.sub.2 cyclohexane).
NMR no. 59-(b): 1H at 8.67 ppm (D, J=9 Hz, CONH)--3H at 7.70 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.82 ppm (S, H thiazol)--1H at 5.94 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.13 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.56 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3,87 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--2H at 3.55 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--2H at 2.60 ppm (M, CH.sub.2 NH.sub.2)--5H between 2.0 and 2.5 ppm, 6H between 1.6 and 2.0 ppm, 3H between 1.1 and 1 6 ppm, 2H at 0.90 ppm (M, ##STR177##
NMR no. 60-(b): 1H at 8.60 ppm (2D, J=9 Hz, CONH)*--3H at 7.70 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.30 ppm S.e., N.sup.+ H.sub.3)--1H at 6.82 ppm (2S, H thiazol)*--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.13 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (2D, H.sub.6)*--2H at 4.60 ppm (M, CH.sub.2 OCO+CHON)--1H at 3.86 ppm (2D, J=17 Hz, CH.sub.2 SO)*--1H at 3.56 ppm (2D, J=17 Hz, CH.sub.2 SO)*--2H at 2.75 ppm (M, CH.sub.2 NH.sub.2)--2H at 2.40 ppm (T, J=7 Hz, CH.sub.2 CO.sub.2)--2H at 1.75 ppm (M, CH.sub.2 CH.sub.2 CH.sub.2 NH.sub.2)--3H at 1.39 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 61-(b): 1H at 8.70 ppm (2D, J=9 Hz, CONH)*--3H at 7.70 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.30 ppm S.e., N.sup.+ H.sub.3)--1H at 6.82 ppm (2S, H thiazol)*--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.12 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.94 ppm (2D, H.sub.6)*--2H at 4.60 pm (M, HCON, and CH.sub.2 OCO)--1H at 3,86 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--2H at 2.75 ppm (M, CH.sub.2 NH.sub.2)--2H at 2.31 ppm (M, CH.sub.2 CO.sub.2)--4H at 1.50 ppm (M, CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 NH.sub.2)--3H at 1.45 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 62-(b): 2H at 8.60 ppm (M, CONH, N.sup.+ H.sub.3)--1H at 8.40 ppm (S.e., N.sup.+ H.sub.2)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.82 ppm (2S, H thiazol)*--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.14 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (2D, H.sub.6)*--2H at 4.60 ppm (M, CH--ON, and CH.sub.2 OCO)--1H at 3.88 ppm (2D, J=17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.20 ppm and 2H at 2.95 ppm (M, ##STR178## 1H at 2.66 ppm (M, CHCO.sub.2)--2H at 1.95 ppm and 2H at 1.70 ppm (M, ##STR179## 3H at 1.45 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 63-(b): 1H at 8.70 ppm (2D, J=9 Hz, CONH)*--3H at 8.20 ppm (S.e., N.sup.+ H.sub.3)--2H at 7.95 ppm (D, J=Hz, H ortho CO.sub.2)--2H at 7.55 ppm (D, J=8 Hz, H meta CO.sub.2)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3) 1H at 6.82 ppm (2S, H thiazol)*--1H at 5 95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.44 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.96 ppm (2D, H.sub.6)*--1H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.60 ppm (Q, J=7 Hz, CHON)--2H at 4.10 ppm (M, CH.sub.2 NH.sub.2)--1H at 3.90 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.70 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 1.45 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 64-(b): 1H at 8.60 ppm (2D, J=9 Hz, CONH)*--3H at 7.70 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.80 ppm (2S, H thiazol)*--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--5H between 4 and 6 ppm (S.e., N.sup.+H.sub.3 CO.sub.2 H)--1H 5.13 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H 4.95 ppm (2D, H.sub.6)*--2H at 4.60 ppm (M, CH.sub.2 OCO and CHON)--1H at 3.86 ppm (A of AB, J=17 Hz, CH.sub.2 SO)--1H at 3.55 ppm (B of AB, J=17 Hz, CH.sub.2 SO)--2H at 2.61 ppm (M, CH.sub.2 NH.sub.2)--1H at 2.21 ppm (M, CHCO.sub.2)--4H at 1.80 ppm (M, ##STR180## 3H at 1.45 ppm (D, J=7 Hz, CH.sub.3 CH)--2H at 1.25 ppm and 2H at 0.90 ppm (M, ##STR181##
NMR no. 65-(b): 1H at 8.66 ppm (D, J=9 Hz, CONH)--3H at 8.15 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 8.05 ppm (S, HAr 2')--1H at 7.94 ppm (D, J=7 Hz, HAr 6')--1H at 7.71 ppm (D, J=7 Hz, HAr 4')--1H at 7.55 ppm (T, J=7 Hz, H5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7) 1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.87 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.05 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 et CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 1.48 ppm (S, CH.sub.3)--3H at 1.47 ppm (S, CH.sub.3).
NMR no. 66-(b): 1H at 8.80 ppm (D, J=9 Hz, CONH)--3H at 8.05 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.20 ppm (2D superposed, J=13 Hz, CH.sub.2 OCO)--1H at 5.10 ppm (2D, J=4 Hz, H.sub.6)--1H at 4.56 ppm (2D superposed, J=13 Hz, CH.sub.2 OCO)--4H at 3.90 ppm (M, CH.sub.2 SO and CH.sub.2 N.sup..sym. H.sub.3)--3H at 2.80 ppm (M, CHCO.sub.2, CHCH.sub.2 N.sup..sym. H.sub.3, and H Eq in .alpha. du CO.sub.2)--1H at 2.00 ppm (M, H Ax in .alpha. of CO.sub.2)--6H at 1.50 ppm (2S (CH.sub.3).sub.2 C)--6H between 1.20 and 1.80 ppm (M, 3CH.sub.2 reminder of cyclohexane.
NMR no. 67-(b): 3H at 8.50 ppm (M, N.sup..sym. H.sub.2 and CONH)--2H at 7.50 ppm (Se., NH.sub.2 thiazol)--1H at 6.79 ppm (S, H thiazol)--1H at 5.99 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.16 ppm (2D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz H.sub.6)--1H at 4.66 ppm (D, J=13 Hz, OCO)--1H at 3.92 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.58 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.36 ppm (M, CHN.sup..sym. H.sub.2)--1H at 3.25 ppm (M, CH.sub.2 .alpha.N.sup..sym. H.sub.2)--1H at 2.95 ppm (M, CH.sub.2 .alpha.N.sup..sym. H.sub.2)--2H at 2.60 ppm (2D superposed CH.sub.2 CO.sub.2)--3H at 1.70 ppm (M, H piperidine)--6H at 1.48 ppm (2S(CH.sub.3).sub.2 C)--3H at 1.45 ppm (M, H piperidine).
NMR no. 68-(b): 1H at 8.60 ppm (Se., N.sup..sym. H.sub.2 piperidine)--1H at 8.45 ppm (Se., NH.sup..sym..sub.2 piperidine)--1H at 8.45 ppm (D, J=9 Hz, CONH)--1H at 7.50 ppm (Se., NH.sub.2 thiazol)--1H at 6.70 ppm (S, H thiazol)--1H at 5.97 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5 10 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6) 1H at 4.63 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.90 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.57 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.20 ppm (M, CH.sub. 2 .alpha.N.sup..sym. H.sub.2)--2H at 2.70 ppm (M, CH.sub.2 .alpha.N.sup..sym. H.sub.2)--2H at 2.30 ppm (D, J=7 Hz, CH.sub.2 CO.sub.2)--1H at 2.05 ppm (M, CHCH.sub.2 CO.sub.2)--3H at 1.55 ppm (M, CH.sub.2 piperidine)--6H at 1.48 ppm (2S, (CH.sub.3).sub.2 C)--1H at 1.20 ppm (M, CH.sub.2 piperidine).
NMR no. 69-(b): 1H at 10.9 ppm (Se., ArNHCO)--1H at 8.45 ppm (D, J=9 Hz, CONH)--4H at 8.15 ppm (2S, CH.sub.2 N.sup..sym. H.sub.3 and HAr 2')--1H at 7.81 ppm (D, J=7 Hz, HAr 6')--1H at 7.67 ppm (D, J=7 Hz, HAr 4')--1H at 7.50 ppm (T, J=7 Hz, HAr 5')--2H at 7.20 ppm (Se., NH.sub.2 thiazol)--1H at 6.78 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.00 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.75 ppm (M, ##STR182## and CH.sub.2 SO)--6H 1.47 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 70-(b): 1H at 8.70 ppm (D, J=9 Hz, CONH)--3H at 8.50 ppm (Se., CH.sub.2 --N.sup..sym. H.sub.3)--1H at 8.05 ppm (S, HAr 2')--1H at 7.80 ppm (D, J=7 Hz, HAr 6')--1H at 7.34 ppm (D, J=7 Hz HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.05 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.05 ppm (M, ArCH.sub.2 N.sup..sym. H.sub. 3 and CH.sub.2 SO)--1H at 3.80 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.37 ppm (S, CH.sub.3 Ar)--6H at 1.48 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 71-(b): 1H at 8.70 ppm (D, J=9 Hz, CONH)--9H at 8.50 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--2H at 7.78 ppm (M, HAr 2', 6')--1H at 7.50 ppm (D, J=7 Hz, HAr 5')--1H at 6.92 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H of 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H of 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.81 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.05 ppm (M, ArCH.sub.2 N.sup..sym. H.sub.3 CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 S0)--3H at 2.36 ppm (S, CH.sub.3 Ar)--6H at 1.47 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 72-(b): 1H at 8.70 ppm (D, J=9 Hz, CONH)--2H at 7.95 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.67 ppm (D, J=8 Hz, HAr 3', 5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.16 ppm (M, ArCH.sub.2 NHCH.sub.3)--1H at 4.08 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.78 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.43 ppm (S, CH.sub.3 N)--6H at 1.48 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 73-(b): 1H at 8.70 ppm (D, J=9 Hz, CONH)--2H at 7.95 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.67 ppm (D, J=8 Hz, HAr 3', 5')--1H at 6.92 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.43 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.18 ppm (M, CH.sub.2 Ar)--1H at 4.10 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.76 ppm (D, J=17 Hz, CH.sub. 2 SO)--2H at 2.90 ppm (M, CH.sub.3 CH.sub.2 NH)--6H at 1.47 ppm (2S, (CH.sub.3).sub.2 C)--3H at 1.16 ppm (T, J=7 Hz, CH.sub.3 CH.sub.2).
NMR no. 74-(b): 1H at 8.70 ppm (D, J=9 Hz, CONH)--2H at 7.95 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.67 ppm (D, J=8 Hz, HAr 3', 5')--1H at 6.95 ppm (S, H thiazol)--1H 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.16 ppm (M, ArCH.sub.2 NPr)--1H at 4.08 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.78 ppm (D, J=17 Hz, CH.sub.2 SO)-- 1H at 3.20 ppm (M, NH--CH(CH.sub.3).sub.2)--6H at 1.48 ppm (2S, (CH.sub.3).sub.2 C)--6H at 1.26 ppm (D, J=7 Hz, (CH.sub.3).sub.2 CH).
NMR no. 75-(b): 1H at 8,62 ppm (D, J=9 Hz, CONH)--3H at 8,10 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7,68 ppm (D, J=7 Hz, HAr 6')--1H at 7,55 ppm (D, J=7 Hz, HAr 4')--1H at 7,34 ppm (T, J=7 Hz, HAr 5')--1H at 6,92 ppm (S, H thiazol)--1H at 6,00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5,37 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5,00 ppm (D, J=4 Hz, H.sub.6)--1H at 4,84 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4,10 ppm (M, CH.sub.2 N.sup. .sym. H.sub.3 et CH.sub.2 SO)--1H at 3,75 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2,40 ppm (S, CH.sub.3 Ar)--6H at 1,47 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 76-(b): 1H at 8.62 ppm (D, J=9 Hz, CONH)--3H at 8.00 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.31 ppm (D, J=7 Hz, HAr 4')--1H at 7.14 ppm (D, J=7 Hz, HAr 5')--1H at 6.90 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.27 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.92 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.00 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 et CH.sub.2 SO)--1H at 3.64 ppm (D, J= 17 Hz, CH.sub.2 SO)--6H at 2.18 ppm (S, CH.sub.3 --Ar)--6H at 1.48 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 77 (b): 1H at 8.65 ppm (D, J=9 Hz, CONH)--3H at 7.90 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.00 ppm (S, HAr)--1H at 6.90 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.25 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.92 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.00 ppm (M, ArCH.sub.2 N.sup..sym. H.sub.3 and CH.sub.2 SO)--1H at 3.65 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.31 ppm (S, CH.sub.3 Ar)--3H at 2.25 ppm (S, CH.sub. 3 Ar)--3H at 2.14 ppm (S, CH.sub.3 Ar)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 78-(b): 1H at 8.70 ppm (D, J=9 Hz, CONH)--3H at 8.00 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.45 ppm (D, J=7 Hz, HAr 4')--2H at 6.92 ppm (M, H thiazol and HAr 5')--1H at 6 00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.42 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 3.95 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 and CH.sub.2 SO)--3H at 3.78 ppm (S, OCH.sub.3)--3H at 3.73 ppm (S, OCH.sub.3 )--1H at 3.58 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.47 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 79-(b): 1H at 8.62 ppm (D, J=9 Hz, CONH)--5H at 8.00 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 and HAr 2', 6')--1H at 7.20 ppm (D, J=7 Hz, HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.00 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 and CH.sub.2 SO)--3H at 3.88 ppm (S, OCH.sub.3)--1H at 3.72 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 1.48 ppm (S, (CH.sub.3).sub.2 C)--3H at 1.47 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 80-(B): 1H at 8.66 ppm (D, J=9 Hz, CONH)--3H at 8.05 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--3H at 7.50 ppm (M, HAr)--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.00 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 et CH.sub.2 SO)--3H at 3.86 ppm (S, CH.sub.3 O--Ar)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 1.48 ppm (S, (CH.sub. 3).sub.2 C)--3H at 1.47 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 81-(b): 1H at 8.82 ppm (D, J=9 Hz, CONH)--3H at 8.20 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 8.13 ppm (Se., HAr 2')--1H at 7.95 ppm (D, J=7 Hz, HAr 6')--1H at 7.69 ppm (D, J=7 Hz, HAr 4')--1H at 7.55 ppm (T, J=7 Hz, HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.48 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6) 1H at 4.86 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.05 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 and CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--4H at 2.40 ppm (M, ##STR183## 2H at 1.90 ppm (M, ##STR184##
NMR no. 82-(b): 1H at 8.82 ppm (D, J=9 Hz, CONH)--3H at 8.20 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--2H at 7.80 ppm (M, HAr 2', 6')--1H at 7.45 ppm (D, J=7 Hz, HAr 5')--1H at 6.92 ppm (S, H thiazol)--1H at 5.97 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.05 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 and CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--4H at 2.40 ppm (M, ##STR185## 3H at 2.34 ppm (S, CH.sub.3 Ar)--2H at 1.90 ppm (M, ##STR186##
NMR no. 83-(b): 1H at 8.97 ppm (D, J=9 Hz, CONH)--2H at 8.79 ppm (Se., CH.sub.2 N.sup..sym. H.sub.2)--2H at 8.00 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.58 ppm (D, J=8 Hz, HAr 3', 5')--1H at 6.95 ppm (S, H thiazol)--1H at 5.97 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.19 ppm (M, CH.sub.2 N.sup..sym. H.sub.2 --CH.sub.3)--1H at 4.08 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.50 ppm (M, CH.sub.2 N.sup..sym. H.sub.2 --CH.sub.3)--4H at 2.40 ppm (M, ##STR187## 2H at 1.90 ppm (M, ##STR188##
NMR no. 84(b): 1H at 10.7 ppm (S, CONHAr)--1H at 8.60 ppm (D, J=9 Hz, CONH)--1H at 8.20 ppm (S, HAr 2')--1H at 7.80 ppm (D, J=8 Hz, HAr 6')--3H at 7.65 ppm (Se., CH.sub.2 N.sup.+ H.sup.3)--1H at 7.60 ppm (D, J=8 Hz, HAr 4')--1H at 7.45 ppm (T, J=8 Hz, HAr 5')--1H at 6.92 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1 H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.00 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.05 ppm (Q, J=7 Hz, CH.sub.2 CH.sub.2 N.sup..sym. H.sub.3)--2H at 2.70 ppm (T, J=7 Hz, CH.sub.2 CH.sub.2 N.sup..sym. H.sub.3)--6H at 1.47 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 85-(b): 1H at 8.80 ppm (D, J=9 Hz, CONH)--4H at 8.20 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 and H thiazol in 3)--1H 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.38 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.98 ppm (D, J=4 Hz, H.sub.6)--1H at 4.78 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.98 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.82 ppm (Q, J=7 Hz, CH.sub.2 N.sup..sym. H.sub.3)--1H at 3.66 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.49 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 86 (b): 1H at 10.75 ppm (S, ArNHCO)--1H at 8.70 ppm (D, J=9 Hz, CONH)--3H at 8.07 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--2H at 7.94 ppm (D, J=8 Hz, HAr 2' 6')--2H at 7.70 ppm (D, J=8 Hz, HAr 3' 5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.40 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.98 ppm (D, J=4 Hz, H.sub.6)--1H at 4.80 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.05 ppm (D, J=17 Hz, CH.sub. 2 SO)--3H at 3.80 ppm (M, CH.sub.2 SO and CH.sub.2 N.sup..sym. H.sub.3)--6H at 1.48 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 87-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--1H at 8.50 ppm (Se., NH.sub.2.sup..sym. piperidine)--1H at 8.40 ppm (Se., NH.sub.2.sup..sym. piperidine)--2H at 7.40 ppm (Se., NH.sub.2 thiazol)--1H at 6.78 ppm (S, H thiazol)--1H at 5 95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.16 ppm (2D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.68 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.92 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3 60 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.40 ppm (M, CHN.sup..sym. H.sub.2)--1H at 3.25 ppm (M, CH.sub.2 N.sup..sym. H.sub.2)--1H at 2.89 ppm (M, CH.sub.2 N.sup..sym. H.sub.2)--2H at 2.60 ppm (2D superposed, J=7 Hz, CH.sub.2 COO)--4H at 2.40 ppm (M, ##STR189## 5H at 1.85 ppm (M, 3H of the piperidine and ##STR190## 3H at 1.45 ppm (M, 3H piperidine).
NMR no. 88-(b): 1H at 8.80 ppm (D, J=9 Hz, CONH)--1H at 8.60 ppm (Se., N.sup..sym. H.sub.2 piperidine)--1H at 8.45 ppm (Se., N.sup..sym. H.sub.2 piperidine)--2H at 7.25 ppm (Se., NH.sub.2 thiazol)--1H at 6.79 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.16 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.69 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.90 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.60 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.24 ppm (M, CH.sub.2 in .alpha. of N.sup..sym. H.sub.2 piperidine)--2H at 2.70 ppm (M, CH.sub.2 in .alpha. of N.sup..sym. H.sub.2 piperidine)--6H at 2.40 ppm (M, ##STR191## and CH.sub.2 COO)--6H between 1.5 and 2.2 ppm (M, ##STR192## CHCH.sub.2 CO.sub.2, 3H piperidine)--1H at 1.20 ppm (M, H piperidine).
NMR no. 89-(b): 1H at 8.80 ppm (D, J=9 Hz, CONH)--2H at 8.30 ppm (2 Se., NH.sub.2.sup..sym. piperidine)--2H at 7.40 ppm (Se., NH.sub.2 thiazol)--1H at 6.78 ppm (S, H thiazol)--1H at 5.92 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.14 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.96 ppm (D, J=4 Hz, H.sub.6)--1H at 4.60 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.89 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.58 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.18 ppm (M, H.alpha.N.sup..sym. H.sub.2 piperidine)--2H at 2.81 ppm (M, H.alpha.N.sup..sym. H.sub.2 piperidine)--4H at 2.40 ppm (M, ##STR193## 2H at 2.28 ppm (D, J=7 Hz, CH.sub.2 CO--O)--5H at 1.90 ppm (M, ##STR194## CHCH.sub.2 COO, 2H.beta.N.sup..sym. H.sub.2 piperidine) 2H at 1.30 ppm (M, 2H.beta.N.sup..sym. H.sub.2 piperidine).
NMR no. 90-(b): 1H at 8.45 ppm (D, J=9 Hz, CONH)--1H at 8.50 ppm (Se., NH.sub.2.sup..sym. piperidine)--1H at 8.20 ppm (Se., NH.sub.2.sup..sym. piperidine)--2H at 7.30 ppm (Se., NH.sub.2 thiazol)--1H at 6.77 ppm (S, H thiazol)--1H 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.11 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.61 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.89 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.58 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.21 ppm (M, CH.sub.2 and .alpha.N.sup..sym. H.sub.2 piperidine)--2H at 2.81 ppm (M, CH.sub.2 in .alpha.N.sup..sym. H.sub.2 piperidine)--2H at 2.27 ppm (D, J=7 Hz, CH.sub.2 COO)--1H at 1.95 ppm (M, CHCH.sub.2 COO)--2H at 1.75 ppm (M, CH.sub.2 .beta.N.sup..sym. H.sub.2 piperidine)--6H at 1.47 ppm (2S, (CH.sub.3).sub.2 C)--2H at 1.40 ppm (M, CH.sub.2 .beta.N.sup.+ H.sub.2 piperidine).
NMR no. 91-(b): 2H at 8.70 ppm (Se., CH.sub.2 N.sup..sym. H.sub.2 CH.sub.3)--1H at 8.60 ppm (D, J=9 Hz, CONH)--1H at 8.10 ppm (Se., HAr 2')--1H at 7.96 ppm (D, J=8 Hz, Har 6')--1H at 7.75 ppm (D, J=8 Hz, HAr 4')--1H at 7.56 ppm (T, J=8 Hz, Har 5')--1H at 6.92 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.87 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.16 ppm (M, ArCH.sub.2 N.sup..sym. H.sub.2 CH.sub.3)--1H at 4.05 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.50 ppm (M, CH.sub.3 N.sup..sym. H.sub.2 CH.sub.2)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 92-(b): 2H at 8.70 ppm (Se., CH.sub.2 N.sup..sym. H.sub.2 CH.sub.2 CH.sub.3)--1H at 8.60 ppm (D, J=9 Hz, CONH)--1H at 8.10 ppm (Se., HAr 2')--1H at 7.96 ppm (D, J=8 Hz, HAr 6')--1H at 7.75 ppm (D, J=8 Hz, HAr 4')--1H at 7.56 ppm (T, J=8 Hz, HAr 5')--1H at 6.92 ppm (S, H thiazol)--1H at 6.02 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7) 1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.87 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.17 ppm (Se., Ar, CH.sub.2 N.sup..sym. H.sub.2 Et)--1H at 4.05 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 2.95 ppm (M, CH.sub.3 CH.sub.2 N.sup..sym. H.sub.2)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C)--3H at 1.15 ppm (T, J=7 Hz, CH.sub.3 CH.sub.2 N.sup..sym. H.sub.2).
NMR no. 93(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--2H at 8.70 ppm (Se., CH.sub.2 N.sup..sym. H.sub.2 --i Pr)--1H at 8.10 ppm (Se., HAr 2')--1H at 7.95 ppm (D, J=8 Hz, HAr 6')--1H at 7.75 ppm (D, J=8 Hz, HAr 4')--1H at 7.58 ppm (T, J=8 Hz, HAr 5')--1H at 7.00 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.46 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.87 ppm (D, J= 13 Hz, CH.sub.2 OCO)--2H at 4.19 ppm (M, ArCH.sub.2 N.sup..sym. H.sub.2 i Pr)--1H at 4.05 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.79 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.31 ppm (M, (CH.sub.3).sub.2 --CH)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C)--6H at 1.22 ppm (D, J=7 Hz, (CH.sub.3).sub.2 CHN.sup..sym. H.sub.2).
NMR no. 94-(b): 1H at 8.90 ppm (D, J=9 Hz, CONH)--3H at 8.10 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.66 ppm (D, J=8 Hz, HAr 6')--1H at 7.55 ppm (D, J=8 Hz, HAr 4')--1H at 7.45 ppm (T, J=8 Hz, HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.40 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.86 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.07 ppm (M, ArCH.sub.2 N.sup. .sym. H.sub.3 and CH.sub.2 SO)--1H at 3.67 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.40 ppm (S, CH.sub.3 Ar)--4H at 2.50 ppm (M, ##STR195## 2H at 1.90 ppm (M, ##STR196##
NMR no. 95-(b): 1H at 8.90 ppm (D, J=9 Hz, CONH)--3H at 8.05 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.40 ppm (D, J=8 Hz, HAr 4')--1H at 7.20 ppm (D, J=8 Hz, HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.30 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.95 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.00 ppm (ArCH.sub.2 N.sup..sym. H.sub.3 et CH.sub.2 SO)--1H at 3.63 ppm (D, J=17 Hz, CH.sub.2 SO)--4H at 2.40 ppm (M, ##STR197## 6H at 2.20 ppm (S, CH.sub.3 Ar)--2H at 1.90 ppm (M, ##STR198##
NMR no. 96-(b): 1H at 8.90 ppm (D, J=9 Hz, CONH)--3H at 7.90 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.00 ppm (S, HAr)--1H at 6.9 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.30 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.94 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.00 ppm (M, ArCH.sub.2 N.sup..sym. H.sub.3 et CH.sub.2 SO)--1H at 3.62 ppm (D, J=17 Hz, CH.sub.2 SO)--4H at 2.50 ppm (M, ##STR199## 3H at 2.32 ppm (S, CH.sub.3 Ar)--3H at 2.2 ppm (S, CH.sub.3 Ar)--3H at 2.16 ppm (S, CH.sub.3 Ar)--2H at 1.90 ppm (M, ##STR200##
NMR no. 97-(b): 1H at 10.30 ppm (S, ArNHCO)--1H at 8.70 ppm (D, J=9 Hz, CONH)--1H at 8.30 ppm (Se., HAr 2')--3H at 8.05 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--2H at 7.70 ppm (M, HAr 5', 6')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.80 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.03 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.85 ppm (M, CH.sub.2 N.sup. .sym. H.sub.3)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.47 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 98-(b): 1H at 9.90 ppm (S, ArNHCO)--1H at 8.66 ppm (D, J=9 Hz, CONH)--1H at 8.28 ppm (S, HAr 2')--5H at 7.70 ppm (M, HAr 5', 6' at CH.sub.2 N.sup..sym. H.sub.3)--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.03 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.68 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.05 ppm (M, ##STR201## 2H at 2.75 ppm (T, J=7 Hz, ##STR202## 6H at 1.46 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 99-(b): 1H at 10.5 ppm (S, ArNHCO)--1H at 8.56 ppm (D, J=9 Hz, CONH)--2H at 7.89 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.70 ppm (D, J=8 Hz, HAr 3', 5')--3H at 7.70 ppm (Se., (CH.sub.2).sub.2 N.sup..sym. H.sub.3)--1H at 6.95 ppm (S, H thiazol)--1H at 5.98 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.40 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.98 ppm (D, J=4 Hz, H.sub.6)--1H at 4.79 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.05 ppm (D, J=17 Hz, CH.sub. 2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.06 ppm (M, ##STR203## 2H at 2.70 ppm (M, ##STR204## 6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 100-(b): 1H at 12.75 ppm (Se., thiazol NHCO)--1H at 8.90 ppm (D, J=9 Hz, CONH)--4H at 8.15 ppm (M, CH.sub.2 NH.sub.3 and H thiazol in 3)--1H at 6.96 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.40 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.98 ppm (D, J=4 Hz, H.sub.6)--1H at 4.81 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.0 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.86 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 3.66 ppm (D, J=17 Hz, CH.sub.2 SO)--4 H at 2.5 ppm (M, ##STR205## 2H at 1.90 ppm (M, ##STR206##
NMR no. 101-(b): 1H at 10.8 ppm (S, ArNHCO)--1H at 8.95 ppm (D, J=9 Hz, CONH)--3H at 8.15 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--2H at 7.90 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.70 ppm (D, J=8 Hz, HAr 3', 5')--1H at 6.97 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.36 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.05 ppm (D, J=17 Hz, CH.sub.2 SO)-- 3H at 3.80 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 and CH.sub.2 SO)--4H at 2.40 ppm (M, ##STR207## 2H at 1.90 ppm (M, ##STR208##
NMR no. 102-(b): 1H at 8.45 ppm (D, J=9 Hz, CONH)--3H at 8.0 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 6.79 ppm (S, H thiazol)--1H at 5.98 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.15 ppm (2D, J=13 Hz, CH.sub.2 OCO) 1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.62 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.15 ppm (De., J=12 Hz, H.sub.2 Eq piperidine)--3H at 3.84 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 and CH.sub.2 SO)--2H at 3.58 ppm (M, CH.sub.2 SO and H.sub.6 Eq piperidine)--1H at 3.05 ppm (Te., J= 12 Hz, H.sub.2 Ax piperidine)--1H at 2.81 ppm (Te., J=12 Hz, H.sub.6 Ax piperidine)--1H at 2.60 ppm (M, CHCO.sub.2)--2H at 1.84 ppm (M, H.sub.3 and H.sub.5 piperidine) 2H at 1.50 ppm (M, H.sub.3 and H.sub.5 piperidine)--6H at 1.45 ppm (2D, (CH.sub.3).sub.2 C).
NMR no. 103-(b): 1H at 8.72 ppm (D J=9 Hz, CONH)--3H at 8.25 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--3H at 7.75 ppm (M, HAr)--1H at 6.97 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.05 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 and CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 104-(b): 2H at 8.80 ppm (Se., CH.sub.2 N.sup..sym. H.sub.2 CH.sub.3)--1H at 8.77 ppm (D, J=9 Hz, CONH)--3H at 7.75 ppm (M, HAr)--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.86 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.25 ppm (M, CH.sub.2 N.sup..sym. H.sub.2 CH.sub.3)--1H at 4.10 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.74 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.58 ppm (M, CH.sub.2 N.sup..sym. H.sub.2 --CH.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 105-(b): 1H at 10.70 ppm (S, ArNHCO)--2H at 8.70 ppm (Se., CH.sub.2 N.sup..sym. H.sub.2 CH.sub.3)--1H at 8.68 ppm (D, J=9 Hz, CONH)--1H at 8.16 ppm (S, HAr 2')--1H at 7.92 ppm (D, J=8 Hz, HAr 6')--1H at 7.66 ppm (D, J=8 Hz, HAr 4')--1H at 7.50 ppm (T, J=8 Hz, HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1 H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.02 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.90 ppm (M, CH.sub.2 N.sup..sym. HCH.sub.3)--1H at 3.74 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.60 ppm (M, CH.sub.2 N.sup..sym. H.sub.2 CH.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 106-(b): 1H at 10.80 ppm (S, ArNHCO)--3H at 8.70 ppm (M, CH.sub.2 N.sup..sym. H.sub.2 CH.sub.3 et CONH)--2H at 7.92 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.69 ppm (D, J=8 Hz, HAr 3', 5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.42 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.81 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.05 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.95 ppm (M, CH.sub. 2 N.sup..sym. H.sub.2 CH.sub.3)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.62 ppm (M, CH.sub.2 N.sup..sym. H.sub.2 CH.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 107-(b): 1H at 9.95 ppm (S, ArNHCO)--1H at 8.75 ppm (D, J=9 Hz, CONH)--3H at 8.05 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.61 ppm (D, J=8 Hz, HAr 6')--1H at 7.52 ppm (D, J=8 Hz, HAr 4')--1H at 7.31 ppm (T, J=8 Hz, HAr 6')--1H at 6.96 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.40 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.81 ppm (D, J=13 Hz, CH.sub.2 OCO)-- 1H at 4.05 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.81 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 3.72 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.28 ppm (S, ArCH.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 108-(b): 1H at 9.75 ppm (S, ArNHCO)--1H at 8.70 ppm (D, J=9 Hz, CONH)--3H at 7.70 ppm (Se., CH.sub.2 CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.60 ppm (D, J=8 Hz, HAr 6')--1H at 7.50 ppm (D, J=8 Hz, HAr 4')--1H at 7.25 ppm (T, J=8 Hz, HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.39 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.05 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.72 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.02 ppm (M, CH.sub.2 CH.sub.2 N.sup..sym. H.sub.3)--2H at 2.69 ppm (T, J=7, CH.sub.2 CH.sub.2 N.sup..sym. H.sub.3)--3H at 2.29 ppm (S, ArCH.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 109-(b): 1H at 12.7 ppm (Se., NHCO thiazol)--1H at 8.79 ppm (D, J=9 Hz, CONH)--1H at 8.08 ppm (S, H thiazol in 3)--3H at 7.75 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 6.98 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.37 ppm (D, J=13 Hz CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.81 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.03 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.68 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.06 ppm (M, CH.sub. 2 CH.sub.2 N.sup..sym. H.sub.3)--2H at 2.77 ppm (T, J=7 Hz, CH.sub.2 CH.sub.2 N.sup..sym. H.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 110-(b): 1H at 8.70 ppm (D, J=9 Hz, CONH)--5H at 7.96 ppm (M, HAr 2', 6' and CH.sub.2 N.sup..sym. H.sub.3)--2H at 7.55 ppm (D, J=8 Hz, HAr 3', 5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.46 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.99 ppm (D, J=4 Hz, H.sub.6)--1H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.06 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.74 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.55 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--3H at 3.25 ppm (Se., NCH.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 111-(b): 1H at 10.5 ppm (Se., ArNHCO)--1H at 8.95 ppm (D, J=9 Hz, CONH)--2H at 7.89 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.71 ppm (D, J=8 Hz, HAr 3', 5')--1H at 6.96 ppm (S, H thiazo)--1H at 5.98 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.42 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.80 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.05 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)-- 2H at 3.05 ppm (M, CH.sub.2 CH.sub.2 N.sup..sym. H.sub.3)--2H at 2.70 ppm (T, J=7 Hz, CH.sub.2 CH.sub.2 N.sup..sym. H.sub.3)--4H at 2.40 ppm (M, ##STR209## 2H at 1.90 ppm (M, ##STR210##
NMR no. 112-(b): 1H at 8.80 ppm (D, J=9 Hz, CONH)--3H at 7.90 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 6.80 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.17 ppm (2D, J=13 Hz, CH.sub.2 OCO)--1H at 4.96 ppm (D, J=4 Hz, H.sub.6)--1H at 4.60 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.18 ppm (M, H.sub.2 e piperidine) 3H at 3.90 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 and CH.sub.2 SO)--2H at 3.58 ppm (M, CH.sub.2 SO et H.sub.6 e piperidine)--1H at 3.06 ppm (M, H.sub.2 a piperidine)--1H at 2.75 ppm (M, H.sub.6 a piperidine)--1H at 2.60 ppm (M, H.sub.4 piperidine)--4H at 2.40 ppm (M, ##STR211## 4H at 1.80 ppm et 2H 1.50 ppm ##STR212## et H.sub.3 et H.sub.5 piperidine).
NMR no. 113-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--3H at 8.40 ppm (Se., CHN.sup..sym. H.sub.3)--1H at 8.13 ppm (S, HAr 6')--1H at 8.00 ppm (D, J=8 Hz, HAr 2')--1H at 7.64 ppm (D, J=8 Hz, HAr 3')--1H at 6.97 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.86 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.19 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1 H at 4.10 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.76 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 114-(b): 1H at 8.72 ppm (D, J=9 Hz, CONH)--3H at 8.40 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--2H at 8.11 ppm (M, HAr 2', 6')--1H at 7.86 ppm (M, HAr 3')--1H at 6.99 ppm (S, H thiazol)--1H at 6.01 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.46 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.89 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.18 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 4.06 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.78 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 115-(b): 1H at 10.20 ppm (Se., ArNHCO)--1H at 8.70 ppm (D, J=9 Hz, CONH)--1H at 8.16 ppm (Se., HAr 2')--1H at 7.84 ppm (D, J=8 Hz, HAr 6')--3H at 7.66 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.60 ppm (D, J=8 Hz, HAr 4')--1H at 7.45 ppm (T, J=8 Hz, HAr 5')--1H at 6.97 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1 H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.05 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 2.81 ppm (M, CH.sub.2 --N.sup..sym. H.sub.3)--2H at 2.40 ppm (T, J=7 Hz, CH.sub.2 CO.sub.2)--2H at 1.82 ppm (M, CH.sub.2 CH.sub.2 CO.sub.2)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 116-(b): 1H at 10.3 ppm (Se., ArNHCO)--1H at 8.70 ppm (D, J=9 Hz, CONH)--2H at 7.90 ppm (D, J=8 Hz, HAr 2', 6')--1H at 7.67 ppm (D, J=8 Hz, HAr 3', 5')--3H at 7.60 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.42 ppm (D, J=13 Hz CH.sub.2 OCO)--1H at 4.98 ppm (D, J=4 Hz, H.sub.6)--1H at 4.79 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.06 ppm (D, J=17 Hz, CH.sub.2 SO)-- 1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 2.79 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--2H at 2.42 ppm (M, CH.sub.2 --CONHAr)--2H at 1.84 ppm (M, CH.sub.2 CH.sub.2 N.sup..sym. H.sub.3)--6H at 1.48 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 117-(b): 1H at 10.30 ppm (Se., ArNHCO)--1H at 8.75 ppm (D, J=9 Hz, NHCO)--2H at 7.84 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.72 ppm (D, J=8 Hz, HAr 3', 5')--3H at 7.60 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 6.97 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.40 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.90 ppm (D, J=4 Hz, H.sub.6)--1H at 4.78 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.05 ppm (D, J=17 Hz, CH.sub.2 SO)-- 1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 2.75 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--2H at 2.36 ppm (M, CH.sub.2 CONHAr)--4H at 1.58 ppm (M, --COCH.sub.2 (CH.sub.2).sub.2 CH.sub.2 N.sup..sym. H.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 118-(b): 1H at 12.7 ppm (Se, NHCO thiazol)--1H at 8.65 ppm (D, J=9 Hz, CONH)--3H at 8.20 ppm (Se, CH.sub.2 N.sup..sym. H.sub.3)--1H at 6.93 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.02 ppm (D, J=4 Hz, H.sub.6)--1H at 4.75 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.02 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.90 ppm (M, CH.sub.2 Gly)--1H at 3.70 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.50 ppm (S, CH.sub.3 thiazol-- 6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 119-(b): 1H at 8.45 ppm (D, J=9 Hz, CONH)--3H at 7.80 ppm (Se., CH--N.sup..sym. H.sub.3)--1H at 6.80 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.10 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.58 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 3.90 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.56 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.00 ppm (2M, CHN.sup..sym. H.sub.3)--1H at 2.25 ppm (M, CHCO.sub.2)--4H at 1.80 ppm and 4H at 1.40 ppm (M, CH.sub.2 cyclohexane)--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 120-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--2H at 7.80 ppm (Se., HAr 2', 6')--3H at 7.65 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.57 ppm (D, J=8 Hz HAr 4')--1H at 7.47 ppm (T, J=8 Hz, HAr 5')--1H at 7.00 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.98 ppm (D, J=4 Hz, H.sub.6)--1H at 4.82 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.05 ppm (D, J=17 Hz, CH.sub. 2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 3.00 ppm (M, ##STR213## 6H at 1.50 ppm (2S, (CH.sub.3).sub.2 C)--3H at 1.20 ppm (D, J=7 Hz, ##STR214##
NMR no. 121-(b): 1H at 10.0 ppm (Se., ArNHCO)--1H at 8.85 ppm (D, J=9 Hz, CONH)--3H at 8.05 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.45 ppm (S, HAr 6')--1H at 7.30 ppm (S, HAr 4')--1H at 7.00 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.43 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.78 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.05 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.80 ppm (M, CH.sub.2 Gly)--1 H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 2.25 ppm (2S, CH.sub.3 Ar)--6H at 1.50 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 122-(b): 1H at 10.45 ppm (Se., ArNHCO)--1H at 8.70 ppm (D, J=9 Hz, CONH)--1H at 8.50 ppm (Se., N.sup..sym. H.sub.2, piperidine)--1H at 8.20 ppm (Se., N.sup..sym. H.sub.2, piperidine)--2H at 7.84 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.70 ppm (D, J=8 Hz, HAr 3', 5')--1H at 6.98 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.42 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.98 ppm (D, J=4 Hz, H.sub.6)--1H at 4.78 ppm (D, J=13 Hz, CH.sub.2 OCO)--1 H at 4.05 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.30 ppm (M, CH.sub.2 in .alpha.N.sup..sym. H.sub.2 piperidine)--2H at 2.90 ppm (M, CH.sub.2 in .alpha.N.sup..sym. H.sub.2 piperidine)--1H at 2.66 ppm (M, CHCONH)--4H at 1.80 ppm (M, CH.sub.2 in .beta.N.sup..sym. H.sub.2 piperisine)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 123-(b): 1H at 10.25 ppm (Se., ArNHCO)--1H at 8.70 ppm (D, J=9 Hz, CONH)--1H at 8.50 ppm (Se., N.sup..sym. H.sub.2, piperidine)--1H at 8.25 ppm (Se, N.sup..sym. H.sub.2, piperidine)--1H at 8.19 ppm (Se, HAr 2')--1H at 7.86 ppm (D, J=8 Hz, HAr 6')--1H at 7.60 ppm (D, J=8 Hz, HAr 4')--1H at 7.42 ppm (T, J=8 Hz, HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.81 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.05 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.71 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.30 ppm (M, CH.sub.2 in .alpha.N.sup..sym. H.sub.2 Piperidine)--2H at 2.90 ppm (M, CH.sub.2 in .alpha.N.sup..sym. H.sub.2 piperidine)--1H at 2.66 ppm (M, CHCONH)--4H at 1.80 ppm (M, CH.sub.2 in .beta.N.sup..sym. H.sub.2 piperidine)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 124-(b): 1H at 10.75 ppm (Se., ArNHCO)--1H at 8.80 ppm (D, J=9 Hz, CONH)--3H at 8.20 ppm (Se., CHN.sup..sym. H.sub.3)--2H at 7.92 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.70 ppm (D, J=8 Hz, HAr 3', 5')--1H at 7.00 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.80 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.00 ppm (M, H.alpha.Ala and CH.sub.2 SO)--1 H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.50 ppm (2S, (CH.sub.3).sub.2 C)--3H at 1.42 ppm (D, J=7 Hz, CH.sub.3 Ala).
NMR no. 125-(b): 1H at 10.80 ppm (Se., ArNHCO)--1H at 9.00 ppm (D, J=9 Hz, CONH)--3H at 8.20 ppm (Se., CH--N.sup..sym. H.sub.3)--2H at 7.85 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.75 ppm (D, J=8 Hz, HAr 3', 5')--1H at 7.00 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.80 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.00 ppm (M, H.alpha.Ala and CH.sub.2 SO)--1 H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--4H at 2.40 ppm (M, ##STR215## 2H at 1.80 ppm (M, ##STR216## 3H at 1.43 ppm (D, J=7 Hz, CH.sub.3 Ala).
NMR no. 126-(b): 1H at 8.45 ppm (D, J=9 Hz, CONH)--3H at 8.00 ppm (Se., N.sup..sym. H.sub.3 Ala)--3H at 7.90 ppm (Se., N.sup..sym. H.sub.3 thiazol)--1H at 6.80 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.20 ppm (M, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.50 ppm (D, CH.sub.2 OCO)--1H at 3.15 ppm (M, H.sub.2 a piperidine)--1H at 2.80 ppm (M, H.sub.6 a piperidine)--1H at 2.60 ppm (M, --CHCO.sub.2 piperidine)--2H at 1.80 ppm et 2H at 1.50 ppm (2M, H.sub.3 and H.sub.5 piperidine)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C)--3H at 1.20 ppm (2D, CH.sub.3 CH).
NMR no. 127-(b): 1H at 8.43 ppm (D, J=9 Hz, CONH)--6H at 7.50 ppm (Se., N.sup..sym. H.sub.3)--1H at 6.80 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.16 ppm (2D, J=13 Hz, CH.sub.2 OCO)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.58 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.20 ppm (M, H.sub.2 e piperidine)--1H at 3.90 ppm (D, J=17 Hz CH.sub.2 SO)--1H at 3.64 ppm (M, H.sub.6 e piperidine)--1H at 3.57 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.07 ppm (M, H.sub.2 a piperidine)--2H at 2.96 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 2.75 ppm (M, H.sub.6 a piperidine)--3H at 2.65 ppm (M, CHCO.sub.2 and CH.sub.2 CON)--2H at 1.80 ppm et 2H at 1.50 ppm (H.sub.3 and H.sub.5 piperidine)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 128-(b): 1H at 8.45 ppm (D, J=9 Hz, CONH)--6H at 7.70 ppm (Se., N.sup..sym. H.sub.3)--1H at 6.80 ppm (S, H thiazol)--1H at 5.98 ppm (D de D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.20 ppm (2D, J=13 Hz, CH.sub.2 OCO)--1H at 4.96 ppm (D, J=4 Hz, H.sub.6)--1H at 4.58 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.18 ppm (H.sub.2 e piperidine)--1H at 3.90 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.75 ppm (M, H.sub.6 e piperidine)--1H at 3.55 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.00 ppm (M, H.sub.2 a piperidine)-- 4H at 2.65 ppm (M, CH.sub.2 N.sup..sym. H.sub.3, H.sub.6 a et H.sub.4 piperidine)--2H at 2.40 ppm (T, CH.sub.2 CON)--4H at 1.70 ppm (M, CHCH.sub.2 CH.sub.2 N.sup..sym. H.sub.3, H.sub.3 and H.sub.5 piperidine)--2H at 1.50 ppm (M, H.sub.3 and H.sub.5 piperidine)--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 129-(b): 1H at 8.50 ppm (Se., N.sup..sym. H.sub.2 piperidinium)--1H at 8.45 ppm (D, J=9 Hz, CONH)--1H at 8.25 ppm (Se., N.sup..sym. H.sub.2 piperidinium)--3H at 7.40 ppm (Se., N.sup..sym. H.sub.3 thiazol)--1H at 6.80 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.16 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.15 ppm (M, H.sub.2 e piperidine)--2H at 3.90 ppm (M, H.sub.6 e piperidine and CH.sub.2 SO)--1H at 3.55 ppm (D, J=17 Hz, CH.sub.2 SO)--2H at 3.25 ppm (M, H.sub.2 e and H.sub.6 e piperidinium)--1H at 3.15 ppm (M, H.sub. 2 a piperidine)--3H at 2.85 ppm (M, H.sub.6 a piperidine and H.sub.2 a and H.sub.6 a piperidinium)--2H at 2.70 ppm (M, H.sub.4 piperidine and H.sub.4 piperidinium)--6H at 1.75 ppm and 2H at 1.50 ppm (2M, H.sub.3 and H.sub.5 piperidinium H.sub.3 and H.sub.5 piperidine)--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 130-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--3H at 8.20 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.80 ppm (D, J=8 Hz, HAr 6')--2H at 7.45 ppm (M, HAr 3', 5') 1H at 7.00 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.42 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.80 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.00 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 and CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.45 ppm (S, CH.sub.3 Ar)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 131-(b): 1H at 8.85 ppm (D, J=9 Hz, CONH)--3H at 8.20 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.80 ppm (D, J=8 Hz, HAr 6')--2H at 7.45 ppm (M, HAr 3', 5')--1H at 6.95 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.45 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.80 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 4.00 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 et CH.sub.2 SO)--1H at 3.73 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.50 ppm (S, CH.sub.3 Ar)--4H at 2.40 ppm (M, ##STR217## 2H at 1.80 ppm (M, ##STR218##
NMR no. 132-(b): 1H at 8.80 ppm (D, J=9 Hz, CONH)--3H at 8.10 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.55 ppm (S, HAr)--1H at 7.45 ppm (S, HAr)--1H at 7.00 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.40 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.83 ppm (D, J=13 Hz, CH.sub.2 OCO)--3H at 3.70 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 et CH.sub.2 SO)--1H at 3.70 ppm (D, J=17 Hz, CH.sub.2 SO)--3H at 2.40 ppm (S, CH.sub.3 Ar)-- 3H at 2.34 ppm (S, CH.sub.3 Ar)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 133-(b): 1H at 12.5 ppm (Se., ArNHCO)--1H at 8.78 ppm (D, J=9 Hz, CONH)--3H at 8.30 ppm (Se., ##STR219## 1H at 8.20 ppm (S, H thiazol in 3)--1H at 7.00 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.42 ppm (2D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.90 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.15 ppm (M, ##STR220## 1H at 4.00 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.76 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C)--3H at 1.40 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 134-(b): 1H at 8.85 ppm (D, J=9 Hz, CONH)--1H at 8.50 ppm (S, H thiazol in 3)--3H at 7.90 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.00 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.42 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.99 ppm (D, J=4 Hz, H.sub.6)--1H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.00 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.75 ppm (D, J=17 Hz, CH.sub.2 SO)--4H at 3.20 ppm (M, CH.sub.2 CH.sub.2 N.sup..sym. H.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 135-(b): 1H at 8.80 ppm (D, J=9 Hz, CONH)--1H at 8.57 ppm (S, H thiazol in 3)--3H at 8.50 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.00 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.40 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.90 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.45 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 4.00 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.72 ppm (D, J=17 Hz, CH.sub.2 SO)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 136-(b): 1H at 8.90 ppm (D, J=9 Hz, CONH)--1H at 8.60 ppm (S, H thiazol in 3)--1H at 8.50 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 6.98 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.42 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.84 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.45 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 4.00 ppm (D, J=17 Hz, CH.sub.2 SO)--1H at 3.72 ppm (D, J=17 Hz, CH.sub.2 SO)--4H at 2.40 ppm (M, ##STR221## 2H at 1.86 ppm (M, ##STR222##
NMR no. 137-(b): 1H at 8.90 ppm (T, J=8 Hz, ##STR223## 1H at 8.75 ppm (D, J=9 Hz, CONH)--3H at 8.00 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--2H at 7.88 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.40 ppm (D, J=8 Hz, HAr 3', 5')--1H at 6.96 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.44 ppm (D, J=13 Hz, CH.sub.2 OCO)--1H at 4.98 ppm (D, J=4 Hz, H.sub.6)--1H at 4.80 ppm (D, J=13 Hz, CH.sub.2 OCO)--2H at 4.40 ppm (D, J=8 Hz, ArCH.sub.2 NH)--1H at 4.06 ppm 1H at 3.70 ppm (D, J=17 Hz, CH.sub.2 S.fwdarw.O)--2H at 3.57 ppm (M, OCCH.sub.2 N.sup..sym. H.sub.3)--2H at 1.47 ppm (2S, (CH.sub.3).sub.2 C).
By operating as in Example 2 of Example 3, the compounds according to the invention are obtained, in the form of trifluoroacetates described in Table II below. ##STR224##
These compounds are identified by a reference number and for each of them are given the values of R.sub.1, R.sub.2, n and B and the NMR spectrum.
The chromatography eluant is also given which serves to isolate (V): the last intermediate product before deblocking of the acid and amine functions of the molecule. This intermediate V is characterized by its infra-red spectrum, the wavelengths indicated in cm.sup.-1 correspond in order to the elongation vibration frequencies of the carbonyl at the 8 position of the beta lactam, the tertiobutylic esters and the thioester at the 3 position, the amide at the 7 position and the protective carbonate of the amine. When 2 wavelengths only are indicated the second corresponds to a wide band which covers the elongation vibration frequencies both of the esters, the amide and the protective carbonate of the amine and the thioester.
It happens for certain products that the vibration frequency of the thioester is at the same wavelength as that of the tertiobutylic esters. This is indicated in the table by +COS opposite the corresponding vibration frequency.
TABLE II__________________________________________________________________________ SR no. n ##STR225## B vol/volintermediate Veluant fromChromatography Vintermediate.delta.CO cm.sup.-1IR NMR no.__________________________________________________________________________41970 0 ##STR226## (CH.sub.2).sub.3 NH.sub.2 CH.sub.2 Cl.sub.2 AcOEt 90 10 1800 1720 1690 141971 " " (CH.sub.2).sub.4 NH.sub.2 CH.sub.2 Cl.sub.2 90 1800 2 AcOEt 10 1715 169041972 " " (CH.sub.2).sub.5 NH.sub.2 CH.sub.2 Cl.sub.2 92 1800 3 AcOEt 8 1720 169041973 " " ##STR227## CH.sub.2 Cl.sub.2 AcOEt 90 10 1800 1725 1690 442074 " " ##STR228## CH.sub.2 Cl.sub.2 AcOEt 90 10 1800 1725 1690 542076 " " (CH.sub.2).sub.3 NHCH.sub.3 CH.sub.2 Cl.sub.2 90 1800 6 AcOEt 10 1725 169042077 " " (CH.sub.2).sub.7 NH.sub.2 CH.sub.2 Cl.sub.2 95 1800 7 AcOEt 5 1720 169042118 " " ##STR229## CH.sub.2 Cl.sub.2 AcOEt 95 5 1803 1720 1690 842119 " " ##STR230## CH.sub.2 Cl.sub.2 AcOEt 92.5 7.5 1805 1720 942187 " " ##STR231## CH.sub.2 Cl.sub.2 AcOEt 95 5 1805 1725 1042199 " CH.sub.2 ##STR232## CH.sub.2 Cl.sub.2 AcOEt 90 10 1800 1725 1690 1142218 " ##STR233## " CH.sub.2 Cl.sub.2 AcOEt 92.5 7.5 1805 1725 1690 1242219 " ##STR234## ##STR235## CH.sub.2 Cl.sub.2 AcOEt 92.5 7.5 1805 1725 1690 1342220 " CH.sub.2 ##STR236## CH.sub.2 Cl.sub.2 AcOEt 95 5 1800 1720 1442221 " ##STR237## " CH.sub.2 Cl.sub.2 AcOEt 95 5 1800 1720 1542222 " ##STR238## " CH.sub.2 Cl.sub.2 AcOEt 95 5 1805 1720 1642531 " ##STR239## ##STR240## CH.sub.2 Cl.sub.2 MeOH 100 0.5 1800 1720 1742532 " ##STR241## ##STR242## CH.sub.2 Cl.sub.2 MeOH 100 0.5 1800 1720 1842533 " ##STR243## ##STR244## CH.sub.2 Cl.sub.2 MeOH 100 0.5 1800 1720 1690 1942534 " ##STR245## ##STR246## CH.sub.2 Cl.sub.2 MeOH 100 0.5 1800 1720 1690 2042535 " ##STR247## ##STR248## CH.sub.2 Cl.sub.2 AcOEt 95 5 1800 1720 2142536 " ##STR249## ##STR250## CH.sub.2 Cl.sub.2 AcOEt 95 5 1800 1720 2242659 " ##STR251## ##STR252## CH.sub.2 Cl.sub.2 MeOH 100 0.4 1802 1720 2342660 " ##STR253## ##STR254## CH.sub.2 Cl.sub.2 MeOH 100 0.5 1802 1720 2442661 " ##STR255## ##STR256## CH.sub.2 Cl.sub.2 AcOEt 95 5 1802 1720 2542662 " ##STR257## ##STR258## CH.sub.2 Cl.sub.2 AcOEt 95 5 1802 1720 2642663 " ##STR259## ##STR260## CH.sub.2 Cl.sub.2 MeOH 100 0.4 1802 1720 1680 2742664 " " ##STR261## CH.sub.2 Cl.sub.2 AcOEt 95 5 1802 1720 2842665 " ##STR262## ##STR263## CH.sub.2 Cl.sub.2 AcOEt 95 5 1802 1720 2942672 1 ##STR264## ##STR265## CH.sub.2 Cl.sub.2 AcOEt 90 10 1802 CH.sub.2 Cl.sub.2 1720 308042673 0 " ##STR266## CH.sub.2 Cl.sub.2 MeOH 101 1 1802 CH.sub.2 Cl.sub.2 1715 319042674 " ##STR267## ##STR268## CH.sub.2 Cl.sub.2 MeOH 100 1 1802 CH.sub.2 Cl.sub.2 1715 329042685 " ##STR269## ##STR270## CH.sub.2 Cl.sub.2 AcOEt 95 5 1805 1725 1695 3342686 " ##STR271## ##STR272## CH.sub.2 Cl.sub.2 AcOEt 95 5 1805 1725 1695 3442847 " ##STR273## ##STR274## CH.sub.2 Cl.sub.2 MeOH 100 1 1800 CH.sub.2 Cl.sub.2 1710 3542850 " " ##STR275## CH.sub.2 Cl.sub.2 MeOH 100 0.7 1805 1720 3642851 " ##STR276## ##STR277## CH.sub.2 Cl.sub.2 MeOH 100 0.7 1805 1720 3742853 " ##STR278## ##STR279## CH.sub.2 Cl.sub.2 AcOEt 95 5 1802 1720 3842854 " ##STR280## ##STR281## CH.sub.2 Cl.sub.2 MeOH 100 0.4 1802 1720 3942856 " ##STR282## ##STR283## CH.sub.2 Cl.sub.2 AcOEt 85 15 1803 1720 1685 4042858 " " ##STR284## CH.sub.2 Cl.sub.2 MeOH 100 1 1802 1725 1690 4142859 " " ##STR285## CH.sub.2 Cl.sub.2 AcOEt 70 30 1802 1720 1690 4242860 " ##STR286## ##STR287## CH.sub.2 Cl.sub.2 AcOEt 70 30 1802 1720 4342863 " ##STR288## ##STR289## CH.sub.2 Cl.sub.2 AcOEt 90 10 1800 1720 1690 4442868 " " ##STR290## CH.sub.2 Cl.sub.2 MeOH 100 0.7 1802 1720 4542902 " " ##STR291## CH.sub.2 Cl.sub.2 MeOH 100 1 1802 1720 1670 46__________________________________________________________________________
NMR Spectra: The spectra are recorded at 60 MHz, indicated by (a) or at 250 MHz, indicated by (b); when two stereoisomers exist in the molecule, the split signals are indicated by *.
NMR no. 1-(a): 8H between 6 and 9 ppm (wide signal, CH.sub.2, TFA, CO.sub.2 H)--1H at 8.40 ppm (D, J=9 Hz, CONH)--1H at 6.86 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.20 ppm (AB, J.sub.AB =13 Hz, CH.sub.2 SCO)--3H at 3.70 ppm (M, CH.sub.2 SCO and CH.sub.2 SO)--4H at 2.75 ppm (M, CH.sub.2 NH.sub.2 and CH.sub.2 COS)--2H at 1.77 ppm (M, CH.sub.2 CH.sub.2 CH.sub.2)--6H at 1.45 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 2-(a): 8H between 6.5 and 9 ppm (wide signal, CO.sub.2 H, TFA, NH.sub.2)--1H at 8.40 ppm (D, J=9 Hz, CONH)--1H at 6.88 ppm (S, H thiazol)--1H at 6.0 ppm (D D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.20 ppm (A of AB, J=13 Hz, CH.sub.2 SCO)--3H at 3.80 ppm (M, CH.sub.2 SO and CH.sub.2 SCO)--4H at 2.65 ppm (M, CH.sub.2 NH.sub.2 and CH.sub.2 COS)--10H 1.45 ppm (S.e., (CH.sub.3).sub.2 C and CH.sub.2 (CH.sub.2).sub.2 CH.sub.2).
NMR no. 3-(a): 8H between 6.5 et 8.7 ppm (wide signal (NH.sub.2, CO.sub.2 H, TFA)--1H at 8.40 ppm (D, J=9 Hz, CONH)--1H at 6.87 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.0 ppm (D, J.sub.1 =4 Hz, H.sub.6)--1H at 4.20 ppm (A of AB, J=13 Hz, CH.sub.2 SO)--3H at 3.70 ppm (M, CH.sub.2 SCO and CH.sub.2 SO)--4H at 2.80 ppm (M, CH.sub.2 NH.sub.2 and CH.sub.2 CO) 12H at 1.45 ppm (S.e., (CH.sub.3).sub.2 C and CH.sub.2 (CH.sub.2).sub.3 CH.sub.2).
NMR no. 4-(a): 7H between 6.5 et 9.5 ppm (Wide signal, NH.sub.2, NH, CO.sub.2 H, TFA)--1H at 8.40 ppm (D, J=9 Hz, CONH)--1H at 6.90 ppm (S, H thiazol)--1H at 6.0 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.20 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 SCO)--3H at 3.70 ppm (M, CH.sub.2 SCO and CH.sub.2 SO)--5H at 3.0 ppm (M, CH.sub.2 N and CHCOS)--4H at 1.90 ppm (M, CH.sub.2 CH.sub.2 N)--6H at 1.45 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 5-(b): 5H between 7 and 9 ppm (wide signal, NH.sub.2, TFA, NH)--1H at 8.34 ppm (2D, J=9 Hz, CONH)*--1H at 6.8 ppm (S, H thiazol)--1H at 5.97 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.16 ppm (2D, J=13 Hz, CH.sub.2 SCO)*--1H at 3.76 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.66 ppm (S, CH.sub.2 SO)--1H at 3.4 ppm, 1H at 3.16 ppm and 2H at 2.95 ppm (M, CH.sub.2 N)--1H at 2.80 ppm (M, CHCOS)--4H between 1.5 and 2.1 ppm (M, CH.sub.2 CH.sub.2 CH.sub.2 N)--6H at 1.44 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 6-(a): 3H at 8.50 ppm (S.e., CONH, N.sup.+ H.sub.2)--3H at 7.80 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.85 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.15 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 SCO)--1H at 3.80 ppm B of AB, J.sub.AB =13 Hz, CH.sub.2 SCO)--2H at 3.70 ppm (S.e., CH.sub.2 SO)--7H at 2.50 ppm (M, CH.sub.3 NH, CH.sub.2 NH, ##STR292## 2H at 1.80 ppm (M, CH.sub.2 CH.sub.2 CH.sub.2 NH)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 7-(a): 1H at 8.35 ppm (D, J=9 Hz, CONH)--8H between 6.5 and 10 ppm (CO.sub.2 H, NH.sub.2, TFA)--1H at 6.82 ppm (S, H thiazol)--1H at 6,00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.00 ppm (D, J=4 Hz, H.sub.6)--1H at 4.15 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 SCO)--3H at 3.66 ppm (M, CH.sub.2 SO and B of AB, CH.sub.2 SCO)--4H at 2.65 ppm (M, CH.sub.2 CO and CH.sub.2 NH.sub.2)--6H at 1.42 ppm (S, (CH.sub.3).sub.2 C)--10H at 1.25 ppm (S.e., (CH.sub.2).sub.5 CH.sub.2 NH.sub.2).
NMR no. 8-(b): 1H at 8.34 ppm (D, J=9 Hz, CONH)--3H at 7.80 ppm (S.e., N.sup.+ H.sub.3)--3H at 7.40 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.78 ppm (S, H thiazol)--1H at 5.94 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.94 ppm (D, J=4 Hz, H.sub.6)--1H at 4.14 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.69 ppm (D, J=13 Hz, CH.sub.2 SO)--2H at 3.63 ppm (S, CH.sub.2 SO)--2H at 2.60 ppm (M, CH.sub.2 NH.sub.2)--1H at 2.45 ppm (M, CHCOS)--4H at 1.84 ppm (M, CH.sub.2 CHCOS)--6H at 1.44 ppm (2 S, (CH.sub.3).sub.2 C)--2H at 1.40 ppm and 2H at 1.0 ppm (M, CH.sub.2 CHCH.sub.2 NH.sub.2). NMR no. 9-(b): 1H at 8.36 ppm (D, J=9 Hz, NHCO)--3H at 8.30 ppm (S.e., N.sup.+ H.sub.3)--2H at 7.94 ppm (D, J=8 Hz, H ortho CO)--2H at 7.55 ppm (D, J=8 Hz, H meta CO)--3H at 7.40 ppm (S.e. N.sup.+ H.sub.3)--1H at 6.76 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.40 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.10 ppm (M, CH.sub.2 NH.sub.2)--1H at 3.90 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.74 ppm (S, CH.sub.2 SO)--6H at 1.42 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 10-(a): 1H at 8.30 ppm (D, J=9 Hz, CONH)--8H between 6.5 and 9 ppm (S.e., N.sup.+ H.sub.3, CO.sub.2 H)--1H at 6.80 ppm (S, H thiazol)--1H at 5.95 ppm (M, H.sub.7)--1H at 4.90 ppm (D, J=4 Hz H.sub.6)--1H at 4.25 ppm (A of AB, J.sub.AB =13 Hz, CH.sub.2 SCO)--1H at 3.90 ppm (B of AB, J.sub.AB =13 Hz, CH.sub.2 SCO)--2H at 3.65 ppm (S.e., CH.sub.2 SO)--10H between 1 and 2.3 ppm (M, ##STR293## 6H at 1.43 ppm (S, (CH.sub.3).sub.2 C).
NMR no. 11-(b): 1H at 8.79 ppm (D, J=9 Hz, CONH)--1H at 8.60 ppm and 1H at 8.40 ppm (S.e., N.sup.+ H.sub.2)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.84 ppm (S, H thiazol)--1H at 5.84 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.90 ppm (D, J=4 hz, H.sub.6)--2H at 4.55 ppm (S, CH.sub.2 ON)--1H at 4.15 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.74 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.54 ppm (S, CH.sub.2 SO)--2H at 3.20 ppm and 3H at 2.90 ppm (M, CH.sub.2 NH and CHCOS)--2 H at 1.95 ppm et 2H at 1.65 ppm (M, CH.sub.2 CH.sub.2 NH).
NMR no. 12-(b): 2H at 8.60 ppm (M, CONH, N.sup.+ H.sub.2)--1H at 8.40 ppm (S.e., N.sup.+ H.sub.2)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.81 ppm (2S, H thiazol)*--1H at 5.92 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.92 ppm (2D superposed, H.sub.6)*--1H at 4.60 ppm (Q, J=7 Hz, CHON)--1H at 4.16 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.75 ppm (D, J=13 Hz, CH.sub.2 SCO) 2H at 3.65 ppm (S, CH.sub.2 SO)--2H at 3.25 ppm and 3H at 2.95 ppm (M, CHCOS and ##STR294## 2H at 1.95 ppm et 2H at 1.70 ppm (M, ##STR295## 3H at 1.45 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 13-(b): 2H at 8.70 ppm (M, CONH and N.sup.+ H.sub.2)--1H at 8.40 ppm (M, N.sup.+ H.sub.2)--3H at 7.40 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.79 ppm (S, H thiazol)--1H at 5.90 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.94 ppm (D, J=4 Hz, H.sub.6)--1H at 4.16 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.74 ppm (D, J=13 Hz, CH.sub.2 SCO) 2H at 3.70 ppm (S, CH.sub.2 SO)--2H at 3.25 ppm (M, CH.sub.2 NH)--3H at 2.90 ppm (M, CH.sub.2 NH and CHCOS)--4H at 2.40 ppm (M, ##STR296## 6H at 1.80 ppm (M, ##STR297##
NMR no. 14-(b): 1H at 8.65 ppm (D, J=9 Hz, CONH)--3H at 8.20 ppm (S.e., N.sup.+ H.sub.3)--2H at 7.92 ppm (D, J=8 Hz, H ortho CO)--2H at 7.56 ppm (D, J=8 Hz, H meta CO)--3H at 7.30 ppm S.e., N.sup.+ H.sub.3)--1H at 6.82 ppm (S, H thiazol)--1H at 5.88 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.92 ppm (D, J=4 Hz, H.sub.6)--2H at 4.55 ppm (S, CH.sub.2 ON)--1H at 4.37 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.13 ppm (M, CH.sub.2 NH.sub.2)--1H at 4.42 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.74 ppm (S, CH.sub.2 SO).
NMR no. 15-(b): 1H at 8.60 ppm (2D, J=9 Hz, CONH)*--3H at 8.20 ppm (S.e., N.sup.+ H.sub.3)--2H at 7.92 ppm (D, J=8 Hz, H ortho CO)--2H at 7.56 ppm (D, J=8 Hz, H meta CO)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.82 ppm (2S, H thiazol)*--1H 5.92 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (2D, superposed, H.sub.6)*--1H at 4.60 ppm (Q, J=7 Hz, CHON)--1H at 4.40 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.13 ppm (M, CH.sub.2 NH.sub.2)--1H at 3.90 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.75 ppm (S, CH.sub.2 SO)--3H at 1.45 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 16-(b): 1H at 8.61 ppm (D, J=9 Hz, CONH)--5H at 8.40 ppm (S.e., N.sup.+ H.sub.3, CO.sub.2 H)--2H at 7.95 ppm (D, J=8 Hz, H ortho CO)--2H at 7.61 ppm (D, j+8 Hz, H meta CO)--3H at 7.30 ppm (S.e., N.sup.+ H.sub.3)--1H at 6.76 ppm (S, H thiazol)--1H at 5.92 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.93 ppm (D, J=4 Hz, H.sub.6)--1H at 4.42 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.10 ppm (S.e., CH.sub.2 NH.sub.2)--1H at 3.92 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.74 ppm (S, CH.sub.2 SO)--4H at 2.35 ppm (M, ##STR298## 2H at 1.85 ppm (M, ##STR299##
NMR no. 17-(b): 1H at 8.62 ppm (D, J=9 Hz, CO NH)--3H at 8.20 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 8.00 ppm (Se., HAr 2')--1H at 7.90 ppm (D, J=8 Hz, HAr 6')--1H at 7.72 ppm (D, J=8 Hz, HAr 4')--1H at 7.55 ppm (T, J=8 Hz, HAr 5')--1H at 6.93 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.93 ppm (D, J=4 Hz H.sub.6)--1H at 4.43 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.10 ppm (Q, J=7 Hz, CH.sub.2 N.sup..sym. H.sub.3)--1H at 3.94 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.75 ppm (Se., CH.sub.2 SO)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 18-(b): 1H at 8.80 ppm (D, J=9 Hz, CONH)--3H at 8.20 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 8.00 ppm (Se., HAr 2')--1H at 7,90 ppm (D, J=8 Hz, HAr 6')--1H at 7.72 ppm (D, J=8 Hz, HAr 4')--1H at 7.55 ppm (T, J=8 Hz, HAr 5')--1H at 6.92 ppm (S, H thiazol)--1H at 5.94 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.96 ppm (D, J=4 Hz, H.sub.6)--1H at 4.44 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.10 ppm (Q, J=7 Hz, CH.sub.2 N.sup..sym. H.sub.3)--1H at 3.94 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.77 ppm (Se., CH.sub.2 SO)--4H at 2.40 ppm (M, ##STR300## 2H at 1.90 ppm (M, ##STR301## NMR no. 19-(b): 2H at 8.80 ppm (Se., N.sup..sym. H.sub.2 CH.sub.3)--1H at 8.60 ppm (D, J=9 Hz, CONH)--2H at 7.95 ppm (D, J=8 Hz, HAr 2',6')--2H at 7.60 ppm (D, J=8 Hz, Ar 3', 5')--1H at 6.94 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.42 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.16 ppm (T, J=7 Hz, CH.sub.2 N.sup..sym. H.sub.2 CH.sub.3)--1H at 3.92 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.75 ppm (Se., CH.sub.2 SO)--3H at 2.55 ppm (T, J=7 Hz CH.sub.2 N.sup..sym. H.sub.2 CH.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 20-(b): 1H at 8.84 ppm (D, J=9 Hz, CONH)--2H at 8.80 ppm (Se., N.sup..sym. H.sub.2 --CH.sub.3)--2H at 7.95 ppm (D, J=8 Hz, HAr, 2', 6')--2H at 7.60 ppm (D, J=8 Hz, HAr 3', 5')--1H at 6.95 ppm (S, H thiazol)--1H at 5.94 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.45 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.16 ppm (T, J=7 Hz, CH.sub.2 N.sup..sym. H.sub.2 CH.sub.3)--1H at 3.92 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.75 ppm (Se., CH.sub.2 SO)--3H at 2.55 ppm (T, J=7 Hz, CH.sub.2 N.sup..sym. H.sub.2 --CH.sub.3)--4H at 2.40 ppm (M, ##STR302## 2H at 1.90 ppm (M, ##STR303##
NMR no. 21-(b): 1H at 8.66 ppm (D, J=9 Hz, CONH)--3H at 8.10 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--2H at 7.55 ppm (M, HAr 4', 6')--1H at 7.37 ppm (T, J=8 Hz, HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H at 5.96 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.96 ppm (D, J=4 Hz, H.sub.6)--1H at 4.39 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.07 ppm (M, ArCH.sub.2 N.sup..sym. H.sub.3)--1H at 3.90 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.78 ppm (S, CH.sub.2 SO)--3H at 2.26 ppm (S, CH.sub.3 Ar)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 22-(b): 1H at 8.89 ppm (D, J=9 Hz, CONH)--3H at 8.10 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--2H at 7.55 ppm (M, HAr 4', 6')--1H at 7.37 ppm (T, J=8 Hz, HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 5.0 ppm (D, J=4 Hz, H.sub.6)--1H at 4.40 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.05 ppm (M, ArCH.sub.2 N.sup..sym. H.sub.3)--1H at 3.90 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.79 ppm (S, CH.sub.2 SO)--4H at 2.40 ppm (M, ##STR304## 3H at 2.25 ppm (S, CH.sub.3 Ar)--2H at 1.90 ppm (M, ##STR305##
NMR no. 23-(b): 1H at 8.64 ppm (D, J=9 Hz, CONH)--3H at 8.14 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.95 ppm (S, HAr 2')--1H at 7.60 ppm (D, J=8 Hz, HAr 6')--1H at 7.39 ppm (D, J=8 Hz, HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.96 ppm (D, J=4 Hz, H.sub.6)--1H at 4.37 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.08 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 3.94 ppm (D, J=13 Hz, CH.sub. 2 SCO)--2H at 3.74 ppm (Se., CH.sub.2 SO)--3H at 2.37 ppm (S, ArCH.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 24-(b): 1H at 8.80 ppm (2D, J=9 Hz CONH)--3H at 8.20 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.94 ppm (S, HAr 2')--1H at 7.80 ppm (D, J=8 Hz, HAr 6')--1H at 7.39 ppm (D, J=8 Hz, HAr 5')--1H at 6.95 ppm (2S, H thiazol)--1H at 5.94 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (2D, J=4 Hz, H.sub.6)--1H at 4.70 ppm (M, CH.sub.3 CHON)--1H at 4.37 ppm (2D, J=13 Hz, CH.sub.2 SCO)--2H at 4.08 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 3.94 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.73 ppm (Se., CH.sub.2 SO)--3H at 2.36 ppm (S, ArCH.sub.3)--3H at 1.42 ppm (D, J=7 Hz, CH.sub.3 CHON).
NMR no. 25-(b): 1H at 8.66 ppm (D, J=9 Hz, CONH)--3H at 8.17 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--2H at 7.80 ppm (M, HAr 2', 6')--1H at 7.50 ppm (D, J=8 Hz, HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.40 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.06 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 3.90 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.74 ppm (S, CH.sub.2 SO)--3H at 2.46 ppm (S, ArCH.sub.3)--6H at 1.46 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 26-(b): 1H at 8.80 ppm (2D, J=9 Hz, CONH)--3H at 8.20 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--2H at 7.80 ppm (M, HAr 2', 6')--1H at 7.46 ppm (D, J=8 Hz, HAr 5')--1H at 6.95 ppm (2S, H thiazol)--1H at 5.94 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (2D, J=4 Hz, H.sub.6)--1H at 4.66 ppm (M, CH.sub.3 CH--ON)--1H at 4.40 ppm (2D, J=13 Hz, CH.sub.2 SCO)--2H at 4.06 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 3.90 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.76 ppm (Se., CH.sub.2 SO)--3H at 2.40 ppm (S, ArCH.sub.3)--3H at 1.44 pm (D, J=7 Hz, CH.sub.3 CHON).
NMR no. 27-(b): 1H at 8.66 ppm (D, J=9 Hz, CONH)--3H at 7.80 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 6.95 ppm (S, H thiazol)--1H at 5.98 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.18 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.78 ppm (D, J=13 Hz, CH.sub.2 SO)--2H at 3.69 ppm (Se., CH.sub.2 SO)--2H at 2.95 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 --C--O)--6H at 1.22 ppm (S, (CH.sub.3).sub.2 CCOS).
NMR no. 28-(b): 1H at 10.80 ppm (S, ArNHCO)--1H at 8.66 ppm (D, J=9 Hz, CONH)--3H at 8.05 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--2H at 7.89 ppm (D, J=8 Hz HAr 2', 6')--2H at 7.74 ppm (D, J=8 Hz HAr 3', 5')--1H at 6.96 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.42 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.88 ppm (D, J=13 Hz, CH.sub.2 SCO)--4H at 3.80 ppm (M, CH.sub.2 SO and CH.sub.2 N.sup. .sym. H.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 29-(b): 1H at 10.83 ppm (S, ArNHCO)--1H at 8.89 ppm (D, J=9 Hz, CONH)--3H at 8.10 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--2H at 7.90 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.71 ppm (D, J=8 Hz, HAr 3', 5')--1H at 6.95 ppm (S, H thiazol)--1H at 5.94 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.45 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.87 ppm (D, J=13 Hz, CH.sub.2 SCO)--4H at 3.80 ppm (M, CH.sub.2 SO and CH.sub.2 N.sup. .sym. H.sub.3)--4H at 2.40 ppm (M, ##STR306## 2H at 1.90 ppm (M, ##STR307##
NMR no. 30(b): 1H at 8.50 ppm (Se., N.sup..sym. H.sub.2 piperidine)--1H at 8.20 ppm (Se., N.sup..sym. H.sub.2 piperidine)--1H at 8.36 ppm (D, J=9 Hz, CONH)--1H at 6.76 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.92 ppm (D, J=4 Hz, H.sub.6)--1H at 4.16 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.72 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.14 ppm (S, CH.sub.2 SO)--2H at 3.17 ppm 2H at 2.80 ppm (M, 6H .sub.2 in .alpha. N.sup..sym. H.sub.2)--2H at 2.55 ppm (D, J= 7 Hz CH.sub.2 COS)--1H at 2.00 ppm (M, CHCH.sub.2 COS)--2H at 1.75 ppm and 2H 1.30 ppm (M, CH.sub.2 in .beta. N.sup..sym. H.sub.2)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 31-(b): 1H at 8.34 ppm (D, J=9 Hz, CONH)--3H at 7.92 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--3H at 7.30 ppm (Se., N.sup..sym. H.sub.3 thiazol)--1H at 6.76 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.92 ppm (D, J=4 Hz, H.sub.6)--1H at 4.26 ppm (DE, J=12 Hz, H.sub.2 Eq piperidine)--1H at 4.15 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.84 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 3.72 ppm (D, J=13 Hz, CH.sub.2 SCO)--3H at 3.60 ppm (M, CH.sub.2 SO+H.sub.6 Eq piperidine)--1H at 3.05 ppm (TE, J=12 Hz, H.sub.2 Ax piperidine)--1H at 2.87 ppm (TE, CHCOS)--H at 2.74 ppm (TE, J=12 Hz, H.sub.6 Ax piperidine)--2H at 1.86 ppm (M, H en 3 in 5 piperidine)--2H at 1.45 ppm (M, H en 3 and 5 piperidine)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 32-(b): 1H at 8.66 ppm (D, J=9 Hz, CONH)--3H at 7.90 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--3H at 7.30 ppm (Se., --N.sup..sym. H.sub.3 thiazol)--1H at 6.78 ppm (S, H thiazol)--1H at 5.90 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.94 ppm (D, J=4 Hz, H.sub.6)--1H at 4.26 ppm (De., J=12 Hz, H.sub.2 Eq piperidine)--1H at 4.16 (D, J=13 Hz, CH.sub.2 SCO)--2 H at 3.82 ppm (M, CH.sub.2 Gly)--1H at 3.74 ppm (D, J=13 Hz, CH.sub.2 SO)--3H at 3.63 ppm (Se., CH.sub.2 SOH.sub.6 Eq piperidine)--1H at 3.05 ppm (Te., J=13 Hz, H.sub.2 Ax piperidine)--1H at 2.87 ppm (Te., J=12 Hz, ##STR308## 1H at 2.75 ppm (Te., J=12 Hz, H.sub.6 Ax piperidine)--4H at 2.44 ppm (M, ##STR309## 4H at 1.90 ppm (M, ##STR310## and H.sub.3 Eq and H.sub.5 Eq piperidine)--2H at 1.50 ppm (M, H.sub.3 Ax and H.sub.5 Ax piperidine).
NMR no. 33-(b): 1H at 10.70 ppm (S, ArNHCO)--1H at 8.70 ppm (D, J=9 Hz, CONH)--1H at 8.30 ppm (S, HAr 2')--3H at 8.10 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.75 ppm (D, J=8 Hz, HAr 6')--1H at 7.60 ppm (D, J=8 Hz, HAr 4')--1H at 7.50 ppm (T, J=8 Hz, HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 H, H.sub.7)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.45 ppm (D, J=13 Hz, CH.sub.2 SCO)-- 1 H at 3.90 ppm (D, J=13 Hz, CH.sub.2 SCO)--4H at 3.75 ppm (M, CH.sub.2 SO and CH.sub.2 Gly)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 34-(b): 1H at 10.65 ppm (Se., ArNHCO)--1H at 8.80 ppm (D, J=9 Hz, NHCO)--1H at 8.25 ppm (Se., HAr 2')--3H at 8.05 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.75 ppm (D, J=8 Hz, HAr 6')--1H at 7.58 ppm (D, J=8 Hz, HAr 4')--1H at 7.50 ppm (T, J=8 Hz, HAr 5')--1H at 6.95 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.45 ppm (D, J=13 Hz, CH.sub.2 SCO)--1 H at 3.90 ppm (D, J=13 Hz, CH.sub.2 SCO)--4H at 3.75 ppm (M, CH.sub.2 SO and CH.sub.2 Gly)--4H at 2.40 ppm (M, ##STR311## 2H at 1.90 ppm (M, ##STR312##
NMR no. 35-(b): 1H at 8.40 ppm (D, J=9 Hz, CONH)--6H at 7.60 ppm (Se., N.sup..sym. H.sub.3)--1H at 6.80 ppm (S, H thiazol)--1H at 5.95 ppm (D de D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.30 ppm (M, H.sub.2 e piperidine)--1H at 4.16 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.75 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.60 ppm (S, CH.sub.2 SO)--1H at 3.55 ppm (M, H.sub.6 e piperidine)--4H at 2.90 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 et H.sub.2 a and H.sub.6 a piperidine)--3H at 2.60 ppm (M, CH.sub.2 CH.sub.2 N.sup..sym. H.sub.3 H.sub.4 piperidine)--2H at 1.80 ppm et 2H at 1.50 ppm (2M, H.sub.3 at H.sub.5 piperidine)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 36-(b): 1H at 8.70 ppm (D, J=9 Hz, CONH)--3H at 8.20 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.75 ppm (D, J=8 Hz, HAr 6')--2H at 7.43 ppm (M, HAr 3', 5')--1H at 6.98 ppm (Se., H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.34 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.00 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 3.90 ppm (D, J=13 Hz, CH.sub.2 SCO) 2H at 3.77 ppm (Se., CH.sub.2 SO--1H at 2.34 ppm (S, CH.sub.3 Ar)--6H at 1.46 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 37-(b): 1H at 8.80 ppm (D, J=9 Hz, CONH)--3H at 8.15 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.72 ppm (D, J=8 Hz, HAr 6')--2H at 7.40 ppm (M, HAr 3', 5')--1H at 6.95 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.93 ppm (D, J=4 Hz, H.sub.6)--1H at 4.34 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 4.00 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 3.90 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.78 ppm (Se., CH.sub.2 SO)--2H at 2.34 ppm (S, CH.sub.3 Ar)--4H at 2.30 ppm (M, ##STR313## 2H at 1.80 ppm (M, ##STR314##
NMR no. 38-(b): 1H at 8.60 ppm (D, J=9 Hz, CONH)--7H at 7.70 ppm (M, HAr et CH.sub.2 N.sup..sym. H.sub.3)--1H at 6.98 ppm (S, H thiazol)--1H at 5.98 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.96 ppm (D, J=4 Hz, H.sub.6)--1H at 4.38 ppm (D, J=13 Hz, CH.sub.2 SCO) 1H at 3.94 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.75 ppm (Se., CH.sub.2 SO)--3H at 3.00 ppm (M, CHCH.sub.2 N.sup..sym. H.sub.3)--6H at 1.47 ppm (2S, (CH.sub.3).sub.2 C)--3H at 1.19 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 39-(b): 1H at 8.80 ppm (D, J=9 Hz, CONH)--7H at 7.80 ppm (M, HAr et N.sup..sym. H.sub.3 CH.sub.2)--1H at 6.95 ppm (S, H thiazol)--1H at 5.95 ppm (D de D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.40 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.93 ppm (D, J=13 Hz CH.sub.2 SCO)--2H at 3.75 ppm (Se., CH.sub.2 SO)--3H at 3.00 ppm (M, CHCH.sub.2 N.sup..sym. H.sub.3)--4H at 2.40 ppm (M, ##STR315## 2H at 1.85 ppm (M, ##STR316## 3H at 1.25 ppm (D, J=7 Hz, CH.sub.3 CH).
NMR no. 40-(b): 1H at 12.6 ppm (Se., ArNHCO)--1H at 8.75 ppm (D, J=9 Hz, CONH)--1H at 8.00 ppm (S, H thiazol in 3)--3H at 7.75 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.00 ppm (S, H thiazol)--1H at 5.98 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.40 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.78 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.75 ppm (Se., CH.sub.2 SO)--2H at 3.50 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--2H at 2.80 ppm (M, CH.sub.2 CH.sub.2 N.sup..sym. H.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 41-(b): 1H at 12.8 ppm (Se., NHCOCH.sub.2)--1H at 8.80 ppm (D, J=9 Hz, CONH)--3H at 8.25 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 8.16 ppm (S, H thiazol in 3)--1H at 7.00 ppm (S, H thiazol)--1H at 5.96 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.40 ppm (D, J=13 Hz, CH.sub.2 SCO) 3H at 3.90 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 et CH.sub.2 SCO)--2H at 3.75 ppm (Se., CH.sub.2 SO)--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 42-(b): 1H at 10.6 ppm (S, ArNHCO)--1H at 8.70 ppm (D, J=9 Hz, CONH)--2H at 7.90 ppm (M, HAr 2', 6')--5H at 7.60 ppm (M, CH.sub.2 N.sup..sym. H.sub.3 et HAr 3', 5')--1H at 7.00 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (D, J=4 Hz, H.sub.6)--1H at 4.42 ppm (D, J=13 Hz, CH.sub.2 SCO) 1H at 3.90 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.75 ppm (Se., CH.sub.2 SO)--2H at 3.05 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--2H at 2.72 ppm (M, CH.sub.2 CH.sub.2 N.sup.+ H.sub.3)--6H at 1.45 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 43-(b): 1H at 10.5 ppm (S, ArNHCO)--1H at 8.85 ppm (D, J=9 Hz, CONH)--2H at 7.90 ppm et 2H at 7.75 ppm (M, HAr)--3H at 7.70 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 6.95 ppm (S, H thiazol)--1H at 5.45 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.40 ppm (D, J=13 Hz, CH.sub.2 SCO) 1H at 3.86 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.75 ppm (Se., CH.sub.2 SO)--2H at 3.02 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--2H at 2.72 ppm (M, CH.sub.2 CH.sub. 2 N.sup..sym. H.sub.3)--4H at 2.40 ppm (M, ##STR317## 2H at 1.85 ppm (M, ##STR318##
NMR no. 44-(b): 1H at 10.9 ppm (S, ArNHCO)--2H at 8.80 ppm (Se., CH.sub.2 N.sup..sym. H.sub.2 CH.sub.3)--1H at 8.70 ppm (D, J=9 Hz, CONH)--2H at 7.90 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.70 ppm (D, J=8 Hz, HAr 3', 5')--1H at 6.98 ppm (S, H thiazol)--1H at 6.00 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.97 ppm (D, J=4 Hz, H.sub.6)--1H at 4.42 ppm (D, J=13 Hz, CH.sub.2 SCO)--3H at 3.90 ppm (M, CH.sub.2 N.sup..sym. H.sub.2 CH.sub.3 at CH.sub.2 SCO)--2H at 3.75 ppm (Se., CH.sub.2 SO)--3H at 2.55 ppm (M, CH.sub.3 N.sup..sym. H.sub.2 --CH.sub.2) 6H at 1.46 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 45-(b): 1H at 8.75 ppm (D, J=9 Hz, CONH)--1H at 8.55 ppm (D, H thiazol in 3)--3H at 8.50 ppm (Se., CH.sub.2 N.sup..sym. H.sub.3)--1H at 7.00 ppm (S, H thiazol)--1H at 5.95 ppm (D of D J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.96 ppm (D, J=4 Hz, H.sub.6)--2H at 4.46 ppm (M, CH.sub.2 N.sup..sym. H.sub.3)--1H at 4.30 ppm (D, J=13 Hz, CH.sub.2 SCO)--1H at 3.90 ppm (D, J=13 Hz, CH.sub.2 SCO)--2H at 3.73 ppm (Se., CH.sub.2 SO)--6H at 1.44 ppm (2S, (CH.sub.3).sub.2 C).
NMR no. 46-(b): 1H at 8.87 ppm (T, J=8 Hz, NHCH.sub.2 Ar)--1H at 8.64 ppm (D, J=9 Hz, NHCO)--3H at 8.00 ppm (Se., H.sub.3 N.sup..sym. CH.sub.2)--2H at 7.84 ppm (D, J=8 Hz, HAr 2', 6')--2H at 7.42 ppm (D, J=8 Hz, HAr3', 5')--1H at 6.94 ppm (S, H thiazol)--1H at 5.95 ppm (D of D, J.sub.1 =9 Hz, J.sub.2 =4 Hz, H.sub.7)--1H at 4.95 ppm (D of D, J=4 Hz, H.sub.6)--3H at 4.40 ppm (M, ArCH.sub.2 NH et CH.sub.2 SCO)--1H at 3.88 ppm D, J=13 Hz, CH.sub.2 SCO)--2H at 3.74 ppm) (Se., CH.sub. 2 S.fwdarw.O)--2H at 3.58 ppm (M, OCCH.sub.2 N.sup..sym. H.sub.3)--6H at 1.47 ppm (2S, (CH.sub.3).sub.2 C).
The products of the invention have been studied as regards their pharmacological properties and, more especially, bacteriostatic action. This has been determined in vitro by the dilution method, and the study was on Gram negative strains.
Results, expressed in minimum inhibiting concentrations (MIC-- .mu.g/ml), are collected in the following table (Table III).
TABLE III__________________________________________________________________________MIC (.mu.g/ml) ON DIFFERENT STRAINS STRAINS Escherichia ProteusPRODUCTS coli Citrobacter vulgaris Serratia Klebsiella Enterobacter PseudomonasSR No. SOL RL 90 49 RL 99 bis RL 72 RO 30 RO 154 RL 112__________________________________________________________________________41 730 0.5 0.25 .ltoreq.0.12 1 0.25 0.25 441 733 2 2 0.5 8 1 1 841 806 1 1 0.5 4 0.5 8 841 854 0.25 0.5 .ltoreq.0.12 0.5 0.25 2 441 855 0.25 1 .ltoreq.0.12 0.5 0.25 2 841 856 0.5 2 .ltoreq.0.12 2 0.25 4 1641 858 2 1 0.5 4 0.5 8 841 859 1 2 0.25 4 0.5 8 1641 860 2 1 0.5 4 0.5 8 1641 862 0.25 0.25 .ltoreq.0.12 0.5 0.25 1 441 885 1 4 0.5 4 0.5 8 841 887 2 4 0.25 4 0.5 8 841 888 2 2 1 8 1 8 841 889 1 1 0.5 4 1 8 841 891 0.5 0.5 0.5 4 0.5 8 841 967 0.25 0.5 .ltoreq.0.12 0.5 0.25 2 441 975 0.25 0.5 0.5 4 0.5 8 841 976 1 0.5 0.25 8 0.5 8 842 022 0.5 0.25 .ltoreq.0.12 0.5 0.25 2 442 024 0.5 0.5 0.25 0.5 0.25 2 442 025 0.5 0.5 0.25 1 0.5 4 442 026 0.5 0.25 .ltoreq.0.12 1 0.25 4 842 027 0.25 0.25 .ltoreq.0.12 0.5 0.25 2 442 028 0.25 0.5 .ltoreq.0.12 0.5 0.25 2 442 029 0.25 0.25 .ltoreq.0.12 0.5 0.25 2 842 042 .ltoreq.0.12 .ltoreq.0.12 .ltoreq.0.12 2 .ltoreq.0.12 1 442 073 1 0.5 0.5 2 0.5 4 442 074 1 0.5 0.5 4 0.5 8 842 117 0.25 0.25 .ltoreq.0.12 0.5 .ltoreq.0.12 1 442 118 1 0.5 0.25 4 0.5 16 842 119 0.5 0.25 .ltoreq.0.12 4 0.5 8 842 208 0.5 0.5 .ltoreq.0.12 1 0.5 0.25 442 209 0.25 .ltoreq.0.12 .ltoreq.0.12 0.5 0.25 .ltoreq.0.12 442 210 1 0.5 0.25 1 0.5 0.25 442 211 .ltoreq.0.12 .ltoreq.0.12 .ltoreq.0.12 .ltoreq.0.12 .ltoreq.0.12 .ltoreq.0.12 6442 212 .ltoreq.0.12 .ltoreq.0.12 .ltoreq.0.12 0.25 .ltoreq.0.12 .ltoreq.0.12 432 213 0.25 .ltoreq.0.12 .ltoreq.0.12 0.5 0.25 .ltoreq.0.12 1642 214 .ltoreq.0.12 .ltoreq.0.12 .ltoreq.0.12 0.5 .ltoreq.0.12 .ltoreq.0.12 1642 215 .ltoreq.0.12 .ltoreq.0.12 .ltoreq.0.12 0.25 .ltoreq.0.12 .ltoreq.0.12 842 216 .ltoreq.0.12 .ltoreq.0.12 .ltoreq.0.12 0.5 .ltoreq.0.12 .ltoreq.0.12 842 217 .ltoreq.0.12 .ltoreq.0.12 .ltoreq.0.12 0.25 .ltoreq.0.12 .ltoreq.0.12 1642 218 0.5 0.25 0.5 2 0.5 0.5 6442 219 0.5 .ltoreq.0.12 .ltoreq.0.12 1 0.5 0.5 442 221 0.25 .ltoreq.0.12 .ltoreq.0.12 2 .ltoreq.0.12 0.25 6442 222 0.5 .ltoreq.0.12 .ltoreq.0.12 1 0.5 0.5 842 320 .ltoreq.0.125 .ltoreq.0.125 .ltoreq.0.125 0.5 .ltoreq.0.125 .ltoreq.0.125 442 321 0.5 0.5 .ltoreq.0.125 1 0.5 0.25 842 371 0.5 0.25 .ltoreq.0.125 0.5 0.25 0.25 842 372 0.25 .ltoreq.0.125 .ltoreq.0.125 0.25 0.25 .ltoreq.0.125 442 374 0.5 0.25 .ltoreq.0.125 1 0.25 0.25 442 379 0.25 .ltoreq.0.125 .ltoreq.0.125 0.5 .ltoreq.0.125 .ltoreq.0.125 842 380 .ltoreq.0.125 .ltoreq.0.125 .ltoreq.0.125 1 .ltoreq.0.125 .ltoreq.0.125 442 395 .ltoreq.0.125 .ltoreq.0.125 .ltoreq.0.125 0.5 .ltoreq.0.125 .ltoreq.0.125 442 396 .ltoreq.0.125 .ltoreq.0.125 .ltoreq.0.125 1 .ltoreq.0.125 .ltoreq.0.125 842 397 .ltoreq.0.125 .ltoreq.0.125 .ltoreq.0.125 1 .ltoreq.0.125 .ltoreq.0.125 842 456 0.25 .ltoreq.0.125 .ltoreq.0.125 0.5 .ltoreq.0.125 .ltoreq.0.125 442 457 0.5 0.25 .ltoreq.0.125 0.5 0.25 0.25 842 461 0.25 .ltoreq.0.125 .ltoreq.0.125 2 .ltoreq.0.125 .ltoreq.0.125 842 462 0.25 .ltoreq.0.125 .ltoreq.0.125 0.5 .ltoreq.0.125 .ltoreq.0.125 442 463 .ltoreq.0.125 .ltoreq.0.125 .ltoreq.0.125 0.5 .ltoreq.0.125 .ltoreq.0.125 442 464 .ltoreq.0.125 .ltoreq.0.125 .ltoreq.0.125 0.5 .ltoreq.0.125 .ltoreq.0.125 442 465 .ltoreq.0.125 .ltoreq.0.125 .ltoreq.0.125 2 0.5 0.5 842 466 0.5 0.25 .ltoreq.0.125 2 0.5 0.5 442 467 0.25 .ltoreq.0.125 .ltoreq.0.125 2 0.25 0.5 442 471 0.5 0.25 .ltoreq.0.125 0.5 0.25 0.25 842 472 0.25 .ltoreq.0.125 .ltoreq.0.125 0.25 .ltoreq.0.125 .ltoreq.0.125 442 473 0.25 .ltoreq.0.125 .ltoreq.0.125 0.25 .ltoreq.0.125 .ltoreq.0.125 442 474 0.25 .ltoreq.0.125 .ltoreq.0.125 0.25 0.25 .ltoreq.0.125 442 531 0.5 0.25 .ltoreq.0.125 0.5 0.25 0.5 842 532 0.5 0.25 .ltoreq.0.125 1 0.25 0.5 842 533 0.5 0.25 .ltoreq.0.125 1 0.25 0.5 842 534 0.5 0.25 .ltoreq.0.125 1 0.25 0.5 842 535 0.5 0.25 .ltoreq.0.125 1 0.25 0.5 842 536 0.5 0.25 .ltoreq.0.125 0.5 0.25 0.5 842 537 0.25 0.25 .ltoreq.0.125 0.5 0.25 0.25 842 538 0.5 0.25 .ltoreq.0.125 0.5 0.25 0.25 842 540 0.25 0.125 .ltoreq.0.125 0.25 .ltoreq.0.125 .ltoreq.0.125 442 541 0.5 0.25 .ltoreq.0.125 0.5 .ltoreq.0.125 0.25 442 542 0.5 0.5 .ltoreq.0.125 0.5 .ltoreq.0.25 0.5 842 546 0.25 0.25 .ltoreq.0.125 1 0.25 0.25 442 547 0.5 0.25 .ltoreq.0.125 0.5 0.25 0.5 442 548 0.25 .ltoreq.0.125 .ltoreq.0.125 0.5 0.125 0.25 242 549 0.25 .ltoreq.0.125 .ltoreq.0.125 0.5 0.25 0.25 442 581 0.125 0.125 2 442 582 0.25 0.25 2 842 583 1 0.5 4 842 584 0.25 0.25 2 442 585 0.25 0.25 8 442 586 0.25 0.25 16 442 587 0.25 0.25 8 442 657 0.25 0.25 4 842 658 0.125 0.125 8 442 661 0.5 0.25 1 842 663 4 1 4 842 664 1 4 0.5 4 842 665 0.5 0.5 2 842 674 1 0.5 2 842 675 0.125 0.125 1 442 676 0.25 0.25 2 842 685 2 1 2 842 686 2 1 2 842 687 2 1 4 842 688 0.125 0.25 4 442 689 0.125 0.25 4 442 690 0.5 0.5 8 442 781 0.25 0.125 2 442 782 0.25 0.125 2 442 783 0.25 0.125 2 842 811 0.125 0.125 2 442 814 0.5 0.25 8 842 815 0.125 0.25 8 842 817 0.125 0.25 4 442 818 0.125 0.125 4 442 848 0.125 0.125 2 442 849 0.125 0.125 2 442 850 0.5 0.25 2 842 851 0.5 0.25 1 842 852 0.25 0.125 1 842 857 0.5 1 8 8__________________________________________________________________________
The results presented in Table III show good activity on Gram negative bacteria of the products according to the invention.
To evaluate the stability of these products towards beta-lactamases, their MIC was determined on isogenic strains producing and not producing beta-lactamases.
The results are expressed in .mu.g/ml in Table IV.
TABLE IV__________________________________________________________________________MIC (.mu.g/ml) ON STRAINS PRODUCING BETA-LACTAMASES ANDNOT PRODUCING (indicated by*) Strains Escherichia coli Serrtia liquefaciens Proteus vulgarisPRODUCTS 255/L.7 SL 1326 S GN 76/C.1/3SR no. 255 * SL/326 A * GN 76/C.1 *__________________________________________________________________________41 730 0.25 .ltoreq.0.12 0.5 .ltoreq.0.12 0.25 0.2541 854 .ltoreq.0.12 .ltoreq.0.12 0.25 .ltoreq.0.12 0.25 0.2541 855 .ltoreq.0.12 .ltoreq.0.12 0.25 .ltoreq.0.12 .ltoreq.0.12 .ltoreq.0.1241 862 .ltoreq.0.12 0.12 .ltoreq.0.25 .ltoreq.0.12 .ltoreq.0.12 .ltoreq.0.1241 967 .ltoreq.0.12 .ltoreq.0.12 0.25 .ltoreq.0.12 .ltoreq.0.12 .ltoreq.0.1241 973 0.25 0.25 0.25 .ltoreq.0.12 0.5 0.541 975 0.5 0.5 0.25 .ltoreq.0.12 0.5 0.542 022 0.25 0.25 .ltoreq.0.12 .ltoreq.0.12 .ltoreq.0.12 .ltoreq.0.1242 024 0.25 .ltoreq.0.12 0.25 0.06 0.25 0.2542 027 0.12 0.06 0.25 .ltoreq.0.06 0.12 0.1242 028 0.12 0.12 0.12 .ltoreq.0.06 0.25 0.2542 042 .ltoreq.0.12 .ltoreq.0.12 0.25 .ltoreq.0.12 .ltoreq.0.12 .ltoreq. 0.1242 073 0.5 0.25 0.25 .ltoreq.0.12 0.5 0.542 074 0.5 0.25 0.25 0.12 0.5 0.542 117 0.125 0.06 0.12 .ltoreq.0.06 .ltoreq.0.06 .ltoreq.0.0642 118 0.5 0.25 0.25 0.12 0.5 0.542 119 0.25 0.12 0.25 .ltoreq.0.06 0.12 0.1242 320 0.0625 0.0625 0.125 .ltoreq.0.0312 .ltoreq.0.0312 0.12542 395 0.0625 0.0625 0.125 .ltoreq.0.0312 .ltoreq.0.0312 .ltoreq.0.031242 456 0.0625 .ltoreq.0.0312 0.25 0.0625 .ltoreq.0.0312 0.12542 457 0.125 .ltoreq.0.0312 0.0625 0.0625 .ltoreq.0.0312 0.062542 466 0.125 0.125 1 .ltoreq.0.0312 .ltoreq.0.0312 0.062542 467 0.0625 .ltoreq.0.0312 0.125 0.125 .ltoreq.0.0312 0.062542 474 0.0625 0.0625 0.125 .ltoreq.0.0312 0.0625 0.062542 531 0.125 0.0625 0.125 0.0625 0.062542 533 0.125 0.0625 0.125 .ltoreq.0.0312 0.0625 0.12542 535 0.125 .ltoreq.0.0312 0.0625 0.125 0.0625 0.12542 546 0.0625 .ltoreq.0.0312 0.25 .ltoreq.0.0312 .ltoreq.0.0312 0.12542 547 0.125 .ltoreq.0.0312 2 0.125 0.0625 0.2542 548 0.625 .ltoreq.0.0312 0.125 .ltoreq.0.0312 0.0625 0.062542 549 0.125 0.0625 0.125 .ltoreq.0.0312 .ltoreq.0.0312 0.062542 664 0.25 0.0625 0.25 0.0625 0.125 0.2542 673 0.25 0.25 0.25 0.0625 0.25 0.25__________________________________________________________________________
According to the results of table IV, the products according to the invention have an equal or comparable activity on strains producing or not producing beta-lactamases, which shows the good stability towards beta-lactamases.
The therapeutic effectiveness of the products was determined on the septicemic model of the mouse. the septicemia was initiated by the intraperitoneal innoculation of 0.5 ml of a suitable dilution of a suspension of the Escherichia coli SOL 90 strain. The products were administered in solution in a phosphate buffer pH 7.0 in a volume of 0.2 ml sub-cutaneously to batches of 10 mice, 1 to 5 hours after innoculation of the microorganism. After 4 days of observation in the course of which the mortality was noted, the 50% effective doses (DE 50) were calculated by the Muench and Reed method.
The results obtained are shown in Table V.
TABLE V______________________________________DE.sub.50 (mg/kg) IN THE SEPTICEMIC MODELIN THE MOUSE STRAINSPRODUCTS Escherichia coli KlebsiellaSR no. SOL 90 RO 30______________________________________41 730 1.4 0.7941 854 0.23 0.1941 855 0.16 0.1741 862 0.13 0.1041 973 0.22 0.442 042 0.05 ND42 073 0.33 ND42 117 0.11 ND42 119 0.16 ND______________________________________ ND = not determined
According to the results of table V, the products, according to the invention, show good IN VIVO therapeutic activity.
In addition, according to tests carried out up till now on animals, the toxicity of the products according to the invention has appeared to be sufficiently low to enable their use in therapeutics.
The products of the invention can hence be employed as antibiotics in human or veterinarian medicine. They have a wide spectrum on Gram negative organisms and can be used in all germ sensitive bacterial infections.
The products can be administered by the general route (parenteral, oral or topically).
The pharmaceutical compositions are produced from the compounds (I) in soluble forms obtained by salification of one of the acid functions of the molecule or of one of the amine functions of the B chain.
The pharmaceutical compositions can be solid or liquid and be presented, for example, in the form of injectable preparations, tablets, gelules, granules, pommades, creams, gels or suppositories. The posology can vary within wide proportions, in particular according to the type and seriousness of the infection to be treated and according to the mode of administration. Mostly, in the adult, by the injectable route, it is comprised between 0.250 g and 4 g per day.
By way of example of pharmaceutical composition, there may be prepared injectable solutions of the sodium salt of SR 41 973:
To a solution of 3 g of dihydrochloride of SR 41 973 in 25 ml of water, is added drop by drop a saturated solution of sodium bicarbonate. When the pH is 3, the solution is filtered. The pH is then adjusted to 3.6 by the addition of some drops of saturated solution of sodium bicarbonate. The solution is cooled to +4.degree. C. and the SR 41 973 starts to crystallize. 75 ml of acetone are added slowly drop by drop. After 1/2 hour of stirring at +4.degree. C., the crystals are filtered and washed twice with a mixture (1-1) of water and acetone and finally washed twice with 20 ml of acetone. The product is dried in the dessicator over P.sub.2 O.sub.5. 1.9 g of the compound SR 41 973 is obtained.
1.25 g of the SR 41 973 so obtained is suspended in 15 ml of water at +4.degree. C. A solution of 0.168 g of sodium bicarbonate in 3 ml of water is added drop by drop. The clear solution thus obtained is frozen and freeze-dried, after sterile filtration, to obtain the sodium salt of 41 973 ready for injection.

Number	Name	Date
3935204	Dahlen et al.	Jan 1976
4034090	Berger et al.	Jul 1977
4097595	Heymes	Jun 1978
4152432	Haymes et al.	May 1979
4278671	Ochiai et al.	Jul 1981
4338438	Christensen et al.	Jul 1982
4366153	Takaya et al.	Dec 1982
4396619	Lunn et al.	Aug 1983
4399131	Durekhermer et al.	Aug 1983

Number	Date	Country
768844	Jun 1971	BEX
29557	Jun 1981	EPX
55465	Jul 1982	EPX
127543	Dec 1984	EPX
2485540	Dec 1981	FRX
2501209	Sep 1982	FRX
2506307	Nov 1982	FRX

Antibiotic compounds derived from cephalosporins, process for their production and pharmaceutical compositions

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