US 2007/0167459 A1 · Nitrogen-containing heterocyclic compounds and medicinal use thereof

Abstract

The compound represented by formulae (I) and (II), the salt thereof, the N-oxide thereof or the solvate thereof, or the prodrug thereof and the pharmaceutical composition comprising thereof have a CXCR4-regulating effect, and they are effective in treatment and prevention of various inflammatory disease, various allergic disease, acquired immunodeficiency syndrome infection with human immunodeficiency virus, or agents for regeneration therapy. (wherein ring A represents a nitrogen-containing heterocyclic group which may have a substituent(s); ring B represents a homocyclic group which may have a substituent(s) or a heterocyclic group which may have a substituent(s); and Y represents a hydrocarbon group which may have a substituent(s), a heterocyclic group which may have a substituent(s), an amino group which may be protected, a hydroxyl group which may be protected or a mercapto group which may be protected; T represents ring A or an amino group which may be protected.)

Claims34

Dependent claims

A compound represented by formula (I):

wherein ring A represents a nitrogen-containing heterocyclic group which may have a substituent(s);
ring B represents a homocyclic group which may have a substituent(s) or a heterocyclic group which may have a substituent(s);
and Y represents a hydrocarbon group which may have a substituent(s), a heterocyclic group which may have a substituent(s), an amino group which may be protected, a hydroxyl group which may be protected or a mercapto group which may be protected,
a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof.

1 more element

A compound represented by formula (I-A):

wherein ring AA represents a 4- to 15-membered monocyclic, bicyclic or tricyclic heterocyclic group which is saturated or has one double bond and which contains at least one nitrogen atom and may further contain 1 to 3 nitrogen atoms, 1 or 2 oxygen atoms and/or one sulfur atom;
ring BA represents BA1 or BA2;
BA1 represents:
R4 represents (i) hydrogen, (ii) C1-15 alkyl, C2-15 alkenyl or C2-15 alkynyl which may be substituted with 1 to 5 of R10, (iii) a C3-8 carbocyclic group which may be substituted with 1 to 5 of R3, (iv) a 5- to 15-membered heterocyclic group which contains 1 or 2 nitrogen atoms, 1 or 2 oxygen atoms and/or one sulfur atom and which may be substituted with 1 to 5 of R3, (v) COR5 wherein R5 represents C1-15 alkyl, C2-15 alkenyl, C2-15 alkynyl or phenyl, or (vi) COOR6 wherein R6 represents C1-15 alkyl, C2-15 alkenyl, C2-15 alkynyl or phenyl;
the upward arrow represents a binding position to ring AA;
and the right-downward arrow represents a binding position to the nitrogen atom bound to L;
L represents (1) a bond, (2) C1-8 alkylene, C2-8 alkenylene or C2-8 alkynylene, wherein the alkylene, alkenylene and alkynylene each may be substituted with 1 to 5 of R10, or (3) a C3-8 carbocyclic group which may be substituted with R3;
Q represents (1) NR1R2 wherein R1 and R2 each independently represents (i) hydrogen, (ii) C1-15 alkyl, C2-15 alkenyl or C2-15 alkynyl which may be substituted with 1 to 5 of R10, (iii) a C3-8 carbocyclic group which may be substituted with 1 to 5 of R3, or (iv) a 5- to 15-membered heterocyclic group which contains 1 or 2 nitrogen atoms, 1 or 2 oxygen atoms and/or one sulfur atom and which may be substituted 1 to 5 of R3, or (2) ring C;
ring C represents a 4- to 15-membered heterocyclic group which contains at least one nitrogen atom and may further contain 1 or 2 nitrogen atoms, 1 or 2 oxygen atoms and/or one sulfur atom and which may be substituted with 1 to 5 of R3;
plural R3's each independently represents (1) C1-15 alkyl, C2-15 alkenyl or C2-15 alkynyl, wherein the alkyl, alkenyl and alkynyl may be substituted with 1 to 5 of R10, (2) oxo, or (3) R10;
plural R10's each independently represents (1) OR11, (2) OCOR12, (3) OCOOR13, (4) NR14 R15, (5) NR16COR12, (6) NR16CONR14R15, (7) NR16or COOR13, (8) COOR13, (9) COR12, (10) CONR14R15, (11) SO2R12, (12) SOR22, (13) SO2NR24R25, (14) NR16SO2R12, (15) B(OH)2, (16) SR11, (17) halogen, (18) nitro, (19) cyano, or (20) ring D;
R11 represents (i) hydrogen, (ii) C1-15 alkyl, C2-15 alkenyl or C2-15 alkynyl, wherein the alkyl, alkenyl and alkynyl may be substituted with 1 to 5 of halogen, NR14R15, OR21, SR21, COOR13, or ring D, or (iii) ring D;
R12, R13, R14, R15 and R16 each independently represents (i) hydrogen, (ii) C1-15 alkyl, C2-15 alkenyl or C2-15 alkynyl which may be substituted with ring D, or (iii) ring D;
ring D represents a C3-15 monocyclic, bicyclic or tricyclic carbocyclic group, or a 5- to 15-membered monocyclic, bicyclic or tricyclic heterocyclic group which contains 1 to 4 nitrogen atoms, 1 or 2 oxygen atoms and/or one sulfur atom;
and
ring D may be substituted with 1 to 5 of the groups selected from the following (1) to (22):
(1) C1-15 alkyl, C2-15 alkenyl or C2-15 alkynyl, wherein the alkyl, alkenyl or alkynyl may be substituted with 1 to 5 of OR21, OCOR22, OCOOR23, NR24R25, NR26COR22, NR26CONR24R25, NR26COOR23, COOR23, COR22, CONR24R25, SO2R22, SOR22, SO2NR24R25, NR26SO2R22, B(OH)2, SR21, halogen, nitro or cyano, (2) oxo, (3) OR21, (4) OCOR22, (5) OCOOR23, (6) NR24R25, (7) NR26COR22, (8) NR26CONR24R25, (9) NR26COOR23, (10) COOR23, (11) COR22, (12) CONR24R25, (13) SO2R22, (14) SOR22, (15) SO2NR24R25, (16) NR26SO2R22, (17) B(OH)2, (18) SR21, (19) halogen, (20) nitro, (21) cyano or (22) ring E;
R21 represents (i) hydrogen, (ii) C1-15 alkyl, C2-15 alkenyl or C2-15 alkynyl which may be substituted with COR22, NR24R25 or ring E, or (iii) ring E;
R22, R23, R24, R25 and R26 each independently represents (i) hydrogen, (ii) C1-15 alkyl, C2-15 alkenyl or C2-15 alkynyl which may be substituted with ring E, or (iii) ring E;
ring E represents a C3-15 monocyclic, bicyclic or tricyclic carbocyclic group, or a 5- to 15-membered monocyclic, bicyclic or tricyclic heterocyclic group which contains 1 to 4 nitrogen atoms, 1 or 2 oxygen atoms and/or one sulfur atom, and
ring E may be substituted with 1 to 5 of (i) C1-15 alkyl which may be substituted with phenyl, (ii) halogen, (iii) phenyl, (iv) C1-15 alkoxy, (v) hydroxyl, (vi) amino, (vii) mono(C1-8 alkyl)amino, or (viii) di(C1-8 alkyl)amino;
ring AA may be substituted with 1-5 of Ra;
ring BA may be substituted with 1-5 of Rb;
Ra and Rb each independently represents a group which has the same meaning as the group represented by R3;
and
wherein the following compounds (1) to (6) are excluded:
(1) N-[4-(4-morpholinyl)-2-quinazolinyl]-1,2-ethanediamine dihydrochloride,
(2) N,N-dimethyl-N′-[2-(4-phenyl-1-piperidinyl)-4-pyrimidinyl]-1,2-ethylenediamine,
(3) N-[(3,4-dihydro-2H-1-benzopyran-2-yl)methyl]-N′-[2-(1-piperidinyl)-4-pyrimidinyl]-1,3-propanediamine,
(4) N-[(3,4-dihydro-2H-1-benzopyrane-2-yl)methyl]-N′-[2-(1-piperidinyl)-4-pyrimidinyl]-1,3-propanediamine oxalate,
(5) N,N-diethyl-N′-[2-(1-pyrrolidinyl)-4-quinazolinyl-1,2-ethanediamine, and
(6) N,N-diethyl-N′-[2-(1-pyrrolidinyl)-4-quinazolinyl-1,2-ethanediamine dihydrochloride,
a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof.

30 more elements

Dependencies are inferred from the claim text.

Nitrogen-containing heterocyclic compounds and medicinal use thereof

Life of this patent

Nitrogen-containing heterocyclic compounds and medicinal use thereof

Life of this patent

Abstract

Claims34