Derivatives of 4-aminopiperidine and their use a medicament
1 Assignment
0 Petitions
Accused Products
Abstract
A subject of the present application is new derivatives of 4-aminopiperidines of formula
in which R1, R2 and R3 represent various radical, and their preparation processes by synthetic methods in parallel in liquid and solid phase. These products having a good affinity with certain sub-types of somatostatin receptors, they are particularly useful for treating the pathological states or diseases in which one (or more) somatostatin receptors are involved.
19 Citations
26 Claims
-
1. A compound of the formula
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14)
-
2. A compound of claim 1 wherein
i) the substituents carried by aryl represented by Z11, and Z12 and heteroaryl represented by Z12 are independently selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkoxy, alkylthio, — - CF3, —
OCF3, phenyl, phenoxy and aminosulfonyl;
ii) the substituents carried by the heterocycloalkyl represented by Z12 are independently oxy or alkyl;
iii) the substituents carried by aryl and heteroaryl represented by Z22 are independently selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkenyl, alkoxy, alkylthio, —
CF3, —
OCF3, nitro, cyano, azido, aminosulfonyl, piperidinosulfonyl, mono- or di-alkylamino, —
C(O)—
O-alkyl, —
C(O)-alkyl, phenyl, phenoxy, phenylthio and benzyloxy, the phenyl optionally substituted;
iv) the substituents carried by aryl represented by Z23 and Z24, cycloalkyl and heteroaryl represented by Z24 are selected independently from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkoxy, alkylthio, —
CF3, —
OCF3, —
OCHF2, —
SCF3, nitro, cyano, azido, hydroxy, —
C(O)O-alkyl, —
O—
C(O)-alkyl, —
NH—
C(O)-alkyl, alkylsulfonyl, mono- or di-alkylamino, amino, aminoalkyl, pyrrolyl, pyrrolidinyl, phenyl, phenoxy, phenylthio, benzyl and benzyloxy, the aryl is optionally substituted by at least one member selected from the group consisting of alkyl, CF3 and halo;
v) the substituents carried by aryl and heteroaryl represented by Z25 are independently selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkoxy, —
CF3, —
OCF3, nitro, cyano, —
NH—
C(O)-alkyl, alkylsulfonyl, amino, mono- and di-alkylamino, phenyl and pyridino;
vi) the substituents carried by alkyl represented by R3 is cyano;
vii) the substituents carried by aralkyl represented by R3 are independently selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkoxy, —
CF3, —
OCF3, —
OCHF2, —
SCF3, —
SCHF2, nitro, cyano, —
C(O)O-alkyl, alkylsulfonyl, thiadiazolyl, phenyl and phenoxy optionally substituted by at least one halo andviii) the substituents carried by heteroarylalkyl represented by R3 are independently selected from the group consisting of fluoro, chloro, bromo and nitro.
- CF3, —
-
3. A compound of claim 1 wherein
R1 is selected from the group consisting of (C1-C6)alkyl, — - (CH2)m—
Y-Z11 and —
(CH2)m-Z12,Z11 is (C1-C6)alkyl, Z12 is selected from the group consisting of bis-phenyl, (C3-C7)cycloalkyl, (C3-C7)heterocycloalkyl optionally substituted, aryl or heteroaryl optionally substituted by at least one member selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl and alkoxy, or Z12 is Y is oxygen, or R1 is R2 is selected from the group consisting of —
C(Y)NHX1, —
C(O)X2 and SO2X3 whereinX1 is (C1-C15)alkyl, or —
(CH2)pZ22,Z22 is selected from the group consisting of cyclohexenyl, bis-phenyl, (C3-C7)cycloalkyl, (C3-C7)heterocycloalkyl, mono- or di-alkylamino, —
C(O)—
O-alkyl, aryl and heteroaryl unsubstituted or substituted by at least one member selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkoxy, alkylthio, —
CF3, —
OCF3, nitro, cyano, azido, piperidinosulfonyl, —
C(O)—
O-alkyl, —
C(O)-alkyl, or phenyl,or Z22 is X2 is selected from the group consisting of (C1-C10)alkyl, alkynyl, —
(CH2)m—
W—
(CH2)q—
U-Z23 and —
(CH2)p—
U-Z24,W is SO2, U is a covalent bond, Z23 is aryl;
Z24 is selected from the group consisting of cyclohexenyl, bis-phenyl, (C3-C7)cycloalkyl optionally substituted by an aminoalkyl, aryl and heteroaryl unsubstituted or substituted by at least one member selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkoxy, —
CF3, —
OCF3, —
SCF3, hydroxy, —
O—
C(O)-alkyl, mono- or di-alkylamino, aminoor Z24 is or X2 is X3 is —
(CH2)pZ25, Z25 is aryl optionally substituted by at least one member selected from the group consisting of alkoxy and —
CF3,R3 is selected from the group consisting of hydrogen, alkyl, alkenyl, heteroarylalkyl optionally substituted, —
C(Y)—
NHX1, —
C(O)X2 and SO2X3 in whichX1 is —
(CH2)pZ22,Z22 is aryl unsubstituted or substituted by at least one member selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkoxy, —
CF3, nitro and phenoxy;
X2 is vinyl substituted by phenyl, unsubstituted or substituted by at least one member selected from the group consisting of halo or —
(CH2)p—
U-Z24,Z24 is selected from the group consisting of alkyl, (C3-C7)cycloalkyl, (C3-C7) heterocycloalkyl, bis-phenyl, amino, mono or di-alkylamino, and aryl and heteroaryl unsubstituted or substituted by at least one member selected from the group consisting of alkoxy, bromo, chloro, fluoro, hydroxy, —
CF3, nitro, amino, mono- and di-alkylamino and pyrrolyl,or X2 is selected from the group consisting of X3 is selected from the group consisting of (C1-C10)alkyl, vinyl substituted by phenyl optionally substituted, —
CF3 and —
(CH2)pZ25Z25 is aryl or heteroaryl unsubstituted or substituted by at least one member selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkoxy, —
CF3, nitro, —
NH—
C(O)-alkyl and mono- and di-alkylamino.
- (CH2)m—
-
4. A compound of claim 1 wherein R1 is (C1-C6)alkyl, —
- (CH2)m—
Y-Z11 and —
(CH2)m-Z12,Z11 is (C1-C6)alkyl, Z12 is selected from the group consisting of naphthyl, morpholino, bis-phenyl, pyrrolidinyl substituted by oxy and phenyl, piperazinyl, pyridinyl and indolyl, all unsubstituted or substituted by at least one member selected from the group consisting of bromo, fluoro, chloro, alkyl, alkoxy, —
CF3 and —
OCF3;
or Z12 is Y is oxygen, or R1 is
- (CH2)m—
-
5. A compound of claim 1 wherein R2 is selected from the group consisting of —
- C(Y)NHX1, —
C(O)X2 and SO2X3X1 is (C1-C10)alkyl, or —
(CH2)pZ22,Z22 is selected from the group consisting of cyclohexyl, cyclohexenyl, bis-phenyl, morpholino, piperidino, mono- or di-alkylamino, —
C(O)—
O-alkyl, and phenyl, naphthyl and furyl unsubstituted or substituted by at least one member selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkoxy, alkylthio, —
CF3, —
OCF3, nitro, cyano, azido, piperidinosulfonyl, —
C(O)—
O-alkyl, —
C(O)-alkyl, —
C(O)-alkyl and phenyl,or Z22 is X2 is selected from the group consisting of alkyl, alkynyl, —
(CH2)m—
W—
(CH2)q-Z23 and —
(CH2)pZ24,W is SO2;
Z21 is phenyl;
Z24 is selected from the group consisting of cyclohexenyl, bis-phenyl, cyclohexyl optionally substituted by an aminoalkyl, and phenyl, naphthyl, benzothienyl, thienyl and indolyl unsubstituted or substituted by at least one member selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkoxy, —
CF3, —
OCF3, —
SCF3, hydroxy, —
O—
C(O)-alkyl, —
NH—
C(O)-alkyl, mono- or di-alkylamino and amino, orZ24 is or X2 is X3 is —
(CH2)pZ25, Z25 is phenyl unsubstituted or substituted by at least one alkoxy or —
CF3.
- C(Y)NHX1, —
-
6. A compound of claim 1 wherein R3 is selected from the group consisting of hydrogen, alkyl, alkenyl, or furyl-methyl substituted by at least one member selected from the group consisting of nitro, —
- C(Y)—
NHX1, —
C(O)X2 and SO2X3,X1 is —
(CH2)pZ22Z22 is phenyl or naphthyl unsubstituted or substituted by at least one member selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkoxy, —
CF3, nitro and phenoxy,X2 is vinyl substituted by phenyl unsubstituted or substituted by at least one member selected from the group consisting of halo, or —
(CH2)p—
U-Z24,Z24 is selected from the group consisting of alkyl, cyclohexyl, tetrahydrofuryl, bis-phenyl, amino, mono- or di-alkylamino, and phenyl, indolyl, thienyl, pyridinyl, benzothienyl and furyl, all unsubstituted or substituted by at least one member selected from the group consisting of alkoxy, bromo, chloro, fluoro, amino, mono- and di-alkylamino, nitro, hydroxy and pyrrolyl or X2 is selected from the group consisting of X3 is (C1-C10)alkyl, vinyl substituted by phenyl, —
CF3, or —
(CH2)pZ25,Z25 is selected from the group consisting of phenyl, naphthyl, thienyl, pyrazolyl and thiazolyl, all unsubstituted or substituted by at least one member selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkoxy, —
CF3, nitro, —
NH—
C(O)-alkyl and mono- and di-alkylamino.
- C(Y)—
-
7. A compound of claim 1 wherein R1 is —
- (CH2)mZ2 in which m=2 and Z12 is bis-phenyl or indolyl substituted by at least one member selected from the group consisting of alkyl and alkoxy.
-
8. A compound of claim 1 wherein R2 is —
- C(Y)NHX1 or —
C(O)X2,Y is S;
X1 is phenyl optionally substituted by, at least one azido, X2 is —
(CH2)pZ24,p is 1, 2 or 3, Z24 is cyclohexyl, or phenyl or benzothienyl optionally substituted by at least one member selected from the group consisting of fluoro, chloro, bromo, iodo, —
CF3.
- C(Y)NHX1 or —
-
9. A compound of claim 1 wherein R3 is hydrogen or methyl.
-
10. A process for the liquid phase preparation of a compound of claim 1, comprising
reducing amination of a N-substituted piperidone of the formula wherein R is methyl or Boc, in the presence of an amine of the formula R1NH2 in which R1 is as defined in claim 1, to obtain a compound of the formula which compound is reacted with A) either a compound of the formula X1NC(Y) in which X1 and Y have the meaning of claim 1, to obtain a compound of the formula which compound is the corresponding compound of formula (I) in which R3 is Me or Boc and which, when R3 is Boc, can be subjected to an acid treatment to obtain the corresponding compound of formula (I) in which R3 is hydrogen, which compound of formula (I) thus obtained can be reacted with a compound of the formula X1NC(Y) or X2CO2H or X3SO2Cl in which X1, Y, X2 and X3 have the meaning of claim 1, to obtain the corresponding compound of formula I in which R2 is — - C(Y)NHX1 and R3 is —
C(Y)—
NHX1, —
C(O)X2 or —
SO2X3, respectively;
B) or a compound of the formula X2CO2H in which X2 has the meaning of claim 1, to obtain a compound of the formula which compound of formula (3) is the corresponding compound of formula (I) in which R3 is Me or Boc and which, when R3 is Boc, can be subjected to an acid treatment to obtain the corresponding compound of formula (I) in which R3 is hydrogen, which compound of formula (I) thus obtained can be reacted with a compound of the X1NC(Y), X2CO2H or X3SO2Cl which X1, Y, X2 and X3 have the meaning of claim 1, to obtain the corresponding compound of formula I in which R2 is —
C(O)X2 and R3 is —
C(Y)—
NHX1, —
C(O)X2 or SO2X3 respectively.
- C(Y)NHX1 and R3 is —
-
11. A solid phase preparation process for a compound of claim 1, comprising
reducing the amination of the ketonic resin in the presence of an amine of the formula R1NH2 in which R1 has the meaning of claim 1, to obtain a compound of the formula which compound of formula (4) is reacted with A) either a compound of the formula X1NC(Y) in which X1 and Y have the meaning of claim 1, to obtain a compound of the formula followed by cleavage of the resin to obtain the corresponding compound of formula (I) in which R3 is hydrogen, B) or a compound of the formula X3SO2Cl in which X3 has the meaning of claim 1, to obtain a compound of the formula followed by cleavage of the resin to obtain the corresponding compound of formula (I) in which R3 is hydrogen, C) or a compound of the formula X2CO2Cl in which X2 has the meaning of claim 1, to obtain a compound of the formula followed by cleavage of the resin to obtain the corresponding compound of formula (I) in which R3 is hydrogen; D) or a compound of the formula X2CO2H in which X2 has the meaning of claim 1, to obtain a compound of formula (7) as defined above, followed by the cleavage of the resin to obtain the corresponding compound of formula (I) in which R3 is hydrogen.
-
12. A solid phase preparation process for a compound of claim 1, comprising
reducing amination of the ketonic resin in the presence of an amine of the formula R1NH2 in which R1 has the meaning of claim 1, to obtain a compound of the formula which compound of formula (8) is reacted with A) either a compound of the formula X1NC(O) in which X1 has the meaning of claim 1, to obtain a compound of the formula which compound (9) is reacted with a compound of the formula R3X in which R3 is defined as in claim 1 and X is Br or I, followed by cleavage of the resin to obtain the corresponding compound of formula (I); -
B) or a compound of the formula X3SO2Cl in which X3 has the meaning of claim 1, to obtain a compound of the formula which compound (10) is reacted with a compound of the formula R3X in which R3 is defined as in claim 1 and X is Br or I, followed by cleavage of the resin to obtain the corresponding compound of formula (I);
C) or a compound of the formula X2CO2Cl in which X2 has the meaning of claim 1, to obtain a compound of the formula which compound (11) is reacted with a compound of the formula R3X in which R3 is defined as in claim 1 and X is Br or I, followed by cleavage of the resin to obtain the corresponding compound of formula (I);
D) or a compound of the formula X2CO2H in which X2 has the meaning of claim 1, to obtain a compound of formula (11) as defined above, which compound (11) is reacted with a compound of the formula R3X in which R3 is defined as in claim 1 and X is Br or I, followed by cleavage of the resin to obtain the corresponding compound of formula (I).
-
-
14. A pharmaceutical composition having an affinity for somatostatin receptors comprising an effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
-
2. A compound of claim 1 wherein
-
13. (canceled)
-
15. A method of treating a disease involving a receptor of somatostatin in warm-blooded animals comprising administering to warm-blooded animals in need thereof an amount of a compound of the formula
- View Dependent Claims (16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26)
-
16. The method of claim 15, wherein
i) the substituents carried by aryl represented by Z11 and Z12 and heteroaryl represented by Z12 are selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkoxy, alkylthio, — - CF3, —
OCF3, phenyl, phenoxy and aminosulfonyl;
ii) the substituents carried by the heterocycloalkyl represented by Z12 are oxy or alkyl;
iii) the substituent carried by aryl and heteroaryl represented by Z22 are selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkenyl, alkylthio, —
CF3, —
OCF3, nitro, cyano, azido, aminosulfonyl, piperidinosulfonyl, mono- or di-alkylamino, —
C(O)—
(O)-alkyl, —
C(O)-alkyl, and phenyl, phenoxy, phenylthio and benzyloxy with the phenyl unsubstituted or substituted;
iv) the substituents carried by aryl represented by Z23 and Z24, cycloalkyl and heteroaryl represented by Z24 are selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkoxy, alkylthio, —
CF3, —
OCF3, —
OCHF2, —
SCF3, nitro, cyano, azido, hydroxy, —
C(O)O-alkyl, —
(O)—
C(O)-alkyl, —
NH—
C(O)-alkyl, alkylsulfonyl, mono- or di-alkylamino, amino, aminoalkyl, pyrrolyl, pyrrolidinyl and phenyl, phenoxy, phenylthio, benzyl and benzyloxy, the aryl of which is unsubstituted or substituted by at least one member selected from the group consisting of alkyl, —
CF3 and halogen,v) the substituents carried by aryl and heteroaryl represented by Z25 are selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkoxy, —
CF3, —
OCF3, nitro, cyano, —
NH—
C(O)-alkyl, alkylsulfonyl, amino, mono- and di-alkylamino, phenyl and pyridino;
vi) the substituent carried by alkyl represented by R3 is cyano, vii) the substituents carried by aralkyl represented by R3 are selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkoxy, —
CF3, —
OCF3, —
OCHF2, —
SCF3, —
SCHF2, nitro, cyano, —
C(O)O-alkyl, alkylsulfonyl, thiadiazolyl and phenyl and phenoxy unsubstituted or substituted by at least one halogen andviii) the substituents carried by heteroarylalkyl represented by R3 are selected from the group consisting of fluoro, chloro, bromo or nitro.
- CF3, —
-
17. The method of claim 15, wherein R1a is (C1-C6)alkyl, —
- (CH2)m—
Y-Z11 and —
(CH2)m-Z12,Z11 is (C1-C6)alkyl, Z12 is bis-phenyl, (C3-C7) cycloalkyl, (C3-C7)hetero-cycloalkyl optionally substituted and aryl or heteroaryl unsubstituted or substituted by at least one member selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl and alkoxy, or Z12 is Y is oxygen, or R1a is
- (CH2)m—
-
18. The method of claim 15 wherein R2a is selected from the group consisting of —
- C(Y)NHX1, —
C(O)X2 and —
SO2X3 in whichX1 is (C1-C15)alkyl, or —
(CH2)pZ22,Z22 is selected from the group consisting of cyclohexenyl, bis-phenyl, (C3-C7)cycloalkyl, (C3-C7)heterocycloalkyl, mono- or di-alkylamino, —
C(O)—
O-alkyl and aryl or heteroaryl unsubstituted or substituted by at least one member selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkoxy, alkylthio, —
CF3, —
OCF3, nitro, cyano, azido, piperidinosulfonyl, —
C(O)—
O-alkyl, —
C(O)-alkyl and phenyl,or Z22 is X2 is selected from the group consisting of (C1-C10)alkyl, alkynyl, —
CH2)m—
W—
(CH2)q-Z23 and —
(CH2)p—
U-Z24,W is SO2, U is a covalent bond, Z23 is aryl;
Z24 is selected from the group consisting of cyclohexenyl, bis-phenyl, (C3-C7) cycloalkyl unsubstituted or substituted by an aminoalkyl and aryl or heteroaryl unsubstituted or substituted by at least one member selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkoxy, —
CF3, —
OCF3, —
SCF3, hydroxy, —
O—
C(O)-alkyl, mono- or di-alkylamino and amino,or Z24 is or X2 is X3 is —
(CH2)pZ25, Z25 is aryl optionally substituted by at least one alkoxy or CF3.
- C(Y)NHX1, —
-
19. The method of claim 15 wherein R3a is selected from the group consisting of hydrogen, alkyl, alkenyl, heteroarylalkyl optionally substituted, —
- C(Y)—
NHX1, —
C(O)X2 and SO2X3,X1 is —
(CH2)pZ22,Z22 is aryl unsubstituted or substituted by at least one member selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkoxy, —
CF3, nitro and phenoxy,X2 is vinyl substituted by phenyl unsubstituted or substituted by at least one halogen, or —
(CH2)p—
U-Z24,Z24 is selected from the group consisting of alkyl, (C3-C7)cycloalkyl, (C3-C7)heterocycloalkyl, bis-phenyl, amino, mono or di-alkylamino and aryl or heteroaryl unsubstituted or substituted by at least one member selected from the group consisting of alkoxy, bromo, chloro, fluoro, hydroxy, CF3, nitro, amino, mono- and di-alkylamino and pyrrolyl, or X2 is selected from the group consisting of X3 is selected from the group consisting of (C1-C10)alkyl, vinyl substituted by phenyl optionally substituted, —
CF3 and —
(CH2)pZ25,Z25 is aryl or heteroaryl unsubstituted or substituted by at least one member selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkoxy, —
CF3, nitro, —
NH—
C(O)-alkyl and mono- and di-alkylamino.
- C(Y)—
-
20. The method of claim 15 wherein R1a is (C1-C6)alkyl, —
- (CH2)m—
Y-Z11 and —
(CH2)m-Z12,Z11 is (C1-C6)alkyl, Z12 is selected from the group consisting of naphthyl, morpholino, bis-phenyl, pyrrolidinyl substituted by oxy and phenyl, piperazinyl, pyridinyl and indolyl unsubstituted or substituted by at least one member selected from the group consisting of bromo, fluoro, chloro, alkyl, alkoxy, —
CF3 and —
OCF3;
or Z12 is Y is oxygen, or R1a is
- (CH2)m—
-
21. The method of claim 15 wherein R2, selected from the group consisting of —
- C(Y)NHX1, —
C(O)X2 and SO2X3,X1 is (C1-C10)alkyl, or —
(CH2)pZ22,Z22 is selected from the group consisting of cyclohexyl, cyclohexenyl, bis-phenyl, morpholino, piperidino, mono- or di-alkylamino, —
C(O)—
O-alkyl and phenyl, naphthyl and furyl unsubstituted or substituted by at least one member selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkoxy, alkylthio, —
CF3, —
OCF3, nitro, cyano, azido, piperidinosulfonyl, —
C(O)—
O-alkyl, —
C(O)-alkyl and phenyl,or Z22 is X2 is selected from the group consisting of alkyl, alkynyl, —
(CH2)m—
W—
(CH2)q-Z23 and —
(CH2)p-Z24,W is SO2;
Z23 is phenyl;
Z24 is selected from the group consisting of cyclohexenyl, bis-phenyl, cyclohexyl optionally substituted by aminoalkyl and phenyl, naphthyl, benzothienyl, thienyl and indolyl unsubstituted or substituted by at least one member selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkoxy, —
CF3, —
OCF3, —
SCF3, hydroxy, —
O—
C(O)-alkyl, —
NH—
C(O)-alkyl, mono- or di-alkylamino and amino, orZ24 is or X2 is X3 is —
(CH2)pZ25, Z25 is phenyl unsubstituted or substituted by at least one alkoxy or CF3.
- C(Y)NHX1, —
-
22. The method of claim 15 wherein R3a is selected from the group consisting of hydrogen, alkyl, alkenyl, furyl-methyl substituted by at least one member selected from the group consisting of nitro, —
- C(Y)—
NHX1, —
C(O)X2 and SO2X3X1 is —
(CH2)pZ22,Z22 is phenyl or naphthyl unsubstituted or substituted by at least one member selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkoxy, —
CF3, nitro and phenoxy,X2 is vinyl substituted by phenyl unsubstituted or substituted by at least one halo, or —
(CH2)p—
U-Z24,Z24 is selected from the group consisting of alkyl, cyclohexyl, tetrahydrofuryl, bis-phenyl, amino, mono or di-alkylamino, and phenyl, indolyl, thienyl, pyridinyl, benzothienyl and furyl unsubstituted or substituted by at least one member selected from the group consisting of alkoxy, bromo, chloro, fluoro, amino, mono- and di-alkylamino, nitro, hydroxy and pyrrolyl or X2 is selected from the group consisting of X3 is selected from the group consisting of (C1-C10)alkyl, vinyl substituted by phenyl, —
CF3 and —
(CH2)pZ25,Z2, is selected from the group consisting of phenyl, naphthyl, thienyl, pyrazolyl and thiazolyl, all unsubstituted or substituted by at least one member selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkoxy, —
CF3, nitro, —
NH—
C(O)-alkyl and mono- and di-alkylamino.
- C(Y)—
-
23. The method of claim 15 wherein R1a is —
- (CH2)mZ12, m=2 and Z12 is bis-phenyl or indolyl substituted by at least one alkyl or alkoxy.
-
24. The method of claim 15 wherein R2a is —
- C(Y)NHX1 or —
C(O)X2,Y is S;
X1 is phenyl unsubstituted or substituted by at least one azido, X2 is —
(CH2)pZ24,p is 1, 2 or 3, Z24 is selected from the group consisting of cyclohexyl and phenyl or benzothienyl unsubstituted or substituted by at least one member selected from the group consisting of fluoro, chloro, bromo, iodo and —
CF3.
- C(Y)NHX1 or —
-
25. The method of claim 15 wherein R3a is hydrogen or methyl.
-
26. The method of claim 15 wherein the disease treated is selected from the group consisting of acromegalia, hypophyseal adenomas and endocrine gastroenteropancreatic tumors including carcinoid syndrome.
-
16. The method of claim 15, wherein
Specification
- Resources
Thank you for your request. You will receive a custom alert email when the Litigation Campaign Assessment is available.
×
-
Current AssigneeIpsen Pharma Sas (Ipsen Sa)
-
Original AssigneeSociete de Conseils de Recherches et d'Applications Scientifiques
-
InventorsMoinet, Christophe, Gonzalez, Jerome, Thurieau, Christophe
-
Granted Patent
-
Time in Patent OfficeDays
-
Field of Search
-
US Class Current514/253.10
-
CPC Class CodesA61P 1/00 Drugs for disorders of the ...A61P 1/02 Stomatological preparations...A61P 1/12 AntidiarrhoealsA61P 1/18 for pancreatic disorders, e...A61P 11/00 Drugs for disorders of the ...A61P 13/12 of the kidneysA61P 15/00 Drugs for genital or sexual...A61P 17/06 AntipsoriaticsA61P 19/00 Drugs for skeletal disordersA61P 19/08 for bone diseases, e.g. rac...A61P 19/10 for osteoporosisA61P 25/04 Centrally acting analgesics...A61P 25/06 Antimigraine agentsA61P 25/28 for treating neurodegenerat...A61P 3/04 Anorexiants; Antiobesity ag...A61P 3/10 for hyperglycaemia, e.g. an...A61P 35/00 Antineoplastic agentsA61P 35/02 specific for leukemiaA61P 43/00 Drugs for specific purposes...A61P 5/00 Drugs for disorders of the ...A61P 5/02 : of the hypothalamic hormone...A61P 5/04 : for decreasing, blocking or...A61P 5/08 : for decreasing, blocking or...A61P 5/16 : for decreasing, blocking or...A61P 5/46 : for decreasing, blocking or...A61P 5/48 : of the pancreatic hormonesA61P 9/00 : Drugs for disorders of the ...A61P 9/10 : for treating ischaemic or a...C07D 211/58 : attached in position 4C07D 401/12 : linked by a chain containin...C07D 401/14 : containing three or more he...C07D 405/14 : containing three or more he...C07D 409/14 : containing three or more he...C07D 417/14 : containing three or more he...