RU95121625A

RU95121625A - PHENOXYPHENYLACETIC ACID DERIVATIVES

Info

Publication number: RU95121625A
Application number: RU95121625/04A
Authority: RU
Inventors: В.Бэгли Скотт; П.Бротен Теодор; К.Чакраварти Прасун; С.Дханоа Далджит; Дж.Фитч Кеннет; Дж.Гринли Уильям; Джо Кевин Нэнси; Дж.Петтибоун Дуглас; А.Риверо Ральф; Р.Тата Джеймс; Ф.Уолш Томас; Л.Уилльямс Дэвид (младший)
Original assignee: Мерк Энд Ко., Инк
Priority date: 1993-03-19
Filing date: 1994-03-17
Publication date: 1997-09-27

Claims

1. The compound of structural formula

and its pharmaceutically acceptable salt,
Where
R ¹ , R ² , R ³ ^a and R ³ ^b independently are
(a) H,
(b) F, Cl, Br or I
(c) -NO ₂ ,
(d) -NH ₂ ,
(e) -NH (C ₁ - C ₄ ) -alkyl,
(f) -N [(C ₁ - C ₄ ) -alkyl] ₂ ,
(g) -SO ₂ NHR ⁷ ,
(h) -CF ₃ ,
(i) - (C ₁ - C ₆ ) -alkyl,
(j) -OR ⁷ ,
(k) -S (O) _n - (C ₁ - C ₄ ) -alkyl,
(l) -NHCO- (C ₁ - C ₄ ) -alkyl,
(m) -NHCO- O (C ₁ -C ₄ ) -alkyl,
(n) -CH ₂ O- (C ₁ - C ₄ ) -alkyl,
(o) -O- (CH ₂ ) _m -OR ⁷ ,
(p) -CONR ⁷ R ¹ ¹ or
(q) -COOR ⁷ ,
R ¹ and R ² at adjacent carbon atoms can combine to form a cyclic structure

where A represents
a) -YC (R ⁴ ) = C (R ⁵ ) -,
b) -YC (R ⁴ ) = N-,
c) -YN = C (R ⁴ ) -,
d) -Y- [C (R ⁶ ) (R ⁶ )] ₅ -Y-,
e) -YC (R ⁶ ) (R ⁶ ) -C (R ⁶ ) (R ⁶ ) -,
f) -C (R ⁴ ) = C (R ⁵ ) -Y-,
g) -N = C (R ⁴ ) -Y-,
h) —C (R ⁶ ) (R ⁶ ) —C (R ⁶ ) (R ⁶ ) —Y—, or
i) -C (R ⁴ ) = C (R ⁵ ) -C (R ⁴ ) = C (R ⁵ ) -;
n = 0, 1 or 2;
m = 2, 3 or 4;
s = 1 or 2;
Y represents -O-, -S (O) _n - and NR ⁷ ;
R ⁴ and R ⁵ are independently
(a) H,
(b) (C ₁ - C ₆ ) -alkyl or (C ₂ - C ₆ ) -alkenyl, each of which is unsubstituted or substituted by one or two substituents selected from the group consisting of
(i) - OH,
(ii) -O- (C ₁ - C ₄ ) -alkyl,
(iii) -S (O) _n - (C ₁ - C ₄ ) -alkyl,
(iv) -NR ⁷ - (C ₁ - C ₄ ) alkyl,
(v) -NHR ⁷ ,
(vi) -COOR ⁷ ,
(vii) -CONHR ⁷ ,
(viii) -OCOR ¹ ¹ or
(ix) -CONR ⁷ R ¹ ¹ ,
(c) (C ₃ - C ₇ ) -cycloalkyl,
(d) F, Cl, Br, I,
(e) CF ₃ ,
(f) -COOR ⁷ ,
(g) -CONR ⁷ R ¹ ¹ ,
(h) -NR ⁷ R ¹ ¹ ,
(i) - NR ⁷ CONR ⁷ R ¹ ¹ ,
(j) - NR ⁷ COOR ¹ ¹ ,
(k) - SO ₂ NR ⁷ R ¹ ¹ ,
(l) -O- (C ₁ - C ₄ ) -alkyl,
(m) -S (O) _n - (C ₁ - C ₄ ) -alkyl, or
(n) -NHSO ₂ R ¹ ¹ ;
R ⁶ is
(a) H,
(b) (C ₁ - C ₄ ) -alkyl, unsubstituted or substituted by one of the following substituents:
(i) -OH
(ii) -NR ⁷ R ¹ ¹ ,
(iii) -COOR ⁷ ,
(iv) -CONHR ⁷ ,
(v) -CONR ⁷ R ¹ ¹ ,
R ⁷ is
(a) hydrogen,
(b) (C ₁ - C ₆ ) -alkyl,
(c) phenyl,
(d) (C ₁ - C ₆ ) -alkylphenyl, or
(e) (C ₃ - C ₇ ) -cycloalkyl,
R ⁸ is
(a) H,
(b) (C ₁ - C ₆ ) -alkyl, unsubstituted or substituted by a substituent selected from the group consisting of
(i) phenyl,
(ii) - (C ₃ - C ₇ ) -cycloalkyl,
(iii) -NR ⁷ R ¹ ¹ ,
(iv) morpholin-4-yl,
(v) -OH,
(vi) -CO ₂ R ⁷ , or
(vii) -CON (R ⁷ ) ₂ ,
(c) phenyl, unsubstituted or substituted by a substituent selected from the group consisting of
(i) C ₁ - C ₄ -alkyl,
(ii) -O- (C ₁ - C ₄ ) -alkyl,
(iii) -CONR ⁷ R ¹ ¹ ,
(iv) F, Cl, Br or I, or
(v) -COOR ⁷ ,
R ⁹ and R ¹ ⁰ are independently
(a) H,
(b) (C ₁ -C ₆ ) -alkyl, unsubstituted or substituted (C ₃ -C ₇ ) -cycloalkyl or —CO ₂ R ⁷ ,
(c) (C ₂ - C ₆ ) alkenyl,
(d) (C ₂ - C ₆ ) alkynyl,
(e) Cl, Br, F, I,
(f) (C ₁ - C ₆ ) alkoxy,
(g) perfluoro- (C ₁ -C ₆ ) -alkyl,
(h) - (C ₃ - C ₇ ) -cycloalkyl, unsubstituted or substituted (C ₁ - C ₆ ) -alkyl,
(i) phenyl,
(j) (C ₁ - C ₆ ) -alkyl-S (O) _n - (CH ₂ ) _n -,
(k) hydroxy- (C ₁ - C ₆ ) -alkyl,
(l) -CF ₃ ,
(m) -CO ₂ R ⁷ ,
(n) -OH,
(o) -NR ⁷ R ¹ ¹ ,
(p) - [(C ₁ - C ₆ ) -alkyl] NR ⁷ R ¹ ¹ ,
(q) -NO ₂ ,
(r) - (CH ₂ ) _n -SO ₂ -N (R ⁷ ) ₂ ,
(s) -NR ⁷ CO- (C ₁ - C ₄ ) -alkyl, or
(t) -CON (R ⁷ ) ₂ ;
R ⁹ and R ¹ ⁰ located at adjacent carbon atoms can join to form a fused phenyl ring, unsubstituted or substituted by a substituent selected from the group consisting of
(C ₁ - C ₆ ) -alkyl, (C ₁ - C ₆ ) -alkoxy, (C ₃ - C ₇ ) -cycloalkyl and (C ₁ - C ₆ ) -alkyl- (C ₃ - C ₇ ) -cycloalkyl,
R ¹ ¹ is
(a) (C ₁ - C ₆ ) -alkyl, unsubstituted or substituted by a substituent selected from the group consisting of
(i) -OR ⁷ ,
(ii) -N [R ⁷ ] ₂ ,
(iii) -NH ₂ ,
(iv) -COOR ⁷ , or
(v) -N [CH ₂ CH ₂ ] ₂ Q,
(b) aryl, where aryl is defined as phenyl or naphthyl, which is unsubstituted or substituted by one or two substituents selected from the group consisting of
i) (C ₁ - C ₄ ) -alkyl,
ii) -O- (C ₁ - C ₄ ) -alkyl,
iii) -CO [NR ⁷ ] ₂ ,
iv) F, Cl, Br or I,
v) -COOR ⁷ ,
vi) - NH ₂ ,
vii) - NH [(C ₁ - C ₄ ) -alkyl],
viii) - N [(C ₁ - C ₄ ) -alkyl] ₂ , or
ix) - CON [CH ₂ CH ₂ ] ₂ Q;
(c) (C ₁ - C ₄ ) -alkylaryl, where aryl is as defined above,
(d) (C ₃ - C ₇ ) -cycloalkyl,
(e)

R ⁷ and R ¹ ¹ on the same nitrogen atom can combine to form a ring selected from the group consisting of morpholinyl, piperazinyl or pyrrolyl, or Q is O, S or -NR ⁷ ;
R ¹ ² is
(a) H,
(b) (C ₁ -C ₆ ) -alkyl, unsubstituted or substituted by one or two substituents selected from the group consisting of
i) -OH
ii) -O- (C ₁ - C ₄ ) -alkyl,
iii) -O- (C ₁ - C ₄ ) -cycloalkyl,
iv) -S (O) _n - (C ₁ - C ₄ ) -alkyl,
v) -NR ⁷ R ¹ ¹ ,
vi) -COOR ⁷ ,
vii) -CONHR ⁷ ,
viii) -OCOR ¹ ¹ ,
ix) -CONR ⁷ R ¹ ¹ ,
x) -NR ⁷ CONR ⁷ R ¹ ¹ ,
xi) -NR ⁷ COOR ¹ ¹ ,
xii) -C (R ⁶ ) (OH) -C (R ⁶ ) (R ⁷ ) (OH), or
xiii) -SO ₂ NR ⁷ R ¹ ¹ ,
(c) (C ₃ - C ₇ ) -cycloalkyl,
(d) -OR ⁷ ,
(e) -COOR ⁷ ,
(f) -CONH ₂ ,
(g) -CONR ⁷ R ¹ ¹ ,
(h) -CONR ⁷ CO ₂ R ⁷ ,
(i) -NH ₂ ,
(j) -NR ⁷ R ¹ ¹ ,
(k) -NR ⁷ CONR ⁷ R ¹ ¹ ,
(l) -NR ⁷ COOR ¹ ¹ ,
(m) -C (R ⁶ ) (OH) -C (R ⁶ ) (R ⁷ ) (OH),
(n) -SO ₂ NR ⁷ R ¹ ¹ ,
(o) -S (O) ₂ NR ⁷ COR ¹ ¹ ,
(p) -S (O) ₂ NR ⁷ CO ₂ R ¹ ¹ ,
(q) -S (O) ₂ NR ⁷ CONR ⁷ R ¹ ¹ ,
(r) -NHSO ₂ R ¹ ¹ ,
(s) -NR ⁷ SO ₂ NR ⁷ R ¹ ¹ ,
(t) -CONHSO ₂ R ¹ ¹ ,
(u) -CO-amino acid, where the amino acid is defined as L - or D-amino acid selected from the group consisting of Ala, Ile, Phe, Asp, Pro and Val and which can also be substituted (C ₁ - C ₆ ) -alkyl ether or amide, or

X is
(a) -O-,
(b) -S (O) _n -,
(c) -NR ⁷ -,
(d) -CH ₂ O-,
(e) -CH ₂ S (O) _n -,
(f) -CH ₂ NR ⁷ -,
(g) -OCH ₂ -,
(h) -N (R ⁷ ) CH ₂ -,
(i) -S (O) _n CH ₂ -, or
(j) - a simple bond.

Z is
(a) -CO ₂ H,
(b) -CO ₂ R ¹ ³ ,
(c) -CONH- (tetrazol-5-yl),
(d) -CONHSO ₂ OR ¹ ¹
(e) -CONHSO ₂ -aryl, where aryl is defined as phenyl or naphthyl, which are unsubstituted or substituted by one or two substituents selected from the group consisting of
i) (C ₁ - C ₄ ) -alkyl,
ii) -O- (C ₁ - C ₄ ) -alkyl,
iii) -CONR ⁷ R ¹ ¹ ,
iv) F, Cl, Br or I,
v) -COOR ⁷ ,
vi) -NH ₂ ,
vii) -NH [(C ₁ - C ₄ ) alkyl],
viii) -N [(C ₁ - C ₄ ) -alkyl] ₂ ,
ix) - phenyl,
x) -OH,
xi) -OCH ₂ CH ₂ OH,
xii) -CF ₃ ;
(f) -CONHSO ₂ - (C ₁ -C ₈ ) -alkyl, where the alkyl group is unsubstituted or substituted, as defined in R ⁴ (b),
(g) -CONHSO ₂ - (C ₁ - C ₄ ) -perfluoroalkyl,
(h) tetrazol-5-yl,
(i) -CONHSO ₂ -heteroaryl, wherein heteroaryl is defined as carbazolyl, furyl, thienyl, pyrrolyl, isothiazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrazolyl, pyrazinyl, pyridyl, pyrimidyl, purinyl or quinolinyl, which is unsubstituted or substituted by one or two substituents selected from the group consisting of
i) (C ₁ - C ₄ ) -alkyl,
ii) -O- (C ₁ - C ₄ ) -alkyl
iii) -CONR ⁷ R ¹ ¹ ,
iv) F, Cl, Br or I,
v) -COOR ⁷ ,
vi) -NR ⁷ CONR ⁷ R ¹ ¹ and
vii) -NR ⁷ COOR ¹ ¹ ,
(j) -SO ₂ NHCO-aryl, where aryl is as defined above for Z (d),
(k) -SO ₂ NHCO - (C ₁ -C ₈ ) -alkyl, where the alkyl group is unsubstituted or substituted as defined for R ⁴ (b),
(l) -SO ₂ NHCO- (C ₁ - C ₄ ) -perfluoroalkyl,
(m) -SO ₂ NHCO-heteroaryl, where heteroaryl is as defined above for Z (g),
(n) -SO ₂ NHCON (R ¹ ¹ ) ₂ , where the groups R ¹ ¹ are the same or different,
R ¹ ³ is
(a) (C ₁ - C ₄ ) -alkyl,
(b) CHR ¹ ⁴ -O-COR ¹ ⁵ ,
(c) CH ₂ CH ₂ -N [(C ₁ - C ₄ ) -alkyl] ₂ ,
(d) CH ₂ CH ₂ -N [(CH ₂ CH ₂ ] ₂ O,
(e) (CH ₂ CH ₂ O) _y -O - [(C ₁ - C ₄ ) -alkyl], in which y = 1 or 2,
(f) phenyl, naphthyl, CH ₂ -phenyl or CH ₂ -naphthyl, where the phenyl or naphthyl is substituted or not substituted by CO ₂ - (C ₁ -C ₄ ) alkyl,

and R ¹ ⁴ and R ¹ ⁵ are independently (C ₁ - C ₆ ) -alkyl or phenyl,
provided that Z in a compound of structural formula I is CO ₂ H or CO ₂ R ¹ ³ , where R ¹ ³ is (C ₁ -C ₆ ) -alkyl, X is O, R ⁹ is H or (C ₁ -C ₆ ) -alkyl, unsubstituted or substituted hydroxy, R ¹ ⁰ is H, R ₁ ₂ is OR ⁷ , where R ⁷ is H or (C ₁ -C ₆ ) -alkyl, R ³ ^a is H, F, Cl or I and R ³ ^b is F, Cl, Br, J, or OR ⁷ , where R ⁷ is (C ₁ - C ₆ ) -alkyl, then R ¹ and R ² are not both hydrogen, and, in the alternative, R ¹ and R ² do not simultaneously represent -CR ⁴ = CR ⁵ -CR ⁴ = CR ⁵ -, where R ⁴ and R ⁵ are hydrogen, or
when Z in the compound of structural formula I is CO ₂ H or CO ₂ R ¹ ³ , where R ¹ ³ is (C ₁ -C ₆ ) -alkyl; X is a single bond and R ¹ and R ¹ ² are OR ⁷ , where R ⁷ is H, then R ³ ^a , R ³ ^b , R ⁹ and R ¹ ⁰ do not represent Cl, or
when Z in the compound of structural formula I is CO ₂ R ¹ ³ , where R ¹ ³ is (C ₁ - C ₆ ) -alkyl, X is S and R ¹ and R ² represent the cyclic structure A, which is -O-CH ₂ O- and condensed in the 3,4th position of the phenyl ring, then at least one of R ³ ^a , R ³ ^b , R ⁸ , R ⁹ , R ¹ ⁰ and R ¹ ² is different from hydrogen; or
when Z in the compound of structural formula I is CO ₂ H, X is -OCH ₂ - and R ¹ and R ² represent cyclic structure A, which is -O-CH ₂ -O- and condensed in the 3.4-position of the phenyl ring ; R ¹ ² is OR ⁷ , where R ⁷ is (C ₁ -C ₆ ) -alkyl, then at least one of R ³ ^a , R ³ ^b , R ⁸ , R ⁹ and R ¹ ⁰ is different from hydrogen.

2. The compound according to claim 1 of structural formula II

or its pharmaceutically acceptable salt,
where R ¹ , R ² , R ³ ^a and R ³ ^b independently are
(a) H,
(b) F, Cl, Br or I,
(c) -NO ₂ ,
(d) -NH ₂ ,
(e) -NH- (C ₁ - C ₄ ) -alkyl,
(f) -N [(C ₁ - C ₄ ) -alkyl] ₂ ,
(g) -SO ₂ NHR ⁷ ,
(h) -CF ₃ ,
(i) - (C ₁ - C ₆ ) -alkyl,
(j) -OR ⁷ ,
(k) -S (O) _n (C ₁ - C ₄ ) -alkyl,
(l) -NHCO (C ₁ - C ₄ ) -alkyl,
(m) -NHCO-O (C ₁ - C ₄ ) -alkyl,
(n) -CH ₂ O- (C ₁ - C ₄ ) -alkyl,
(o) -O- (CH ₂ ) _m -OR ⁷ ,
(p) -CONR ⁷ R ¹ ¹ , or
(q) -COOR ⁷ ,
R ¹ and R ² at adjacent carbon atoms can combine to form a cyclic structure

where A represents
a) -YC (R ⁴ ) = C (R ⁵ ) -,
b) -YC (R ⁴ ) = N-,
c) -YN = C (R ⁴ ) -,
d) -Y- [C (R ⁶ ) (R ⁶ )] _s -Y-,
e) -YC (R ⁶ ) (R ⁶ ) -C (R ⁶ ) (R ⁶ ) -,
f) -C (R ⁴ ) = C (R ⁵ ) -Y-,
g) -N = C (R ⁴ ) -Y-,
h) —C (R ⁶ ) (R ⁶ ) —O (R ⁶ ) (R ⁶ ) —Y—, or
i) -C (R ⁴ ) = C (R ⁵ ) -C (R ⁴ ) = C (R ⁵ ) -,
m = 2, 3 or 4,
n = 0, 1 or 2,
s = 1 or 2,
Y is equal to -O-, -S- and NR ⁷ ,
R ⁴ and R ⁵ are independently
(a) H,
(b) (C ₁ - C ₆ ) -alkyl or (C ₂ - C ₆ ) -alkenyl, each of which is unsubstituted or substituted by one or two substituents selected from the group consisting of
i) -OH
ii) -O- (C ₁ - C ₄ ) -alkyl,
iii) -S (O) _n - (C ₁ - C ₄ ) -alkyl,
iv) -NR ⁷ - (C ₁ - C ₄ ) alkyl,
v) -NHR ⁷ ,
vi) -COOR ⁷ ,
vii) -CONHR ⁷ ,
viii) -OCOR ¹ ¹ or
ix) -CONR ⁷ R ¹ ¹ ,
(c) (C ₃ - C ₇ ) cycloalkyl,
(d) F, Cl, Br, J,
(e) CF ₃ ,
(f) -COOR ⁷ ,
(g) -CONR ⁷ R ¹ ¹ ,
(h) -NR ⁷ R ¹ ¹ ,
(i) -NR ⁷ CONR ⁷ R ¹ ¹ ,
(j) -NR ⁷ COOR ¹ ¹ ,
(k) -SO ₂ NR ⁷ R ¹ ¹ ,
(l) -O (C ₁ - C ₄ ) -alkyl,
(m) -S (O) _m - (C ₁ - C ₄ ) -alkyl, or
(n) -NHSO ₂ R ¹ ¹ ;
R ⁶ is
(a) H,
(b) (C ₁ - C ₄ ) -alkyl, unsubstituted or substituted by one or two substituents selected from the group consisting of
i) -OH
ii) -NR ⁷ R ¹ ¹ ,
iii) -COOR ⁷ ,
iv) -CONHR ⁷ or
v) -CONR ⁷ R ¹ ¹ ;
R ⁷ is
(a) H,
(b) (C ₁ - C ₆ ) -alkyl,
(c) phenyl,
(d) (C ₁ - C ₆ ) -alkylphenyl,
(e) (C ₃ - C ₇ ) -cycloalkyl,
R ⁸ is
(a) H,
(b) (C ₁ -C ₆ ) -alkyl, unsubstituted or substituted by one or two substituents selected from the group consisting of
(i) phenyl,
(ii) - (C ₃ - C ₇ ) -cycloalkyl,
(iii) -NR ⁷ R ¹ ¹ ,
(iv) morpholine-4-yl,
(v) -OH,
(vi) -CO ₂ R ⁷ , or
(vii) -CON (R ⁷ ) ₂ ,
or
(c) phenyl;
R ⁹ and R ¹ ⁰ are independently
(a) H,
(b) (C ₁ -C ₆ ) -alkyl, unsubstituted or substituted (C ₃ -C ₇ ) -cycloalkyl or —CO ₂ R ⁷ ,
(c) (C ₂ - C ₆ ) alkenyl,
(d) (C ₂ -C ₆ ) alkynyl,
(e) Cl, Br, F, I,
(f) (C ₁ -C ₆ ) -alkoxy,
(g) perfluoro- (C ₃ -C ₆ ) -alkyl,
(h) (C ₃ -C ₇ ) -cycloalkyl, unsubstituted or substituted (C ₁ -C ₆ ) -alkyl,
(i) phenyl,
(j) (C ₁ -C ₆ ) -alkyl-S (O) _n - (CH ₂ ) _n ^- ,
(k) hydroxy- (C ₁ -C ₆ ) -alkyl,
(l) CF ₃ ,
(m) -CO ₂ R ⁷ ,
(n) -OH
(o) -NR ⁷ R ¹ ¹ ,
(p) - [(C ₁ -C ₆ ) -alkyl] NR ⁷ R ¹ ¹ ,
(q) -NO ₂
(r) - (CN ₂ ) _n -SO ₂ -N (R ⁷ ) ₂
(s) -NR ⁷ CO- (C ₁ -C ₄ ) -alkyl, or
(t) -CON (R ⁷ ) ₂ ;
R ⁹ and R ¹ ⁰ at adjacent carbon atoms can combine to form a condensed phenyl ring, unsubstituted or substituted by a substituent selected from the group consisting of (C ₁ -C ₆ ) -alkyl, (C ₁ -C ₆ ) -alkoxy, ( C ₃ - C ₇ ) cycloalkyl and (C ₁ - C ₆ ) alkyl- (C ₃ - C ₇ ) cycloalkyl;
R ¹ ¹ is
(a) (C ₁ - C ₆ ) -alkyl, unsubstituted or substituted by a substituent selected from the group consisting of
i) -OR ⁷ ,
ii) - N [R ⁷ ] ₂ ,
iii) -NH ₂ ,
iv) -COOR ⁷ or
v) -N [CH ₂ CH ₂ ] ₂ Q;
(b) aryl, where aryl is defined as phenyl or naphthyl, which is unsubstituted or substituted by one or two substituents selected from the group consisting of
i) (C ₁ - C ₄ ) -alkyl,
ii) -O- (C ₁ - C ₄ ) -alkyl,
iii) -CO [NR ⁷ ] ₂ ,
iv) F, Cl, Br or I,
v) -COOR ⁷ ,
vi) -NH ₂ ,
vii) -NH [(C ₁ - C ₄ ) alkyl],
viii) -N [(C ₁ - C ₄ ) -alkyl] ₂ or
ix) -CON [(CH ₂ CH ₂ ] ₂ Q,
(c) - (C ₁ - C ₄ ) -alkylaryl, where aryl is as defined above,
(d) - (C ₃ - C ₇ ) -cycloalkyl,

R ⁷ and R ¹ ¹ on the same nitrogen atom can combine to form a ring selected from the group consisting of morpholinyl, piperazinyl or pyrrolyl, or
Q is O, S or -NR ⁷ ,
R ¹ ² is
(a) H,
(b) (C ₁ - C ₄ ) -alkyl, unsubstituted or substituted by one or two substituents selected from the group consisting of
i) -OH
ii) -O- (C ₁ - C ₄ ) -alkyl,
iii) -O- (C ₁ - C ₄ ) -cycloalkyl,
iv) -S (O) _n - (C ₁ - C ₄ ) -alkyl,
v) -NR ⁷ R ¹ ¹ ,
vi) -COOR ⁷ ,
vii) -CONHR ⁷ ,
viii) -OCOR ¹ ¹ ,
ix) -CONR ⁷ R ¹ ¹ ,
x) -NR ⁷ CONR ⁷ R ¹ ¹ ,
xi) -NR ⁷ COOR ¹ ¹ ,
xii) -C (R ⁶ ) (OH) -C (R ⁶ ) (R ⁷ ) (OH) or
xiii) -SO ₂ NR ⁷ R ¹ ¹ ,
(c) (C ₃ - C ₇ ) -cycloalkyl,
(d) -OR ⁷ ,
(e) -COOR ⁷ ,
(f) -CONH ₂ ,
(g) -CONR ⁷ R ¹ ¹ ,
(h) -CONR ⁷ CO ₂ R ⁷ ,
(i) -NH ₂ ,
(j) -NR ⁷ R ¹ ¹ ,
(k) -NR ⁷ CONR ⁷ R ¹ ¹ ,
(l) -NR ⁷ COOR ¹ ¹ ,
(m) -C (R ⁶ ) (OH) -C (R ⁶ ) (R ⁷ ) (OH),
(n) -SO ₂ NR ⁷ R ¹ ¹ ,
(o) -S (O ₂ ) NR ⁷ COR ¹ ¹ ,
(p) -S (O ₂ ) NR ⁷ CO ₂ R ¹ ¹ ,
(q) -S (O ₂ ) NR ⁷ CONR ⁷ R ¹ ¹ ,
(r) -NHSO ₂ R ¹ ¹ ,
(s) -NR ⁷ SO ₂ NR ⁷ R ¹ ¹ ,
(t) -CONHSO ₂ R ¹ ¹ ,
(u) -CO-amino acid, where the amino acid is defined as L - or D-amino acid selected from the group consisting of Ala, Ile, Phe, Asp, Pro and Val and which can be substituted with (C ₁ -C ₆ ) -alkyl ether or amide, or

X is
(a) -O-,
(b) -S (O) _n -,
(c) -NR ⁷ -,
(d) -CH ₂ O-,
(e) -CH ₂ S (O) _n -,
(f) -CH ₂ NR ⁷ ,
(g) -OCH ₂ -,
(h) -N (R ⁷ ) CH ₂ -,
(i) -S (O) _n CH ₂ - or
(j) - a simple bond.

Z is
(a) -CO ₂ H,
(b) -CO ₂ R ¹ ³ ,
(c) -CONH- (tetrazol-5-yl),
(d) -CONHSO ₂ OR ¹ ¹ ,
(e) -CONHSO ₂ -aryl, where aryl is defined as phenyl or naphthyl, which is unsubstituted or substituted by one or two substituents selected from the group consisting of
i) (C ₁ - C ₄ ) -alkyl,
ii) -O- (C ₁ - C ₄ ) -alkyl,
iii) -CONR ⁷ R ¹ ¹ ,
iv) F, Cl, Br or I,
v) -COOR ⁷ ,
vi) -NH ₂ ,
vii) -NH [(C ₁ - C ₄ ) alkyl],
viii) -N [(C ₁ - C ₄ ) -alkyl] ₂ ,
ix) -phenyl,
x) -OH,
xi) OCH ₂ CH ₂ OH,
xii) CF ₃ ;
(f) -CONHSO ₂ - (C ₁ -C ₈ ) -alkyl, where the alkyl group is unsubstituted or substituted as defined for R ⁴ (b),
(g) -CONHSO ₂ - (C ₁ - C ₄ ) -perfluoroalkyl,
(h) tetrazol-5-yl,
(i) -CONHSO ₂ -heteroaryl, where heteroaryl is defined as carbazolyl, furyl, thienyl, pyrrolyl, isothiazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrazolyl, pyridyl, pyrimidyl, purine or quenolyl, arate, zinc, and arate. selected from the group consisting of
i) (C ₁ - C ₄ ) -alkyl,
ii) -O- (C ₁ - C ₄ ) -alkyl,
iii) -CONR ⁷ R ¹ ¹ ,
iv) F, Cl, Br or I,
v) -COOR ⁷ ,
vi) -NR ⁷ CONR ⁷ R ¹ ¹ and
vii) -NR ⁷ COOR ¹ ¹ ,
(j) -SO ₂ NHCO-aryl, where aryl is as defined for Z (d),
(k) -SO ₂ NHCO- (C ₁ -C ₈ ) -alkyl, where the alkyl group is unsubstituted or substituted, as defined for R ⁴ (b),
(l) -SO ₂ NHCO- (C ₁ - C ₄ ) -perfluoroalkyl,
(m) -SO ₂ NHCO-heteroaryl, where heteroaryl is as defined for Z (g),
(n) -SO ₂ NHCON (R ¹ ¹ ) ₂ , where the groups R ¹ ¹ are the same or different,
R ¹ ³ is
(a) (C ₁ - C ₄ ) -alkyl,
(b) CHR ¹ ⁴ -O-COR ¹ ⁵ ,
(c) CH ₂ CH ₂ -N [(C ₁ - C ₂ ) -alkyl] ₂ ,
(d) CH ₂ CH ₂ -N [CH ₂ CH ₂ ] ₂ O,
(e) (CH ₂ CH ₂ O) _y -O - [(C ₁ - C ₄ ) -alkyl], where y = 1 or 2,
(f) phenyl, naphthyl, CH ₂ -phenyl or CH _2- naphthyl, where the phenyl or naphthyl is substituted or not substituted by CO ₂ - (C ₁ -C ₄ ) alkyl,

or

and

R ¹ ⁴ and R ¹ ⁵ are independently (C ₁ - C ₆ ) -alkyl or phenyl.

3. The compound according to claim 2 of structural formula III

or its pharmaceutically acceptable salt,
Where
R ¹ , R ² , R ³ ^a and R ³ ^b independently are
(a) H,
(b) F, Cl, Br or I,
(c) -NO ₂ ,
(d) (C ₁ - C ₆ ) -alkyl,
(e) -OR ⁷ ,
(f) -NHCO- (C ₁ - C ₄ ) -alkyl,
(g) -NHCO-O (C ₁ - C ₄ ) -alkyl,
(h) -O- (CH ₂ ) _m -OR ⁷ ,
(i) -CONR ⁷ R ¹ ¹ ,
(j) -COOR ⁷ ,
R ¹ and R ² at adjacent carbon atoms can combine to form a cyclic structure

A represents
a) -YC (R ⁴ ) = C (R ⁵ ) -,
b) -YC (R ⁴ ) = N-,
c) -YN = C (R ⁴ ) -,
d) -Y- [C (R ⁵ ) (R ⁶ )] _s -Y-,
e) -YC (R ⁶ ) (R ⁶ ) -C (R ⁶ ) (R ⁶ ) -,
f) -C (R ⁴ ) -C (R ⁵ ) -Y-,
g) -N = C (R ⁴ ) -Y-,
h) —C (R ⁶ ) (R ⁶ ) —C (R ⁶ ) (R ⁶ ) —Y—, or
i) -C (R ⁴ ) = C (R ⁵ ) -C (R ⁴ ) = C (R ⁵ ) -,
m = 2, 3 or 4,
n = 0, 1 or 2,
S = 1 or 2,
Y is equal to -O-, -S- and NR ⁷ ,
R ⁴ and R ⁵ are independently
(a) H,
(b) (C ₁ - C ₆ ) -alkyl,
(c) (C ₃ - C ₇ ) -cycloalkyl,
(d) F, Cl, Br, I,
(e) -NR ⁷ COOR ¹ ¹ ,
(f) -SO ₂ NR ⁷ R ¹ ¹ ,
(g) -O- (C ₁ - C ₄ ) -alkyl,
(h) -S (O) _n - (C ₁ - C ₄ ) -alkyl or
(i) -NHSO ₂ R ¹ ¹ ,
R ⁶ is
(a) H or
(b) (C ₁ - C ₄ ) -alkyl,
R ⁷ is
(a) H,
(b) (C ₁ - C ₆ ) -alkyl,
(c) phenyl or
(d) benzyl,
R ⁸ is
(a) H,
(b) (C ₁ - C ₆ ) -alkyl or
(c) phenyl,
R ⁹ and R ¹ ⁰ are independently
(a) H,
(b) (C ₁ - C ₆ ) -alkyl, unsubstituted or substituted (C ₃ - C ₇ ) -cycloalkyl,
(c) Cl, Br, F, I,
(d) (C ₁ -C ₆ ) alkoxy or
(e) hydroxy- (C ₁ - C ₆ ) -alkyl,
R ¹ ¹ is
(a) (C ₁ - C ₆ ) -alkyl, unsubstituted or substituted by a substituent selected from the group consisting of
i) -OR ⁷ ,
ii) -N [R ⁷ ] ₂ ,
iii) -NH ₂ ,
iv) -COOR ⁷ or
v) -N [CH ₂ CH ₂ ] ₂ Q,
(b) aryl, where aryl is defined as phenyl or naphthyl, which are unsubstituted or substituted by one or two substituents selected from the group consisting of
i) (C ₁ - C ₄ ) -alkyl,
ii) -O- (C ₁ - C ₄ ) -alkyl,
iii) -CO [NR ⁷ ] ₂ ,
iv) - F, Cl, Br or I,
v) -COOR ⁷ ,
vi) -NH ₂ ,
vii) -NH [(C ₁ - C ₄ ) alkyl],
viii) -N [(C ₁ - C ₄ ) -alkyl] ₂ or
ix) -CON [CH ₂ CH ₂ ] ₂ Q,
(c) - (C ₁ - C ₄ ) -alkylaryl, where aryl is as defined above,
(d) (C ₃ - C ₇ ) -cycloalkyl,

R ⁷ and R ¹ ¹ on the same nitrogen atom can combine to form a ring selected from the group consisting of morpholinyl, piperazinyl or pyrrolyl, or
Q is O, S or -NR ⁷ ,
R ¹ ² is
(a) H,
(b) (C ₁ - C ₄ ) -alkyl, unsubstituted or substituted by one or two substituents selected from the group consisting of
i) -OH
ii) -O- (C ₁ - C ₄ ) -alkyl,
iii) -O- (C ₁ - C ₄ ) -cycloalkyl,
iv) -S (O) _n - (C ₁ - C ₄ ) -alkyl,
v) -NR ⁷ - (C ₁ - C ₄ ) -alkyl,
vi) -NR ⁷ R ¹ ¹ ,
vii) -COOR ⁷ ,
viii) -CONHR ⁷ ,
ix) -OCOR ¹ ¹ ,
x) -CONR ⁷ R ¹ ¹ ,
xi) -NR ⁷ CONR ⁷ R ¹ ¹ ,
xii) -NR ⁷ COOR ¹ ¹ ,
xiii) -C (R ⁶ ) (OH) - C (R ⁶ ) (R ⁷ ) (OH) or
xiv) -SO ₂ NR ⁷ R ¹ ¹ ,
(c) -COOR ⁷ ,
(d) -CONH ₂ ,
(e) -CONR ⁷ R ¹ ¹ ,
(f) -CONR ⁷ CO ₂ R ⁷ ,
(g) -C (R ⁶ ) (OH) -C (R ⁶ ) (R ⁷ ) (OH),
(h) -CONHSO ₂ R ¹ ¹ ,
(i) -SO ₂ NR ⁷ R ¹ ¹ ,
(j) -NR ⁷ SO ₂ NR ⁷ R ¹ ¹ ,
(k) -CO-amino acid, where the amino acid is defined as L - or D-amino acid selected from the group consisting of Ala, Ile, Phe, Asp, Pro and Val and which can be substituted with (C ₁ - C ₆ ) -alkyl ether or amide

X is
(a) -O-,
(b) -NR ⁷ - or
(c) - simple bond;
Z is
(a) -CO ₂ H,
(b) -CO ₂ R ¹ ³ ,
(c) -CONH- (tetrazol-5-yl),
(d) -CONHSO ₂ -aryl, where aryl is defined as phenyl or naphthyl, which is unsubstituted or substituted by two substituents selected from the group consisting of
i) (C ₁ - C ₄ ) -alkyl,
ii) -O- (C ₁ - C ₄ ) -alkyl,
iii) -CONR ⁷ R ¹ ¹ ,
iv) F, Cl, Br or I,
v) -COOR ⁷ ,
vi) -NH ₂ ,
vii) -NH [(C ₁ - C ₄ ) alkyl],
viii) -N [(C ₁ - C ₄ ) -alkyl] ₂ ,
ix) phenyl,
(e) -CONHSO ₂ - (C ₁ -C ₈ ) -alkyl, where alkyl is unsubstituted or substituted as defined in R ⁴ (b),
(f) -CONHSO ₂ -heteroaryl, where heteroaryl is defined as carbazolyl, furyl, thienyl, pyrrolyl, isothiazolyl, oxazolyl, isoxazolyl, thiazolyl, pyrazolyl, pyrazinyl, pyridyl, pyrimidyl, purinyl or quinolinyl, which is not substituted. selected from the group consisting of
i) (C ₁ - C) ₄ -alkyl,
ii) -O- (C ₁ -C ₄ ) -alkyl,
iii) -CONR ⁷ R ¹ ¹ ,
iv) F, Cl, Br or I,
v) -COOR ⁷ ,
vi) -NR ⁷ CONR ⁷ R ¹ ¹ or
vii) -NR ⁷ COOR ¹ ¹ ,
(g) tetrazol-5-yl, and
R ¹ ³ is (C ₁ - C ₄ ) -alkyl.

4. The compound according to claim 3 of structural formula IV

or its pharmaceutically acceptable salt,
Where
R ¹ and R ² taken together form a cyclic structure

where A - represents
(a) -Y- [C (R ⁶ ) (R ⁶ )] _s -Y- or
(b) -C (R ⁴ ) = C (R ⁵ ) -C (R ⁴ ) = C (R ⁵ ) -,
s = 1 or 2,
Y is equal to -O-,
R ³ ^a is
(a) H,
(b) F, Cl, Br or I,
(c) (C ₁ - C ₆ ) -alkyl,
(d) -OR ⁷ ,
(e) -O- (CH ₂ ) _m -OR ⁷ ,
(f) -CONR ⁷ R ¹ ¹ or
(g) -COOR,
m = 2, 3 or 4;
R ⁴ and R ⁵ are independently
(a) H,
(b) (C ₁ - C ₆ ) -alkyl,
(c) (C ₃ - C ₇ ) -cycloalkyl,
(d) F, Cl, Br, I,
(e) -NR ⁷ COOR ¹ ¹ ,
(f) -SO ₂ NR ⁷ R ¹ ¹ ,
(g) -O- (C ₁ - C ₄ ) -alkyl,
(h) -S (O) _n - (C ₁ - C ₄ ) -alkyl or
(i) -NHSO ₂ R ¹ ¹ ,
n = 0, 1 or 2,
R ⁶ is
(a) H or
(b) (C ₁ - C ₄ ) -alkyl,
R ⁷ is
(a) H,
(b) (C ₁ - C ₆ ) -alkyl,
(c) phenyl or
(d) benzyl;
R ⁸ is
(a) H,
(b) (C ₁ - C ₆ -alkyl or
(c) phenyl;
R ⁹ is
(a) H,
(b) (C ₁ - C ₆ ) -alkyl, unsubstituted or substituted (C ₃ - C ₇ ) -cycloalkyl,
(c) Cl, Br, F, I,
(d) (C ₁ -C ₆ ) alkoxy or
(e) hydroxy- (C ₁ - C ₆ ) -alkyl,
R ¹ ¹ is
(a) (C ₁ - C ₆ ) -alkyl, unsubstituted or substituted by a substituent selected from the group consisting of
i) -OR ⁷ ,
ii) -N [R ⁷ ] ₂ ,
iii) -NH ₂ ,
iv) -COOR ⁷ or
v) -N [CH ₂ CH ₂ ] ₂ Q,
(b) aryl, where aryl is defined as phenyl or naphthyl, which are unsubstituted or substituted by one or two substituents selected from the group consisting of
i) (C ₁ - C ₄ ) -alkyl,
ii) -O- (C ₁ - C ₄ ) -alkyl,
iii) -CO [NR ⁷ ] ₂ ,
iv) F, Cl, Br or I,
v) -COOR ⁷ ,
vi) -NH ₂ ,
vii) -NH [(C ₁ - C ₄ ) alkyl],
viii) -N [(C ₁ - C ₄ ) -alkyl] ₂ or
ix) -CON [CH ₂ CH ₂ ] ₂ Q,
(c) - (C ₁ - C ₄ ) -alkylaryl, where aryl is as defined above,
(d) (C ₃ - C ₇ ) -cycloalkyl,

R ⁷ and R ¹ ¹ on the same nitrogen atom can combine to form a ring selected from the group consisting of
morpholinyl, piperazinyl or pyrrolyl, or
Q is O, S or -NR ⁷ ,
R ¹ ² is
(a) H,
(b) (C ₁ -C ₆ ) -alkyl, unsubstituted or substituted by one or two substituents selected from the group consisting of
i) -OH
ii) -O- (C ₁ - C ₄ ) -alkyl,
iii) -O- (C ₁ - C ₄ ) -cycloalkyl,
iv) -S (O) _n - (C ₁ - C ₄ ) -alkyl,
v) -NR ⁷ R ¹ ¹ ,
vi) -COOR ⁷ ,
vii) -CONHR ⁷ ,
viii) -OCOR ¹ ¹ ,
ix) -CONR ⁷ R ¹ ¹ ,
x) -NR ⁷ CONR ⁷ R ¹ ¹ ,
xi) -NR ⁷ COOR ¹ ¹
xii) -C (R ⁶ ) (OH) -C (R ⁶ ) (R ⁷ ) (OH) or
xiii) -SO ₂ NR ⁷ R ¹ ¹ ,
(c) -COOR ⁷ ,
(d) -CONH ₂ ,
(e) -CONR ⁷ R ¹ ¹ ,
(f) -CONR ⁷ CO ₂ R ⁷ ,
(g) -C (R ⁶ ) (OH) -C (R ⁶ ) (R ⁷ ) (OH) or
(h) -CONHSO ₂ R ¹ ¹ ,
(i) -SO ₂ NR ⁷ R ¹ ¹ ,
(j) -NR ⁷ SO ₂ NR ⁷ R ¹ ¹ ,
(k) -CO-amino acid, where the amino acid is defined as L - or D-amino acid selected from the group consisting of Ala, Ile, Phe, Asp, Pro and Val and which can be substituted with (C ₁ - C ₆ ) -alkyl ether or amide, or

X is
(a) -O-,
(b) -NR ⁷ - or
(c) - simple bond;
Z is
(a) -CO ₂ H,
(b) -CO ₂ R ¹ ³ ,
(c) -CONH- (tetrazol-5-yl),
(d) -CONHSO ₂ -aryl, where aryl is defined as phenyl or naphthyl, which are unsubstituted or substituted by two substituents selected from the group consisting of
i) (C ₁ - C ₄ ) -alkyl,
ii) -O- (C ₁ - C ₄ ) -alkyl,
iii) -CONR ⁷ R ¹ ¹ ,
iv) F, Cl, Br or I,
v) -COOR ⁷ ,
vi) -NH ₂ ,
vii) -NH [(C ₁ - C ₄ ) alkyl],
viii) -N [(C ₁ - C ₄ ) -alkyl] ₂ ,
ix) phenyl,
(e) -CONHSO ₂ - (C ₁ -C ₈ ) -alkyl, where alkyl is unsubstituted or substituted as defined for R ⁴ (b),
(f) -CONHSO ₂ -heteroaryl, where heteroaryl is defined as carbazolyl, furyl, thienyl, pyrrolyl, isothiazolyl, oxazolyl, isoxazolyl, thiazolyl, pyrazolyl, pyrazinyl, pyridyl, pyrimidyl, purinyl or quinolinyl, which are non substituted. selected from the group consisting of
i) (C ₁ - C ₄ ) -alkyl,
ii) -O- (C ₁ - C ₄ ) -alkyl,
iii) -CONR ⁷ R ¹ ¹ ,
iv) F, Cl, Br or I,
v) -COOR ⁷ ,
vi) -NR ⁷ CONR ⁷ R ¹ ¹ and
vii) -NR ⁷ COOR ¹ ¹ , or
(g) tetrazol-5-yl; and
R ¹ ³ is (C ₁ - C ₄ ) -alkyl.

5. The compound according to claim 2 of structural formula V

or its pharmaceutically acceptable salt,
Where
R ¹ , R ² , R ³ ^a and R ³ ^b independently are
(a) H,
(b) F, Cl, Br or I,
(c) -NO ₂ ,
(d) - (C ₁ - C ₆ ) -alkyl,
(e) -OR ⁷ ,
(f) -NHCO- (C ₁ - C ₄ ) -alkyl,
(g) -NHCO-O (C ₁ - C ₄ ) -alkyl,
(h) -O- (CH ₂ ) _m -OR ⁷ ,
(i) -CONR ⁷ R ¹ ¹ or
(j) -COOR ⁷ ,
m = 2, 3 or 4,
R ⁴ and R ⁵ are independently
(a) H,
(b) (C ₁ - C ₆ ) -alkyl,
(c) (C ₃ - C ₇ ) -cycloalkyl,
(d) F, Cl, Br, I,
(e) -NR ⁷ COOR ¹ ¹ ,
(f) -SO ₂ NR ⁷ R ¹ ¹ ,
(g) -O- (C ₁ - C ₄ ) -alkyl,
(h) -S (O) _n - (C ₁ - C ₄ ) -alkyl or
(i) -NHSO ₂ R ¹ ¹ ,
n = 0, 1 or 2,
R ⁶ is
(a) H, or
(b) (C ₁ - C ₄ ) -alkyl,
R ⁷ is
(a) H,
(b) (C ₁ - C ₆ ) -alkyl,
(c) phenyl or
(d) benzyl;
R ⁸ is
(a) H,
(b) (C ₁ - C ₆ ) -alkyl or
(c) phenyl;
R ⁹ and R ¹ ⁰ are independently
(a) H,
(b) (C ₁ - C ₆ ) -alkyl, unsubstituted or substituted (C ₃ - C ₇ ) -cycloalkyl,
(c) Cl, Br, I, F,
(d) (C ₁ -C ₆ ) alkoxy or
(e) hydroxy- (C ₁ - C ₆ ) -alkyl,
R ¹ ¹ is
(a) (C ₁ -C ₆ ) -alkyl, unsubstituted or substituted by a substituent selected from the group consisting of
i) -OR ⁷ ,
ii) -N [R ⁷ ] ₂ ,
iii) -NH ₂ ,
iv) -COOR ⁷ or
v) -N [CH ₂ CH ₂ ] ₂ O,
(b) aryl, where aryl is defined as phenyl or naphthyl, which are unsubstituted or substituted by one or two substituents selected from the group consisting of
i) (C ₁ - C ₄ ) -alkyl,
ii) -O- (C ₁ - C ₄ ) -alkyl,
iii) -CO [NR ⁷ ] ₂ ,
iv) F, Cl, Br or I,
v) -COOR ⁷ ,
vi) -NH ₂ ,
vii) -NH [(C ₁ - C ₄ ) alkyl],
viii) -N [(C ₁ - C ₄ ) -alkyl] ₂ or
ix) -CON [CH ₂ CH ₂ ] ₂ Q,
(c) - (C ₁ -C ₄ ) -alkylaryl, where aryl is as defined above,
(d) (C ₃ - C ₇ ) -cycloalkyl,

R ⁷ and R ¹ ¹ on the same nitrogen atom can combine to form a ring selected from the group consisting of
morpholinyl, piperazinyl or pyrrolyl, or
Q is O, S or -NR ⁷
R ¹ ² is
(a) H,
(b) (C ₁ -C ₆ ) -alkyl, unsubstituted or substituted by one or two substituents selected from the group consisting of
i) -OH
ii) -O- (C ₁ - C ₄ ) -alkyl,
iii) -O- (C ₁ - C ₄ ) -cycloalkyl,
iv) -S (O) _n - (C ₁ - C ₄ ) -alkyl,
v) -NR ⁷ R ¹ ¹ ,
vi) -COOR ⁷ ,
vii) -CONHR ⁷ ,
viii) -OCOR ¹ ¹ ,
ix) -CONR ⁷ R ¹ ¹ ,
x) -NR ⁷ CONR ⁷ R ¹ ¹ ,
xi) -NR ⁷ COOR ¹ ¹ ,
xii) -C (R ⁶ ) (OH) -C (R ⁶ ) (R ⁷ ) (OH) or
xiii) -SO ₂ NR ⁷ R ¹ ¹ ,
(c) -COOR ⁷ ,
(d) -CONH ₂ ,
(e) CONR ⁷ R ¹ ¹ ,
(f) -CONR ⁷ CO ₂ R ⁷ ,
(g) -C (R ⁶ ) (OH) -C (R ⁶ ) (R ⁷ ) (OH),
(h) -CONHSO ₂ R ¹ ¹ ,
(i) -SO ₂ NR ⁷ R ¹ ¹ ,
(j) -NR ⁷ SO ₂ NR ⁷ R ¹ ¹ ,
(k) -CO-amino acid, where the amino acid is defined as L - or D-amino acid selected from the group consisting of Ala, Ile, Phe, Asp, Pro and Val and which can be substituted with (C ₁ - C ₆ ) -alkyl ether or amide, or

X is
(a) -O-,
(b) -NR ⁷ - or
(c) - simple connection,
Z is
(a) -CO ₂ H,
(b) -CO ₂ R ¹ ³ ,
(c) -CONH- (tetrazol-5-yl),
(d) -CONHSO ₂ -aryl, where aryl is defined as phenyl or naphthyl, which are unsubstituted or substituted by two substituents selected from the group consisting of
i) (C ₁ - C ₄ ) -alkyl,
ii) -O- (C ₁ -C ₄ ) -alkyl,
iii) -CONR ⁷ R ¹ ¹ ,
iv) F, Cl, Br or I,
v) _COOR ⁷ ,
vi) -NH ₂ ,
vii) -NH [(C ₁ -C ₄ ) -alkyl],
viii) -N [(C ₁ -C ₄ ) -alkyl] ₂ ,
ix) phenyl,
e) -CONHSO ₂ - (C ₁ -C ₈ ) -alkyl, where alkyl is unsubstituted or substituted as defined for R ⁴ (b).

(f) -CONHSO ₂ -heteroaryl, where heteroaryl is defined as carbazolyl, furyl, thienyl, pyrrolyl, isothiazolyl, imidazolyl, isoxazolyl, thiazolyl, pyrazolyl, pyrazinyl, pyridyl, pyrimidyl, purinyl or quinolinyl, which is not substituted. selected from the group consisting of:
i) (C ₁ -C ₄ ) -alkyl,
ii) -O- (C ₁ -C ₄ ) -alkyl,
iii) -CONR ⁷ R ¹¹ , iv) F, Cl, Br or I,
v) -COOR ⁷ ,
vi) -NR ⁷ CONR ⁷ R ¹ ¹ or
vii) -NR ⁷ COOR ¹ ¹ ,
(g) tetrazol-5-yl; and
R ¹ ³ is (C ₁ -C ₄ ) -alkyl.

6. The compound according to claim 2 of structural formula VI

or its pharmaceutically acceptable salt,
R ¹ and R ^{2 are} represented by the following ring structure:

where A represents
(a) -Y- [C (R ⁶ ) (R ⁶ )] _s -Y- or
(b) -C (R ⁴ ) = C (R ⁵ ) -C (R ⁴ ) = C (R ⁵ ) -,
s = 1 or 2,
Y is equal to -O-, -S- and NR ⁷ ,
R ³ ^a and R ³ ^b independently are
(a) H,
(b) F, Cl, Br or I,
(c) -NO ₂ ,
(d) (C ₁ - C ₆ ) -alkyl,
(e) -OR ⁷ ,
(f) -NHCO- (C ₁ - C ₄ ) -alkyl,
(g) -NHCO-O (C ₁ - C ₄ ) -alkyl,
(h) -O- (CH ₂ ) _m -OR ⁷ ,
(i) -CONR ⁷ R ¹ ¹ or
(j) -COOR ⁷ ,
m = 2, 3 or 4,
R ⁴ and R ⁵ are independently
(a) H,
(b) (C ₁ - C ₆ ) -alkyl,
(c) (C ₃ - C ₇ ) -cycloalkyl,
(d) F, Cl, Br, I,
(e) -NR ⁷ COOR ¹ ¹ ,
(f) -SO ₂ NR ⁷ R ¹ ¹ ,
(g) -O- (C ₁ - C ₄ ) -alkyl,
(h) -S (O) _n - (C ₁ - C ₄ ) -alkyl or
(i) -NHSO ₂ R ¹ ¹ ,
n = 0, 1 or 2,
R ⁶ is
(a) H or
(b) (C ₁ - C ₄ ) -alkyl,
R ⁷ is
(a) H,
(b) (C ₁ - C ₆ ) -alkyl,
(c) phenyl or
(d) benzyl,
R ⁸ is
(a) H,
(b) (C ₁ - C ₆ ) -alkyl or
(c) phenyl,
R ⁹ and R ¹ ⁰ are independently
(a) H,
(b) (C ₁ - C ₆ ) -alkyl, unsubstituted or substituted (C ₃ - C ₇ ) -cycloalkyl,
(c) Cl, Br, I, F,
(d) (C ₁ -C ₆ ) alkoxy, or
e) hydroxy- (C ₁ -C ₆ ) -alkyl,
R ¹ ¹ is
(a) (C ₁ - C ₆ ) -alkyl, unsubstituted or substituted by a substituent selected from the group consisting of
i) -OR ⁷ ,
ii) -N [R ⁷ ] ₂ ,
iii) -NH ₂ ,
iv) -COOR ⁷ or
v) -N [CH ₂ CH ₂ ] ₂ Q,
(b) aryl, where aryl is defined as phenyl or naphthyl, which are unsubstituted or substituted by one or two substituents selected from the group consisting of
i) (C ₁ -C ₄ ) -alkyl,
ii) -O- (C ₁ - C ₄ ) -alkyl,
iii) -CO [NR ⁷ ] ₂ ,
iv) F, Cl, Br or I,
v) -COOR ⁷ ,
vi) -NH ₂
vii) -NH [(C ₁ - C ₄ ) alkyl],
viii) -N [(C ₁ - C ₄ ) -alkyl] ₂ or
ix) -CON [CH ₂ CH ₂ ] ₂ Q,
(c) - (C ₁ - C ₄ ) -alkylaryl, where aryl is as defined above, (d) - (C ₃ - C ₇ ) -cycloalkyl,

R ⁷ and R ¹ ¹ on the same nitrogen atom can combine to form a ring selected from the group consisting of morpholinyl, piperazinyl or pyrrolyl, or
Q is O, S or -NR ⁷ ,
R ¹ ² is
(a) H,
(b) (C ₁ - C ₄ ) -alkyl, unsubstituted or substituted by one or two substituents selected from the group consisting of
i) -OH
ii) -O- (C ₁ - C ₄ ) -alkyl,
iii) -O- (C ₁ - C ₄ ) -cycloalkyl,
iv) -S (O) _n - (C ₁ - C ₄ ) -alkyl,
v) -NR ⁷ R ¹ ¹ ,
vi) -COOR ⁷ ,
vii) -CONHR ⁷ ,
viii) -OCOR ¹ ¹ ,
ix) -CONR ⁷ R ¹ ¹ ,
x) -NR ⁷ CONR ⁷ R ¹ ¹ ,
xi) -NR ⁷ COOR ¹ ¹ ,
xii) -C (R ⁶ ) (OH) -C (R ⁶ ) (R ⁷ ) (OH),
xiii) -SO ₂ NR ⁷ R ¹ ¹ or
xiv) -NR ⁷ - (C ₁ - C ₄ ) -alkyl,
(c) -COOR ⁷ ,
(d) -CONH ₂ ,
(e) -CONR ⁷ R ¹ ¹ ,
(f) -CONR ⁷ CO ₂ R ⁷ ,
(g) -C (R ⁶ ) (OH) -C (R ⁶ ) (R ⁷ ) (OH),
(h) -CONHSO ₂ R ¹ ¹ ,
(i) -SO ₂ NR ⁷ R ¹ ¹ ,
(j) -NR ⁷ SO ₂ NR ⁷ R ¹ ¹ ,
(k) -CO-amino acid, where the amino acid is defined as L - or D-amino acid selected from the group consisting of Ala, Ile, Phe, Asp, Pro and Val and which can be substituted with (C ₁ - C ₆ ) -alkyl ether or amide, or

X is
(a) -O-,
(b) -NR ⁷ - or
(c) -simple communication,
Z is
(a) -CO ₂ H,
(b) -CO ₂ R ¹ ³ ,
(c) -CONH- (tetrazol-5-yl),
(d) -CONHSO ₂ -aryl, where aryl is defined as phenyl or naphthyl, which are unsubstituted or substituted by two substituents selected from the group consisting of
i) (C ₁ - C ₄ ) -alkyl,
ii) -O- (C ₁ - C ₄ ) -alkyl,
iii) -CONR ⁷ R ¹ ¹ ,
iv) F, Cl, Br or I,
v) -COOR ⁷ ,
vi) -NH ₂ ,
vii) -NH [(C ₁ - C ₄ ) alkyl],
viii) -N [(C ₁ - C ₄ ) -alkyl] ₂ ,
ix) phenyl,
(e) -CONHSO ₂ - (C ₁ -C ₈ ) -alkyl, where alkyl is unsubstituted or substituted as defined for R ⁴ (b),
(f) -CONHSO ₂ -heteroaryl, where heteroaryl is defined as carbazolyl, furyl, thienyl, pyrrolyl, isothiazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrazolyl, pyrazinyl, pyridyl, pyrimidyl, purinyl, or quinoluminyl, pyrazinyl, pyridyl, pyrimidyl, purinyl, pyranyl, pyrazinyl, pyridyl, pyrimidyl, purine, or pyrimolyl, pyrazinyl, pyridyl, pyrimidyl, purine, or pyrimolyl, pyrazinyl, pyridyl, pyrimidyl, puroxyl, pyrazolyl, pyrazinyl, pyridyl, pyrimidyl, isoxazolyl, pyrimyl, pyrazinyl, pyridyl, pyrazinyl, pyridyl, pyriminyl, pyridyl, pyrimidyl, pyrimidine two substituents selected from the group consisting of
i) (C ₁ - C ₄ ) -alkyl,
ii) -O- (C ₁ - C ₄ ) -alkyl,
iii) -CONR ⁷ R ¹ ¹ ,
iv) F, Cl, Br or I,
v) -COOR ⁷ ,
vi) -NR ⁷ CONR ⁷ R ¹ ¹ or
vii) -NR ⁷ COOR ¹ ¹ ,
(g) tetrazol-5-yl; and
R ¹ ³ is (C ₁ - C ₄ ) -alkyl.

7. A method of treating conditions selected from the group consisting of hypertension, pulmonary hypertension, Raynaud’s disease, myocardial infarction, angina pectoris, congestive heart failure, acute renal failure, cerebral infarction, cerebral vasospasm, arteriosclerosis, vascular restenosis, asthma, benignity, asthma, cerebral vasospasm, arteriosclerosis, vascular restenosis, asthma, benign inflammation, cerebral vasospasm, arteriosclerosis, vascular restenosis, asthma, benign inflammation, cerebral vasospasm, arteriosclerosis, vascular restenosis, asthma, benign inflammation, cerebral vasospasm, arteriosclerosis, vascular restenosis, asthma, benign prosthesis, asthma, cerebral vasospasm, arteriosclerosis, vascular restenosis, asthma, benign prostatic hyperplasia , inflammatory internal diseases, endotoxin bacterial toxic shock, repeated organ damage or disseminated intravascular coagulation caused by x endotoxin, or renal failure, or hypertension in mammals caused by cyclosporine, while the treatment of these conditions is carried out or facilitated by reducing the effect of endothelin, including the administration of a compound of formula I, which is described in claim 1, in an amount that is effective for against the effects of endothelin.

8. The method according to claim 7, characterized in that a drug is administered comprising a therapeutically effective amount of a compound of formula I and a pharmaceutically acceptable carrier.

9. Pharmaceutical composition suitable for the treatment of hypertension, which includes a pharmaceutically acceptable carrier and a pharmaceutically effective amount of the compounds of formula I.

10. The composition according to claim 9, characterized in that it includes another antihypertensive agent selected from A ₂ -adrenosine receptor agonists, alpha-adrenergic antagonists, angiotensin II antagonists, angiotensin-converting enzyme inhibitors, beta adrenergic antagonists, inhibitors of the themes, and they can also be applied to them. ), calcium channel blockers, diuretics, potassium channel agonists, renin inhibitors, serotonin antagonists, sympatholytic agents, and other antihypertensive agents selected from the group, oyaschey of

2- (2-cyclohexylethylaminoadenosine (CSG 22492C), 1- (2-hydroxy-5 methyl-1-phenylmethylhexylamino) megiscarbonyl) -2-phenylethyl-N'-morpholinocarbonyl-N ₁ , N ₄ - dimethylethylenediamine-N ₄ -carboxylate FK906, Kandia isradipine, ketanserin, losartan, metolazone, meth optolate, tartar trimethophan, verapamil, benzthiazide, chinetasone, tikrinafana, triamterene, acetazolamide, aminophylline, cyclothiazide, ethacrynic acid, furozemide, meretoksilinprokainina, sodium ethacrylate, captopril, hydrochloride ide delapril, enalapril, enalaprilat, natriyfozinoprila, lisinopril, pentopril, quinapril, quinapril hydrochloride, ramaprila, teprotide zofenopril kaltsiyzofenoprila, difluzinala, diltiazema, felodipine, nicardipine, nifedipine, niludipina, nimodipine, nisoldipine, nitrendipine.