Cinnoline compounds

US 6,887,874 B2
Filed: 08/07/2001
Issued: 05/03/2005
Est. Priority Date: 08/09/2000
Status: Expired due to Fees

First Claim

Patent Images

1. A compound of the formula I:

wherein;

either any one of G₁, G₂, G₃, G₄and G₅is nitrogen and the other four are —

CH—

, or G₁, G₂, G₃, G₄and G₅are all —

CH—

;

Z is —

O—

, —

NH—

, —

S—

, —

CH₂—

or a direct bond;

Z is linked to any one of G₁, G₂, G₃and G₄which is a free carbon atom;

n is an integer from 0 to 5;

any of the substituents R¹may be attached at any free carbon atom of the indole, azaindole or indazole group, such free carbon atoms may be G₁, G₂, G₃, G₄or G₅or may be at the 3-position of the indole, azaindole or indazole group;

m is an integer from 0 to 3;

R^arepresents hydrogen;

R^brepresents hydrogen, C_1-4alkyl, C_1-4alkoxyC_1-4alkyl, aminoC_1-4alkyl, C_1-3alkylaminoC_1-4alkyl, di(C_1-3alkyl)aminoC_1-4alkyl, C_2-5alkenylaminoC_1-4alkyl, C_2-5alkynylaminoC_1-4alkyl, —

C_1-5alkyl(ring A) wherein ring A is selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholino and thiomorpholino and wherein ring A may bear one or more substituents selected from C_1-4alkyl, C_2-5alkenyl, C_2-5alkynyl, hydroxy, oxo, halogeno, cyano, cyanoC_1-4alkyl, C_1-4alkylsulphonyl and C_1-4alkanoyl;

R¹represents hydrogen, oxo, hydroxy, halogeno, C_1-4alkyl, C_1-4alkoxy, C_1-4alkoxyC_1-4alkyl, aminoC_1-4alkyl, C_1-3alkylaminoC_1-4alkyl, di(C_1-3alkyl)aminoC_1-4alkyl, —

C_1-5alkyl(ring B) wherein ring B is selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, morpholino and thiomorpholino;

R²represents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C_1-3alkyl, C_1-3alkoxy, C_1-3alkylsulphanyl, —

NR³R⁴(wherein R³and R⁴, which may be the same or different, each represents hydrogen or C_1-3alkyl), or R⁵X¹—

(wherein X¹represents a direct bond, —

O—

, —

CH₂—

, —

OC(O)—

, —

C(O)—

, —

S—

, —

SO—

, —

SO₂—

, —

NR⁶C(O)—

, —

C(O)NR⁷—

, —

SO₂NR⁸—

, —

NR⁹SO₂—

or —

13 NR¹⁰—

(wherein R⁶, R⁷, R⁸, R⁹and R¹⁰each independently represents hydrogen, C_1-3alkyl or C_1-3alkoxyC_2-3alkyl), and R⁵is selected from one of the following twenty-two groups;

1) hydrogen, oxiranylC_1-4alkyl or C_1-5alkyl which may be unsubstituted or which may be substituted with one or more groups selected from hydroxy, fluoro, chloro, bromo and amino;

2) C_1-5alkylX²C(O)R¹¹(wherein X²represents —

O—

or —

NR¹²—

(in which R¹²represents hydrogen, C_1-3alkyl or C_1-3alkoxyC_2-3alkyl) and R¹¹C_1-3alkyl, —

NR¹³R¹⁴or —

OR¹⁵(wherein R¹³, R¹⁴and R¹⁵which may be the same or different each represents hydrogen, C_1-5alkyl or C_1-3alkoxyC_2-3alkyl));

3) C_1-5alkylX³R¹⁶(wherein X³represents —

O—

, —

S—

, —

SO—

, —

SO₂—

, —

OC(O)—

, —

NR¹⁷C(O)—

, —

C(O)NR¹⁸, —

SO₂NR¹⁹—

, —

NR²⁰SO₂—

or —

NR²¹—

(wherein R¹⁷, R¹⁸, R¹⁹, R²⁰and R²¹each independently represents hydrogen, C_1-3alkyl or C_1-3alkoxyC_2-3alkyl) and R¹⁶represents hydrogen, C_1-3alkyl, cyclopentyl, cyclohexyl or a 4-, 5- or 6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which C_1-3alkyl group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno and C_1-4alkoxy and which cyclic group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno, cyano, C_1-4cyanoalkyl, C_1-4alkyl, C_1-4hydroxyalkyl, C_1-4alkoxy, C_1-4alkoxyC_1-4alkyl, C_1-4alkylsulphonylC_1-4alkyl, C_1-4alkoxycarbonyl, C_1-4aminoalkyl, C_1-4alkylamino, di(C_1-4alkyl)amino, C_1-4alkylaminoC_1-4alkyl, di(C_1-4alkyl)aminoC_1-4alkyl, C_1-4alkylaminoC_1-4alkoxy, di(C_1-4alkyl)aminoC_1-4alkoxy and a group —

(—

O—

)_f(C_1-4alkyl)_gringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a 4-, 5- or 6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which cyclic group may bear one or more substituents selected from C_1-4alkyl));

4) C_1-5alkylX⁴C_1-5alkylX⁵R²²(wherein X⁴and X⁵which may be the same or different are each —

O—

, —

S—

, —

SO—

, —

SO₂—

, —

NR²³C(O)—

, —

C(O)NR²⁴—

, —

SO₂NR²⁵—

, —

NR²⁶SO₂or —

NR²⁷—

(wherein R²³, R²⁴, R²⁵, R²⁶and R²⁷each independently represents hydrogen, C_1-3alkyl or C_1-3alkoxyC_2-3alkyl) and R²represents hydrogen, C_1-3alkyl or C_1-3alkoxyC_2-3alkyl);

5) R²⁸(wherein R²⁸is a 4-, 5- or 6-membered saturated heterocyclic group (linked via carbon or nitrogen) with 1-2 heteroatoms, selected independently from O, S and N, which heterocyclic group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno, cyano, C_1-4cyanoalkyl, C_1-4alkyl, C_1-4hydroxyalkyl, C_1-4alkoxy, C₁alkanoyl, C_1-4alkoxyC_1-4alkyl, C_1-4alkylsulphonyl, C_1-4alkylsulphonylC_1-4alkyl, C_1-4alkoxycarbonyl, C_1-4aminoalkyl, C_1-4alkylamino, di(C_1-4alkyl)amino, C_1-4alkylaminoC_1-4alkyl, di(C_1-4alkyl)aminoC_1-4alkyl, C_1-4alkylaminoC_1-4alkoxy, di(C_1-4alkyl)aminoC_1-4alkoxy and a group —

(—

O—

)_f(C_1-4alkyl)_gringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a 4-, 5- or 6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which cyclic group may bear one or more substituents selected from C_1-4alkyl));

6) C_1-5alkylR²⁸(wherein R²⁸is as defined herein);

7) C_2-5alkenylR²⁸(wherein R²⁸is as defined herein);

8) C_2-5alkynylR²⁸(wherein R²⁸is as defined herein);

9) R²⁹(wherein R²⁹represents a pyridone group, a phenyl group or a 5-6-membered aromatic heterocyclic group (linked via carbon or nitrogen) with 1-3 heteroatoms selected from O, N and S, which pyridone, phenyl or aromatic heterocyclic group may carry up to 5 substituents selected from hydroxy, halogeno, amino, C_1-4alkyl, C_1-4alkoxy, C_1-4hydroxyalkyl, C_1-4aminoalkyl, C_1-4alkylamino, C_1-4hydroxyalkoxy, carboxy, trifluoromethyl, cyano, —

C(O)NR³⁰R³¹, —

NR³²C(O)R³³(wherein R³⁰, R³¹, R³²and R³³, which may be the same or different, each represents hydrogen, C_1-4alkyl or C_1-3alkoxyC_2-3alkyl) and a group —

(—

O—

)_f(C_1-4alkyl)_gringD (wherein f is 0 or 1, is 0 or 1 and ring D is a 4-, 5- or 6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which cyclic group may bear one or more substituents selected from C_1-4alkyl));

10) C_1-5alkylR²⁹(wherein R²⁹is as defined herein);

11) C_2-5alkenylR²⁹(wherein R²⁹is as defined herein);

12) C_2-5alkynylR²⁹(wherein R²⁹is as defined herein);

13) C_1-5alkylX⁶R²⁹(wherein X⁶represents —

O—

, —

S—

, —

SO—

, —

SO₂—

, —

NR³⁴C(O)—

, —

C(O)NR³⁵—

, —

SO₂NR³⁶—

, —

NR³⁷SO₂—

or —

NR³⁸—

(wherein R³⁴, R³⁵, R³⁶, R³⁷and R³⁸each independently represents hydrogen, C_1-3alkyl or C_1-3alkoxyC_2-3alkyl) and R²⁹is as defined herein);

14) C_2-5alkenylX⁷R²⁹(wherein X⁷represents —

O—

, —

S—

, —

SO—

, —

SO₂—

, —

NR³⁹C(O)—

, —

C(O)NR⁴⁰—

, —

SO₂NR⁴¹—

, —

NR⁴²SO₂—

or —

NR⁴³—

(wherein R³⁹, R⁴⁰, R⁴¹, R⁴²and R⁴³each independently represents hydrogen, C_1-3alkyl or C_1-3alkoxyC_2-3alkyl) and R²⁹is as defined herein);

15) C_2-5alkynylX⁸R²⁹(wherein X⁸represents —

O—

, —

S—

, —

SO—

, —

SO₂—

, —

NR⁴⁴C(O)—

, —

C(O)NR⁴⁵—

, —

SO₂NR⁴⁶—

, —

NR⁴⁷SO₂—

or —

NR⁴⁸—

(wherein R⁴⁴, R⁴⁵, R⁴⁶, R⁴⁷and R⁴⁸each independently represents hydrogen, C_1-3alkyl or C_1-3alkoxyC_2-3alkyl) and R²⁹is as defined herein);

16) C_1-4alkylX⁹C_1-4alkylX²⁹(wherein X⁹represents —

O—

, —

S—

, —

SO—

, —

SO₂—

, —

NR⁴⁹C(O)—

, —

C(O)NR⁵⁰—

, —

SO₂NR⁵¹, —

NR⁵²SO₂—

or —

NR⁵³—

(wherein R⁴⁹, R⁵⁰, R⁵¹, R⁵²and R⁵³each independently represents hydrogen, C_1-3alkyl or C_1-3alkoxyC_2-3alkyl) and R²⁹is as defined herein);

17) C_1-4alkylX⁹C_1-4alkylR²⁸(wherein X⁹and R²⁸are as defined herein);

18) C_2-5alkenyl which may be unsubstituted or which may be substituted with one or more groups selected from hydroxy, fluoro, amino, C_1-4alkylamino, N,N-di(C_1-4alkyl)amino, aminosulphonyl, N-C_1-4alkylaminosulphonyl and N,N-di(C_1-4alkyl)aminosulphonyl;

19) C_2-5alkynyl which may be unsubstituted or which may be substituted with one or more groups selected from hydroxy, fluoro, amino, C_1-4alkylamino, N,N-di(C_1-4alkyl)amino, aminosulphonyl, N-C_1-4alkylaminosulphonyl and N,N-di(C_1-4alkyl)aminosulphonyl;

20) C_2-5alkenylX⁹C_1-4alkylR²⁸(wherein X⁹and R²⁸are as defined herein);

21) C_2-5alkynylX⁹C_1-4alkylR²⁸(wherein X⁹and R²⁸are as defined herein); and

22) C_1-4alkylR⁵⁴(C_1-4alkyl)_q(X⁹)_rR⁵⁵(wherein X⁹is as defined herein, q is 0 or 1, r is 0 or 1, and R⁵⁴and R⁵⁵are each independently selected from hydrogen, C_1-3alkyl, cyclopentyl, cyclohexyl and a 4-, 5- or 6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which C_1-3alkyl group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno and C_1-4alkoxy and which cyclic group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno, cyano, C_1-4cyanoalkyl, C_1-4alkyl, C_1-4hydroxyalkyl, C_1-4alkoxy, C_1-4alkoxyC_1-4alkyl, C_1-4alkylsulphonylC_1-4alkyl, C_1-4alkoxycarbonyl, C_1-4aminoalkyl, C_1-4alkylamino, di(C_1-4alkyl)amino, C_1-4alkylaminoC_1-4alkyl, di(C_1-4alkyl)aminoC₄alkyl, C_1-4alkylaminoC_1-4alkoxy, di(C_1-4alkyl)aminoC_1-4alkoxy and a group —

(—

O—

)_f(C_1-4alkyl)_gringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a 4-, 5- or 6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which cyclic group may bear one or more substituents selected from C_1-4alkyl), with the proviso that R⁵⁴cannot be hydrogen);

and additionally wherein any C_1-5alkyl, C_2-5alkenyl or C_2-5alkynyl group in R⁵X¹—

may bear one or more substituents selected from hydroxy, halogeno and amino);

or a salt thereof.

View all claims

1 Assignment

Timeline View

Assignment View

0 Petitions

Accused Products

Abstract

The invention relatest to compounds of the formula (I) wherein either any one of G₁, G₂, G₃, G₄and G₅is nitrogen and the other four are —CH—, or G₁, G₂, G₃, G₄and G₅are all —CH—; Z is —O—, —NH—, —S—, —CH₂— or a direct bond; Z is linked to any one of G₁, G₂, G₃and G₄which is a free carbon atom; n is an integer from 0 to 5; any of the substitutents R¹may be attached at any free carbon atom of the indole, azaindole or indazole group; m is an integer from 0 to 3; R^arepresents hydrogen; R^brepresents hydrogen or another value as defined herein; R¹represents hydrogen, oxo, hydroxy, halogeno, C_1-4alkyl, C_1-4alkoxy, C_1-4alkoxy, C_1-4-alkyl, aminoC_1-4alkyl, C_1-3alkylaminoC_1-4alkyl, di(C_1-3alkyl)aminoC_1-4alkyl, —C_1-5alkyl(ring B) wherein ring B is selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, N-methylpiperazinly, N-ethylpiperazinyl, morpholino and thiomorpholino; R²represents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C_1-3alkyl, C_1-3alkoxy, C_1-3aklylsulphanyl, —NR³R⁴(wherein R³and R⁴, which may be the same or different, each represents hydrogen or C_1-3alkyl), or R⁵X¹— (wherein R⁵and X¹are as defined herein) and salts thereof, processes for the preparation of such compounds, pharmaceutical compositions containing a compound of formula I or a pharmaceutically acceptable salt thereof as active ingredient and the use of a compound of formula I in the manufacture of medicament for the production of an antiangiogenic and/or vascular permeability reducing effect in warm-blooded animals. The compounds of formula I and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.

Citations

15 Claims

1. A compound of the formula I:
- wherein;
  
  either any one of G₁, G₂, G₃, G₄and G₅is nitrogen and the other four are —
  
  CH—
  
  , or G₁, G₂, G₃, G₄and G₅are all —
  
  CH—
  
  ;
  
  Z is —
  
  O—
  
  , —
  
  NH—
  
  , —
  
  S—
  
  , —
  
  CH₂—
  
  or a direct bond;
  
  Z is linked to any one of G₁, G₂, G₃and G₄which is a free carbon atom;
  
  n is an integer from 0 to 5;
  
  any of the substituents R¹may be attached at any free carbon atom of the indole, azaindole or indazole group, such free carbon atoms may be G₁, G₂, G₃, G₄or G₅or may be at the 3-position of the indole, azaindole or indazole group;
  
  m is an integer from 0 to 3;
  
  R^arepresents hydrogen;
  
  R^brepresents hydrogen, C_1-4alkyl, C_1-4alkoxyC_1-4alkyl, aminoC_1-4alkyl, C_1-3alkylaminoC_1-4alkyl, di(C_1-3alkyl)aminoC_1-4alkyl, C_2-5alkenylaminoC_1-4alkyl, C_2-5alkynylaminoC_1-4alkyl, —
  
  C_1-5alkyl(ring A) wherein ring A is selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholino and thiomorpholino and wherein ring A may bear one or more substituents selected from C_1-4alkyl, C_2-5alkenyl, C_2-5alkynyl, hydroxy, oxo, halogeno, cyano, cyanoC_1-4alkyl, C_1-4alkylsulphonyl and C_1-4alkanoyl;
  
  R¹represents hydrogen, oxo, hydroxy, halogeno, C_1-4alkyl, C_1-4alkoxy, C_1-4alkoxyC_1-4alkyl, aminoC_1-4alkyl, C_1-3alkylaminoC_1-4alkyl, di(C_1-3alkyl)aminoC_1-4alkyl, —
  
  C_1-5alkyl(ring B) wherein ring B is selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, morpholino and thiomorpholino;
  
  R²represents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C_1-3alkyl, C_1-3alkoxy, C_1-3alkylsulphanyl, —
  
  NR³R⁴(wherein R³and R⁴, which may be the same or different, each represents hydrogen or C_1-3alkyl), or R⁵X¹—
  
  (wherein X¹represents a direct bond, —
  
  O—
  
  , —
  
  CH₂—
  
  , —
  
  OC(O)—
  
  , —
  
  C(O)—
  
  , —
  
  S—
  
  , —
  
  SO—
  
  , —
  
  SO₂—
  
  , —
  
  NR⁶C(O)—
  
  , —
  
  C(O)NR⁷—
  
  , —
  
  SO₂NR⁸—
  
  , —
  
  NR⁹SO₂—
  
  or —
  
  13 NR¹⁰—
  
  (wherein R⁶, R⁷, R⁸, R⁹and R¹⁰each independently represents hydrogen, C_1-3alkyl or C_1-3alkoxyC_2-3alkyl), and R⁵is selected from one of the following twenty-two groups;
  
  1) hydrogen, oxiranylC_1-4alkyl or C_1-5alkyl which may be unsubstituted or which may be substituted with one or more groups selected from hydroxy, fluoro, chloro, bromo and amino;
  
  2) C_1-5alkylX²C(O)R¹¹(wherein X²represents —
  
  O—
  
  or —
  
  NR¹²—
  
  (in which R¹²represents hydrogen, C_1-3alkyl or C_1-3alkoxyC_2-3alkyl) and R¹¹C_1-3alkyl, —
  
  NR¹³R¹⁴or —
  
  OR¹⁵(wherein R¹³, R¹⁴and R¹⁵which may be the same or different each represents hydrogen, C_1-5alkyl or C_1-3alkoxyC_2-3alkyl));
  
  3) C_1-5alkylX³R¹⁶(wherein X³represents —
  
  O—
  
  , —
  
  S—
  
  , —
  
  SO—
  
  , —
  
  SO₂—
  
  , —
  
  OC(O)—
  
  , —
  
  NR¹⁷C(O)—
  
  , —
  
  C(O)NR¹⁸, —
  
  SO₂NR¹⁹—
  
  , —
  
  NR²⁰SO₂—
  
  or —
  
  NR²¹—
  
  (wherein R¹⁷, R¹⁸, R¹⁹, R²⁰and R²¹each independently represents hydrogen, C_1-3alkyl or C_1-3alkoxyC_2-3alkyl) and R¹⁶represents hydrogen, C_1-3alkyl, cyclopentyl, cyclohexyl or a 4-, 5- or 6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which C_1-3alkyl group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno and C_1-4alkoxy and which cyclic group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno, cyano, C_1-4cyanoalkyl, C_1-4alkyl, C_1-4hydroxyalkyl, C_1-4alkoxy, C_1-4alkoxyC_1-4alkyl, C_1-4alkylsulphonylC_1-4alkyl, C_1-4alkoxycarbonyl, C_1-4aminoalkyl, C_1-4alkylamino, di(C_1-4alkyl)amino, C_1-4alkylaminoC_1-4alkyl, di(C_1-4alkyl)aminoC_1-4alkyl, C_1-4alkylaminoC_1-4alkoxy, di(C_1-4alkyl)aminoC_1-4alkoxy and a group —
  
  (—
  
  O—
  
  )_f(C_1-4alkyl)_gringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a 4-, 5- or 6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which cyclic group may bear one or more substituents selected from C_1-4alkyl));
  
  4) C_1-5alkylX⁴C_1-5alkylX⁵R²²(wherein X⁴and X⁵which may be the same or different are each —
  
  O—
  
  , —
  
  S—
  
  , —
  
  SO—
  
  , —
  
  SO₂—
  
  , —
  
  NR²³C(O)—
  
  , —
  
  C(O)NR²⁴—
  
  , —
  
  SO₂NR²⁵—
  
  , —
  
  NR²⁶SO₂or —
  
  NR²⁷—
  
  (wherein R²³, R²⁴, R²⁵, R²⁶and R²⁷each independently represents hydrogen, C_1-3alkyl or C_1-3alkoxyC_2-3alkyl) and R²represents hydrogen, C_1-3alkyl or C_1-3alkoxyC_2-3alkyl);
  
  5) R²⁸(wherein R²⁸is a 4-, 5- or 6-membered saturated heterocyclic group (linked via carbon or nitrogen) with 1-2 heteroatoms, selected independently from O, S and N, which heterocyclic group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno, cyano, C_1-4cyanoalkyl, C_1-4alkyl, C_1-4hydroxyalkyl, C_1-4alkoxy, C₁alkanoyl, C_1-4alkoxyC_1-4alkyl, C_1-4alkylsulphonyl, C_1-4alkylsulphonylC_1-4alkyl, C_1-4alkoxycarbonyl, C_1-4aminoalkyl, C_1-4alkylamino, di(C_1-4alkyl)amino, C_1-4alkylaminoC_1-4alkyl, di(C_1-4alkyl)aminoC_1-4alkyl, C_1-4alkylaminoC_1-4alkoxy, di(C_1-4alkyl)aminoC_1-4alkoxy and a group —
  
  (—
  
  O—
  
  )_f(C_1-4alkyl)_gringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a 4-, 5- or 6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which cyclic group may bear one or more substituents selected from C_1-4alkyl));
  
  6) C_1-5alkylR²⁸(wherein R²⁸is as defined herein);
  
  7) C_2-5alkenylR²⁸(wherein R²⁸is as defined herein);
  
  8) C_2-5alkynylR²⁸(wherein R²⁸is as defined herein);
  
  9) R²⁹(wherein R²⁹represents a pyridone group, a phenyl group or a 5-6-membered aromatic heterocyclic group (linked via carbon or nitrogen) with 1-3 heteroatoms selected from O, N and S, which pyridone, phenyl or aromatic heterocyclic group may carry up to 5 substituents selected from hydroxy, halogeno, amino, C_1-4alkyl, C_1-4alkoxy, C_1-4hydroxyalkyl, C_1-4aminoalkyl, C_1-4alkylamino, C_1-4hydroxyalkoxy, carboxy, trifluoromethyl, cyano, —
  
  C(O)NR³⁰R³¹, —
  
  NR³²C(O)R³³(wherein R³⁰, R³¹, R³²and R³³, which may be the same or different, each represents hydrogen, C_1-4alkyl or C_1-3alkoxyC_2-3alkyl) and a group —
  
  (—
  
  O—
  
  )_f(C_1-4alkyl)_gringD (wherein f is 0 or 1, is 0 or 1 and ring D is a 4-, 5- or 6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which cyclic group may bear one or more substituents selected from C_1-4alkyl));
  
  10) C_1-5alkylR²⁹(wherein R²⁹is as defined herein);
  
  11) C_2-5alkenylR²⁹(wherein R²⁹is as defined herein);
  
  12) C_2-5alkynylR²⁹(wherein R²⁹is as defined herein);
  
  13) C_1-5alkylX⁶R²⁹(wherein X⁶represents —
  
  O—
  
  , —
  
  S—
  
  , —
  
  SO—
  
  , —
  
  SO₂—
  
  , —
  
  NR³⁴C(O)—
  
  , —
  
  C(O)NR³⁵—
  
  , —
  
  SO₂NR³⁶—
  
  , —
  
  NR³⁷SO₂—
  
  or —
  
  NR³⁸—
  
  (wherein R³⁴, R³⁵, R³⁶, R³⁷and R³⁸each independently represents hydrogen, C_1-3alkyl or C_1-3alkoxyC_2-3alkyl) and R²⁹is as defined herein);
  
  14) C_2-5alkenylX⁷R²⁹(wherein X⁷represents —
  
  O—
  
  , —
  
  S—
  
  , —
  
  SO—
  
  , —
  
  SO₂—
  
  , —
  
  NR³⁹C(O)—
  
  , —
  
  C(O)NR⁴⁰—
  
  , —
  
  SO₂NR⁴¹—
  
  , —
  
  NR⁴²SO₂—
  
  or —
  
  NR⁴³—
  
  (wherein R³⁹, R⁴⁰, R⁴¹, R⁴²and R⁴³each independently represents hydrogen, C_1-3alkyl or C_1-3alkoxyC_2-3alkyl) and R²⁹is as defined herein);
  
  15) C_2-5alkynylX⁸R²⁹(wherein X⁸represents —
  
  O—
  
  , —
  
  S—
  
  , —
  
  SO—
  
  , —
  
  SO₂—
  
  , —
  
  NR⁴⁴C(O)—
  
  , —
  
  C(O)NR⁴⁵—
  
  , —
  
  SO₂NR⁴⁶—
  
  , —
  
  NR⁴⁷SO₂—
  
  or —
  
  NR⁴⁸—
  
  (wherein R⁴⁴, R⁴⁵, R⁴⁶, R⁴⁷and R⁴⁸each independently represents hydrogen, C_1-3alkyl or C_1-3alkoxyC_2-3alkyl) and R²⁹is as defined herein);
  
  16) C_1-4alkylX⁹C_1-4alkylX²⁹(wherein X⁹represents —
  
  O—
  
  , —
  
  S—
  
  , —
  
  SO—
  
  , —
  
  SO₂—
  
  , —
  
  NR⁴⁹C(O)—
  
  , —
  
  C(O)NR⁵⁰—
  
  , —
  
  SO₂NR⁵¹, —
  
  NR⁵²SO₂—
  
  or —
  
  NR⁵³—
  
  (wherein R⁴⁹, R⁵⁰, R⁵¹, R⁵²and R⁵³each independently represents hydrogen, C_1-3alkyl or C_1-3alkoxyC_2-3alkyl) and R²⁹is as defined herein);
  
  17) C_1-4alkylX⁹C_1-4alkylR²⁸(wherein X⁹and R²⁸are as defined herein);
  
  18) C_2-5alkenyl which may be unsubstituted or which may be substituted with one or more groups selected from hydroxy, fluoro, amino, C_1-4alkylamino, N,N-di(C_1-4alkyl)amino, aminosulphonyl, N-C_1-4alkylaminosulphonyl and N,N-di(C_1-4alkyl)aminosulphonyl;
  
  19) C_2-5alkynyl which may be unsubstituted or which may be substituted with one or more groups selected from hydroxy, fluoro, amino, C_1-4alkylamino, N,N-di(C_1-4alkyl)amino, aminosulphonyl, N-C_1-4alkylaminosulphonyl and N,N-di(C_1-4alkyl)aminosulphonyl;
  
  20) C_2-5alkenylX⁹C_1-4alkylR²⁸(wherein X⁹and R²⁸are as defined herein);
  
  21) C_2-5alkynylX⁹C_1-4alkylR²⁸(wherein X⁹and R²⁸are as defined herein); and
  
  22) C_1-4alkylR⁵⁴(C_1-4alkyl)_q(X⁹)_rR⁵⁵(wherein X⁹is as defined herein, q is 0 or 1, r is 0 or 1, and R⁵⁴and R⁵⁵are each independently selected from hydrogen, C_1-3alkyl, cyclopentyl, cyclohexyl and a 4-, 5- or 6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which C_1-3alkyl group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno and C_1-4alkoxy and which cyclic group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno, cyano, C_1-4cyanoalkyl, C_1-4alkyl, C_1-4hydroxyalkyl, C_1-4alkoxy, C_1-4alkoxyC_1-4alkyl, C_1-4alkylsulphonylC_1-4alkyl, C_1-4alkoxycarbonyl, C_1-4aminoalkyl, C_1-4alkylamino, di(C_1-4alkyl)amino, C_1-4alkylaminoC_1-4alkyl, di(C_1-4alkyl)aminoC₄alkyl, C_1-4alkylaminoC_1-4alkoxy, di(C_1-4alkyl)aminoC_1-4alkoxy and a group —
  
  (—
  
  O—
  
  )_f(C_1-4alkyl)_gringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a 4-, 5- or 6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which cyclic group may bear one or more substituents selected from C_1-4alkyl), with the proviso that R⁵⁴cannot be hydrogen);
  
  and additionally wherein any C_1-5alkyl, C_2-5alkenyl or C_2-5alkynyl group in R⁵X¹—
  
  may bear one or more substituents selected from hydroxy, halogeno and amino);
  
  or a salt thereof.
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 13, 14, 15)
- - 2. A compound according to claim 1 wherein Z is —
    - O—
      
      or —
      
      NH—
      
      .
  - 3. A compound according to claim 1 wherein G₁, G₂, G₃, G₄and G₅are all —
    - CH—
      
      which may be substituted as defined in claim 1.
  - 4. A compound according to claim 3 wherein the optionally substituted indole moiety of formula II¹:
5. A compound according to claim 1 wherein R^bis hydrogen.
6. A compound according to claim 1 wherein R¹represents methyl, ethyl, trifluoromethyl or halogeno.
7. A compound according to claim 1 whereinR²represents hydroxy, halogeno, nitro, trifluoromethyl, C_1-3alkyl, cyano, amino or R⁵X¹—
- [wherein X¹is as defined in claim 1 and R⁵is selected from one of the following twenty groups;
  
  1) C_1-3alkyl which may be unsubstituted or which may be substituted with one or more groups selected from fluoro, chloro and bromo, or C_2-3alkyl which may be unsubstituted or substituted with one or more groups selected from hydroxy and amino;
  
  2) 2-(3,3-dimethylureido)ethyl, 3-(3,3-dimethylureido)propyl, 2-(3-methylureido)ethyl, 3-(3-methylureido)propyl, 2-ureidoethyl, 3-ureidopropyl, 2-(N,N-dimethylcarbamoyloxy)ethyl, 3-N,N-dimethylcarbamoyloxy)propyl, 2-(N-methylcarbamoyloxy)ethyl, 3-(N-methylcarbamoyloxy)propyl, 2-(carbamoyloxy)ethyl, 3-(carbamoyloxy)propyl, or 2-(N-methyl-N-(butoxycarbonyl)amino)ethyl;
  
  3) C_2-3alkylX³R¹⁶(wherein X³is as defined in claim 1 and R¹⁶is a group selected from C_1-3alkyl, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, piperazinyl, azetidinyl, imidazolidinyl and tetrahydropyranyl which group is linked to X³through a carbon atom and which C_1-3alkyl group may bear 1 or 2 substituents selected from hydroxy, halogeno and C_1-2alkoxy and which cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, piperazinyl, azetidinyl, imidazolidinyl or tetrahydropyranyl group may bear one substituent selected from oxo, hydroxy, halogeno, cyano, C_1-2cyanoalkyl, C_1-2alkyl, C_1-2hydroxyalkyl, C_1-2alkoxy, C_1-2alkoxyC_1-3alkyl, C_1-2alkylsulphonylC_1-3alkyl, C_1-2alkoxycarbonyl, C_1-3alkylamino, di(C_1-3alkyl)amino, C_1-3alkylaminoC_1-3alkyl, di(C_1-3alkyl)aminoC_1-3alkyl, C_1-3alkylaminoC_1-3alkoxy, di(C_1-3alkyl)aminoC_1-3alkoxy and a group —
  
  (—
  
  O—
  
  )_f(C_1-3alkyl)_gringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a heterocyclic group selected from pyrrolidinyl, methylpiperazinyl, piperidinyl, azetidinyl, morpholino and thiomorpholino));
  
  4) C_2-3alkylX⁴C_2-3alkylX⁵R²²(wherein X⁴and X⁵are as defined in claim 1 and R²²represents hydrogen or C_1-2alkyl);
  
  5) R²⁸(wherein R²⁸is as defined in claim 1);
  
  6) C_1-3alkylR⁵⁹(wherein R⁵⁹is a group selected from pyrrolidinyl, piperazinyl, piperidinyl, azetidinyl, imidazolidinyl, 1,3-dioxolan-2-yl, 1,3-dioxan-2-yl, 1,3-dithiolan-2-yl and 1,3-dithian-2-yl, which group is linked to C_1-3alkyl through a carbon atom and which group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno, cyano, C_1-2cyanoalkyl, C_1-2alkyl, C_1-2hydroxyalkyl, C_1-2alkoxy, C_1-2alkanoyl, C_1-2alkoxyC_1-3alkyl, C_1-2alkylsulphonyl, C_1-2alkylsulphonylC_1-3alkyl, C_1-2alkoxycarbonyl, C_1-3alkylamino, di(C_1-3alkyl)amino, C_1-3alkylaminoC_1-3alkyl, di(C_1-3alkyl)aminoC_1-3alkyl, C_1-3alkylaminoC_1-3alkoxy, di(C_1-3alkyl)aminoC_1-3alkoxy and a group —
  
  (—
  
  O—
  
  )_f(C_1-3alkyl)_gringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a heterocyclic group selected from pyrrolidinyl, methylpiperazinyl, piperidinyl, azetidinyl, morpholino and thiomorpholino)) or C_2-3alkylR⁶⁰(wherein R⁶⁰is a group selected from morpholino, thiomorpholino, azetidin-1-yl, pyrrolidin-1-yl, piperazin-1-yl and piperidino which group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno, cyano, C_1-2cyanoalkyl, C_1-2alkyl, C_1-2hydroxyalkyl, C_1-2alkoxy, C_1-2alkanoyl, C_1-2alkoxyC_1-3alkyl, C_1-2alkylsulphonyl, C_1-2alkylsulphonylC_1-3alkyl, C_1-2alkoxycarbonyl, C_1-3alkylamino, di(C_1-3alkyl)amino, C_1-3alkylaminoC_1-3alkyl, di(C_1-3alkyl)aminoC_1-3alkyl, C_1-3alkylaminoC_1-3alkoxy, di(C_1-3alkyl)aminoC_1-3alkoxy and a group —
  
  (—
  
  O—
  
  )_f(C_1-3alkyl)_gringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a heterocyclic group selected from pyrrolidinyl, methylpiperazinyl, piperidinyl, azetidinyl, morpholino and thiomorpholino));
  
  7) R²⁹(wherein R²⁹is as defined in claim 1);
  
  8) C_1-4alkylR²⁹(wherein R²⁹is as defined in claim 1);
  
  9) 1-R²⁹but-2-en-4-yl (wherein R²⁹is as defined in claim 1);
  
  10) 1-R²⁹but-2-yn-4-yl (wherein R²⁹is as defined in claim 1);
  
  11) C_1-3alkylX⁶R²⁹(wherein X⁶and R²⁹are as defined in claim 1);
  
  12) 1-(R²⁹X⁷)but-2-en-4-yl (wherein X⁷and R²⁹are as defined in claim 1);
  
  13) 1-(R²⁹X⁸)but-2-yn-4-yl (wherein X⁸and R²⁹are as defined in claim 1);
  
  14) C_2-3alkylX⁹C_1-3alkylR²⁹(wherein X⁹and R²⁹are as defined in claim 1);
  
  15) C_2-3alkylX⁹C_1-3alkylR²⁸(wherein X⁹and R²⁹are as defined in claim 1);
  
  16) C_2-5alkenyl which may be unsubstituted or which may be substituted with one or more fluorine atoms or with one or two groups selected from hydroxy, fluoro, amino, C_1-4alkylamino, N,N-di(C_1-4alkyl)amino, aminosulphonyl, N-C_1-4alkylaminosulphonyl and N,N-di(C_1-4alkyl)aminosulphonyl;
  
  17) C_2-5alkynyl which may be unsubstituted or which may be substituted with one or more fluorine atoms or with one or two groups selected from hydroxy, fluoro, amino, C_1-4alkylamino, N,N-di(C_1-4alkyl)amino, aminosulphonyl, N-C_1-4alkylaminosulphonyl and N,N-di(C_1-4alkyl)aminosulphonyl;
  
  18) C_2-3alkenylX⁹C_1-3alkylR²⁸(wherein X⁹and R²⁸are as defined in claim 1);
  
  19) C_2-3alkynylX⁹C_1-3alkylR²⁸(wherein X⁹and R²⁸are as defined in claim 1); and
  
  20) C_1-3alkylR⁵⁴(C_1-3alkyl)_q(X⁹)_rR⁵⁵(wherein X⁹, q, r, R⁵⁴and R⁵⁵are as defined in claim 1);
  
  and additionally wherein any C_1-5alkyl, C_2-5alkenyl or C_2-5alkynyl group in R⁵X¹—
  
  may bear one or more substituents selected from hydroxy, halogeno and amino].
8. A compound according to claim 1 wherein one of the R²substituents is R⁵X¹—
- , wherein R⁵and X¹are as defined in claim 1, and the substituent R⁵X¹—
  
  , is at the 7-position of the cinnoline ring.
9. A compound according to claim 7 wherein one of the R²substituents is R⁵X¹—
- , wherein R⁵and X¹are as defined in claim 7, and the substituent R⁵X¹—
  
  is at the 7-position of the cinnoline ring.
10. A compound according to claim 8 wherein the R²substituent at the 6-position of the cinnoline ring is hydrogen, methoxy or cyano.
12. A compound according to any one of claims 1 to 11 in the form of a pharmaceutically acceptable salt.
13. A process for the preparation of a compound of formula I or salt thereof which comprises:
- (a) the reaction of a compound of the formula III;
  
  (wherein R^a, R²and m are as defined in claim 1 and L¹is a displaceable moiety), with a compound of the formula IV;
  
  (wherein R^b, R¹, G₁, G₂, G₃, G₄, G₅, Z and n are as defined in claim 1);
  
  (b) a compound of formula I or a salt thereof wherein at least one R²is R⁵X¹wherein R⁵is as defined in claim 1 and X¹is —
  
  O—
  
  , —
  
  S—
  
  , —
  
  OC(O)—
  
  or —
  
  NR¹⁰—
  
  (wherein R¹⁰independently represents hydrogen, C_1-3alkyl or C_1-3alkoxyC_2-3alkyl) may be prepared by the reaction of a compound of the formula V;
  
  (wherein R^a, R^b, Z, G₁, G₂, G₃, G₄, G₅, R¹, R²and n are as defined in claim 1 and X¹is as herein defined in this section and s is an integer from 0 to
  
  2) with a compound of formula VI;
  
  R⁵-L¹
  
  (I)(wherein R⁵is as defined in claim 1 and L¹is as defined herein);
  
  (c) a compound of the formula I or a salt thereof wherein at least one R²is R⁵X¹wherein R⁵is as defined in claim 1 and X¹is —
  
  O—
  
  , —
  
  S—
  
  , —
  
  OC(O)—
  
  or —
  
  NR¹⁰—
  
  (wherein R¹⁰represents hydrogen, C_1-3alkyl or C_1-3alkoxyC_2-3alkyl) may be prepared by the reaction of a compound of the formula VII;
  
  with a compound of the formula VII;
  
  R⁵—
  
  X¹—
  
  H
  
  (VIII) (wherein R^a, R^b, R¹, R², R⁵, G₁, G₂, G₃, G₄, G₅, Z and n are as defined in claim 1 and L¹and s are as defined herein and X¹is as defined herein in this section);
  
  (d) a compound of the formula I or a salt thereof wherein at least one R²is R⁵X¹wherein X¹is as defined in claim 1 and R⁵is C_1-5alkylR⁶², wherein R⁶²is selected from one of the following nine groups;
  
  1) X¹⁰C_1-3alkyl (wherein X¹⁰represents —
  
  O—
  
  , —
  
  S—
  
  , —
  
  SO₂—
  
  , —
  
  NR⁶³C(O)—
  
  or —
  
  NR⁶⁴SO₂—
  
  (wherein R⁶³and R⁶⁴which may be the same or different are each hydrogen, C_1-3alkyl or C_1-3alkoxyC_2-3alkyl);
  
  2) NR⁶⁵R⁶⁶(wherein R⁶⁵and R⁶⁶which may be the same or different are each hydrogen, C_1-3alkyl or C_1-3alkoxyC_2-3alkyl);
  
  3) X¹¹C_1-5alkylX⁵R²²(wherein X¹¹represents —
  
  O—
  
  , —
  
  S—
  
  , —
  
  SO₂—
  
  , —
  
  NR⁶⁷C(O)—
  
  , —
  
  NR⁶⁸SO₂—
  
  or —
  
  NR⁶⁹—
  
  (wherein R⁶⁷, R⁶⁸, and R⁶⁹which may be the same or different are each hydrogen, C_1-3alkyl or C_1-3alkoxyC_2-3alkyl) and X⁵and R²²are as defined in claim 1);
  
  4) R²⁸(wherein R²⁸is as defined in claim 1);
  
  5) X¹²R²⁹(wherein X¹²represents —
  
  O—
  
  , —
  
  S—
  
  , —
  
  SO₂—
  
  , —
  
  NR⁷⁰C(O)—
  
  , —
  
  NR⁷¹SO₂—
  
  , or —
  
  NR⁷²—
  
  (wherein R⁷⁰, R⁷¹, and R⁷²which may be the same or different are each hydrogen, C_1-3alkyl or C_1-3alkoxyC_2-3alkyl) and R²⁹is as defined in claim 1); and
  
  6) X¹³C_1-3alkylR⁹(wherein X¹³represents —
  
  O—
  
  , —
  
  S—
  
  , —
  
  SO₂—
  
  , —
  
  NR⁷³C(O)—
  
  , —
  
  NR⁷⁴SO₂—
  
  or —
  
  NR⁷⁵—
  
  (wherein R⁷³, R⁷⁴and R⁷⁵each independently represents hydrogen, C_1-3alkyl or C_1-3alkoxyC_2-3alkyl) and R²⁹is as defined in claim 1);
  
  7) R²⁹(wherein R²⁹is as defined in claim 1);
  
  8) X¹³C_1-4alkylR²⁸(wherein X¹³and R²⁸are as defined in claim 1); and
  
  9) R⁵⁴(C_1-4alkyl)_q(X⁹)_rR⁵⁵(wherein q, r, X⁹, R⁵⁴and R⁵⁵are as defined in claim 1);
  
  maybe prepared by reacting a compound of the formula IX;
  
  (wherein X¹, R^a, R^b, R¹, R², G₁, G₂, G₃, G₄, G₅, Z and n are as defined in claim 1 and L¹and s are as defined herein) with a compound of the formula X;
  
  R⁶²—
  
  H
  
  (X) (wherein R⁶²is as defined herein) to give a compound of the formula I or salt thereof, (e) a compound of the formula I or a salt thereof wherein one or more of the substituents (R²)_mis represented by —
  
  NR⁷⁶R⁷⁷, where one (and the other is hydrogen) or both of R⁷⁶and R⁷⁷are C_1-3alkyl, may be effected by the reaction of a compound of formula I wherein the substituent (R²)_mis an amino group and an alkylating agent;
  
  (f) a compound of the formula I or a salt thereof wherein X¹is —
  
  SO—
  
  or —
  
  SO₂—
  
  may be prepared by oxidation from the corresponding compound in which X¹is —
  
  S—
  
  or —
  
  SO—
  
  (when X¹is —
  
  SO₂—
  
  is required in the final product);
  
  and when a salt of a compound of formula I is required, reaction of the compound obtained with an acid or base whereby to obtain the desired salt.
14. A pharmaceutical composition which comprises a compound of the formula I as defined in any one of claims 1-11, or a pharmaceutically acceptable salt thereof, in association with a pharmaceutically acceptable excipient or carrier.
15. A method for producing an antiangiogenic and/or vascular permeability reducing effect in a warm-blooded animal in need thereof which comprises administering to said animal an effective amount of a compound of formula I as defined in any one of claims 1-11, or a pharmaceutically acceptable salt thereof.

11. A compound selected from:
- 4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)cinnoline, 4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxy-7-(piperidin-4-ylmethoxy)cinnoline, 4-(4-fluoro-2-methylindol-5-yloxy)-7-(R)-(2-hydroxy-3-(piperidin-1-yl)propoxy)-6-methoxycinnoline, 4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)cinnoline, 7-benzyloxy-4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxycinnoline, 4-(4-fluoro-2-methylindol-5-yloxy)-7-(R)-(2-hydroxy-3-(pyrrolidin-1-yl)propoxy)-6-methoxycinnoline, 4-(4-fluoro-2-methylindol-5-yl)oxy-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)cinnoline, and 4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxy-7-(3-(piperidin-1-yl)propoxy)cinnoline, or a salt thereof.

Specification

Resources

Litigation Campaign Assessment

Current Assignee
Astrazeneca AB (Astrazeneca PLC)
Original Assignee
Astrazeneca AB (Astrazeneca PLC)
Inventors
Hennequin, Laurent Francois Andre
Primary Examiner(s)
Raymond, Richard L.
Assistant Examiner(s)
Habte, Kahsay

Application Number

US10/333,592
Publication Number

US 20030212055A1
Time in Patent Office

1,365 Days
Field of Search

544/235, 514/248
US Class Current

514/248
CPC Class Codes

A61P 15/00   Drugs for genital or sexual...

A61P 17/06   Antipsoriatics

A61P 19/02   for joint disorders, e.g. a...

A61P 27/02   Ophthalmic agents

A61P 29/00   Non-central analgesic, anti...

A61P 3/10   for hyperglycaemia, e.g. an...

A61P 35/00   Antineoplastic agents

A61P 37/06   Immunosuppressants, e.g. dr...

A61P 9/10   for treating ischaemic or a...

C07D 401/14   containing three or more he...

C07D 403/12   linked by a chain containin...

Cinnoline compounds

First Claim

1 Assignment

0 Petitions

Accused Products

Abstract

Citations

15 Claims

Specification

Solutions

Use Cases

Quick Links

Cinnoline compounds

First Claim

1 Assignment

Subscription Required

Subscription Required

0 Petitions

Subscription Required

Accused Products

Subscription Required

Abstract

Citations

15 Claims

Specification

Subscription Required

Solutions

Use Cases

Quick Links