PROCESS FOR PRODUCING ANTIBIOTIC COMPOUNDS DERIVED FROM CEPHALOSPORINS

The present invention relates to antibiotic compounds derived from cephalosporins, processes for the production

5 thereof and pharmaceutical compositions containing the same.

These compounds correspond to the formula:

. 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

20 pharmaceutically acceptable ester radical;

. X denotes an oxygen atom or a sulfur atom;

. n is zero or 1;

. Ri and R₂ each denote independently hydrogen or a lower alkyl group, preferably a methyl group; or

25 . Ri and R₂ taken together with the carbon atom to which they are linked form a cyclobutyl or cyclopentyl nucleus;

. B is the rèsidue of a primary or secondary amine selected from the following groups:

- Z-NH-R where Z is an alkylene group with a sttàight or

30 branched chain alkylene group having from 2 to 7 carbon atoms, optionally interrupted by a sulfur atom and optionally substituted by a hydroxyl, thiol, methylthio, amino, acetamido, carbamoyl, phenyl, hydroxyphenyl or imidazolyl group, Z can also be a σyclopentylidene or cyclohexylidene 35 group, and R represents a hydrogen atom or an alkyl group having from 1 to 3 carbon atoms,

- Z*-Aik-NH-R where Z’ represents a 1,2-phenylene or 1,3phenylene or 1,4-phenylene group optionally 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, 1,3cyclohexylene or 1,4-cyclohexylene group, Aik represents a straight or branched alkyl group having from 1 to 3 carbon atoms, and

R is as defined above,

- Z'-N-CO-Y-NH-R" where Z' is as defined above,

R'

Y denotes an alkyl group (CH2)_m in which m = 0,1,2,3 or 4, a branched alkyl group having 2 or 3 carbon atoms

10

or also Y with NH-R" constitutes a ring

R' and R", identical or different, have the same meaning as that given for R above,

15 -− Z"-NH~R where Z" is a 1,3-cyclohexylene or 1,4cyclohexylene group and R is as previously defined,

^R3i f Jl (NH-C)_n - Aik -NH-R where R3 represents a

s ό hydrogen atom or a methyl group, 20 n ≈ 0 or 1 and Aik and R are as previously defined,

1 -s

(NH-C)_n - Aik 6 NH-R

where n ≈ 0 or 1 and Aik and R are as previously defined,

25 - a 2-piperidyl, 3-piperidyl or 4-piperidyl group optionally substituted on the nitrogen atom by a -C0-Alk-NH2 group

or -CQ·K NH where Aik is as previously defined. n

Thfer-Salts that the compounds of Formula (I) are

30 capable of giving with the pharmaceutically acceptable acids form an integral part of the invention.

Consequent on the presence in the formula of an oxime group, the compounds (I) exist in 2 isomeric forms syn and anti. The syn isomers whose therapeutic activity is higher 35 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'):

According to the reaction diagram below, the process of the invention consists of first acylating 4-tertiobutyl-l-S-oxide 7-amino-3-bromomethyl-3-cepheme carboxylate (II) with 15 the acid (III) to obtain the compound (IV) described in European patent application number 60,745. To the compound IV, is then added the acid B - (CH2)_n - COOH or the thioacid B(CH2)_n COSH whose amine function must be previously protected, according to a known method, by a protective group 20 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' - (CH₂)_nC00H to the compound (IV) is preferably done 25 in an aprotic polar solvent, for example dimethylformamide, whilst the addition of the sodium or potassium salt of the thioacid B^# - (CH₂)_n^{C0SH σan} be done in an apolar solvent like tetrahydrofuran. The compound (V) is obtained.

In the case of the thioacids, to prepare the compounds 30 (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 tertiσbutyl 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.

(IV) + B'-CCH₂)jj- C - XH

0

-> CV)

(V) + H⁺ CD

T_r represents trityl> tBü tertiobutyl> X, Rj, R₂>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.

5 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 10 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 15 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 20 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 dimethyl-formamide.

The syn and anti form isomers are obtained by 25 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, 30 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 35 60 MUz 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

5 ± 0.5 Hz.

The following abbreviations^ will be used:

- S : singlet

- D : doublet

- D of D : doublet of doublet

10 - S. e. : widened singlet

- M : multiplet

- Q : quadruplet

- AB : AB system

- J : represents the coupling constant.

15 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 20 between 4,000 cm”¹ and 600 cm”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 25 elongation vibration frequency of the carbonyl groups of the molecule is noted ( £) CO).

EXMSM--i

7-f2~(2-Amino 4-thiazolvli 2-(2-carboxv 2-propvl oxvimino) acetamidol 3 -f 4 30 pjperidinvlΐcarbonvl oxvmethvl 3-cepheme 4carboxvlic 1-β-S-oxide acid trifluoroaσetate svn isomer. SR 41 862.

a) 7 - r 2-(2-tritvlamino-4-thiazolvl)

2-(2-tertiobutoxvcarbonvl 2-propvl 35 oxvimino' acetamidol 3 - f1tertiobutoxvcarbonvl 4-pjp℮ridinvl carbonvl oxvmethvli 3-c℮Pheme 1-β-

S-oxide carboxvlate of Tertiobutvl: svn isomer.

tBu and T have the previously indicated meanings, Boc denotes the tertiobutoxycarbonyl group.

To a solution of 1.38 of 4-tertiobutyl 1-β-S-oxide 7-[2-(2-tritylamino 4-thiazolyl) 2-(2tertiobutoxycarbonyl 2-propyl oxyimino) acetamido] 3-bromomethyl 3-cepheme carboxylate syn isomer, in 20 ml of anhydrous dimethylformamide, are added 1 g of l-tertiobutyloxycarbonyl 4-piperidinyl carboxylic acid and 1.5 of potassium bicarbonate.

After 17 hours of stirring at ambient temperature (20-25"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; 9 CO

. 1805 cm¹: C ≈ 0 at 8 of the β lactame

-1

. 1735 cm : C = 0 of the tertiobutyl esters and

of the ester at the 3 position

-I

. 1695 cm : C = 0 of the tertiobutoxycarbonyl protecting group of the piperidine.

NMR Spectrum at 250 MHz.

1H at 8.75 ppm (S, NH Tr) - 1H at 8.10 ppm (D, J=9 Hz, CONH) - 15 H at 7.25 ppm (M, H aromatics) - 1H at 6.73 ppm (S, H thiazole) - 1H at 5.81 ppm (M, Hj) - 1H at 5.25 ppm (D, J≈13 Hz, CH^ 0C0) - 1H at 4.94 ppm (D, J=4 Hz, Hβ) - 1H at 4.55 ppm (D, J=13 Hz, CH2 OCO) - 1H at 3.90 ppm (D, J=17 Hz, CH₂SO) - 2H at 3.79 ppm (D, J=12 Hz, gCN Boc equatorials) - 1H at 3.53 ppm (D, J=17 Hz, CH2 SO) - 2H at 2.75 ppm (M, HCH Boc arials) - 1H at 2.50 ppm (M, acco₂) - 2H at 1.75 ppm (D, J=12 Hz, HCHC0₂ equatorials) - 9H at 1.46 ppm (S, C0₂, tBU) - 2H at 1.40 ppm (M, HCCHC0₂ axials) - 6H at 1.39 ppm (S, (CH₃)₂C) - 9H at 1.36 ppm (S, C0₂tBU - 9H at 1.29 ppm <sΠS& 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 °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; 3 CO

. 1795 cm”¹: C ≈ 0 at 8 of the β lactam . 1735 cm”¹: C = 0 of the ester at 3

. 1680 cm”¹ wide band: C = 0 of the acids of the molecule, of the amide at 7, of the ions CF3CO2^- .

NMR Spectrum at 250 MHz.

5 2H at 8.60 ppm (S.e., NH₂⁺) - 1H at 8.50 ppm (D, J+9 Hz, CONH) - 3H at 8.40 ppm (S.e., NH₃⁺) - 1H at 6.68 ppm (S, H thiazole) - 1H at 6.0 ppm (D of D, J₃ = 9 Hz, J₂=4 Hz, H2) “ 1H at 5.16 ppm (D, J=13 Hz, CH₂OCO) - 1H at 4.97 ppm (D, J=4 Hz, Hg) - 1H at 4.60 ppm (D, J=13 Hz, 10 CH^OCO) - 1H at 3.90 ppm (D, J=17 Hz, CH^SO) - 1H at 3.55 ppm (D, J=17 Hz, CHgSO) - 2H at 3.25 ppm (M, CHgNH)

- 2H at 2.90 ppm (M, CHgNH) - 1H at 2.66 ppm (M, CHC0₂)

- 2H at 1.90 ppm (M, CH^CH) - 2H at 1.70 ppm (M, CH₂CH)

- 6H at 1.44 ppm (2S, CH₃)₂C).

15 EXAMPLE 2

7-f 2 -(2-amino 4-thiazolvl) 2-(2-carboxv 2-propvl oxyΐmino) acetanidol (3-amino propionvll 3-thio-mβthvl 3-c℮pheme 4carboxvlic β 1-s-oxide acid trifluoracetate 20 svn isomer SR 41884.

^a) Tertiobutoxvcarbonvl 3-amino thiopropionic acid.

1.8 g of tert iobutoxycarbonyl 3-aminσ propionic acid was solubilized in 50 ml of anhydrous 25 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 30 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 35 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- r2-(2-tritvlamino 4-thiazolvlï 2-f 2tertiobutoxvcarbonyl 2-propvl oxv iτnino1 acetamidol (3-tertiobutoxvcarboxvl-amino⁵propionvl^ 3-thiomethvl 3-cβpheme 1 β-S-oxlde carboxvlate of 4-Tertiobutvl; svn isomer.

To a solution of 0.46 g of 4-Tertiobutyl 1 β S-oxide 7-[2-(2-tritylamino 4-thiazolyl) 2- (210 tertiobutoxy-carbonyl 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 ambient 15 temperature the solvent was evaporated and the residue taXen 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 20 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; D co

25 . 1805 cm : C = 0 at 8 of the β lactame . 1720 cm : C = 0 of the tertiobutylic esters

. 1690 cm : C == 0 of the amide at 7, of the thioester at 3 and of the 30 tertiobutoxy carbonyl protecting the amine.

N M R Spectrum at 250 MHz fCD CL₃ΐ.

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 35 ppm (S, H thiazole) - 1H at 6.21 ppm (D of D, J^≈9 Hz, J₂≈4 Hz, Hj) 1H at 4.85 ppm (S.e., NH-Boc) - 1H at 4.50 ppm (D, J=4 Hz, Hg) - 1H at 4.29 ppm (D, J=13 Hz, CH^S CO) - 1H at 3.75 ppm (D, J=13 Hz, CHg S CO) - 1H at 3.58 ppm (A of AB, J=17 Hz, CH₂ SO) - 2H at 3.36 ppm (M, CH₂ NH Boc) - 1H at 3.22 ppm (B of AB, J=17 Hz, CH₂ SO) - 2H at 2.75 ppm (T, J=6 Hz, CH₂ - CS) - 15H at 1.52 ppm (S, 5 Boc NH and (CH3)₂ C) - 18H at 1.39 ppm (2S, C0₂ t Bu).

C) SR 41 884

The whole of the compound obtained above was solubilized in 10 ml of trifluoroacetic acid. After 45 minutes at 23“C the acid was evaporated under vacuum 10 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.

15 0.37 g of the expected product was obtained.

IR Spectrum: 0 CO

. 1785 cm "*■: C = 0 at 8 of the β lactam . 1680 cm¹ wide band: C = O of the acids of the molecule, of the amide 20 at 7, of the thioester, of the CF3CO;}” ions.

NMR Spectrum at 250 MHz.

1H at 8.40 ppm (D, J==9 Hz, CONH)- 3H at 7.80 ppm (S.e., NH3) - 3H at 7.30 ppm (S.e., NH3) - 1H at 6.78 ppm (S, 25 H, thiazole) - 1H at 5.95 ppm (D of D, J_α=9 Hz, J₂=4 HZ, Hj) - 1H at 4.92 ppm (D, J≈4 Hz, H₆) - 1H at 4.18 ppm (D, J=13 Hz, CH^S CO) - 1H at 3.79 ppm (D, J=13 Hz, CH₂ S CO) - 2H at 3.66 ppm (S, CH₂ SO) - 2H at 3.0 ppm 30 ppm (S, (CHj )₂ C). ~ (M, CHg NH) - 2H at 2.92 ppm (M, CH₂ COS) - 6H at 1.44

EXAMPLE 3 Trifluoroacetate of

To 0.46 g of 4-Tertiobutyl 1 β-S-oxide 7-[2(2-tritylamino 4-thiazolyl) 2-(2-tertiobutoxy carboxylamino 2-propyl oxyimino) acetamido] 3-bromomethyl 310 cepheme carboxylate syn isomer in 10 ml of anhydrous acetone, were added 0.4 of 3-tertiobutoxycarbonylamino thio-propionic acid, 0.6 g of potassium bicarbonate and 0.25 g of sodium iodide.

After 2 hours stirring at room temperature, 15 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, 20 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 25 spectrum) to the product of Example 2 b) was obtained.

b) SR_41-9M.

The deprotection was carried out as indicated in Example 2 c).

By operating as in Example 1, the compounds 30 according to the invention were prepared in the form of trifluoroacetate, described in Table I below.

0- C -(·CH₉) B, TFA ii <- n

These compounds are identified by a reference number. For each among them the values of R_lf R₂, B and n and the NMR spectrum are given.

The acid B' - (CH₂)_n -COOH which reacts on 15 (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 20 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

- 1

cm correspond in order to the elongation vibration frequencies of the carbonyl at the 8 position of the 25 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 30 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.

41 807 A

ch₃ ch₃

©

CH - NH₂

ch₃ - CH₂-C0-NH₂

CH₂ Cl₂ 50

AcEt 50

1805

1735

1680

41 810 ■CH - NH₂ ©

CH₂0H

CH₂ Cl₂ 80

AcEt 20

1805

1725

41 354 ·<^ch2>3^NH2

■(ch₂)₅nh₂

CH₂ Cl₂ 90

AcEt 10

1805

1725

41 855 CH₂ Cl₂ 90

1805

1725

1690

41 855 (ch₂)₇nh₂

CHj Clg 90

AcEt 10

1805

1725

1595

10

41 857

-CH - NH, ©

I²

CH₂S - CH₂NHCOCH₃

CH₂ Cl₂ 100

Ha

1.5

1805

1725

1630

11

41 858 ch₃

- C - NH,

£h

3

CH₂ Cl₂ 90

AcEt 10

1805

1725

12

41 859 “pH* nh₂ ©

CH₂ Clg 92.5

AcEt 7.5

1810

1725

13

41 860 Cl, 92.5

AcEt 7.5

1805

1725

14

-a

- 18 -

-a

- 24 -

S

o

KMK SPECTRAi

The spectra are recorded at 60 Mtlz, indicated by

(a) or at 2.50 MHz, indicated by (b); when there exist two dinsteroo-isomers in a molecule, the split signals are indicated by

NMR n° 1 - ftp ;

1H at 8.44 ppm (D, J=9 Hz, CONH) - 3H at 7.90 ppm (S.e., NHj) ~ 3H at 7.50 ppm NH^) - 1H at 6.78 ppm (S, H 5 thiazol) - 1H at 5.97 ppm (D of D, J_x = 9 Hz, J₂=4 Hz, H7) - 1H at 5.18 ppm (D, J=13 Hz, CH₂OCO) - 1H at 4.94 ppm (D, J=4 Hz, H₅) - 1H at 4.64 ppm (D, J=13 Hz, CH₂OCO) - 1H at 3.90 ppm (D, J=17 Hz, CH₂ SO) - 1H at 3.58 ppm (D, J=17 Hz, CH₂ SO) - 2H at 3.00 ppm (M, 10 CH₂NH₂) - 2H at 2.61 ppm (M, CH₂ C0₂) - 6H at 1.44 ppm (S~ («13)2 C). ~~

NMR n' 2 - fb):

4H at 8.45 ppm (M, NH₃,CONH) - 3H at 7.35 ppm (S.e., NH^) - 5H at 7.25 ppm (M, H aromatics - 1H at 6.82 ppm 15 (S, H thiazol) - 1H at 6.0 ppm (D of D, J_x=9 Hz, J₂=4 Hz, H₇) - 1H at 5.20 ppm (D, J=13 Hz, CH₂OCO) - 1H at 4.92 ppm (D, J≈4 Hz, H₆) - 1H at 4.81 ppitT (D, J=13 Hz, CH₂0C0) - 1H at 4.31 ppm (S.e., CH NH₂) - 1H at 3.50 ppm (D, J=17 Hz, CH₂ SO) - 1H at 3.30 ppm (D, J=17 Hz, CH^ 20 SO) - 2H at 3.10 ppm (M, CH₂C₆H₅) - 6H at 1.44 ppm (2 S, (CH3)2 C). ~

NMR n· 3 - fbΐ :

5H at, 8.45 ppm (S.e., NH₂, OH, CONH) “ 3H at 7.50 ppm (S.e., NH3)- 2H at 6.95 ppm (D, J=8 Hz, H meta OH) - 1H 25 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_x=9 Hz, J₂=4 Hz, H7) - 1H at 5.16 ppm (D, J≈13 Hz, CH^OCO) - 1H at 4.92 ppm (D, J≈>4 Hz, Hg) - 1H at 4.74 ppm (D, J=13 Hz, CHa 0C0) - 1H at 4.19 ppm (M, CHNH₂) - 1H at 3.66 ppm (D, 30 J=>17 Hz, (CHgSO) - 1H at 3.34 ppm (D, J=17 Hz, CH^SO) 2H at 2.93 ppm (M, CH₂ - CH - NH₂) - 6H at 1.44 ppm (2 S, (CH3)2 C). “

NMR n" 4 - fb):

1H at 8.50 ppm (D, J=9 Hz, CONH) - 3H at 8.40 ppm (S.e. 35 NH₃) - 3H at 7.60 ppm (S.e. NH₃) - 1H at 6.79 ppm (S, H thiazol) - 1H at 6.00 ppm (D of D, J₃=9 Hz, J₂=4 Hz,

H7) - 1H at 5.45 ppm (D, J=13 Hz, CHsOCO) - 1H at 4.97 ppm (D, J=4 Hz, Hg) - 1H at 4.80 ppm (D, J=13 Hz,

CHgOCO) - 1H at 4.08 ppm (M, CHNH₂) - 1H at 3.92 ppm (D, J=17 Hz, CHjgSO) - 1H at 3.58 ppm (D, J=17 Hz, CH₂SO)

- 6H at 1.44 ppm (S, (CH3)₂C) - 3H at 1.34 ppm (D, J=7 5 Hz, CH3CH).

NMR n° 5 - :

1H at 8.45 ppm (D, J=9 Hz, CO NH) - 3H at 8.40 ppm (S.e., NHg) - 3H at 7.60 ppm (S.e., Sh^) - 1H at 6.78 ppm (S, H thiazol) - 1H at 6.0 ppm (D of D, Jj=9 Hz, 10 J₂=4 Hzn H₇) - 1H at 5.25 ppm (D, J=13 Hz, CH₂OCO) - 1H at 4.95 ppm (D, J≈4 Hz, H₆) - 1H at 4.82 ppm (D, J=13 Hz, CH₂OCO) - 2H at 3.92 ppm (M, CH NH₂ and CH₂SO) 1H at 3.56 ppm (D, J=17 Hz, CH^SO) - 1H at 2.11 ppm (M, CH (CH₃)₂) - 6H at 1.44 ppm (2 S, (CH₃)₂ C) - 6H at 0.9 15 ppm (D, J=7 Hz, (CH₃)₂ CH).

NMR n" 6 - (bï:

1H at 8.45 ppm (D, J=9 Hz, CONH) - 3H at 8.35 ppm (S.e., NH₃) - 4H at 7.40 ppm (S.e., CONH₂, &H₃) - 1H at 6.92 ppm (S.e., CONH₂) - 1H at 6.76 ppm (S, H thiazol) - 1H 20 at 6.0 ppm (D of D, J_χ=9 Hz, J₂=4 Hz, Hj) - 1H at 5.25 ppm (D, J=13 HZ, CHgOCO) - 1H at 5.00 ppm (D, J=4 Hz, Hg) - 1H at 4.82 ppm (D, J=13 Hz, CH3OCO) - 1H at 4.00 ppm (M, CH NH₂) - 1H at 3.95 ppm (D, J=17 Hz, ClfgSO) 1H at 3.56 ppm (D, J≈17 Hz, CH₂SO) - 2H at 2.20 ppm (M, 25 CH₂-CONH₂) - 2H at 1.95 ppm (M, CH₂-CH) - 6H at 1.44 ppm (2~S, (CH3)₂C). ~

MMBL. n^α .7 - (b) Î

1H at 8.50 ppm (D, J≈9 Hz, CONH) - 3H at 8.40 ppm (S.e., italg) - 3H at 7.40 ppm (S.e., &%) - 1H at 6.76 ppm (S, H 30 thiazol) - 1H at 6.0 ppm'(D of D, J_x≈9 Hz, J₂=4 Hz, l^j)

- 1H at 5.25 ppm (D, J=13 Hz, CH₂OCO) - 1H at 4.92 ppm (D, J=4 Hz, H₆) - 1H at 4.82 ppm (D, J=13 Hz, CH₂OCO) 1H at 4.16 ppm (M, CHNH₂) - 1H at 3.95 ppm (D, J=17 Hz, CHgSO) - 1H at 3.81 ppm (A of AB, J_Aβ=13 Hz, CHgOH) 35 1H at 3.69 ppm (B of AB, J_AB=13 Hz, CHgOH) - 1H at 3.55 ppm (D, J=17 Hz, CHg SO) - 6H at 1.44 ppm (2 S, (CH₃)2 C). ~ NMR n” 8 - (aï :

8H between 5.5 and 8.5 ppm (widened signal, NH₂, C0₂H, TFA) - 1H at 8.40 ppm (D, J=9 Hz, CONH) - 1H at 6.82 ppm 5 (S, H thiazol) - 1H at 6.0 ppm (D of D, J_χ=9 Hz, J₂=4 Hz, H^) - 1H at 5.15 ppm (A of AB, Jab~^{13 Hz}» CH₂0C0) 1H at 5.0 ppm (D, J=4 Hz, H₆) - 1H at 4.67 ppm (B of AB, J=13 Hz, CH^OCO) - 1H at 3.85 ppm (A of AB, J=17 Hz:

CH₂S0) - 1H at 3.62 ppm (B of AB, J=17 Hz, CH₂SO) - 2H 10 at 2.80 ppm (M, CH₂NH₂) - 2H at 2.40 ppm (M, CH₂C0₂) 2H at 1.80 (M, CH₂CH₂CH₂) - 6H at 1.43 ppm (S, (CH3)₂C). ~

NMR n’ 9 - faΐ:

8H between 5.5 and 8.7 ppm (wide signal, C0₂H, NH₂, TFA) 15 - 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, J₃=9 Hz, J₂ = 4 Hz, H7) - 1H at 5.15 ppm (A of AB, J=13 Hz, CH₂OCO) - 1H at 5.0 ppm (D, J=4 Hz, H₆) - 1H at 4.60 ppm (B of AB, J=13 Hz, CH₂OCO) - 1H at 3.85 ppm (A of AB, J=17 Hz, CH₂SO)20 1H at 3.60 ppm (B of AB, J=17 Hz, CH₂S0) - 2H at 2.80 ppm (M, CH₂NH₂) - 2H at 2.30 ppm (M, CH₂CO) - 12 H at 1.45 ppm (S.e., (CH3)₂C and CH₂(CH^)₃CH₂).

NMR n* 10 - fa):

8H between 5.5 and 8.0 ppm (wide signal, NH₂, C0₂H, TFA) 25 - 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_x≈9 Hz, J₂=4 Hz, H₇) - 1H at 5.15 ppm (A of AB, J=13 Hz, CH₂0C0) - 1H at 5.0 ppm (D, J=4 Hz, H^) - 1H at 4.65 ppm (B of AB, J≈13 Hz, CHgOCO) - 1H at 3.85 ppm (A of AB, J=17 Hz, CHgSO) 30 1H at 3.62 ppm (B of AB, J=17 Hz, CH₂S0) - 2H at 2.80 ppm (M, ℮H₂NH₂) - 2H at 2.30 ppm (M, CH^CO^ - 6H at 1.45 ppm (S, (CH3)₂C) - 10H at 1.35 ppm (S.e., CH₂(CH2)₅CH₂).

NMR n“ 11 - (a):

35 2H at 8.40 ppm (M, CONH, CH₃CONH) - 8H at 7.50 ppm (S.e., Sh₃, C0₂H) - 1H at 6.90 ppm (S, H thiazol) - 1H at 6.05 ppm (D of D, J!=9 Hz, J₂=4 Hz, H7) - 1H at 5.40 CONH, CH₃CONH) - 8H at 7.50 ppm 1H at 6.90 ppm (S, H thiazol) - 1H J!=9 Hz, J₂=4 Hz, H7) - 1H at 5.40 ppm (A of AB, J==13 Hz, CH₂OCO) - 1H at 4.98 ppm (D, J=4 Hz, Hg) - 1H at 4.90 ppm" (B of AB, J=13 Hz, CH₂0C0) 3H at 4.30 ppm (M, CH·^NHCOCH;j,CHNH₂) - 1H at 4.00 ppm (A 5 of AB, Jab=^{17 Hz}» CH₂SO) - 1H at 3.65 ppm (B of AB,^JAB=¹⁷ Hz, CH₂SO) - 2H at 3.00 ppm (M, CHgS) - 3H at 1.80 ppm (S, CH3CONH), - 6H at 1.45 ppm (S,(CH₃)₂C).

NMR n° 12 - fa^;

8H between 6.5 and 9 ppm (wide signal, C0₂H, TFA, NH₂) 10 - 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^-9 Hz, J₂=4 Hz, H^)

- 1H at 5.30 ppm (A of AB, J=13 Hz, CH₂0C0) -- 1H at 5.0 ppm (D, J=4 Hz, H^) - 1H at 4.80 ppm (B of AB, J=13 Hz, CH2OCO) - 1H at 3.92 ppm (A of AB, J=17 Hz, CHg SO) - 1H 15 at 3.67 ppm (B of AB, J=17 Hz, CH₂SO) - 12H at 1.45 ppm (S, (CH3)₂C-C0₂H, (CH3)₂CNH₂).

NMR n· 13 - (aï :

8H between 6.5 and 9.5 ppm (wide signal, C0₂H» NH₂, TFA)

- 1H 8.5 ppm (D, J=9 Hz, CONH) - 1H at 6.90 ppm (S, H 20 thiazol) - 1H at 6.05 ppm (D of D, J_χ=9 Hz, J₂=4 Hz, H7)

- 1H at 5.30 ppm (A of AB, J≈13 Hz, CHgOCO) - 1H at 5.05 ppm (D, J=4 Hz, Hg) - 1H at 4.90 ppm (B of AB, J=13 Hz, CH₂0C0) - 3H at 3.80 ppm (M, CHNH₂ and CH₂S0) - 3H at 1.50 ppm (M, CH₂-CH) - 6H at 1.45 ppm (S, 7ch₃)₂C) 25 6H at 0.85 ppm (D, J=7 Hz, (CH^CH).

NMR n‘ 14 - (a) :

8H between 7 and 9 ppm (wide signal, NH₂, C0₂H, 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_x=9 Hz, J₂≈4 Hz, H₇) 30 1H at 5.30 ppm (A of AB, Jab^{≈13 Hz}' CH₂OCO) - 1H at 5.05 ppm (D, J=4 Hz, Hg) - 1H at 4.49 ppm (B of AB, Jab⁼¹³ HZ, CHgOCO) - 3H at 3.90 ppm (M, CH₂SO and CH CH₂) - 1H at 1.80 ppm (M, CH CH₃) - 6H at 1.45 ppm (S, (CH^)₂C) 2H at 1.30 ppm (M, CH2 CH₃) - 6H at 0.88 ppm (M, CH^ CH₂ 35 and CH^CH).

NMR n° 15 - :

1H at 8.5 ppm (D, J=9 Hz, CONH) - 3H at 8.30 ppm (S.e., NH_S) - 3H at 7.40 ppm (S.e., &H₃) - 1H at 6.76 ppm (S, H thiazol) - 1H at 6.0 ppm (D of D, J_χ=9 Hz, J₂=4 Hz, H7)

- 1H at 5.24 ppm (D, J=13 Hz, CH₂OCO) - 1H at 4.92 ppm (D, J=4 Hz, Hg) - 1H at 4.84 ppm (D, J=13 Hz, CH^OCO) 5 1H at 4.10 ppm (M, CH-NH₂) - 1H at 3.97 ppm (M, CH-OH) 1H at 3.94 ppm (D, J=17 Hz, CH^SO) - 1H at 3.55 ppm (D, J =17 Hz, CH^SO) - 6H at 1.44 ppm (S, (CHg^C) - 3H at 1.14 ppm (D, J=7 Hz, CHjCH).

NMR n° 16 - (b):

10 1H at 8.5 ppm (D, J=9 Hz, CONH) - 3H at 8.40 ppm (S.e., Ntfj) - 1H at 7.66 ppm (S, CONH₂) - 3H at 7.50 ppm (S.e., NH3) - 1H at 7.22 ppm (S, CO NH₂) - 1H at 6.78 ppm (S, H thiazol) - 1H at 6.0 ppm (D of D, J_±=9 Hz, J₂=4 Hz, Hj)

- 1H at 5.29 ppm (D, J=13 Hz, CH^OCO) - 1H at 4.92 ppm 15 (D, J≈4 Hz, Hg) - 1H at 4.79 ppm (D, J=13 Hz, CH₂OCO) 1H at 4.26 ppm (M, CHNH₂) - 1H at 3.92 ppm (D, J=17 Hz, CH₂ SO) - 1H at 3.52 ppm (D, J=17 Hz, CH₂SO) - 2H at 2.71 ppm (M, CH₂CONH₂) - 6H at 1.44 ppm (S,(CH₃)₂C).

NMR n⁰ 17-fbi;

20 1H at 8.50 ppm (D, J≈9 Hz, CONH) “ 3H at 8.45 ppm (S.e., iiWj) - 3H at 7.45 ppm (S.e., NH₃) - 1H at 6.78 ppm (S, H thiazol) - 1H at 6.0 ppm (D of D, Jχ=9 Hz, J₂=4 Hz, H7)

- 1H at 5.24 ppm (D, J=13 Hz, CH₂OCO) - 1H at 4.98 ppm (D, J≈4 Hz, Hg) - 1H at 4.82 ppm (D, J=13 Hz, CH₂OCO) 25 1H at 4.13 ppm (M, CHNH₂) - 1H at 3.92 ppm (D, ~J≈17 Hz, CH₂S0) - 1H at 3.10 ppm (D, J=17 Hz, CH₂S0) - 1H at 2.1θ ppm (M, CH₂S) - 5H at 2.0 ppm (M, CH₃S~ and CH₂-CH₂-S) - 6H at 1.44 ppm (S, (CH₃)₂C).

NMR n* 13 - (hi

30 4H at 8.50 ppm (M, CONH, NH₃) - 3H at 7.80 ppm (S.e., NH^) - 3H at 7.50 ppm (S.e.,”!^) - 1H at 6.79 ppm (S, H thiazol) - 1H at 6.0 ppm (D of D, J_x=9 Hz, J₂=4 Hz, H7)

- 1H at 5.24 ppm (D, J=13 Hz, CHgOCO) - 1H at 4.97 ppm (D, J=4 Hz, Hg) - 1H at 4.82 ppm (D, J≈13 Hz, CH₂OCO)35 1H at 3.97 ppm (M, CHNH₂) - 1H at 3.92 ppm (D, J^Ï7 Hz, CH₂SO) - 1H at 3.60 ppm (D, J=17 Hz, CH₂SO) - 2H at 2.75 ppm (M, CH₂NH₂, - 1H at 1.75 ppm (M CH^CH) - 11H at 1.40 ppm (S.e. TfCH^C, (CH2)₃CH₂NH₂).

NMR n· 19- fb):

, , +

1H at 9 ppm (S, H2 îmidazol) - 3H at 8.6 ppm (S.e., NH₃)

- 1H at 8.5 ppm (D, J=9 Hz, CONH) - 1H at 7.40 ppm (S, 5 H₄ imidazol) - 3H at 7.30 ppm (S.e., NH₃) - 1H at 6.79 ppm (S, H thiazol) - 1H at 6.0 ppm (D of D, J^=9 Hz, J₂=4 Hz, H₇) - 1H at 5.22 ppm (D, J=13 Hz, CH₂OCO) - 1H at 4.97 ppm (D, J=4 Hz, H₆) - 1H at 4.90 ppm (D, J=13 Hz, CH₂OCO) - 1H at 4.40 ppm (M, CHNH₂) - 1H at 3.89 ppm 10 (D, J=17 Hz, CH₂SO) - 1H at 3.52 ppm (D, J=17 Hz, CH₂SO)

- 2H at 3.20 ppm (M, CH₂CH) - 6H at 1.44 ppm (S, (CH₃)₂ C) .

NMR n‘ 20 -fbΐ:

1H at 8.50 ppm (D, J=9 Hz, CONH) - 3H at 8.40 ppm (S.e., 15 NH^) - 3H at 7.40 ppm (S.e., NH3) - 1H at 6.77 ppm (S, H thiazol) - 1H at 6.0 ppm (D of D, J_χ=9 Hz, J₂=4 Hz, H₇)

- 1H at 5.76 ppm (D, J=13 Hz, CH^OCO) - 1H at 4.95 ppm (D, J=4 Hz, Hg) - 1H at 4.81 ppm (D, J=13 Hz, CH^OCO)1H at 4.06 ppm (M, CHNH₂) - 1H at 3.95 ppm (D, J=17 Hz, 20 CH^SO) - 1H at 3.63 ppm (D, J=17 Hz, CHgSO) - 6H at 1.44 ppm (S, (CHj^C) - 3H at 1.36 ppm (D, J=7 Hz, CH3CH).

NMR n‘ 21 - (a^;

8H between 6.5 and 9 ppm (widened signal, NH₂, C0₂H, TFA) - 1H at 8.35 ppm (D, J=9 Hz, CONH) - 1H at 6.80 ppm 25 (S, H thiazol) - 1H at 6.0 ppm (D of D, J_x=9 Hz, J₂=4 HZ, Hjz) - 1H at 5.15 ppm (A of AB, J_AB=13 Hz, CHjOCO)1H at 5.0 ppm (D, J=4 Hz, Hg) - 1H at 4.65 ppm (B of AB, J_AB≈13 HZ, CH₂0C0) - 1H at 3.95 ppm (A of AB, J_AB=17 Hz, CH₂SO) - 1H at 3.65 ppm (B of AB, J_AB≈17 Hz, CH₂SO) - 2H 30 at 2.80 ppm (M, CH₂NH₂) - 2H at 2.35 ppm (M, CH^CO)10H at 1.45 ppm (S.e., (CH₃)₂C + CH₂(CH₂)₂CH₂).

NMR n' 22 - (a):

8H between 6 and 9 ppm (wide signal, TFA, NH₂, C0₂H)1H at 8.42 ppm (D, J=9 Hz, CONH) - 1H at 6.85 ppm (S, H 35 thiazol) - 1H at 6.05 ppm (D of D, Jj=9 Hz, J₂==4 HZ, 1*7)

- 1H at 5.30 ppm (A of AB, J=13 Hz, CH^OCO) - 1H at 5.05 ppm (D, J=4 Hz, Hg) - 1H at 4.68 ppm (B of AB, J_AB=13 Hz, CH₂0C0) - 1H at 4.0 ppm (A of AB, J_AB=17 Hz, CH₂S0)

- 1H at 3.65 ppm (B of AB, J_Ab^{=17 Hz}> CH₂SO) - 8H at 1.75 ppm (M, H, cyclopentane) - 6H at 1.45 ppm (S, (CH3)₂C).

5 NMR n· 23 - (a^:

8H between 7 and 10 ppm (wide signal, TFA, NH₂, C0₂H) 1H at 8.50 ppm (D, J=9 Hz, CONH) - 1H at 6.92 "ppm (S, H thiazol) - 1H at 6.10 ppm (D of D, J₃=9 Hz, J₂=≈4 Hz, H7)

- 1H at 5.35 ppm (A of AB, J=13 Hz, CH₂OCO) - 1H at 5.0 10 ppm (D, J=4 Hz, H₆) - 1H at 4.75 ppm (B of AB, J=13 Hz, CH^OCO) ~ 1H at 4.0 ppm (A of AB, J_Ab=1⁷ Hz, CH₂SO) - 1H at 3.70 ppm (B of AB, J_Ab=1^{7 Hz}/ CH₂SO) - 16H~between 1 and 2.3 ppm (M, (CH₃)₂C and cyclohexane).

NMR n° 24 - (a);

15 9H between 8 and 10 ppm (wide signal, NH₂, OH, C0₂H, 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, J₃=9 Hz, J₂=4 Hz, H7) - 1H at 5.80 ppm (A 20 of AB, J≈13 Hz, CH₂0C0) - 1H at 5.05 ppm (D, J==4 Hz, Hg)

- 1H at 4.80 ppm (B of AB, J=13 Hz, CHj;OCO) - 1H at 4.30 ppm (M, CflNH₂) - 2H at 3.70 ppm (M, CHgSO) - 2H at 3.0 ppm (M, CHg-CgH^OH - 6H at 1.46 ppm (S, (CMjJgC).

MMR_.n° 25 - (a).ΐ

25 10H between 6.5 and 9.5 ppm (wide signal, NH₂, C0₂H, TFA) - 1H at 8.40 ppm (D, J=9 Hz, CONH) " 1H at 6.85 ppm (S, h thiazol) - 1H at 6.05 ppm (D of D, J_x=9 Hz, J₂=4 Hz, H7) - 1H at 5.30 ppm (A of AB, Jab³¹³ Hz, CH₂0C0)1H at 5.0 ppm (D, J=4 Hz, Hg) - 1H at 4.85 ppm (B of AB,^{30 J}AB⁼¹³ Hz, CH₂0C0) - 1H at 4.20 ppm (M, CHNH₂) - 2H 3.80 ppm (M, CH₂S0) - 2H at 2.95 ppm (M, CH₂NH₂) - 2H at 2.20 ppm (M, CH₂CH₂NH₂) - 6H at 1.45 ppm (S, (CH3)₂C).

NMR n° 26 - fb^:

3H at 8.60 ppm (S.e., NH₃) - 1H at 8.44 ppm (D, J=9 Hz, 35 CONH) - 1H at 6.78 ppm (S, H thiazol) - 1H at 6.0 ppm (D of D, J_λ=9 Hz, H₇) - 1H at 5.16 ppm (2D, J=13 Hz, CH^OCO)* - 1H at 4.97 ppm (D, J=4 Hz, Hg) - 1H at 4.66 ppm (2D, J==13 Hz, CH₂OCO) * - 1H at 3.92 ppm (D, J=17 Hz, CH₂SO) - 1H at 3.56 ppm (D, J=17 Hz, CH₂SO) - 5H between 2.5 and 3.5 ppm (M, CH₂N and CHC0₂) - 4H between 1.5 and 2.0 ppm (M, (CH₂)₂ CH₂N) - 6H at 1.44 ppm (S, 5 <CH3)₂C). ~

NMR n· 27 - (bi:

-4*

3H at 8.50 ppm (S.e., NH3) - 1H at 8.44 ppm (D, J=9 Hz,

CONH) - 3H at 7.80 ppm (S.e., NH^) - 3H at 7.30 ppm (S.e., NH^) - 1H at 6.78 ppm (S, H thiazol) - 1H at 6.0 10 ppm (D of D, J_χ=9 Hz, J₂=4 Hz, Hy) - 1H at 5.26 ppm (D, J=13 Hz, CH₂OCO) - 1H at 4.97 ppm (D, J=4 Hz, Hg) - 1H at 4.84 ppm (D, J=13 Hz, CH₂OCO) - 1H at 4.08 ppm (M, ℮HC0₂) - 1H at 3.94 ppm (D, J=17 Hz, CH₂SO) - 1H at 3.56 ppm (D, J=17 Hz, CH₂S0) - 2H at 2.80~ppm (M, CH₂NH₂)15 4H at 1.60 ppm (M, 7cH2>2^CH2 NH₂) - 6H at 1.44 ppm (S, (CH3)₂C) .

NMR n° 28 - (b):

1H at 8.37 ppm (D, J=9 Hz, CONH) - 3H at 7.90 (S.e., NΗ3) - 3H at 7.20 ppm (S.e., NH₃) - 1H at 6.76 ppm (S, H 20 thiazol) - 1H at 6.0 ppm (D of”D, J_x==9 Hz, J₂=4 Hz, Hy)

- 1H at 5.16 ppm (D, J=13 Hz, CH₂OCO) - 1H at 4.97 ppm (D, J≈4 Hz, Hg) - 1H at 4.66 ppm (D, J=13 Hz, CH^OCO)1H at 3.92 ppm (D, J=17 Hz, CH₂SO) - 1H at 3.58 ppm (D, J=17 Hz, CH₂S0) - 1H at 3.50~ppm (M, CH NH₂) - 2H at 25 2.56 ppm (M7 CH2|CHNH₂) 6H at 1.44 ppm (S, (CH^C) - 3H at 1.16 ppm (D, J=6 Hz, CH3-CH).

NMR n° 29 - (b):

1H at 8.44 ppm (D, J≈9 Hz, CONH) “ 3H at 7.95 ppm (S.e., fa^) - 3H at 7.50 ppm (S.e., NH₃) - 1H at 6.78 ppm (S,H 30 thiazol) - 1H at 6.0 ppm (D of~D, J_x≈9 Hz, J₂=4 Hz, Hy) 1H at 5.20 ppm (2D, J≈13 Hz, CH^jOCO) * ~ 1H at 4.95 ppm (M, Hg) - 1H at 4.62 ppm (2D, J=13 Hz, CH₂OCO) * - 1H at 3.94 ppm (D, J=17 Hz, CH₂SO) - 1H at 3.58 ppm (D, J=17 Hz, CH₂SO) - 1H at 3.0 ppm (M, CHC0₂) - 2H at 2.75 ppm 35 (M, CH^NH₂) - 6H at 1.44 ppm (M, (CH₃)₂ C) - 3H at 1.10 ppm (D, J≈7 Hz, CH3CH).

NMR n’ 30 - (bΐ:

4" +■*

4H at 8.45 ppm (M, NH^, CONH) - 8H at 7.35 ppm (M, NH3,

H aromatic) - 1H at 6.78 ppm (S, H thiazol) - 1H at 6.0 5 ppm (M, H₇) - 1H at 5.05 ppm (2D, J=13 Hz, CH₂OCO)* - 1H at 4.94 ppm (2D, J=4 Hz, H₆)* - 1H at 4.60 ppm (M, CH NH₂) - 1H at 3.66 ppm (2D, J=17 Hz, CH₂SO)* - 1H at 3.40 ppm (2D, J=17 Hz, CH₂SO)* - 2H at 3.0 ppm (M, CH₂C0₂) 6H at 1.44 ppm (S, (CH₃)₂C).

10 NMR n' 31 -− ;

1H at 8.40 ppm (D, J=9 Hz, CONH) - 3H at 7.74 ppm (S.e., 4- -V

NH₃) - 3H at 7.40 ppm (S.e., NH₃) - 1H at 6.81 ppm (S, H

thiazol) - 1H at 6.0 ppm (D of~D, Hz, J₂=4 Hz, H₇) 1H at 5.13 ppm (D, J=13 Hz, CH₂OCO) - 1H at 4.97 ppm (D, 15 J=4 Hz, Hg) - 1H at 4.63 ppm (D, J=13 Hz, CH₂OCO) - 1H at 3.90 ppm (D, J=17 Hz, CH₂SO) - 1H at 3.55 ppm (D, J=17 Hz, CH^SO) - 1H at 3.16 ppm (M, CHNH₂) - 2H at 2.40 ppm (M, CH₂CO) -1H 1.77 ppm (M, CH₂CHNH₂) - 1H at 1.61 ppm (M, CH₂CHNH₂) - 6H at 1.44 ppm~(2S, (CH₃)₂C) - 1H at 20 1.1 ppm (D, J=7 Hz, CHβ-CH).

NMR n* 32 - (a) :

7H between 7 and 9 ppm (NH, NH₂, C0₂H, 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, Jχ=9 Hz, J₂=4 Hz, ) - 1H at 25 5.15 ppm (A of AB, J=13 Hz, CHgOCO) - 1H at 5.0 ppm (D, J=4 Hz, Hg) - 1H at 4.70 ppm (B of AB, J=13 Hz, CH₂OCO)

- 1H at 3.95 ppm (A of AB, J_AB≈17 Hz, CH₂S0) - 1H at 3.65 ppm (B Of AB, J_AB =17 Hz, CHgSO) - 2H at 2.90 ppm (M, CH₂NH) - 3H at 2.45 ppm (D, J=6 Hz, CHgNH) - 2H at 30 2.4 ppm (M, CH₂C0) - 2H at 1.70 ppm (M, CH₂CH₂CH₂) - 6H at 1.42 ppm (S, (CH₃)₂C).

NMR n* 33 - (al:

7H between 7 and 9.5 ppm (NH₂, NH, C0₂H, TFA) - 1H at 8.46 ppm (D, J=9 Hz, CONH) - 1H at 6.90 ppm (S, H 35 thiazol) - 1H at 6.05 ppm (D of D, J_χ=9 Hz, J₂=4 Hz, Hj)

- 1H at 5.15 ppm (A of AB, J_AB=13 Hz, CH₂0C0) - 1H at 5.0 ppm (D, J=4 Hz, Hg) - 1H at 4.70 ppm (B of AB,^JAB^{=13 Hz}' CH₂OCO) - 1H at 3.90 ppm (A of AB, J_AB=17 Hz, CH₂SO) - 1H at 3.65 ppm (B of AB, J_AB≈17 Hz, CH₂SO) - 2H at 2.75 ppm (M, CH^ NH CH₃) - 5H at 2.45 ppm (M, CH·jNH and CH₂CO) - 10H at 1.45 ppm (S.e., (CH₃)₂C and CH₂ 5 (CH2)₂CH₂).

NMR~n’ 34 -raΐ:

8H between 6 and 9 ppm (widened signal, NH₂, TFA, OH, C0₂H) - 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^=9 Hz, 10 J₂=4 Hz, H₇) - 1H at 5.35 ppm (AB, J_AB=13 Hz, CI^OCO)1H at 5.0 ppm (D, J=4 Hz, H₆) - 1H at 4.85 ppm (B of AB,^JAB=^{13 Hz}' CH₂OCO) - 4H at 3.95 ppm (M, CHjSO and CHOH CHNH₂) - 6H at 1.45 ppm (S, (CH^C) - 3H at 1.20 ppm (D, J=7 Hz, CH₃CH0H).

15 NMR n‘ 35 - (bΐ:

1H at 8.50 ppm (D, J=9 Hz, CONH) - 3H at 8.35 ppm (S.e., NH₃) - 2H at 7.94 ppm (D, J=8 Hz, H ortho CO) - 2H at 7.55ppm (D, J=8 Hz, H meta CO) - 1H at 6.84 ppm (S, H thiazol) - 1H at 6.0 ppm (D of D, J_x==9 Hz, J₂=4 Hz, Hj) 20 - 1H at 5.44 ppm (D, J≈13 Hz, CH^OCO) - 1H at 4.99 ppm (D, J≈4 Hz, Rg) - 1H at 4.86 ppm (D, J=13 Hz, CH^OCO) 3H at 4.1 ppm (M, CH2NH2, CH^SO) - 1H at 3.72 ppm (D, J≈17 Hz, CH₂SO) - 6H at 1.44 ppm (2S, (CH^C).

NMR if 36 - (a):

25 3H at 9.30 ppm (S.e., NH₃) - 1H at 8.55 ppm (D, J=9 Hz, CONH) “ 3H at 8.05 ppm (S.e., NH3) - 1H at 6.92 ppm (S, H thiazol) - 1H at 6.05 ppm (D of D, J-±≈9 Hz, J₂=4 Hz, H7) - 1H at 5.30 ppm (A of AB, J_AB=13 Hz, CH^OCO) - 1H at 5.05 ppm (D, J=4 Hz, Hg) - 1H at 4.70 ppm (B of AB,^{30 J}AB^{=13 Hz}' CH2OCO) - 1H at 3.95 ppm (A of AB, J_AB=17 Hz, CH₂SO) - 1H at 3.65 ppm (B of AB, J_AB=17 Hz, CH^SO) - 2H at 3.0 ppm (S.e., CH₂NH₂) - 6H at 1.45 ppm (S, (CHAC-ON) - 6H at 1.17 ppm (S, (CH^)₂C0₂CH₂).

NMR n‘ 37 - (b):

35 8H between 6 and 9 ppm (wide signal, C0₂H, TFA, NH₂)~ 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, J₂=4 Hz, H7)

- 1H at 5.15 ppm (D, J=13 Hz, CH^OCO) - 1H at 5.0 ppm (D, J=4 Hz, H₆) - 1H at 4.58 ppm (D, J=13 Hz, CH₂OCO)1H at 3.9 ppm (D, J=17 Hz, CH₂SO) - 1H at 3.54 ppm (D, J=17 HZ, CH₂SO) - 2H at 2.6 ppm (M, CH₂NH₂) - 1H at 2.25 ppm (T, J=12 Hz, CH C0₂) - 4H at 1.84 ppm (M, CH^CHCO)6H at 1.45 ppm (S, (CH^C) - 3H at 1.25 ppm (M, CHCH₂NH₂ and CH₂CHCH₂NH₂) - 2H at 0.95 ppm (M, CH₂CHCH₂NH₂).

NMR n‘ 38 - fb):

1H at 8.37 ppm (D, J=9 Hz, CONH) - 3H at 7.90 ppm (S.e., NH3) - 3H at 7.40 ppm (S.e., NH3) - 1H at 6.79 ppm (S, H thiazol) - 1H at 6.0 ppm (D of D, J₃=9 Hz, J₂=4 Hz, H7)

- 1H at 5.11 ppm (2D, J=13 Hz, CH^OCO) * - 1H at 4.98 ppm (D, J=4 Hz, H₆) - 1H at 4.61 ppm (2D, J=13 Hz, CH2_OCO)* - 1H at 3.90 ppm (D, J=17 Hz, CH₂SO) - 1H at 3."59 ppm (D, J=17 Hz, CHgSO) - 1H at 3.0 ppm (S.e., CHNH₂) - 1H at 2.40 ppm (M, CHC0₂) - 1H at 2.10 ppm (M, CH₂CHNH₂) - 3H at 1.80 ppm (M, CH₂CHNH₂) - 6H at 1.44 ppm (2S, (CH3)₂C) - 4H between 1 and 1.5 ppm (M, CH₂2CH^-CH-CO^ .

3_§..-_Cfel:

1H at 8.5 ppm (D, J=9 He, CONH) " 6H between 7 and 8 ppm (wide signal, NH₂, TFA) - 1H at 6.81 ppm (S, H thiazol)

- 1H at 6.0 ppm~(D of D, J_χ=9 Hz, J₂≈4 Hz, Hj) - 1H at 5.15 ppm (2D, J≈13 Hz, CH₂OCO)* - 1H at 5.0 ppm (D, J=4 Hz, H₆) - 1H at 4.63 ppm (2D, J=13 Hz, CH^OCO)* - 1H at 3.89~ppm (D, J≈17 Hz, CH^SO) - 1H at 3.56 ppm (D, J=17 Hz, CH₂SO) - 2H at 2.77 ppm (M, CH£NH₂) - 1H at 2.52 ppm (M, CHC0₂) - 1H at 1.84 ppm (M, CH_₂CH) - 1H at 1.56 ppm (M, CH₂CH) - 6H at 1.44 ppm (S, (CH₃)₂C) - 3H at 1.06 ppm (D, J=7 HZ, CH3CH).

NMR n° 40 - (a):

1H at 8.45 ppm (D, J=9 Hz, CONH) - 8H at 7.30 ppm (S.e., NHj, C0₂H) - 1H at 6.80 ppm S, H thiazol) - 1H at 6.0 ppm (M, H7) - 1H at 5.20 ppm (A of AB, Jab≈^{13 Hz}' CHgOCO) - 1H at 4.90 ppm (B of AB, J_AB=¹³ Hz, CH^OCO) 1H at 4.90 ppm (D, J=4 Hz, Hg) - 3H at 3.80 ppm (M, CH₂SO, CHNH₂) - 1H at 2.00 ppm (M, CH(CH₃)₂) - 6H at 1.45 ppm (S, (CH₃)₂C) - 6H at 0.95 ppm (2D, J=7 Hz, (CH3)₂CH).

NMR n^α 41 - fa) :

5 2H at 8.50 ppm (S.e·, NHjg) - 1H at 8.45 ppm (D, J=9 Hz, CONH) - 3H at 7.30 ppm (S.e·, NH₃) - 1H at 6.80 ppm (S, H thiazol) - 1H at 6.0 ppm (M, H₇) - 1H at 5.15 ppm (A of AB, J_AB=13^Hz» CH₂OCO) - 1H at 4.96 ppm (D, J=4 Hz, Hg) - 1H at 4.65 ppm (B of AB, 13 Hz, CH₂OCO) - 1H at 10 3.90 ppm (A of AB, J=17 Hz, CH₂SO) - 1H at 3.65 ppm (B of AB, J=17 HZ, CH^SO) - 2H at”3.00 ppm (M, CH_₂NH) - 5H at 2.50 ppm (M, CH^NH, CH^CO^ - 6H at 1.42 ppm (S, (CH₃)₂C) .

NMR n° 42 - faΐ;

*+■ 4*

15 7H at 9.4 ppm (S.e·, NH₃, NH₂, C0₂H) - 1H at 8.45 ppm

(D, J=9 Hz, CONH) - 1H "at 6.85 ppm (S, H thiazol) - 1H at 6.00 ppm (M, Hj) - 1H at 5.00 ppm (D, J=4 Hz, Hg) 1H at (A of AB, J_AB=13 Hz, CH₂OCO) - 1H at 4.65 ppm (B of AB, J_AB=13 Hz, CH^OCO) - 1H at 3.85 ppm (A of AB, 20 J_AB≈17 Hz, CHgSO) - 1H at 3.60 ppm (B of AB, J_AB=17 Hz, CH^SO) - 4H at 2.85 ppm (M, CH₂NHCH₂) - 2H at 2.40 ppm (M, CHj| CO) - 2H at 1.80 ppm (M, CH₂CH₂CH₂NH) - 6H at

O

1.45 ppm (S, (CH3)₂C) - 3H at 1.10 ppm (T, J=7 Hz, CH3 25 CH₂NH).

NMR-n.; 4,3 - (a) ;

2H at 8.50 ppm (S.e., NH₂) - 1H at 8.40 ppm (D, J=9 Hz, CONH) - 3H at 7.00 ppm (S.e., NH₃) - 1H at 6.76 ppm (S, H thiazol) - 1H at 5.95 ppm (M, "H7) - 1H at 5.10 ppm (A 30 of AB, J_AB =13 Hz, CHjjOCÔ) - 1H at 5.0 ppm (D, J=4 Hz, Hg) - 1H at 4.65 ppm (B of AB, J_AB=13 Hz, CI^OCO) - 1H at 3.85 ppm (A of AB, J_AB=17 Hz, CH₂S0) - 1H at 3.50 ppm, B of AB, J_AB=17 Hz, CH^SO) - 1H at 3.30 ppm (M, CHNH) “ 5H at 2.45 ppm (M, CH₃NH and CHg CO) - 2H at

35 O

1.80 ppm (M, CH₂CH₂ CO) - 6H at 1.45 ppm (S, (CH₃)₂C)

o

3H at 1.10 ppm (D, J=7 Hz, CH₃CH).

NMR n· 44 - (a):

1H at 8.40 ppm (D, J=9 Hz, CONH) - 7H at 7.80 ppm (S.e., NH/j, NH2, C0₂H) - 1H at 6.80 ppm (S, H thiazol) - 1H at 5 6.00 ppm (M, Hy) - 1H at 5.00 (M, H₆) - 1H at 5.00 ppm (A Of AB, Jab^{=13 Hz}/ CH₂OCO) - 1H at 4.65 ppm (B of AB, J_ab=13 Hz, CH₂OCO) - 1H at 3.85 ppm (A of AB, Jab=^{17 Hz}' CH^SO) - 1H at 3.55 ppm (B of AB, J_AB^{=17 Hz} > CH₂SO) - 2H at 2.80 ppm (M, CH^NH) - 5H at 2.40 ppm (M, CH₃NH, 10 CH₂C0₂) - 12H at 1.45 ppm (S.e., (CHg^C and ChJ(CH2)₃CH₂NH). ~

NMR n· 45 - (b):

1H at 8.75 ppm (D, J=9 Hz, CONH) - 1H at 8.60 ppm (S.e., NH₂) - 1H at 8.40 ppm (S.e., NH₂) - 3H at 7.30 ppm 15 (sTe., NH^) - 1H at 6.78 ppm (S, H thiazol) - 1H at 5.91 ppm (D of D, J_χ=9 Hz, J₂=4 Hz, H₇) - 1H at 5.13 ppm (D, J=13 HZ, CH₂OCO) - 1H at 4.95 ppm (D, J=4 Hz, Hg) - 1H at 4.61 ppm (D, J=13 Hz, CH₂OCO) - 2H at 4.55 ppm (S, CHjjON) - 1H at 3.84 ppm (A of AB, Jab^{=17 Hz}> CH₂SO) - 1H 20 at 3.55 ppm (B of AB, J_AB =17 Hz, CH₂SO) - 2Ü at 3.20 ppm (M, CH^NH) - 2H at 2.90 ppm (M, CH₂NH) - 1H at 2.64 ppm (M, C|iC0₂) - 2H at 1.95 ppm (M, CH₂CH₂NH) - 2H at 1.66 ppm (M, CH₂CH₂NH).

NMR n¹ 46 - (b):

25 1H at 8.75 ppm (D, J=9 Hz, CONH) - 1H at 8.60 ppm (S.e., NH₂) - 1H at 8.40 ppm (S.e., NH₂) - 3H at 7.30 ppm (S.e., [3) - 1H at 6.78 ppm (S, H thiazol) - 1H at 5.94 ppm (D of D, J]_≈9 Hz, J₂≈4 Hz, Hy) - 1H at 5.13 ppm (D, J=13 Hz, CH^OCO) - 1H at 4.95 ppm (D, J≈4 Hz, Hg) - 1H 30 at 4.61 ppm (D, J=13 Hz, CH₂OCO) - 1H at 3.90 ppm (A of AB, J=17 Hz, CHjSO) - 1H at"3.55 ppm (B of AB, J=17 Hz, CHjjSO) - 2H at 3.20 ppm (M, CH₂ NH) - 2H at 2.90 ppm (M, CH₂NH) - 1H at 2.64 ppm (M, Cfl) C0₂) - 4H at 2.40 ppm

O

35 (M, CHg-I C0₂H) - 6H between 1.5 and 2 ppm

CHj

^^CH2

(CH₂ /Kr CH₂-CH₂NH) .

^x ch₂ co₂h

5 NMR n· 47 - (to :

1H at 8.79 ppm (D, J=9 Hz, CONH) - 3H at 8.30 ppm (S.e., NH^) - 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., NH₃) - 1H at 6.84 ppm (S, H thiazol) - 1H at 5.92 ppm (D 10 of D, Ji=9 Hz, J₂=4 Hz, H7) - 1H at 5.40 ppm (D, J=13 Hz, CIPgOCO) - 1H at 4.95 ppm (D, J=4 Hz, H₅) - 1H at 4.84 ppm (D, J=13 Hz, CHgOCO) - 2H at 4.56 ppm (S, CHjON) - 1H at 4.08 ppm (M, CH₂NH₂) - 1H at 4.00 ppm (A of AB, Jab≈^{17 Hz}' CH^SO) - 1H at 3.71 ppm (B of AB,^{15 J}AB=¹⁷ Hz, CH₂S0).

NMR n° 48 - (b):

1H at 8.75 ppm (D, J=9 Hz, CONH) - 3H at 8.30 ppm (S.e., Î1H3) - 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., 20 NH₃) - 1H at 6.78 ppm (S, H thiazol) - 1H at 5.95 ppm (D of" D, J_λ≈9 Hz, J₂=4 Hz, Hj) - 1H at 4.44 ppm (D, J=13 Hz, CH₂0C0) - 1H at 4.98 ppm (D, J=4 Hz, Hg) - 1H at 4.81 ppm (D, J=>13 Hz) - CHgOCO) - 1H at 4.10 ppm (S.e., CHgNH^ - 1H at 4.05 ppm (A of AB, Jab≈^{17 Hz}' CH^SO)25 1H at 3.71 ppm (B of AB, Jab≈^{17 Hz}' CHaSO) - 4H

0

1

2.40 ppm (M, CH₂- c C0₂H) - 2H at 1.85 ppm

CH2

CH₂ O

30 (M, CK£ )•

ⁿch₂ co₂h

NMR n· 49 - (bΐ:

1H at 8.75 ppm (D, J=9 Hz, CONH) - 3H at 7.70 ppm (S.e., NH₃) - 3H at 7.30 ppm (S.e., NH₃) - 1H at 6.82 ppm (S, H 35 thiazol) - 1H at 5.90 ppm (D of D, Jχ=9 Hz, J₂=4 Hz, H7)

- 1H at 5.10 ppm (D, J=13 Hz, CH₂OCO) - 1H at 4.95 ppm (D, J=4 Hz, Hg) - 1H at 4.56 ppm (D, J=13 Hz, CH₂OCO)2H at 4.53 ppm (S, CH₂0N) - 1H at 3.84 ppm (A of AB,

44

5 NMR n· 50 - fbΐ:

10 (D, J==4 Hz, Hg) - 1H at 4.63 ppm (D, J=13 Hz, CH₂OCO)15 CH2

20 1H at 8.75 ppm (D, J=9 Hz, CONH) - 3H at 7.60 ppm (S.e., 25 CH2OCO) - 2H at 4.57 ppm (S, CH^ON) - 1H at 3.81 ppm (A 30 1H at 8.75 ppm (D, J=9 Hz, CONH) - 3H at 7.70 ppm (S.e., J_ab=17 Hz, CH₂SO) - 1H at 3.55 ppm (B of AB, J_AB=17 Hz, CH^SO) - 2H at 2.76 ppm (M, CH₂NH₂) - 2H at 2.40 ppm (M, CH^CC^) - 2H at 1.72 ppm (M, CH₂CH₂CH₂NH₂).

NMR n· 50 - fbΐ:

1H at 8.75 ppm (D, J=9 Hz, CONH) - 3H at 7.75 ppm (S.e., NH3) - 3H at 7.25 ppm (S.e., NH₃) - 1H at 6.77 ppm (S, H thiazσl) - 1H at 5.94 ppm (D of D, Jj=9 Hz, J₂=4 Hz, H7)

- 1H at 5.11 ppm (D, J=13 Hz, CH^OCO) - 1H at 4.95 ppm (D, J==4 Hz, Hg) - 1H at 4.63 ppm (D, J=13 Hz, CH₂OCO)1H at 3.89 ppm (A of AB, J=17 Hz, CH₂SO) - 1H at 3.55 ppm (B of AB, J≈17 Hz, CH^SO) - 2H atH.78 ppm (M,

O

CH₂NH₂) - 6H at 2.40 ppm (M, CH₂ -4 C0₂H, CH2C0₂) - 4H 4H

at 1.85 ppm (M, CH₂CH₂NH₂, CH₂ ).

CH2

ch₂

ch₂ COoH

COoH

).

NMR n" 51 - (bÏ:

1H at 8.75 ppm (D, J=9 Hz, CONH) - 3H at 7.60 ppm (S.e., NH3) -− 3H at 7.30 ppm (S.e., NKh|) - 1H at 6.82 ppm (S, H thiazol) - 1H at 5.87 ppm (D of D, J_x=9 Hz, J₂=4 Hz, Hj) - 1H at 5.61 ppm (D, J=13 Hz, CHgOCO) - 1H at 4.92 ppm (D, J=4 Hz, H^) - 1H at 4.58 ppm (D, J=13 Hz, CH2OCO) - 2H at 4.57 ppm (S, CH^ON) - 1H at 3.81 ppm (A of AB, J≈13 Hz, CH₂S0) - 1H at 3.55 ppm (B of AB, J=13 Hz, CHgSO) - 2H at 2.75 ppm (M, CH^NH;j) - 2H at 2.31 ppm (M, CH2CO2) - 4H at 1.50 ppm (M, CH^(CH₂)2^CH₂N)·

1H at 8.75 ppm (D, J=9 Hz, CONH) - 3H at 7.70 ppm (S.e., NH3) - 3H at 7.30 ppm (S.e., NH3) - 1H at 6.78 ppm (S, H thiazol) - 1H at 5.92 ppm (D of D, J_x=9 Hz, J₂=4 Hz, H7)

- 1H at 5.13 ppm (D, J=13 Hz, CH^OCO) - 1H at 4.95 ppm (D, J=4 Hz, Hg) - 1H at 4.58 ppm (D, J=13 Hz, CH₂OCO) 1H at 3.86 ppm (A of AB, J≈17 Hz, CH^SO) - 1H at 3.55 ppm (B of AB, J=17 HZ, CH₂SO) - 2H at 2.74 ppm (M,

35 1H at 3.86 ppm (A of AB, J≈17 Hz, CH^SO) - 1H at 3.55 5 10 15 20 25 30 35 CH₂NH₂) - 6H at 2.40 ppm (M, CH₂ C0₂ + CH₂-j C0₂H) “ CH2

/ ch₂ o

2H at 1.85 ppm (M, CH_{2 /}>^ ) - 4H at 1.50 ppm (M, CH₂ co₂h

ch₂ch₂ch₂co₂).

NMR n° 53 - fbΐ:

1H at 8.80 ppm (D, J=9 Hz, CONH) - 3H at 8.40 ppm (S.e., NH₃) - 3H at 7.40 ppm (S.e., NH₃) - 1H at 6.78 ppm (S, H thiazol) - 1H at 5.95 ppm (D ofD, J_x=9 Hz, J₂=4 Hz, H₇)

- 1H at 5.25 ppm (D, J=13 Hz, CHgOCO) - 1H at 4.95 ppm (D, J=4 Hz, Hg) - 1H at 4.78 ppm (D, J=13 Hz, CH₂OCO) ~ 1H at 4.08 ppm (M, CHNH₂) - 1H at 3.95 ppm (A "of AB, J=17 HZ, CH₂SO) - 1H at 3.60 ppm (B of AB, J=17 Hz,

O

CH₂SO) - 4H at 2.40 ppm (M, CH_a -j C0₂H) - 2H at 1.80 ' CH₂

ch₂ o

ppm (M, CHg ) - 3H at 1.36 ppm (D, J≈7 Hz,ⁿch₂ co₂h

CH₃CH).

NMR Π * ■■ ■5 4 - (M:

1H at 8.75 ppm (D, J=9 Hz, CONH) - 3H at 7.87 ppm (S.e., NHg) - 3H at 7.30 ppm (S.e., NH₃) - 1H at 6.78 ppm (S, H thiazol) - 1H at 5.95 ppm (D of D, Hz, J₂≈4 Hz, Hy)

- 1H at 5.19 ppm (2D, J=>13 Hz, CH^OCO) * - 1H at 4.95 ppm (D, J=>4 Hz, H₆) - 1H at 4.64 ppm (2D, J=13 Hz, CHgOCO) *

- 1H at 3.92 ppm (A of AB, J=17 Hz, CH₂SO) - 1H at 3.55 ppm (B of AB, J≈17 Hz, CH₂SO) - 1H at 3.0 ppm (M, CHC0₂)

- 2H at 2.80 ppm (M, CH₂NH₂) - 4H at 2.40 ppm (M,

0 0

^CIÎ2-|^C02^h) "^{2H at 1}·⁸⁰ PP^m (M, CH₂

cn_2

) C0₂H

3H at 1.08 ppm (D, J=7 Hz, CH^CH).

NMR n° 55 - (bï:

1H at 8.75 ppm (D, J=9 Hz, CONH) - 3H at 7.80 ppm (S.e., NHjj) - 3H at 7.30 ppm (S.e., NH^) - 1H at 6.80 ppm (S, H 5 thiazol) - 1H at 5.95 ppm (M, H7) - 1H at 5.20 ppm (D, J=13 Hz, CHpOCO) - 1H at 4.95 ppm (S.e., H₆) - 1H at 4.63 pprn (D, J=13 Hz, CH₂OCO) - 1H at 3.90 ppm (A of AB, J=17 Hz, CH^SO) - 1H at 3.58 ppm (B of AB, J=17 Hz, CH₂SO) 2H at 2.93 ppm (M, CH₂NH₂) - 4H at 2.40 ppm (M, 10 0 O

CH₂ j C0₂H) - 2H at 1.90 ppm (M, CH₂ 1 C0₂H) CH_₂ CHj - CH₂

-6H at 1.14 ppm (S, (CH₃)₂C).

NMR n° 56 - (bl:

15 1H at 8.75 ppm (D, J=9 HZ, CONH) - 3H at 7.75 ppm (S.e., NH3) - 3H at 7.35 ppm (S.e., NH₃) - 1H at 6.80 ppm (S, H thiazol) - 1H at 5.95 ppm (D of D, J_x=9 Hz, J₂=4 Hz, H₇)

- 1H at 5.15 ppm (2D, J=13 Hz, CH^OCO)* - 1H at 4.95 ppm (D, J=4 Hz, H₆) - 1H at 4.60 ppm (2D, J=13 Hz, CH₂OCO) * 20 - 1H at 3.90 ppm (A of AB, J=17 Hz, CH₂S0) - 1H at 3.56 ppm (B of AB, J=17 Hz, CH₂SO) - 2H at 2.74 ppm (M, CH^NH;j) - 1H at 2.50 (M, CHC0₂) - 4H at 2.40 ppm (M,

O O

CH₂-I C0₂H) - 3H at 1.90 ppm (M, CH₂ I-C0₂H and 25 CH2 CH-₂ · CH₂ CH3CH2NH2) - 1H at 1.55 ppm (M, CH₂CH₂NH₂) - 3H at 1.08 ppm (D, J=>7 Hz, CH3CH) .

m-n:.-S.7,_r- (hi.:

1H at 8.80 ppm (D, H≈9 Hz, CONH) - 3H at 8.40 ppm (S.e., 30 NH3) - 3H at 7.40 ppm (sie., NH^) - 1H at 6.79 ppm (S H thiazol) - 1H at 5.95 ppm (D of D, Hz, J₂=4 Hz, Hj)

- 1H at 5.28 ppm (D, J=13 Hz, CHgOCO) - 1H at 4.95 ppm (D, J=4 Hz, Hg) - 1H at 4.75 ppm (D, J=13 Hz, CH₂OCO)1H at 3.95 ppm (A of AB, J=17 Hz, CH^SO) - 1H at 3.61 35 ppm (B of AB, J=17 Hz, CHgSO) - 4H at 2.40 ppm (M, Ch₂-| C0₂H) - 2H at 2.10 ppm (M, CH2 cyclopentane)~ GH2

O

2H at 1.90 (M, CH₂ |\ ) - 6H at 1.80 ppm (M, CHg

ch₂ ch₂ ~

cyclopentane).

NMR n° 58 - fb\ :

1H at 8.75 ppm (D, J=9 Hz, CONH) - 3H at 2.70 ppm (S.e., ÜHj) - 3H at 7.30 ppm (S.e., NH₃) - 1H at 6.84 ppm (S, H thiazol) - 1H at 5.89 ppm (D of D, J_χ=9 Hz, J₂=4 Hz, H₇)

- 1H at 5.13 ppm (D, J=13 Hz, CH^OCO) - 1H at 4.95 ppm (D, J=4 Hz, Hg) - 3H at 4.55 ppm (M, CH₂ON and CH₂0C0)

- 1H at 3.82 ppm (A of AB, J=17 Hz, CH₂SO) - 1H at 3.55 ppm (B of AB, J=17 Hz, CH₂SO) - 2H at 2.60 ppm (M, CH₂NH₂) - 1H at 2.21 ppm (M, CH C0₂) - 4H at 1.80 ppm, (M, CH₂ cyclohexane) - 1H at 1.45 ppm (M, CHCH₂NH₂) - 2H at 1.25 ppm (M, CH₂ cyclohexane) - 2H at 0.90 ppm (M, CH₂ cyclohexane).

NMR n° 59 - (bΐ;

1H at 8.67 ppm (D, J≈9 Hz, CONH) - 3H at 7.70 ppm (S.e., ΐfHg) - 3H at 7.30 ppm (S.e., NH3) - 1H at 6.82 ppm (S, H thiazol) - 1H at 5.94 ppm (D of D, J_x=9 Hz, J₂≈4 Hz, Hy)

- 1H at 5.13 ppm (D, J=13 Hz, CHgOCO) - 1H at 4.95 ppm (D, J=4 Hz, H₆) - 1H at 4.56 ppm (D, J=13 Hz, CH₂OCO)1H at 3.87 ppm (A Of AB, J≈17 Hz, CH₂SO) - 2H at 3.55 ppm (B of AB, J≈17 Hz, CHjjSO) - 2H at 2.60 ppm (M, CH₂NH₂) - 5H between 2.0 and 2.5 ppm, 6H between 1.6 and 2.0 ppm, 3H at 1.1 and 1.6 ppm, 2H at 0.90 ppm (M,

yf^CH_2,

^CEj \

CH₂

X

co₂h

and

u CH,CH,

- \ rH²a

oc

0

XX"-

CH₂CH₂

NMR n^a 60 -fb>:

CONH)* - 3H at 7.70 ppm

1H at 6.82 ppm (2S, H thiazol)* - 1H at 5.95 ppm (D of D, J_λ=9 Hz, J₂=4 1H at 8.60 ppm (2D, J=9 Hz,

(S.e, NH3) - 3H at 7.30 ppm (S.e., NH3)

5 10 15 20 25 30 35 Hz, H7) - 1H at 5.13 ppm (D, J=13 Hz, CH₂OCO) - 1H at 4.95 ppm (2D, Hg)* - 2H at 4.60 ppm (M, CH₂OCO + CHON)1H at 3.86 ppm (2D, J=17 Hz, CH^SO)* - 1H at 3.56 ppm (2D, J=17 Hz, CHgSO)* ■- 2H at 2.75 ppm (M, CH₂NH₂) - 2H at 2.40 ppm (T, J=7 Hz, CH₂C0₂) - 2H at 1.75 ppm (M, CH₂CH₂CH₂NH₂) - 3H at 1.39 ppm (D, J==7 Hz, CH3CH) .

NMR n· 61 - fbï: ~

1H at 8.70 ppm (2D, J=9 Hz, CONH)* - 3H at 7.70 ppm (S.e., NH₃) - 3H at 7.30 ppm (S.e., NH₃) - 1H at 6.82 ppm (2S, H thiazol)* - 1H at 5.95 ppm (D of D, Ji=9 Hz, J₂≈4 Hz, H7) - 1H at 5.12 ppm (D, J=13 Hz, CH^OCO) - 1H at 4.94 ppm (2D, Hg)* - 2H at 4.60 ppm (M, HCON, and CH2OCO) - 1H at 3.86 ppm (A of AB, J=17 Hz, CÎ^SO) - 1H at 3.55 ppm (B of AB, J=17 Hz, CH₂SO) - 2H at 2.75 ppm (M, CH₂NH₂) - 2H at 2.31 ppm (M,~CH₂C0₂) - 4H at 1.50 ppm (M, CH₂CH₂CH₂CH₂NH₂) - 3H at 1.45 ppm (D, J=7 Hz, CH^CH).

NMR n" 62 - (bï:

2H at 8.60 ppm (M, CONH, NH₃) - 1H at 8.40 ppm (S.e., NHj*) - 3H at 7.30 ppm (S.e., NH₃) - 1H at 6.82 ppm (2S, H thiazol)* - 1H at 5.95 ppm (D of D, J_x≈9 Hz, J₂=4 Hz, H₇) - 1H at 5.14 ppm (D, J≈13 Hz, CHgOCO) - 1H at 4.95 ppm (2D, Hg)* - 2H at 4.60 ppm (M, CH-ON, and CH₂OCO)1H at 3.88~ ppm (2D, J=17 Hz, CH₂SO) - 1H at 3/55 ppm (D, J=17 Hz, CHgSO) - 2H at 3.20 ppm and 2H at 2.95 ppm (M, CH₂NH ) - 1H at 2.66 ppm (M, CHC0₂) - 2H at 1.95 ppm CH2_

and 2H at 1.70 ppm

CHg

(M, 0₂C

\hj.

3H at 1.45 ppm (D,

J≈7 Hz, CH^CH).

NMR n° 63 - :

1H at 8.70 ppm (2D, J=9 Hz, CONH)* - 3H at 8.20 ppm (S.e., NIPj) - 2H at 7.95 ppm (D, J= Hz, H ortho C0₂)2H at 7.55 ppm (D, J=8 Hz, H meta C0₂) - 3H at 7.30 ppm (S.e., NH₃) - 1H at 6.82 ppm (2S, H thiazol)* - 1H at 5.95 ppm °f 0, J_χ=9 Hz, J₂=4 Hz, H₇) - 1H at 5.44 ppm (D, J=13 Hz, CH₂OCO) - 1H at 4.96 ppm (2D, Hg)*1H at 4.84 ppm (D, jΞi3 Hz, CH₂OCO) - 1H at 4.60 ppiiT(Q, J≈7 Hz, CHON) - 2H at 4.10 ppm (M, CH2NH2) - 1H at 3.90 5 ppm (D, J=17 Hz, CH^SO) - 1H at 3.70 ppm (D, J=17 Hz, CH^SO) - 3H at 1.45 ppm (D, J=7 Hz, CH₃CH).

NMR n° 64 - fb):

1H at 8.60 ppm (2D, J=9 Hz, CONH)* - 3H at 7.70 ppm (S.e·, NH₃) - 1H at 6.80 ppm (2S, H thiazol)* -■ 1H at 10 5.95 ppm (D of D, J₃=9 Hz, J₂=4 Hz, H₇) - 5H between 4 and 6 ppm (S.e., NH₃ C0₂H) - 1H at 5.13 ppm (D, J=13 Hz, CH^OCO) - 1H at 4.95 ppm (2D, Hg) * - 2H at 4.60 ppm (M, CHgOCO and CHON) - 1H at 3.86 ppm (A of AB, J=17 Hz, CHgSO) - 1H at 3.55 ppm (B Of AB, J=17 Hz, CH₂SO) - 2H

15 at 2.61 ppm (M, CH₂NH₂) - 1H at 2.21 ppm (M, CHC0₂) - 4H ,^C^Z «Ig

at 1.80 ppm (M,\ ) ) - 3H at 1.45 ppm (D, J=7 C«2 <*2

Hz, CH₃CH) - 2H at 1.25 ppm and 2H at 0.90 ppm

NMR n° 67 - (bl;

3H at 8.50 ppm (M, N%₂ and CO NH) - 2H at 7.50 ppm 10 (Se., NH₂ thiazol) - 1H at 6.79 ppm (S, H thiazol) - 1H at 5.99 ppm (D of D, J₃ ≈ 9 Hz, J₂ = 4 Hz, H₇) - 1H at 5.16ppm (2D, J = 13 Hz, CH₂ O CO) - 1H at 4.95 ppm (D, J = 4 Hz Hg) - 1H at 4.66 ppm (D, J = 13 Hz, O CO) - 1H at 3.92 ppm (D, J = 17 Hz, CH₂ SO) - 1H at 3.58 ppm (D, 15 J = 17 Hz, CH₂ so) - 1H at 3.36 ppm (M, Cî^T H₂) - 1H at 3.25 ppm (M, CH₂ Ï®H₂) - 1H at 2.95 ppm (M, CH₂cX 1$H₂)

- 2H at 2.60 ppm (2D superposed CH₂ C0₂) - 3H at 1.70 ppm (M, H piperidine) - 6H at 1.48 ppm (2S (CH₃)₂ C) 3H at 1.45 ppm (M, H piperidine).

20 NMR n° 68 - fbl:

1H at 8.60 ppm (Se., N®k₂ piperidine) - 1H at 8.45 ppm (Se., NH^jp piperidine) - 1H at 8.45 ppm (D, J = 9 Hz, CO NH) - 1H at 7.50 ppm (Se., NH₂ thiazol) - 1H at 6.70 ppm (S, H thiazol) - 1H at 5.97 ppm (D of D, J_x = 9 Hz, J₂ = 25 4 Hz, H₇) - 1H at 5.10 ppm (D, J ≈ 13 Hz, CH₂ O CO) - 1H at 4.97 ppm (D, J =■ 4 Hz, Hg) - 1H at 4.63~ppm (D, J = 13 HZ, CH₂ o CO) - 1H at 3.90 ppm (D, J = 17 Hz, CH₂ SO)

- 1H at 3T57 ppm (D, J ≈ 17 Hz, CHg SO) - 2H at 3.20 ppm (M, CHj (X *®H₂) "^{2H at 2}·⁷⁰ PP^m (M, CH₂o4 N®^2) "^{2H at} 30 2.30 ppm (D, J ≈ 7 Hz, CH₂ C0₂) - 1H at 2.05 ppm (M, CH CH₂ C0₂) - 3H at 1.55 ppm (M, CH₂ piperidine) - 6H at lT48 ppm (2 S, (CH₃)₂ C) - 1H at 1.20 ppm (M, CH₂ piperidine).

NMR n' 69 - (bl;

35 1H at 10.9 ppm (Se., Ar NH CO) - 1H at 8.45 ppm (D, J = 9 Hz, CO NH) - 4H at 8.15 ppm (2 S, CH₂ΐβn₃ and H Ar 2') - IE at 7.81 ppm (D, J = 7 Hz, H Ar 6') - 1H at 7.67 ppm (D, J ≈ 7 Hz, H Ar 4') - 1H at 7.50 ppm (T, J = 7 Hz, H Ar 5') - 2H at 7.20 ppm (Se., NH₂ thiazol) - 1H at 6.78 ppm (S, H thiazol) ~ 1H at 6.00 ppm (D of D, J₃ = 9 Hz, J₂ = 4 Hz, H7) - 1H at 5.45 ppm (D, J = 13 Hz, 5 CH₂ O CO) - 1H at 5.00 ppm (D, J = 4 Hz, H₆) - 1H at 4.84 ppm (D, J = 13 Hz, CH₂ O CO) - 1H at 4. <K> ppm (D, J = 17 Hz, CHg SO) - 1H at~3.75 ppm (M, - C - CH₂ *$h₃ O

and CH₂ SO) - 6H at 1.47 ppm (2 S, (CH₃)₂ C).

10 NMR n¹ 70 - ;

1H at 8.70 ppm (D, J = 9 Hz, CO NH) - 3H at 8.50 ppm (Se., CH₂~Î^H₃) - 1H at 8.05 ppm (S, H Ar 2') - 1H at 7.80 ppm (D, J = 7 Hz, H Ar 6') - 1H at 7.34 ppm (D, J = 7 Hz H Ar 5') - 1H at 6.95 ppm (S, H thiazol) - 1H at 15 6.00 ppm (D of D, J_χ = 9 Hz, J₂ = 4 Hz, H₇) - 1H at 5.45 ppm (D, J = 13 Hz, CHg O CO) - 1H at 5.05 ppm (D, J = 4 Hz, Hg) - 1H at 4.82 ppm (D, J = 13 Hz, CH₂ O CO) - 3H at 4.05 ppm (M, Ar CH₂ *Φΐ₃ and CH₂ SO) - 1H at 3.80 ppm (D, J ≈ 17 HZ, CH₂ SO) - 3H at 2.37 ppm (S, CH₃ Ar) - 6H 20 at 1.48 ppm (2S, (CH₃)₂ C).

NMR n* 71 - (bΐ;

1H at 8.70 ppm (D, J ≈ 9 Hz, CO NH) - 9H at 8.50 ppm (Sθ·, CH₂ ï$H₃) - 2H at 7.78 ppm (M, B Ar 2', 6') - 1H at 7.50 ppm (D, J ≈ 7 Hz, H Ar 5') - 1H at 6.92 ppm (S, 25 H thiazol) - 1H at 6.00 ppm (D of D, J_x ≈ 9 Hz, J₂ = 4 Hz, H7) - 1H of 5.45 ppm (D, J ≈ 13 HZ, CH₂ O CO) - 1H of 5.00 ppm (D, J = 4 Hz, Hg) - 1H at 4.81 ppm (D, J =13 Hz, CH₂ 0 CO) - 3H at 4.05 ppm (M, Ar CH₂ Ï$H₃ CHg SO)1H at 3.75 ppm (D, J ≈ 17 Hz, CHg SO) ~ 3H at 2.36 ppm 30 (S, CHg Ar) - 6H at 1.47 ppm (2 S, (CH₃)₂ C).

NMR n° 72 - ; ~

1H at 8.70 ppm (D, J = 9 Hz, CO NH) - 2H at 7.95 ppm (D, J ≈ 8 Hz, H Ar 2', 6') - 2H at 7.67 ppm (D, J = 8 Hz, H Ar 3', 5') - 1H at 6.95 ppm (S, H thiazol) - 1H at 6.00 35 ppm (D of D, J_x = 9 Hz, J₂ = 4 Hz, H₇) - 1H at 5.45 ppm (D, J = 13 Hz, CHg 0 CO) - 1H at 5.00 ppm (D, J = 4 Hz, H₆) - 1H at 4.82 ppm (D, J = 13 Hz, CH₂ O CO) - 2H at 4.16ppm (M, Ar CH₂ NHCH₃) - 1H at 4.08 ppm (D, J = 17 Hz, CH₂ SO) - 1H at 3.78 ppm (D, J = 17 Hz, CH₂ SO) 3H at 2.43 ppm (S, CH₃ N) - 6H at 1.48 ppm (2 S, (CH₃)₂ C) .

5 NMR n° 73 - fb):

1H at 8.70 ppm (D, J = 9 Hz, CO NH) - 2H at 7.95 ppm (D, J = 8 Hz, H Ar 2', 6') - 2H at 7.67 ppm (D, J = 8 Hz, H Ar 3', 5') - 1H at 6.92 ppm (S, H thiazol) - 1H at 6.00 ppm (D of D, J·L = 9 Hz, J₂ = 4 Hz, H₇) - 1H at 5.43 ppm 10 (D, J = 13 HZ, CH₂ O CO) - 1H at 5.00 ppm (D, J = 4 Hz, H₆) - 1H at 4.82 ppm (D, J = 13 Hz, CH₂ O CO) - 2H at 4.18 ppm (M, CH^ Ar) - 1H at 4.10 ppm (d7 J = 17 Hz, CHg SO) - 1H at 3.76 ppm (D, J = 17 Hz, CH₂ SO) - 2H at 2.90 ppm (M, CH₃ CH^ NH) - 6H at 1.47 ppm (2 S, (CH₃)₂ C)15 3H at 1.16 ppm (T, J = 7 Hz, CH₃ CH₂). ~

NMR n* 74 - fbΐ:

1H at 8.70 ppm (D, J = 9 Hz, CO NH) - 2H at 7.95 ppm (D, J = 8 Hz, H Ar 2', 6') - 2H at 7.67 ppm (D, J = 8 Hz, H Ar 3', 5') - 1H at 6.95 ppm (S, H thiazol) - 1H at 6.00 20 ppm (D of D, = 9 Hz, J₂ = 4 Hz, H₇) - 1H at 5.45 ppm (D, J = 13 Hz, CHg O CO) - 1H at 5.00 ppm (D, J = 4 Hz, Hg) - 1H at 4.82 ppm (D, J ≈ 14 Hz, CH₂ O CO) - 2H at 4.16ppm (M, Ar CH₂ N Pr) - 1H at 4.08~ ppm (D, J = 17 Hz, CH₂ SO) - 1H at” 3.78 ppm (D, J ≈ 17 Hz, CH₂ SO) 25 1H at 3.20 ppm (M, NH-CJJ (CH₃)₂) - 6H at 1.41 ppm (2S, (CH₃)₂ C) - 6H at 1.26 ppm (57 J = 7 Hz, (CH₃)₂ CH).

NMR~n° 75 r (b) :

1H at 8.62 ppm (D, J ≈ 9 Hz, CO NH) - 3H at 8.10 ppm (Sa., CH₂ t®K₃) - 1H at 7.68 ppm (D, J = 7 Hz, H Ar 6') 30 - 1H at 7.55 ppm (D, J ≈ 7 Hz, H Ar 4') - 1H at 7.34 ppm (T, J ≈ 7 Hz, H Ar 5^#) - 1H at 6.92 ppm (S, H thiazol)1H at 6.00 ppm (D of D, ≈ 9 Hz, J₂ = 4 Hz, H₇) - 1H at 5.37 ppm (D, J ≈ 13 Hz, CH₂ 0 CO) - 1H at 5.00 ppm (D, J = 4 Hz, H₆) - 1H at 4.84 ppm (D, J = 13 Hz, CH₂ O 35 CO) - 3H at 4.10 ppm (M, CH₂ *Aï₃ et CH₂ SO) - 1H at 3.75 ppm (D, J = 17 Hz, CH₂ SO) - 3H at 2.40 ppm (S, CH₃ Ar) - 6H at 1.47 ppm (2S, TcH₃)₂ C).

NMR n° 76 - (b3:

1H at 8.62 ppm (D, J = 9 Hz, CO NH) - 3H at 8.00 ppm (Se., CH₂ - 1H at 7.31 ppm (D, J ≈ 7 Hz, H Ar 4') 5 - 1H at 7.14 ppm (D, J ≈ 7 Hz, H Ar 5') - 1H at 6.90 ppm (S, H thiazol) - 1H at 6.00 ppm (D of D, = 9 Hz, J₂ = 4 Hz, Hy) - 1H at 5.27 ppm (D, J = 13 Hz, CH₂ O CO) - 1H at 5.00 ppm (D, J = 4 Hz, H₆) - 1H at 4.92 ppm (D, J = 13 Hz, CH₂ O CO) ~ 3H at 4.00 ppm (M, CH₂ lfàï₃ et CH₂ 10 SO) - 1H at 3.64 ppm (D, J = 17 Hz, CH₂ SO) - 6H at 2.18 ppm (S, CH₃ - Ar) - 6H at 1.48 ppm (2 S, (CH₃)₂ C).

NMR n° 77 (b3:

1H at 8.65 ppm (D, J = 9 Hz, CO NH) - 3H at 7.90 ppm (Se. , CH₂ îAî^) - 1H at 7.00 ppm (S, H Ar) - 1H at 6.90 15 ppm (S, H thiazol) - 1H at 6.00 ppm (D of D, = 9 Hz, J₂ = 4 Hz, H₇) - 1H at 5.25 ppm (D, J = 13 Hz, CH₂ O CO)

- 1H at 5.00 ppm (D, J - 4 Hz, Hg) - 1H at 4.92 ppm (D, J = 13 Hz, CH₂ O CO) - 3H at 4.00 ppm (M, Ar CH₂ *Φh₃ and CH₂ SO) - 1H at 3.65 ppm (D, J = 17 Hz, CH₂ SO) - 3H 20 at 2.31 ppm (S, CH₃ Ar) - 3H at 2.25 ppm (sT CH₃ Ar)3H at 2.14 ppm (S, CH₃ Ar) 6H at 1.45 ppm (2S, (CH₃)₂ C) . “

7.8_,._r_(.b,).:

1H at 8.70 ppm (D, J =< 9 Hz, CO NH) - 3H at 8.00 ppm 25 (Se., CH₂ N⁺H₃) - 1H at 7.45 ppm (D, J ≈ 7 Hz, H Ar 4')

- 2H at 6.92 ppm (M, H thiazol and g Ar 5') - 1H at 6.00 ppm (D of D, Ji ≈ 9 Hz, J₂ = 4 Hz, H₇) - 1H at 5.42 ppm (D, J ≈ 13 Hz, CH^ 0 CO) - 1H at 5.00 ppm (D, J = 4 Hz, Hg) - 1H at 4.84 ppm (D, J = 13 Hz, CH₂ O CO) - 3H at 30 3.95 ppm (M, CH₂ΐβa₃ and CH₂ SO) - 3H at 3.78 ppm (S, O CH₃) - 3H at 3.73 ppm (S, 0~CH₃) - 1H at 3.58 ppm (D, J ≈ 17 Hz, CH₂ SO) - 6H at 1.47 ppm (2 S, (CH₃)₂ C).

NMK n° 79 - (b) :

1H at8.62 ppm (D, J = 9 Hz, CO NH) - 5H at8,00 ppm (M, CH^ i^r^and H Ar 2', 6')1H at 7.20 ppm (D, J = 7 Hz, H Ar 5¹) - 1H at6.95 ppm (S, H thiazol ) -

1H at 6,00 ppm (D of D, Jj = 9 Hz, J₂ = 4 Hz, H_?) - l·H at 5.45 ppm (0, J = 13 Hz 5 CH₂ 0 CO) - 1H at 5 00 ppm (D, J = 4 Hz, H_g) - lHat4.82 ppm (D, J =» 13 Hz,

CH₂ 0 CO) - 3H at 4.00 ppm (M, CH₂ N^and CH₂ SO) - 3H at 3 .88 ppm (S, 0 CH₃) 1H at3.72 ppm (D, J = 17 Hz, CH₂ SO) - 3Hat 1.48 ppm (S, (CH₃)₂ C) -

3H at 1.47 ppm (S, (CH^)₂ C)

NMR n° 80 - (B) :

10 1H at 8.66 ppm (D, J = 9 Hz, CO NH) - 3H ats.05 ppm (Se., CH₂ N®H₃) -

3H at 7,50 ppm (M, ji Ar) - 1H at 6.95 ppm (S, H thiazol) - 1H at 6,00 ppm

(D of D = 9 Hz, J₂ = 4 Hz, H_?) - 1H at5.45 ppm (D, J = 13 Hz, CH₂ 0 CO) 1H atδ.OO ppm (D, J = 4 Hz, H_g) - lHat 4.84 ppm (D, J ≈ 13 Hz, CH₂ 0 CO) 3H at4.00 ppm (M, CH₂ et CH₂ SO) - 3H at3,86 ppm (S, CH₃0 - Ar) ~

IS 1H at3.75 ppm (D, J = 17 Hz, Cli, SO) - 3H at 1,48 ppm (S, (CH₃)₂ C) -

3H at 1.47 ppm (S, (CH₃)₂ C)

20

25

NMR n° 81 - (b) :

1H at 8.82 ppm (D, J ≈ 9 Hz, CO NH) - 3H at 8.20 ppm (Se., CH_℮ N^₃) -

1H at 8.13 ppm (Se., H Ar 2') - 1H at7.95 ppm (D, 0 = 7 Hz, H Ar 6') -

1H at7.69 ppm (D, J = 7 Hz, H Ar 4') - 1H at 7.55 ppm. (T, J = 7 Hz, H Ar 5') 1H at 6.95 ppm (S, H_ thiazol) - 1H à 6.00 ppm (D of D, ≈ 9 Hz, J₂ = 4 Hz, H_y) - 1H at 5.48 ppm (D, J = 13 Hz, CH₂ 0 CO) - 1H at 5.00 ppm (D, J = 4 Hz, H_g) 1H at 4.86 ppm (D, J = 13 Hz, CH_℮ 0 CO) - 3Hat4.05 ppm (M, CH₂ N®H₃ and

CH₂ SO) - 1H at 3.75 ppm (D, 0 ≈ 17 Hz, CH₂ SO) - 4H at 2.40 ppm

• CH,

(M, CH_;

■ 0)

^cΐn

2H at 1.90 ppm (M, t-j 0)

CO

10

15

20

1H at 8.82 ppm (D, J = 9 Hz, CO NJJ) - 3Hat8.20 ppm (Se., CH₂ ^₃) -

2H at 7.80 ppm (M, H Ar 2' , 6') - lHat 7.45_ppm (D, J ≈ 7 Hz, H Ar 5') -

1H at 6.92 ppm (S, H thiazol) - 1H à 5.97 ppm (D of D, J₁ = 9 Hz, J₂ = 4 Hz, H_?) - 1H at 5.45 ppm (0, J ≈ 13 Hz, CH₂ 0 CO) - 1H at 5.00 ppm (D, J = 4 Hz, H_g) 1H at 4 .82 ppm (D, J = 13 Hz, CH₂ 0 CO) - 3Hat 4.05 ppm (M, CH₂ fF^and CH₂ SO) -

|-^CH2

1H at3.75 ppm (0, J = 17 Hz, CH₂ SO) - 4H at2·40 ppm (M, CH₂-j-- 0) "

“ “CO

ch₂-

3H at2 .34 ppm (S, CH^ Ar) - 2H at 1,90 ppm (M, t 0)

“ CO

NMRΠ° 83 - (b) :

1H at8.97 ppm (D, 0 ≈ 9 Hz, CO NH) - 2Hat 8.79 ppm (Se., CH₂ N^₂) -

2H atδ.OO ppm (D, J = 8 Hz, JJ.Ar 2' , 5') - 2Hat 7.58 ppm (D, J = 8 Hz,

JH Ar 3', 5') - 1H at6 95 ppm (S, JJ thiazol) - lHat 5.97 ppm (D of D,

J₁ = 9 Hz, J₂ = 4 Hz, H₇) - 1H at 5.45 ppm (D, J ≈ 13 Hz, CH₂ 0 CO) -

1H atδ.OO ppm (D, J = 4 Hz, H_g) - lHat 4.84 ppm (0, J = 13 Hz, CH₂ 0 CO) -

2H at 4,19 ppm' (M, CH₂U%₂ - CH₃) - lHat 4.08 ppm (D, J = 17 Hz, CHg SO) lHat 3.75 ppm (0, J ≈ 17 Hz, CH₂ SO) - 3H at 2.50 ppm (M, CH₂ ^₂ - CH3) -

CH,

4H at 2.40 ppm (M, CHg ■

NMRn⁰ 84 (b) :

0) - '2Hat 1.90 ppm (M,

Cl-L-

.0)

CO

CO

25 1H^at 10.7 ppm (S, CO NH Ar) - 1H atδ.60 ppm (D, J = 9 Hz, CO NJJ) -

1H at 8.20 ppm (S, H Ar 2') - 1H at 7.80 ppm (D,J≈8Hz,HAr6')~

3 “

3H at 7.65 ppm (Se., CH₂ N⁺H ) - 1H at7.60 ppm (D, J = 8 Hz, JJ Ar 4¹) -

lHat 7.45 ppm (T, J = 8 Hz, JJ Ar 5¹) - 1H at℮.92 ppm (S, JJ thiazol) -

lHat 6,00 ppm (D of D, = 9 Hz, J₂ = 4 Hz, H_?) - lHat 5.45 ppm (D, J = 13 Hz, 30 CH₂ 0 CO) - lHat 5,00 ppm (D, J = 4 Hz, H_g) - lHat 4.84 ppm (0, J = 13 Hz,

CH₂ 0 CO) - 1H at 4.00 ppm (D, J = 17 Hz, CH₂ SO) - lHat 3.75 ppm (D, J = 17 Hz, CH₂ SO) - 2H at 3.05 ppm (Q, J = 7 Hz, CH₂ CH₂ N^₃) - 2Hat2.70 ppm (T, J = 7 Hz, CH₂ CH₂ f^H₃) - 6H at 1,47 ppm (2 S, (CH₃)₂ C)

S 1H at 4.98 ppm (D, J ≈ 4 Hz, H_g) - 1H at 4.78_ppm (D, J = 13 Hz, CH₂ 0 CO) -

10 3H at 8.07 ppm (Se., CH₂ I'ftg) - 2Hat 7.94 ppm (0, J = 8 Hz, H Ar 2' 6') -

15 and CHg ^H₃) - 6H at 1.48 ppm (2 S, (CH₃)₂ C)

20

25

5H at 1,85 ppm (M, 3H^ of the piperidine εnd

0) -

30

3H at 1.45 nnm (M, 3H piperidine)

5 10 IS 20 25 îJMR ∩° 88 - (b) :

lHat 8,80 ppm (D, J = 9 Hz, CO N_H) - 1H at 8.60 ppm (Se., ΐ^l₂ P “· pé>”i dine) 1H at 8.45 ppm (Se., I^₂ piperidine) - 2Hat7.25 ppm (Se., NH₂ thiazol ) 1H at 6,79 ppm (S, H thiazol) - 1H at 6.00 ppm (Dot D, = 9 Hz, J₂ ≈ 4 Hz, H_y) - 1H at 5.16 ppm (D, J = 13 Hz, CH₂ 0 CO) - lHat 5.00 ppm (D, J = 4 Hz, Hg) - 1H at 4.69 ppm (D, 0 = 13 Hz, CH₂ 0 CO) - lHat 3.90 ppm (D, J = 17 Hz, CH₂ SO) - 1H at3.60 ppm (D, J * 17 Hz, CH₂ SO) - 2Hat 3.24 ppm (M, CH₂ in

of ΐ^2 piperidine) - 2H at2.70 ppm (M, CH₂ in o< of piperidine) -

r~^ch

6Hat 2,40 ppm (M, CH₂-ΐ-- 0 and CH₂ C00) - 6Hbetweenl.5 and 2.2 ppm

” CO ■ ~

CH₂-.

(M, t- 0 , CHI CHg C0₂ , 3H piperidine) - lHat 1.20 ppm (M, H piperidine) CO

NMR n° 89 - (b) :

lHat 8.80 ppm (D, J = 9 Hz, CO NH) - 2H at 8.30 ppm (2 Se., NH®piperidine) 2H at 7,40 ppm (Se., NHg thiazol ) - 1H at6,78 ppm (S, H thiazol ) -

lHat 5.92 ppm (D of 0, Jj = 9 Hz, J₂ = 4 Hz, H_?) - lHat 5.14 ppm (D, J = 13 Hz, CH₂ 0 CO) - lHat 4,96 ppm (D, J = 4 Hz, H_g) - lHat 4.60 ppm (D, J = 13 Hz, CH₂ 0 CO) - lHat 3.89 ppm (D, J = 17 Hz, CHg SO) - lHat 3.58.ppm (D, 0 = 17 Hz, CH₂ SO) - 2H at 3,18 ppm (M, H N®k₂ piperidine) - 2H at 2.81 ppm (M, H «<

CH

N H₂ piperidine) - 4Hat 2.40 ppm (M, CH₂-

0) - 2H at 2.28 ppm (0, J = 7 Hz,

CO

CH.

CH₂ CO - 0) - 5Hat 1.90 ppm (M, ΐl 0, CH CH₂ COO, 2H β piperidine) CO

2H at 1.30 ppm (M, 2H β O_z

piperidine)

1H at8 .45 ppm (D, J = 9 Hz, CO NH) - 1H at 8,50 ppm (Se., NH_? piperidine) -

, © -

lHat8,20 ppm (Se., piperidine) - 2H at 7.30 ppm (Se., NH₂ thiazol ) -

1H atδ.77 ppm (S, H thiazol ) - 1H 5.95 ppm (D of 0, J₁ = 9 Hz, J₂ = 4 Hz,

5 H_?) - 1Hat 5.11 ppm (D, J = 13 Hz, CH₂ 0 CO) - 1H at4.95 ppm (D, J = 4 Hz,

H_g) - 1Hat 4.51 ppm (D, J = 13 Hz, CH₂ 0 CO) - lHat 3.89 ppm (D, J = 17 Hz, CH₂ SO) - 1H at 3.58 ppm (D, J = 17 Hz, CH₂ SO) - 2Hat 3.21 ppm (M, CHgancKX N^₂ piperidine) - 2Hat2.81 ppm (M, CH₂ in lf®H₂ piperidine) - 2Hat 2.27 ppm (D, 0 = 7 Hz, CH₂ COO) - lHat 1.95_ppm (M, CH CH₂ COO) - 2H at 1.75 ppm

10 (M, CH₂β ^₂ piperidine) - 6H at 1.47 ppm (2 S, (CH₃)₂ C) -

2H at 1,40 ppm (M, CH₂β N⁺H₂ piperidine)

NMR n° 91 - (b) :

2H at 8.70 ppm (Se., CHgl^CH-j") - 1H at 8.50 ppm (D, J = 9 Hz, CONH) -

1H at 8.10 ppm (Se., H Ar 2 ' ) - 1H at 7.96 ppm (D, J = 8 Hz, Ji ar 6' ) -

15 1H at7.75 ppm (D, J ≈ 8 Hz, H Ar 4' ) - 1H at 7.56 ppm (T, J = 8 Hz, H ar 5') 1H at6,92 ppm (S, H thiazol ) - 1H cit6.00 ppm (D of D, = 9 Hz, J₂ = 4 Hz, H_?) - lHat 5.45 ppm (0, ϋ ≈ 13 Hz, CH₂ 0 CO) - lHats.oo ppm (D, J = 4 Hz, H_g) 1H at4.87 ppm (D, J = 13 Hz, CH₂ 0 CO) - 2H at 4.16 ppm (M, Ar CHgAgCHg) 1H at4.05 ppm (D, J = 17 Hz, CHg 'SO) - lHat 3.75 ppm (D, J = 17 Hz, CH₂ SO) 20 3H at 2.50 ppm (M, CH3 N^₂ CH_℮) - 6H at 1.45 ppm (2 S, (CH₃)₂ C)

NMR n° 92 - (b) :

2H at8.70 ppm (Se., CHg ^ CH₂CH₃) - 1H at8.60 ppm (0, J = 9 Hz, CO NH) 1H atδ.10 ppm (Se., H Ar 2') - 1H at7.96 ppm (D, J = 8 Hz, H Ar 6') -

1H at 7,75 ppm (D, J = 8 Hz, H Ar 4') - 1H at7.56 ppm (T, J = 8 Hz, H Ar 5’) 25 1H at 6,92 ppm (S, H_ thiazol ) - lHat 5.02 ppm (D of D, = 9 Hz, J₂ ≈ 4 Hz, Hy) lHat 5.45 ppm (0, J * 13 Hz, CH₂ 0 CO) -‘lHat 5.00 ppm (D, J = 4 Hz, H_g) lHat 4.87 ppm (0, J = 13 Hz, CH₂ 0 CO) - 2H at 4.17 ppm (Se., Ar, CH₂ Et) 1H at4.05 ppm (D, J = 17 Hz, CH₂ SO) - 1H at3.75 ppm (D, J » 17 Hz, CH₂ SO) 2H at2.95 ppm (M, CH₃CH₂ l^₂) - 6H atl.45 ppm (2 S, (CH₃)₂ C) -

.30 3H at 1.15 ppm (T, J ≈ 7 Hz, CH^rPk,)

NMR n° 93 (b) ;

1H at8.75 ppm (D, J ≈ 9 Hz, CO NH) - 2H ate.70 ppm (Se., CH₂ ^-i Pr) 1H at8.10 ppm (Se., H Ar 2') - 7.95 ppm (D, J = 8 Hz, ή Ar 6') -

1H^at7.75 pp_m (D, J = 8 Hz, H_ Ar 4') - lHat 7.58 ppm (T, J = 8 Hz, _H Ar

5 5' ) - 1H at7.00 ppm (S, H thiazol ) - lHat 6.00 ppm (D of D, J_χ= 9 Hz, J₂ = 4 Hz, H₇) - 1H at 5.46 ppm (D, J = 13 Hz, CH₂ 0 CO) - lHatδ.OO ppm (D, 0 = 4 Hz, H_g) - lHat4.87 ppm (D, J = 13 Hz, CH₂ 0 CO) - 2H_at4.19 ppm (M, Ar CH₂ #h₂ i Pr) - lHat 4.05 ppm (D, J = 17 Hz, CH₂ SO) -

1H at3.79 ppm (D, 0 ≈ 17 Hz, CH₂ SO) - lHat 3.31 ppm (M, (CH₃)₂“CH) -

10 6H atl.45 ppm (2S, (CH₃)₂ C) - 6Hnt 1.22 ppm (D, J = 7 Hz, (CH₃)₂ CH ^H_℮) -

15

20

NMK ∩° 94 - (b) :

1H_at8.90 pprn (D, J =* 9 Hz, CO NH) - 3Hat 8.10 ppm (Se., CH₂ N®H₃) -

1H at7.66 ppm (D, J = 8 Hz, H Ar 6') - lHat 7.55 ppm (D, J = 8 Hz, H Ar 4') - 1H at7.45 ppm (T, J = 8 Hz, H Ar 5') - lHat 6.95 ppm (S, H thiazol) 1H at6.00 ppm (0 of D, = 9 Hz, J₂ ≈ 4 Hz, H_y) - 1H at5.40 ppm (D,

J » 13 Hz, CH₂ 0 CO) - lHat 5.00 ppm (D, J = 4 Hz, H_g) - 1H at4.86 ppm (D, 0 * 13 Hz, CH₂ 0 CO) - 3H at 4.07 ppm (M, Ar CH_℮ ^and CH₂ SO) -

1H at3.67 ppm (D, J = 17 Hz^ CH₂ SO) - 3Hat 2.40 ppm (S, CH₃ Ar) -

4H at2.50 ppm (M,

CH

-CH.

) - 2H at 1.90 ppm (M,^Clj¹2

-0

) -

CO

CO

1H at 8.90 pprn (D, J = 9 Hz, CO NH) - 3Hat 8.05 ppm (Se., CH₂ iN®h₃) -

1H at 7,40 ppm (D, J = 8 Hz, H A r 4') - lHat7.20 ppm (D, J = 8 Hz, H

Ar 5¹ ) - lHat 6.95 ppm (S, H thiazol ) - lHat 6.00 ppm (D of D, J₁ = 9 Hz, J₂ = 4 Hz, H_?) - 1H at5.30 ppm (D, J = 13 Hz, CH₂ 0 CO) -

1H at 5.00 ppm (D, J = 4 Hz, H_g) - lHat 4.95 ppm (D, J = 13 Hz, CH₂ 0 CO) 3H at 4.00 ppm (Ar CH₂ N®^₃ et CH₂S0) - lHat3.63 ppm (D, 0 = 17 Hz, CH₂ S0)

4Hat2.40 ppm (M,

_CH

2 ) - 6H at2.20 ppm (S, CH₃ Ar) -

CH

2H at 1.90 ppm (M,^CH2'

il

C0

C0

NMR∩° 96 - (b) :

1H at8.90 ppm (D, 0 = 9 Hz, C0 MH) - 3Hat7.90 ppm (Se., CH₂ ^₃) -

1H at7.00 ppm (S, H_ Ar) - 1H a.t6.9 ppm (S, H_ thiazol ) - lHat6.00 ppm (D of D, J₁ = 9 Hz, J₂ = 4 Hz, H_?) - lHat 5.30 ppm (D, J = 13 Hz, CH₂ 0 C0) 1H at5.00 ppm (D, 0 = 4 Hz, H_g) - lHat4.94 ppm (D, J = 13Hz, CH₂ 0 C0) 3H at4.00 ppm (M, Ar CH₂ et CH₂ S0) - lHat 3.62 ppm (0, J = 17 Hz,

] ™2

CH₂ SO) - 4H at 2.50 ppm (M, CHg-ψ-0) - 3Hat2.32 ppm (S, CH₃ Ar) __ “ CO ~

3H at2.2 ppm (S, CH₃ Ar) ~ 3H at2.1β ppm (S, CH₃Ar) - 2Hat 1.90 ppm

NM R ∩° 97 - (b) :

lHat 10.30 ppm (S, Ar NH CO) - 1H at8.70 ppm ( D, J = 9 Hz, CO NH) -

lHat 8.30 pprn (Se., H Ar 2') - 3H at8.05 ppm (M, CH₂ N®H₃) -

2H_ai 7.70 ppm (M, H Ar 5' , 6' ) - 1H atδ.95 ppm (S, H_ thiazol ) -

5 1H_at 6.00 ppm (Dof 0, J₁ = 9 Hz, J₂ = 4 Hz, H_?) - 1H at5.45 ppm (D, J = 13 Hz, CH₂ 0 CO) - lHat 4.97 ppm (D, J = 4 Hz, H_g) - lHat4.80 ppm (D, J ≈ 13 Hz, CH₂ 0 CO) - 1H aΐ4.03 ppm (D, J = 17 Hz, CH₂ SO) - 2H at 3.85 ppm (M,

CH₂ îβ^) - lH_at3.75 ppm (D, J ≈ 17 Hz, CH₂ SO) - 5H at 1.47 ppm (2S, (CH₃)₂ C) -

NMR π° 98 - (b) :

10 lHat 9.90 ppm (S, Ar NH CO) - lHat8.65 ppm (D, 0 ≈ 9 Hz, CO NH) -

lHat 8.28 ppm (S, H Ar 2') - 5Hat 7.70 ppm (M, H Ar 5' , 5' at CH₂ iPh₃) lHat 6.95 ppm (S, H thiazol ) '− lHat 6. 00 ppm (D of D, ≈ 9 Hz, J₂ = 4 Hz, H_?) - 1H at5,45 ppm (0, J ≈ 13 Hz, CHλ, 0 C0) - lHat5.00 ppm (D, J = 4 Hz, H_℮) - 1H at4.84 ppm (D, J ≈ 13 Hz, CH₂ 0 C0) - lHat4.03 ppm (0, J = 17 Hz,

15 CH_? SO) - 1H at3.68 ppm (D, 0 = 17 Hz, CH_? SO) - 2H at3.05 ppm (M, - C - CH_?

- - 0^e CH₂ N®H₃) - 2H at.2.75 ppm (T, J = 7 Hz, - C -CHg CH₂ N®H₃) -

6Hat 1.46 ppm (2 S, (CH₃)₂ C)

NMR_π° 99 - (b) :

lHat 10.5 ppm (S, Ar NH CO) - lHat8.56 ppm (D, J = 9 Hz, CO NH) -

20 2Hat 7.89 ppm (D, 0 = 8 Hz, H Ar 2¹, 6’) - 2Hat7.70 ppm (D, J = 8 Hz,

H Ar 3’, 5') - 3H at7.70 ppm (Se., (CH₂)₂ lφf₃) - lHat6.95 ppm (S, H

thiazol ) - 1H_at5.98 ppm (D of D, = 9 Hz, J₂ = 4 Hz, H^) -

1H at5.40 ppm (D, J = 13 Hz, CH₂ 0 CO) - 1H at4.98 ppm (D, 0 = 4 Hz, H_g) 1H at4.79 ppm (D, J ≈ 13 Hz, CH₂ 0 CO) - lHat4.05 ppm (D, J = 17 Hz, CH₂ SO) -

25 1H at3.75 ppm (D, J = 17 Hz, CH₂ SO) - 2H at3.06 ppm (M, -C-CHg CH_£ f^₃)

(!

2Hat 2.70 ppm (M, -C-CH₂ CH_℮ fβi₃) - 6Hatl.45 ppm (2S, (CH₃)₂ C)

0

NM R ∩° 100 - (b) :

1H at 12 ,75 ppm (Se., thiazol NH CO) - lHat8.90 ppm (D, 0 = 9 Hz, CO NH) 4H_at8.15 ppm (M, CH^ NH^andjl thiazol in 3) - lHat6,96 ppm (S, _H thiazol ) 1H_at 5.00 ppm (D of D, = 9 Hz, J₂ ≈ 4 Hz, H_?) - lHat5.40 ppm (D, J = 13 Hz, CH₂ 0 CO) - 1H at 4,98 ppm (D, J = 4 Hz, H_g) - 1H at4,81 ppm (D, J ≈ 13 Hz, CH₂ 0 CO) - 1H_at4.0 ppm (D, J = 17 Hz, CH₂ SO) - 2Hat3.86 ppm (M, CH_℮ N^₃) -

CH,

1H at3.66 ppm (D, J = 17 Hz, CH_℮ SO) - 4Hat2.5 ppm (M, CHg.

CH„-

.0) -

2H at 1.90 ppm (M, Ll.

CO

.0)

CO

NM R n° 101 - (b) :

1H at 10.8 ppm (S, Ar NH CO) - lHat 8.95 ppm (D, J = 9 Hz, CO NH) -

3H at8.15 ppm (Se., C»₂ 1^₃) - 2H_at7.90 ppm (0, J ≈ 8 Hz, H Ar 2’, 5') -

2H at 7 .70 ppm (D, J = 8 Hz, H_ Ar 3', 5' ) - 1H at6.97 ppm (S, H_ thiazol ) lHat 6.00 ppm (D of D, ≈ 9 Hz, J₂ = 4 Hz, H-,) - lHat5.36 ppm (D, J = 13 Hz, CH₂ 0 CO) - lHatδ.OO ppm (D, J = 4 Hz, H_g) - 1H at4.82 ppm (D, J = 13 Hz, CH₂ 0 CO) - lHat4.05 ppm (D, J = 17 Hz, CH₂ SO) - 3H at3.80 ppm (M, CH₂ #k₃

CH

antlCHg SO) - 4H at2.40 ppm (M, CHg

.0) - 2H at 1.90 ppm (M,

,0)

CO

CO NMR∩° 102 - (b) :

lHat 8,45 ppm (0, J = 9 Hz, CO NH) - 3Hat8.0 ppm (Se., CH₂ ^₃) -

1H at6.79 ppm (S, H thiazol ) - 1H at5.98 ppm (D of D, = 9 Hz, J₂ = 4 Hz, H₇) - 1H at5.15 ppm (2 D, J = 13 Hz, CH₂ 0 CO)

1H at4,97 ppm (0, J = 4 Hz, H_g) - 11^62 ppm (D, J = 13 Hz, CHg 0 CO) -

1H at4.15 ppm (De., J = 12 Hz, H^Eq piperidine) - 3H at 3.84 ppm (M, CH₂.1^₃ andCH₂ SO) - 2Hat 3.58 ppm (M, CH₂ SO andH_g Eq piperidine) - 1H_at3.05 ppm (Te., J = 12 Hz. H,, 4x piperidine) - 1H at2,Sl ppm (Te., J ≈ 12 Hz, H_g Ax piperidine) - lHat2.50 ppm (M, CH C0₂) - 2H atl.84 ppm (M, H₃andH_g piperidine) 2Hatl.50 ppm (M, H₃ and H_g piperidine) - 6H_at 1.45 ppm (2 0, (CH₃)₂ C)

NMR∩° 103 - (b) :

1H at 8.72 ppm (D J = 9 Hz, CO NH) - 3Hat8.25 ppm (Se., CH₂ N®H₃) -

3H at 7.75 ppm (M, _H Ar) - 1H at 6,97 ppm (S, H thiazol ) -

1H at6.00 ppm (D of D, ^ = 9 Hz, J₂ » 4 Hz, H_?) - lHat5.45 ppm (D,

J = 13 Hz, CH₂ 0 CO) - 1H_at5.00 ppm (D, J = 4 Hz, H_g) -

1H at4.84 ppm (D, J ≈ 13 Hz, CH₂ 0 CO) - 3Hat4.05 ppm (M, CH₂ N^and

CH₂ SO) - 1H at3.75 ppm (D, J ≈ 17 Hz, CH₂ SO) - 6Hatl.45 ppm (2S,

(ch₃)₂ C) -

NMR n° 104 - (b) :

2H at8,80 ppm (Se., CHg ^₂ GH₃) - lHat8.77 ppm (D, J = 9 Hz, CO NH) -

3H at7.75 ppm (M, H Ar) - lHat6.95 ppm (S, H thiazo.l ) - lHatβ.OO ppm

(D of D, = 9 Hz, J₂ = 4 Hz, H_?) - 1H_at5.45 ppm (D, J = 13 Hz, CH₂ 0 CO) 1H at5,00 ppm (D, J ≈ 4 Hz, H_g) - 1H at4.8δ ppm (D, J ≈ 13 Hz, CH_℮ 0 CO) 2H at4.25 ppm (M, CH₂ I'ftlg CH₃) - 1H at4.10 ppm (D, J = 17 Hz, CH₂ SO) -

1H at3,74 ppm (D, J ≈ 17 Hz, CH₂ SO) - 3Hat2.58 ppm (M, CH₂ ^H₂ - CH₃) 6H at 1.45 ppm (2 S, (CH₃)₂ C)

NMRn° 105 - (b) :

1H at 10.70 ppm (S, Ar NH CO) - 2Hat8.70 ppm (Se., CH₂ #k₂ CH₃) -

1H at8.68 ppm '(0, J ≈ 9 Hz, CO NH) - 1H at8.16 ppm (S, H Ar 2’) -

1H at7,92 ppm (D, J = 8 Hz, H Ar 6') - lHat7.66 ppm (D, J = 8 Hz, H Ar 4') 1H at7.50 ppm (T, 0 = 8 Hz, H Ar 5¹ ) - lHat6.95 ppm (S, H thiazol ) lHatβ.OO ppm (Dof D, J_χ = 9 Hz, J₂ = 4 Hz, H_y) - lHat5.45 ppm (D, J = 13 Hz CH₂ 0 CO) - lHat 5.00 ppm (D, 0 = 4 Hz, H_g). - lHat4.82 ppm (D, 0 = 13 Hz, CH₂ 0 CO) - 1H at4,02 ppm (D, J = 17 Hz, CH₂ SO) - 2Hat 3.90 ppm (M, CH₂ CH₃) - 1H at 3.74 ppm (D, J = 17 Hz, CH₂ SO) - 3Hat2.60 ppm (M, CH₂ i^H₂ CH₃) 6Hat 1.45 ppm (2 S, (CH₃)₂ C)

NMR^∩° 106 - (b) :

1H at 10,80 ppm (S, A r NH CO) - 3Hat8.70 ppm (M, CHg N^gtCHj et CO NH) 2H_at7.92 ppm (0, J = 8 Hz, H Ar 2', 6') - 2H at7.69 ppm (D, J = 8 Hz,

H. Ar 3' , 5' ) - 1H_at6.95 ppm (S, H_ thiazol ) - lHat 6.00 ppm (D of D,

= 9 Hz, 0₂ ≈ 4 Hz, H_?) - 1H at5,42 ppm (D, J = 13 Hz, CH_℮ 0 CO) -

lHat 5.00 ppm (D, J = 4 Hz, H_g) - 1H at4.81 ppm (D, J = 13 Hz, CH₂ 0 CO) lH_at 4.05 ppm (D, J = 17 Hz, CH₂ SO) - 2H at3.95 ppm (M, CH₂ N®H₂ CH₃) lHat 3.75 ppm (D, J = 17 Hz, CH₂ SO) - 3H at 2.62 ppm (M, CH₂ ^ CH₃) 6Hat 1.45 ppm (2S, (CH₃)₂ C) -

NMRn⁰ 107 - (b) :

1H atg.95 ppm (S, Ar NH CO) - 1H ate.75 ppm (D, J = 9 Hz, CO NH) -

3H at8.05 ppm (Se., CH₂ N%₃)'- lHat 7.61 ppm (D, J = 8 Hz, H Ar 6‘ ) -

1H at7.52 ppm (D, J = 8 Hz, H_ Ar 4‘ ) - 1H at7.31 ppm (T, J = 8 Hz, H_ Ar 6¹ )-1H at6.96 ppm (S, H_ thiazol ) ~ lHaΐδ.OO ppm (Dof D, = 9 Hz, J₂ = 4 Hz, H₇) - lHat 5.40 ppm (0, J ≈ 13 Hz, CH₂ 0 CO) - lHat 5.00 ppm (D, J = 4 Hz, H_℮) - lHat4.81 ppm (D, J ≈ 13 Hz, CH₂ 0 CO) - lHat 4.05 ppm (D, J = 17 Hz, CH₂ SO) - 2H at3,81 ppm (M, CHg iβy - 1H at3.72 ppm (D, 0 ≈ 17 Hz, CH₂ SO) 3H at2.28 ppm (S, Ar CH₃) - 6H at 1.45 ppm (2S, (CH₃)₂ C) -

NMRΠ° 108 - (b) :

lHat9.75 ppm (S, Ar NH_ CO) - lHat8.70 ppm (D, J =9 Hz, CO NH_) -

3H at7,70 ppm (Se., CH₂ CH₂ !^H₃) - lHat7.60 ppm (D, J = 8 Hz, _H Ar 6’) 1H at7.50 ppm (D, J = 8 Hz, H. Ar 4¹ ) - 1H at7.25 ppm (I, J = 8 Hz, JH Ar 5¹ ) 1H at6.95 ppm (S, H_ thiazol ) - 1H at6.00 ppm (D of D, = 9 Hz, J₂ = 4 Hz, H_?) - 1H at5.39 ppm (0, 0 = 13 Hz, CH_g 0 CO) - 1H at5.00 ppm (D, J = 4 Hz, Hg) - lH_at4.82 ppm (D, J = 13 Hz, CH_℮ 0 CO) - lHat 4.05 ppm (D, J = 17 Hz, CH₂·S0) - 1H at3.72 ppm (D, J = 17 Hz, CH₂ SO) - 2H at3.02 ppm (M, CH_℮

CH₂ ^₃) - 2H at2.69 .ppm (T, J ≈ 7, CH₂ CHg ^H₃) - 3H at2.29 ppm (S, Ar CH₃) 6H atl.45 ppm (2S, (CH₃)₂ C) -

NM R n° 109 - (b) :

5 10 15 20 25 30 1H at 12.7 ppm (Se., NJH CO thiazol ) - lHat8,79 ppm (D, J = 9 Hz, CO NJH) -

1H atδ.03 ppm (S, JH thiazol in 3) - 3H at7.75 ppm (Se., CH_? I'Ph.,) ~

ppm

lHat.6,98 ppm (S, H thiazol ) - lH_at6.00^v(0 of D, = 9 Hz, J₂ = 4 Hz,

Hy) - lHat5.37 ppm (D, J = 13 Hz CH^ 0 CO) - 1H atδ.OO ppm (D, J = 4 Hz,

H_g) - 1H at 4.81 ppm (D, J = 13 Hz, CHg 0 CO) - lHat4.03 ppm (D, J = 17 Hz, CH₂ SO) - 1H_at3.68 ppm (D, J ≈ 17 Hz, CH, SO) - 2H_at3.06 ppm (M, CH₂ CH₂ i#H₃) - 2Hat 2,77 ppm (T, J = 7 Hz, CH₂ CH₂ N®k₃) - 6Hatl.45 ppm (2S'_t (CH₃)₂ C)

1H_at8.70 ppm (D, J ≈ 9 Hz, CO NH_) - 5Hat7.96 ppm (M, H Ar 2', 6' and

CH₂ γ!®H₃) - 2H at7.55 ppm (D, J = 8 Hz, H Ar 3' , 5') -

1H at6.95 ppm (S, JH thiazol )*- 1H atβ.OO ppm (D of C, vh≈ 9 Hz, Jg = 4 Hz, H₇) - 1H at5.46 ppm (D, J = 13 Hz, CH₂ 0 CO) - 1Hat 4.99 ppm (D, j"≈ 4 Hz, Hg) - 1H at4,84 ppm (0, J = 13 Hz, CH₂ 0 CO) - lHat4.06 ppm (D, J = 17 Hz, CH₂ SO) - IHat 3.74 ppm (D, J = 17 Hz, CH₂ SO) - 2H at3.55 ppm (Se., CH₂ ^l₃) - 3H at 3.25 ppm (Se., N Ch'₃) - 6Hatl.45 ppm (2S, (CH₃)₂ C)

NMR n° 111 - (b) :

IHat 10.5 ppm (Se:, Ar NJH CO) - IHat 8.95 ppm (D, J = 9 Hz, CO NJH) -

2H at 7.89 ppm (D, J = 8 Hz, H Ar 2', 6') - 2Hat7.71 ppm (D, J ≈ 8 Hz,

JH Ar 5' , 5' ) - 1H at6.96 ppm (S, JH thiazo ) - 1H at 5.98 ppm (D of D,

J_χ = 9 Hz, 0₂ * 4 Hz, H_?) - 1H at5.42 ppm (D, J = 13 Hz, CH₂ 0 CO) -

1H at5.00 ppm (D, J = 4 Hz, H_g) - 1H at4.80 ppm (D, J ≈ 13 Hz, CH₂ 0 CO) 1H at4.05 ppm (D, J ≈ 17 Hz, CH₂ SO) - lHat3.75 ppm (D, J = 17 Hz, CH₂ SO) 2H at3.05 ppm (M, CH₂ CH₂ ^H₃) - 2H at2.70 ppm (T, J = 7 Hz, CH₂ CH₂ ) I-^2

4H at 2.40 ppm (M, CH₂

-0 )

CO

CH.

-0 )

CO

2H at 1.90 ppm (M,

NM R n° 112 - (b) :

1H at 8,80 ppm (D, J = 9 Hz, CO NH) - 3Hat7,go ppm (Se., CH₂ |φ)₃) -

1H at6.80 ppm (S, H thiazol ) - lHat5.95 ppm (D of d, J₁ = 9 Hz, J₂ = 4 Hz,^h₇) - 1H at5-17 ppm (2 D, J = 13 Hz, CH₂ 0 CO) - lHat4.96 ppm (D, J = 4 Hz, Hg) ~ lH_a-t4.60 ppm (D, J = 13 Hz, CH₂ 0 CO) - 1H at4.18 ppm (M, H₂℮ piperidine) 3H at3.90 ppm (M, CH₂ I^H₃andCH₂ S0) - 2Hat3.58 ppm (M, CH₂ S0 et H^e piperidine) - 1H_at3.06 ppm (M, H₂a piperidine) - 1Hat 2.75 ppm (M, H,a piperidine) - lHat2.60 ppm (M, H^ piperidine) - 4H at2.40 ppm

0

(M, CH, ^CH2 CO) - 4H at 1.80 ppm et 2H 1.50 ppm ( ch₂-i -CO et h₃ et h₅

piperidine)

lHat8.75 ppm (D, J ≈ 9 Hz, CO NH) - 3Hat8.40 ppm (Se., CH f^₃) -

1H at8.13 ppm (S, H Ar 6') - lHatβ.OO ppm (D, J ≈ 8 Hz, H Ar 2') -

1H aΐ7.64 ppm (D, J = 8 Hz, H_ Ar 3') - 1H aΐ6.97 ppm (S, H_ thiazol ) lHatβ.OO ppm (D ofO, ^ ≈ 9 Hz, J₂ => 4 Hz, H_?) - 1H at5.45 ppm (D, J » 13 Hz, CH₂ 0 CO) - 1H at 5.00 ppm (D, J == 4 Hz, H_g) - 1H at4.86 ppm (D, J = 13 Hz, CH₂ 0 CO) - 2H at4.19 ppm (M, CH₂ ^H₃) - lHat4.10 ppm (D, J = 17 Hz, CH_℮ SO) 1H at3.76 ppm (D, J = 17 Hz, CH₂ SO) - 6Hatl.45 ppm (2 S, (CH₃)₂ C)

NM R n° 114 - (b) :

1H at8.72 ppm (D, J = 9 Hz, CO NH) - 3Hat8.40 ppm (Se., CH₂ lΦi₃) -

2H at8.ll ppm (M, H Ar 2', 6’) - 1H at7.86 ppm (M, H Ar 3') -

1H^at6.99 ppm ( S, H thiazol ) - 1H atβ.Ol ppm (D ofO, = 9 Hz,

J₂ = 4 Hz, H_?) - 1H at5.46 ppm (D, J = 13 Hz, CH₂ 0 CO) -

lHat 5.00 ppm (D, J = 4 Hz, H_g) - lHat4.89 ppm (D, J = 13 Hz, CH₂ 0 CO) 2Hat4.18 ppm (M, CH₂ tpHj) - lHat 4.06 ppm (D, J = 17 Hz, CH₂ SO) lHat3.78 ppm (D, J = 17 Hz, CH₂ SO) -,6Hatl.45 ppm (2S, (CH₃)₂ C) -

NMR ∩° 115 - (b) :

lHat 10.20 ppm (Se., Ar NH CO) - lHat8.70 ppm (D, J = 9 Hz, CO NH) -

1Hat 8.16 ppm (Se. , H Ar 2') - 1H at7.84 ppm (D, J = 8 Hz, H Ar 6') -

3Hat 7.66 ppm (Se. , CH₂ rf^₃) - lHat 7.60 ppm (D, J = 8 Hz, H Ar 4') -

S 1H at7,45 ppm (I, J = 8 Hz, _H Ar 5') - 1H at6.97 ppm (S, H thiazol ) -

lHat 6.00 ppm (D of D, = 9 Hz, = 4 Hz, Hy) - lHat5.45 ppm (D, J = 13 Hz, CH₂ 0 CO) - 1H at5,00 ppm (D, J = 4 Hz, H_g) - lHat 4.84 p_pm (D, J ≈ 13 Hz, CH₂ 0 CO) - 1H_at4,05 ppm (D, J = 17 Hz, CH₂ SO) - 1H at3.75 ppm (D, J = 17 Hz, CH₂ SO) - 2H at2.81 ppm (M, CH₂ - f^₃) - 2H at2.40 ppm (T, J = 7 Hz,

10 CH₂ C0₂) - 2H at 1.82 ppm (M, CH₂ CH₂ C0₂) - 6H at 1.45 ppm (2 S, (CH₃)₂ C)

NMR ∩° 116 - (b) :

lHat 10.3 ppm (Se., Ar NH CO) - lHat8.70 ppm (D, J = 9 Hz, CO NH) -

2H_at 7.90 ppm (D, J = 8 Hz, H ·Ar 2', 6') - 1H at7.67 ppm (D, J = 8 Hz, H Ar 3', 5') - 3H at 7.60 ppm (Se., CH₂ #H₃) - lHat 6.95 ppm (S, H thiazol.) -

15 1H atδ.OO ppm (D of D, = 9 Hz, J₂ = 4 Hz, Hy) - lHat5.42 ppm (D, J = 13 Hz CH₂ 0 CO) - 1H at4,98 ppm (D, J = 4 Hz, H_g) - 1H at4.79 ppm (D, J = 13 Hz, CH, 0 CO) - 1H at4.06 ppm (D, J = 17 Hz, CH₂ SO) - 1H at3.75 ppm (D, J ≈ 17 Hz, CH₂ SO) - 2Hat 2.79 ppm (M, CH₂Ph^) - 2Hat2.42 ppm (M, CH₂ - CO NH Ar) 2H atl.84 ppm (M, CH₂ CH₂ N^<®H₃) - 6H at 1.48 ppm (2 S, (CH₃)₂ C)

20 NMRn° 117 - (b) ;

lHat 10.30 ppm (Se., Ar NH CO) - lHat8',75 ppm (D, J = 9 Hz, NH CO) -

2H at 7.84 ppm (0,0 = 8 Hz, H Ar 2’, 6') - 2H at7.72 ppm (D, J = 8 Hz, H Ar 3', 5¹) - 3Hat7.60 ppm (Se., CH₂ ^3) - lHat6,97 ppm (S, _H thiazol ) 1H atδ.OO ppm (D of D, J_χ ≈ 9 Hz, J₂ = 4 Hz, H_y) - lHat 5.40_pprn (d_s j = 13 Hz, 25 CH₂ 0 CO) - lHat4.90 ppm (D, 0 = 4 Hz, H_g) - lHat4.78 ppm (D, J ≈ 13 Hz,

CH₂ 0 CO) - lHat 4.05 ppm (D, J = 17 Hz, CH_℮ SO) - lHat 3.75 ppm (D, J = 17 Hz, CHg.'SO) - 2Hat2.75 ppm (M, CH₂ N^₃) - 2H at2.36 ppm (M, CH₂ CONH Ar) -

4H at 1,58 ppm (M, -CO CH₂ (CH₂)₉ CH₂^₃) - 6H atl.45 ppm (2 S, (CH₃)₂ C)

1H at 12.7 ppm (Se, NH CO thiazol) - 1H at 8.65 ppm (D, J = 9 Hz, CO NH) - 3H at 8.20 ppm (Se, CH₂ t$k₃) - 1H at 5 6.93 ppm (S, H thiazol) - 1H at 6.00 ppm (D of~D, = 9 Hz, J₂ = 4 Hz, Hy) - 1H at 5.45 ppm (D, J = 13 Hz, CH₂ O CO) - 1H at 5.02 ppm (D, J = 4 Hz, H₆) - 1H at 4.75 ppm (D, J = 13 Hz, CH₂ O CO) - 1H at 4.02 ppm (D, J = 17 Hz, CH₂ SO) - 2H at 3.90 ppm (M, CH₂ Gly) - 1H at 3.70 10 ppm (DT J = 17 Hz, CH₂ SO) - 3H at 2.50 ppm (S, CH₃ thiazol) - 6H at 1.45 ppm (2S, (CH₃)₂ C) .

NMR n· 119 - fbΐ:

1H at 8.45 ppm (D, J = 9 Hz, CO NH) - 3H at 7.80 ppm (Se., CH-I$H₃) - 1H at 6.80 ppm (S, H thiazol) - 1H at 15 6.00 ppm (D of D, ^ = 9 Hz, J₂ = 4 Hz, H₇) - 1H at 5.10 ppm (D, J = 13 HZ, CH₂ O CO) - 1H at 4.95 ppm (D, J = 4 Hz, H₆) - 1H at 4.58 ppm (D, J = 13 Hz, CH₂ O CO) - 1H at 3.90 ppm (D, J = 17 Hz, CH₂ SO) - 1H at 3.56 ppm (D, J = 17 Hz, CH₂ SO) - 1H at 3.00 ppm (2M CH 1<%₃) - 1H at 20 2.25 ppm (M, Cg C0₂) - 4H at 1.80 ppm and 4H at 1.40 ppm (M, CH₂ cyclohexane) - 6H at 1.44 ppm (2S, (CH₃)₂ C).

MMR Π.°~12!0 - (b) ;

1H at 8.75 ppm (D, J = 9 Hz, CO Njg) - 2H at 7.80 ppm (Se., ϋ Ar 2', 6') - 3H at 7.65 ppm (Se., CH₂ *Φh₃) - 1H 25 at 7.57 ppm (D, J => 8 Hz H Ar 4') - 1H at 7.47 ppm (T, J = 8 Hz, H Ar 5') - 1H at 7.00 ppm (S, H thiazol) - 1H at 6.00 ppm (D Of D, J_χ => 9 HZ, J₂ = 4 Hz, Hy) - 1H at 5.45 pprn (D, J ≈ 13 HZ, CH₂ O CO) - 1H at 4.98 ppm (D, J ≈ 4 Hz, H₆) - 1H at 4.82 ppm (D, J = 13 Hz, CH₂ O CO) - 1H 30 at 4.05 ppm (D, J = 17 Hz, CH₂ SO) - 1H at 3.75 ppm (D, J = 17 Hz, CH₂ SO) - 3H at 3.00 ppm (M, CH CH₂

ch₃

iΦh₃) - 6H at 1.50 ppm (2S, (CH₃)₂ C) - 3H at 1.20 ppm (D, J ≈ 7 Hz, CH CH₂ K®H₃)

35 CH₃

NMR ∩° 121 - (b) :

1H at 10.0 ppm (Se., Ar NH CO) - 1H atδ.85 ppm (D, J = 9 Hz, CO NH) 3Hat8.05 ppm (Se., CH₂ l^₃) - 1H at 7.45 ppm (S, H Ar 6' ) - lHat7.30 ppm (S,. H Ar 4¹ ) - 1Hat 7.00 ppm (S, thiazol ) - 1H at6.00 ppm (D of D, = 9 Hz, J₂ = 4 Hz, H_y) - 1H at5.43 ppm (D, J = 13 Hz, CH₂ 0 CO) - lHatδ.OO ppm

(D, J = 4 Hz, H_g) - 1H at4.78 ppm (D, J = 13 Hz, CHg 0 CO) - lHat4.05 ppm (D, J = 17 Hz, CH_℮ SO) - 2H at 3.80 ppm (M, CH₂ Gly) - lHat3.75 ppm (D,

J = 17 Hz, CH₂ SO) - 6Hat 2.25 ppm (2 S, CH₃ Ar) - 6H at 1.50 ppm (2 S, (CH₃)₂ C) NMR ri° 12 2 - (b) :

1H atlθ.45 ppm (Se., Ar NH CO) - 1H_at8.70 ppm (D, J = 9 Hz, CO NH) lHat8.50 ppm (Se., ΐFllg, piperidine) - lHat8.20 ppm (Se. , Filg, piperidine) 2H at7.84 ppm (D, J = 8 Hz, H Ar 2¹, 6' ) - 2Hat 7.70 ppm (D, J = 8 Hz, H Ar 3', 5') - 1H atβ,98 ppm (S, _H thiazol ) - lHatδ.OO ppm (D of 0, = 9 Hz, J₂ = 4 Hz, H_?) - 1H at5,42 ppm (D, J = 13 Hz, CH₂ 0 CO) - lHat4.98 ppm (D, J = 4 Hz, Hg ) - 1H at4.78 ppm (D, J » 13 Hz, CHg 0 CO) - lHat4.05 ppm

(D, J = 17 Hz, CH₂ SO) - 1H at3.75 ppm (D, J ≈ 17 Hz, CH₂ SO) -

2H at3.30 ppm (M, CH₂ in !^®Hg piperidine) - 2Hat2.9Q ppm (M, CH₂ in

rPπ₂ piperidine) - lHal2.66 ppm (M, CH CO NH) - 4H at 1.80 ppm (M, CH₂ in β piperisine) - 6H at 1.45 ppm (2 S, (CH₃)₂ C)

NMR n° 123 - (b) :

1H at 10.25 ppm (Se., Ar NH CO) - lHat8.70 ppm (D, J = 9 Hz, CO NH) lHat8.50 ppm (Se., iFkg, piperidine) - lHat8,25 ppm (Se, N®Hg, piperidine) 1Hat8.19 ppm (Se, H Ar 2') - 1H at7.85 ppm (D, J = 8 Hz, Hr 5') -

IHat 7.60 ppm (D, J = 8 Hz, H Ar 4') - lHat7.42 ppm (T, J = 8 Hz, H Ar 5') 1H at6.95 ppm (S, H thiazol ) - IHat 6.00 ppm (D of D, = 9 Hz, J₂ = 4 Hz, H₇) - IHat 5.45 ppm (D, J ≈ 13 Hz, CHg 0 CO) - lHatδ.OO ppm (D, J = 4 Hz, Hg) - IHat 4.81 ppm (D, J ≈ 13 Hz, CHg-.O CO) - lHat4.05 ppm (D, J = 17 Hz, CHg SO) - 1H at 3. 71 ppm (D, J » 17 Hz, CHg SO) - 2H at3.30 ppm (M, CHg in^ fFiΐg Piperidine) - 2Hat2.90 ppm (M, CHg in N®kg piperidine) -

IHat 2.66 ppm (M, CH CO NH) - 4H at 1.80 ppm (M, CHg in jb, ^g piperidine) 6Hat 1.45 ppm (2 S, (CHglg C) -

NMR n° 124 - (b) :

5 1H at6,00 ppm (D ofD, = 9 Hz, J₂ ≈ 4 Hz, H_yj - 1H at5.45 ppm (D, J = 13 Hz, CH₂ 0 CO) - 1Hat 5,00 ppm (D, J ≈ 4 Hz, H_g) - lH_at4,80 ppm (D, J = 13 Hz, CH₂ 0 CO) - 2Hat 4,00 ppm (M, Hx AlaandCHg SO) - 1H at3.75 ppm (D, J = 17 Hz, CH₂ SO) - 6H at 1,50 ppm (2S, (CH₃)₂ C) - 3Hatl.42 ppm (D, J ≈ 7 Hz, CH₃ Ala) -

10 1H atlO,80 ppm (Se., Ar NH CO) - 1H at9,00 ppm (D, J = 9 Hz, CO NH) -

IS CH₂ 0 CO) - 2H at4.00 ppm (M, H o( Ala and CH_℮ SO) - 1H at3.75 ppm (D, J = 17 Hz,

20 NMR_n° 126 -(b) :

1H at 6,00 ppm (Oof 0» Oj = 9 Hz, J₂ ≈ 4 Hz, H_y) - lHat 5,20 ppm (M, CH₂ 0 CO) 1H at4,95 ppm (D, ϋ = 4 Hz, H_g) - lHat 4.50 ppm (0, CH₂ 0 rθ) - lHat 3.15 ppm 25 (M, H_℮a piperidine) - lHat2,80 ppm (M, H_ga piperidine) - lHat 2,60 ppm

NMR n° 127 - (b) :

1H at8.43 ppm (D, J = 9 Hz, CO NH) - 6H at7.50 ppm (Se., -

1H at 6.80 ppm (S, H thiazol) - lHatβ.OO ppm (D of D, = 9 Hz,

J₂ = 4 Hz_/H_?) - 1Hat 5.16 ppm (2D, J ≈ 13 Hz, CH₂ 0 CO) -

1H at 4.95 ppm (D, J ≈ 4 Hz, H_g) - 1H at4.58 ppm (D, J = 13 Hz, CH₂ 0 CO) 1Hat4.20 ppm (M, Hgθ piperidine) - IHat^O ppm (D, J = 17 Hz CH₂ SO) 1H at3.64 ppm (M, H_ge piperidine) - lHat3.57 ppm (D, J ≈ 17 Hz, CH₂ SO) lHat3.07 ppm (M, H₂a piperidine) - 2Hat2.96 ppm (M, CH₂ N®H₃) -

1H at 2.75 ppm (M, H_ga piperidine) - 3H at2.65 ppm (M, CH C0₂andCH₂ CO N) 2H at 1,80 ppm et 2Hatl,50 ppm (H^anclHζ piperidine) -6Hatl,45 ppm (2S, (ch₃)₂ C) -

NMRn° 128 - (b) :

1H at 8.45 ppm (D, J = 9 Hz, CO NH) - 6H at7,70 ppm (Se., N^ΦH₃) lHat6,80 ppm (S, H thiazol ) - 1H at 5.98 ppm (D de D, = 9 Hz,

J₂ ≈ 4 Hz, H_?) - 1H at5.20 ppm (2 C, J = 13 Hz, CHg 0 CO) -

1H at4,96 ppm (D, J = 4 Hz, H_g) - lHat4.58 ppm (D, J = 13 Hz, CH₂ 0 CO) lHat4.18 ppm (H₂℮ piperidine) - lHat3.90 ppm (D, J = 17 Hz, CH₂ SO) lH_at3.75 ppm (M, H_ge piperidine) - lHat3·.55 ppm (D, J ≈ 17 Hz, CH₂ SO) lH_at3.00 ppm (M, H₂a piperidine) - 4Hat 2.65 ppm (M, CH₂ I^Hg, H_ga ℮t H₄ piperidine) - 2Hat2,40 ppm (T, CH₂ CO N) - 4H at 1.70 ppm (M, CH CH₂

Λ ****

CH₂ λ^vH₃, HjandH- piperidine) - -Hat 1.50 ppm (M, H^andHg piperidine) 6H at 1.44 ppm (2S, (CH₃)₂ C) -

lHaΐ8.50 ppm (Se., N^$H₂ piperidinium) - 1H at8.45 ppm (D, J = 9 Hz,

CO NH) - 1H at8,25 ppm (Se., N^ΦH₂ piperidinium) - 3Hat7,40 ppm (Se.,

N®H₃ thiazol ) - lHatβ.80 ppm (S, H thiazol ) - lHatβ.OO ppm (D of D,

5 Jj = 9 Hz, J₂ = 4 Hz, H_?) - 1H atδ.16 ppm (D, J ≈ 13 Hz, CH₂ 0 CO) -

lH_at4 15 ppm (M, H₂℮ piperidine) - 2H at 3 .90 ppm (M, Hg℮ piperidine and CH₂ SO) - 1Hat 3.55 ppm (D, J = 17 Hz, CH₂ SO) - 2Hat 3.25 ppm (M, Hgβ and^Hδ^e piperidinium) - lHat3.15 ppm (M, H₂a piperidine) - 3Hat2.85 ppm (M,

H_ga piperidine and H₂a and Hga piperidinium) - 2Hat2.70 ppm (M, H^

10 piperidine_andH^ piperidinium) - 6H atl.75 ppm and 2H at 1.50 ppm (2M, H^andHg piperidinium H^andHg piperidine) - 6Hatl.44 ppm (2S, (CH₃)₂ C) -

lHat8.75 ppm (D, J 9 Hz, CO NH) - 3H at 8.20 ppm (Se., CH₂ N®H₃) -

1H at7.80 ppm (D, J = 8 Hz, H Ar 6') - 2H at7.45 ppm (M, H Ar 3', 5')

15 1H at7,00 ppm (S, H thiazol ) - lHatβ.OO ppm (D ofD, = 9 Hz,

0₂ = 4 Hz, H₇) - 1H aΐ5.42 ppm (D, J => 13 Hz, CH₂ 0 CO) - 1H at 5.00 ppm (D, 0 = 4 Hz, H_g) -1Hat 4.80 ppm (D, J a ‘13 Hz, CH₂ 0 CO) -

3Hat4.00 ppm (M, CH₂ l^gβndCHg SO) - 1H aΐ3.75 ppm (D, 0 = 17 Hz,

CH₂ SO) - 3H_at2.45 ppm (S, CH3 Ar) - 6Hatl.45 ppm (2S, (CH₃)₂ C) -

20 NM Rⁿ° 131 - (b) : NM Rⁿ° 131 - (b) :

lHat8.85 ppm (D, J ≈ 9 Hz, CO NH) - 3Hat 8.20 ppm (Se., CH₂ N^ΦH₃) -

1H at7,80 ppm (D, J = 8 Hz, H Ar 5') - 2Hat7 45 ppm (M, H Ar 3', 5') lHat6.95 ppm (S, H_ thiazol ) - lHatβ.OO ppm (D of D, = 9 Hz,

J₂ = 4 Hz, H_y) - 1H at5.45 ppm (D, J ≈ 13 Hz, CH₂ 0 CO) - lHats.OO ppm

25 CD, J = 4 Hz, H_g) - lHat4.80 ppm (D, J ≈ 13 Hz, CH₂ 0 CO) - CD, J = 4 Hz, H_g) - lHat4.80 ppm (D, J ≈ 13 Hz, CH₂ 0 CO) -

3H at4.00 ppm (M, CH₂ N^ΦH₃ et CH₂ SO) - 1H at3.73 ppm (D, J a 17 Hz,

CH₂ SO) - 3H at2.50 ppm (S, CH₃ Ar) - 4Hat2.40 ppm (M, CO ) 2H at 1.80 ppm (M, 0 ) - CH, ) - CH,

-CO -CH, -CH,

30 CH, CH,

NMR∩° 132 - (b) :

1H at8.80 ppm (D, J = 9 Hz, CO NH) -3H atδ.10 ppm (Se., CH₂ N^₃) -

1H at7.55 ppm (S, ji Ar) - 1H at7,45 ppm (S, H_ Ar) - 1H at7.00 ppm (S, H thiazol ) - 1Hat6.00 ppm (D of D, Jj ≈ 9 Hz, J₂ = 4 Hz, H_?) -

1H at5,40 ppm (D, J = 13 Hz, CH₂ 0 CO) - 1H at 5.00 ppm (D, J = 4 Hz, H_fi) lH_at4,83 ppm (D, J = 13 Hz, CH₂ 0 CO) - 3Hat3.70 ppm (M, CH₂ N®H₃ et

CH₂ SO) - 1Hat 3.70 ppm (D, J = 17 Hz, CH₂ SO) - 3H at2.4θ ppm (S, CH₃ Ar) - 3H at2,34 ppm (S, CH₃ Ar) - 6Hatl.45 ppm (2S, (CH₃)₂ C) -

NMR n° 133 - (b) :

1Hat 12.5 ppm (Se., Ar NH CO) - lHat8.78 ppm. (D, J = 9 Hz, CO NH) -

3H at 8.30 ppm (Se., - CH - N®H₃) - 1H at 8.20 ppm (S, H thiazol in 3) -

ch₃ "

1H at 7,00 ppm (S, H thiazol) - 1H at 6.00 ppm (D of D, = 9 Hz, J₂ = 4 Hz, H₇) - 1Hat 5.42 ppm (2 D, J = 13 Hz, CHg 0 CO) - lHatδ.OO ppm (D, J = 4 Hz, H_g) - 1Hat4.90 ppm (D, J = 13 Hz, CH₂ 0 CO) - 1H at4.15 ppm (M, CH ^₃) “ ~ ch₃

1H at4.00 ppm (D, J = 17 Hz, CH₂ SO) - lHat3.76 ppm (D, J = 17 Hz, CH₂ SO) 6H at 1.44 ppm (2 S, (CH₃)₂ C) - 3Hat 1.40 ppm (D, 0 = 7 Hz, CH₃ CH)

NMR_n° 134 - (b) :

1H at8,85 ppm (D, J = 9 Hz, CO NH) - 1H at8.50 ppm (S, H thiazol in 3) 3Hat 7.90 ppm (Se., CH₂ 1^3) ~ lHat7.00 ppm (S, H_ thiazol ) -

lHat 6.00 ppm (D of D, = 9 Hz, J₂ = 4 Hz, H_?) - 1H at5.42 ppm (D, J = 13 Hz CH₂ 0 CO) - 1H at4.99 ppm (D, J = 4 Hz, H_g) - lHat 4.84 ppm (D, J ≈ 13 Hz, CH₂.0 CO) - lHat4.00. ppm (D, J ≈ 17 Hz, CH₂ SO) - lHat3.75 ppm (D, J = 17 Hz CH₂ SO) - 4H at3,20 ppm (M, CH₂ CH₂ l^₃) - 6H at 1.45 ppm (2 S, (CH₃)₂ C)

NM R n° 135 ~ (b) :

lHaΐ8.80 ppm (D, J ≈ 9 Hz, CO NH) - 1H at8,57 ppm (S, _H thiazol in 3) 3Hat8.50 ppm (Se., CH₂ ^3) - 1H at 7.00 ppm (S, H_ thiazol ) - lHatδ.OO ppm (D of D, J_χ = 9 Hz, J₂ = 4 Hz, H₇) - 1H at5.40 ppm (D, J = 13 Hz, CH₂ 0C0) -

5 lHatδ.OO ppm (D, J = 4 Hz, H_β) - 1H at4.90 ppm (D, J = 13 Hz, CH_℮ 0 CO) 2H_at4.45 ppm (M, CH₂ N®H₃) - lHat4.00 ppm (D, J ≈ 17 Hz, CH₂ SO) -

1H at 3.72 ppm (D, J ≈ 17 Hz, CH₂ SO) - 6Hatl,45 ppm (2 S, (CH₃)₂ C)

10

15

NMR n° 136 - (b) :

lHat 8.90 ppm (D, J = 9 Hz, CO NH) - 1H at 8.60 ppm (S, H_ thiazol in 3) lHat 8.50 ppm (Se., CH₂ N®H₃) - 1H at6.98 ppm (S, H_ thiazol ) -

lHatδ.OO ppm (D ofD, = 9 Hz, Jg ≈ 4 Hz, Hy) - lHat5.42 ppm (D,

J = 13 Hz, CH₂ 0 CO) - lHatδ.OO ppm (D, J = 4 Hz, H_g) - lHat4.84 ppm (D,

J = 13 Hz, CH₂ 0 CO) - 2Hat 4.45 ppm (M, CH₂ f^H₃) - lHat4.00 ppm (D,

0 = 17 Hz, CH₂ SO) -lHat 3.72 ppm (D, 0 ≈ 17 Hz, CHg SO) -

0 0

4H at2.40 ppm (M, CH₂

-CO) - 2Hatl.86 ppm (M,

-CO)

■■CH,

CH,

NMR n° 137 - (b) :

lHat8.90 ppm (T, J = 8 Hz, C NH CH_?) - lHat8.75 ppm (D, J = 9 Hz, CO NH) -

0^e

20 3H 3.58.00 ppm (Se., CH₂ N®k₃) - 2H at7. 88 ppm (D, 0 = 8 Hz, H 4r 2', 6') -

2H at^.40 ppm (D, J = 8 Hz, ' 1H Ar 3', 5' ) - 1H at6 .96 ppm (S, HI thiazol ) 1H at6.00 ppm (D of 0, Jj_ = 9 Hz, J₂ = 4 Hz, Hy) - 1H atδ.44 ppm (0, J = 13 Hz,^rH₂ 0 CO) - 1H_at4.98 ppm (D, J = 4 Hz', H_g) - 1H at4.80 ppm (D, 0 = 13 Hz, CH₂ 0 CO) - 2H_at4,40 ppm (D, J = 8 Hz, Ar CHg NH) - 1H at4.06 ppm lHat3.70 ppm (D, J = 17 Hz, CH₂ S -> 0) - 2H at3.57 ppm (M, OC CH₂ N^₃) 2Hatl.47 ppm (2 S, (CH₃)₂ C)

25

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 n 5 below.

These compounds are identified by a reference number and for each of them are given the values of R_l7 15 R2, 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 20 infra-red spectrum, the wavelengths indicated in cm^-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 25 protective carbonate of the amine. When 2 wavelengths only are indicated the second corresponds to a wide band which covers the elongation vibration frequecies both of the esters, the amide and the protective carbonate of the amine and the thioester.

30 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 /

78

NMR Spectra

The spectra are recorded at 60 MHz, indicated by (a) or at 250 Mllz, indicated by (b); when two steroisomers exist in the molecule, the split signals are indicated by *.

NMR n° 1 - fa):

8H between 6 and 9 ppm (wide signal, CH₂, TFA, C0₂H)1H at 8.40 ppm (D, J=9 Hz, CONH) - 1H at~6.86 ppm (S, H 5 thiazol) - 1H at 6.00 ppm (D of D, J₃=9 Hz, J₂=4 Hz, H₇)

- 1H at 4.97 ppm (D, J=4 Hz, Hg) - 1H at 4.20 ppm (AB, J_AB=¹³ Hz, CH₂ SCO) - 3H at 3.70 ppm (M, CH^ SCO and CH₂SO) - 4H at 2.75 ppm (M, CH₂NH₂ and CH₂COS) - 2H at 1.77 ppm (M, CH₂CH₂CH₂) - 6H at~1.45 ppm (s’, (CH₃)₂C).

10 NMR n· 2 - (a):

8H between 6.5 and 9 ppm (wide signal, C0₂H, TFA, NH₂)1H at 8.40 ppm (D, J=9 Hz, CONH) - 1H at 6.88 ppm (S~, Ξ thiazol) - 1H at 6.0 ppm (D of D, J_λ=9 Hz, J₂=4 Hz, Hγ)

-1H at 5.0 ppm (D, J=4 Hz, Hg) - 1H at 4.20 ppm (A of 15 AB, J=13 Hz, CH₂SCO) - 3H at 3.80 ppm (M, CHgSO and CH^SCO) - 4H at 2.65 ppm (M, CH2NH₂ and CH^COS) - 10H at 1.45 ppm (S.e., (CH₃)₂C and CH₂ (CH^j·CH^.

NMR n° 3 - fa^ ;

8H between 6.5 and 8.7 ppm (wide signal (NH₂, C0₂H, TFA) 20 - 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^=9 Hz, J₂=4 Hz, H7) - 1H at 5.0 ppm (D, J]_=4 Hz, Hg) - 1H at 4.20 ppm (A of AB, J≈13 Hz, CH₂SO) - 3H at 3.70 ppm (M, CH₂SCO and CH₂SO) - 4H at 2.80 ppm (M, CH₂NH₂ and CH₂C0) - 12H at 25 1.45 ppm (S.e., (CH₃)₂ c and CH₂ (CH₂)₃ CH₂).

NMRn· 4 - (a)i ~ ~

7H between 6.5 and 9.5 ppm (wide signal, NH₂, NH, co₂H, TFA) - 1H at 8.40 ppm (D, J=9 Hz, CONH) - lF at 6.90 ppm (S, H thiazol) - 1H at 6.0 ppm (D of D, J_x=9 Hz, J₂=4 30 Hz, H₇) - 1H at 5.0 ppm (D, J=4 Hz, Hg) - 1H at 4.20 ppm (A Of AB, J_AB=13 Hz, CH₂SCO) - 3H at 3.70 ppm (M, CH₂SCO and CH₂SO) - 5H at 3.0 ppm (M, CH₂N and CHCOS) - 4H at 1.90ppm (M, CH₂CH₂N) - 6H at 1.45 ppm (S, (CH₃)₂C).

NMR n' 5 - (bΐ:

35 5H between 7 and 9 ppm (wide signal, NH₂, 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, J₃=9 Hz, J₂=4 Hz, H7)

- 1H at 4.95 ppm (D, J=4 Hz, H₆) - 1H at 4.16 ppm (2D, J=13 HZ, CH₂SCO)* - 1H at 3.76 ppm (D, J=13 Hz, CH₂SCO)

- 2H at 3.66 ppm (S, CH₂SO) - 1H at 3.4 ppm, 1H at 3.16 ppm and 2H at 2.95 ppm (M, CH₂N) - 1H at 2.80 ppm (M, 5 CHCOS) - 4H between 1.5 and 2.1 ppm (M, CH₂CH₂CH₂N) - 6H at 1.44 ppm (S, (CH₃)₂C).

NMR n' 6 - (a^:

3H at 8.50 ppm (S.e., CONH, NH₂) - 3H at 7.80 ppm (S.e., NH₃) - 1H at 6.85 ppm (S, H thiazol) - 1H at 6.00 ppm (D 10 of D, J-l≈Θ Hz, J₂=4 Hz, H₇) - 1H at 5.00 ppm (D, J==4 Hz, Hg) -1H at 4.15 ppm (A of AB, J_AB=13^Hz/ CH₂SCO) - 1H at 3.80 ppm (B of AB, Jab^{=13 Hz} / CH₂SCO) ~ 2H at 3.70 ppm (S.e., CH₂SO) - 7H at 2.50 ppm (M, CH₃NH, CH₂NH, CH₂ C ~ ~ 0

15 S) - 2H at 1.80 ppm (M, CH₂CH₂CH₂NH) - 6H at 1.45 ppm (2S, (CH3)₂C).

NMR n· 7 - <a);

1H at 8.35 ppm (D, J=9 Hz, CONH) - 8H between 6.5 and 10 ppm (C0₂H, NH₂, TFA) - 1H at 6.82 ppm (S, H thiazol)20 1H at 6.00 ppm (D of D, J_χ=9 Hz, J₂=4 Hz, H₇) - 1H at 5.00 ppm (D, J≈4 Hz, Hg) - 1H at 4.15 ppm (A of AB, J_ab≈13 Hz, CH₂SC0) - 3H~"at 3.66 ppm (M, CH₂S0 and B of AB, CH₂SCO) - 4H at 2.65 ppm (M, CH₂C0 and~CH₂NH₂) - 6H at 1.42 ppm (S, (CH₃)₂C) - 10H at l725 ppm (sTe., (013)5 25 CH₂ NH₂). ~

NMR n” 8 - (b);

1H at 8.34 ppm (D, J≈9 Hz, CONH) - 3H at 7.80 ppm (S.e., &Hτ,) - 3H at 7.40 ppm (S.e., fobj) - 1H at 6.78 ppm (S, H thiazol) - 1H at 5.94 ppm (D of D, J_x=9 Hz, J₂≈4 Hz, Ej) 30 - 1H at 4.94 ppm (D, J≈4 Hz, Hg) - 1H at 4.14 ppm (D, J=13 HZ, CH₂SCO) - 1H at 3.69 ppm (D, J=13 Hz, CH₂SO)2H at 3.63"ppm (S, CH₂S0) - 2H at 2.60 ppm (M, CH₂NH₂)1H at 2.45 ppm (M, CHCOS) - 4H at 1.84 ppm (M, CH^CHCOS) - 6H at 1.44 ppm (2S, (CH₃)₂C) - 2H at 1.40 35 ppm and 2H at 1.0 ppm (M, CH₂CH CH₂ NH₂).

NMR n¹ 9 - fbΐ ;

5 10 15 20 25 30 35 CH2

(M, CH COS and NH) - 2H at 1.95 ppm and 2H at^CHJ.^

CH2

1.70 ppm (M, SC h/ ) - 3H at 1.45 ppm (D, J=7 Hz,

o^Xch₂

CH3CH).

NMR n· 13 - (b):

2H at 8.70 ppm (M, CONH and NH^) - 1H at 8.40 ppm (M, NH2) - 3H at 7.40 ppm (S.e·, NH3) - 1H at 6.79 ppm (S, H thiazol) - 1H at 5.90 ppm (D of D, J_χ=9 Hz, J₂=4 Hz, H₇)

- 1H at 4.94 ppm (D, J=4 Hz, H₆) - 1H at 4.16 ppm (D, J=13 Hz, CH2 SCO) - 1H at 3.74 ppm (D, J≈13 Hz, CH₂ SCO) 2H at 3.70 ppm (S, CH₂S0) - 2H at 3.25 ppm (M, CH₂NH) 3H at 2.90 ppm (M, CH₂NH and CH COS) - 4H at 2.40 ppm

(M, CH₂

and SCO

O

-j C0₂H) - 6H at 1.80 ppm (M, CH₂

ch₂ ch₂

,ch₂

)•

0

co₂h ch₂

ch₂

MR n" 14 - (b) :

1H at 8.65 ppm (D, J=9 Hz, CONfl) - 3H at 8.20 ppm (S.e., NH3) - 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., NH3) - 1H at 6.82 ppm (S, H thiazol) ~ 1H at 5.88 ppm (D of D, J_χ=9 HZ, J₂≈4 Hz, H₇) - 1H at 4.92 ppm (D, J=4 Hz, H$) - 2H at 4.55 ppm (S, CH^ON) - 1H at 4.37 ppm (D, J=13 Hz, CHjSCO) - 2H at 4.13 ppm (M, CH₂NH₂) - 1H at 4.42 ppm (D, J=13 Hz, CHgSCO) - 2H at~ 3.74 ppm (S, CHjSO).

NMR n‘ 15 - (bΐ:

1H at 8.60 ppm (2D, J=9 Hz, CONH)* - 3H at 8.20 ppm (S.e., $113) - 2H at 7.92 ppm (D, 3=8 Hz, H ortho CO)2H at 7.56 ppm (D, J=8 Hz, H meta CO) - 3H at 7.30 ppm (S.e., NH3) - 1H at 6.82 ppm (2S, H thiazol)* - 1H at 5.92 ppm (D of D, J_χ=9 Hz, J₂=4 Hz, H₇) - 1H at 4.95 ppm (2D, superposed, H_δ)* - 1H at 4.60 ppm (Q, J=7 Hz, CHON) - 1H at 4.40 ppm (D, J=13 Hz, CH₂SCO) - 2H at 4.13 ppm (M, CH_₂NH₂) - 1H at 3.90 ppm (D, J=13 Hz, CH₂S CO)5 2H at 3.75 ppm (S, CH₂ SO) - 3H at 1.45 ppm (D, J=7 Hz, CH₃ CH).

NMR n' 16 - i

1H at 8.61 ppm (D, J=9 Hz, CONH) - 5H at 8.40 ppm (S.e., NH3, C0₂H) - 2H at 7.95 ppm (D, J=8 Hz, S ortho CO) - 2H 10 at 7.61 ppm (D, j+8 Hz, H meta CO) - 3H at 7.30 ppm (S.e., NH3) - 1H at 6.76 ppm (S, H thiazol) - 1H at 5.92 ppm (D of D, Ji=9 Hz, J2=4 Hz, H7) - 1H at 4.93 ppm (D, J=4 Hz, H₆) - 1H at 4.42 ppm (D, J=13 Hz, CH₂SCO) - 2H at 4.10 ppm (S.e., CH₂NH₂) - 1H at 3.92 ppm (D, J=13 Hz, 15 CH^SCO) - 2H at 3.74"ppm (S, CH₂ SO) - 4H at 2.35 ppm

0 ^^ch2⁰

(M, CH₂ ) C0₂H) - 2H at 1.85 ppm (M, CHg ^ ).

ch₂ ch₂ co₂h NMR n* 17 - ~7b^ :