JP2006508979A5 - - Google Patents

Claims (1)

Compounds having the following formula (I) (including enantiomers, diastereoisomers, tautomers, pharmaceutically acceptable salts and prodrugs thereof)

[Wherein at least one of the 6 or 7 positions of the quinazoline ring must be substituted by the group A and the remaining positions on the quinazoline ring are optionally substituted by up to 3 R ² groups. You may,
X is an N, CH or C-CN group;
R ¹ is independently an aryl or heteroaryl group substituted with at least one R ⁶ group and optionally substituted with up to 3 R ⁵ groups;
R ⁵ is cyano, chlorine, fluorine, bromine, lower alkyl, trifluoromethyl, difluoromethyl, nitro or OR ⁹ ;
R ⁶ is hydrogen, cyano, chlorine, fluorine, bromine, trifluoromethyl, difluoromethyl, trifluoromethoxy, nitro, C ₁ -C ₁₀ alkyl, C ₂ -C ₁₀ alkenyl, C ₂ -C ₁₀ alkynyl, C ₃ -C _{10 cycloalkyl,} C 3 _{-C 10} cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl, each _C 1 _{-C 10 alkyl,} C 2 _{-C 10} alkenyl, C ₂ -C _{10 alkynyl,} C 3 _{-C 10 cycloalkyl,} C 3 _{-C 10} cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl moiety, oxo, halogen, cyano, nitro, G Lifluoromethyl, difluoromethoxy, trifluoromethoxy, azide, —NR ⁷ SO ₂ R ⁸ , —SO ₂ NR ⁹ R ⁷ , —C (O) R ⁹ , —C (O) OR ⁹ , —OC (O) ^{R 9, -NR 7 C (O} ) OR 8, -NR 7 C (O) R 9, -C (O) NR 7 R 9, -NR 7 R 9, -NR 10 C (O) NR 7 R 9 Optionally up to 5 groups independently selected from, -OR ⁹ , -S (O) R ¹³ , -SO ₂ R ¹³ , aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl. Has been replaced,
R ⁷ and R ¹⁰ independently represent hydrogen or C _1-6 alkyl, or R ⁷ and R ¹⁰ together with the atoms to which they are attached are 4- to 10-membered carbocycle, heteroaryl ring or heterocycle Each of three independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azide, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl Optionally substituted with up to groups
R ⁸ represents trifluoromethyl, C ₁ -C ₁₀ alkyl, C ₃ -C ₁₀ cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl, each alkyl, cycloalkyl, aryl, The heteroaryl and heterocyclyl moieties are independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azide, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl Optionally substituted with 1 to 5 groups,
R ⁹ represents hydrogen, trifluoromethyl, C ₁ -C ₁₀ alkyl, (CH ₂ ) _n C ₃ -C ₁₀ cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl, each The alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl moieties are oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azide, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl and heterocyclyl. Optionally substituted with up to 5 groups independently selected from alkyl, n is 0 or 4, or R ⁷ and R ⁹ together with the atoms to which they are attached are 4-10 members. Carbocycle, heteroa Form a reel or heterocycle, each independently from halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azide, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl Optionally substituted with up to three selected groups;
R ¹³ is trifluoromethyl, difluoromethyl, C ₁ -C ₁₀ alkyl, C ₃ -C ₁₀ alkenyl, C ₃ -C ₁₀ alkynyl, C ₃ -C ₁₀ cycloalkyl, C ₃ -C ₁₀ cycloalkylalkyl, aryl , Arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl, each of the above alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl and heterocyclyl moieties of R ¹³ is oxo, halogen, cyano, nitro, Trifluoromethyl, difluoromethoxy, trifluoromethoxy, azide, —NR ⁷ SO ₂ R ⁸ , —SO ₂ NR ⁹ R ⁷ , —C (O) R ⁹ , —C (O) OR ⁹ , —OC (O) ^{R 9, -NR 7 C (O} ) OR 8, -N ^{7 C (O) R 9,} -C (O) NR 7 R 9, -NR 7 R 9, -NR 10 C (O) NR 7 R 9, -NR 10 C (NCN) NR 7 R 9, -OR ^9, aryl, arylalkyl, heteroaryl, heteroarylalkyl, are optionally substituted with one to five groups independently selected from heterocyclyl and ^{heterocyclylalkyl,} R ^7, R 8, ^{R 9} and ^{R 10} are , R ⁷ , R ⁸ , R ⁹ and R ¹⁰ as defined above,
R ² is hydrogen, halogen, cyano, nitro, trifluoromethyl, difluoromethyl, trifluoromethoxy, C ₁ -C ₁₀ alkyl, C ₂ -C ₁₀ alkenyl, C ₂ -C ₁₀ alkynyl, C ₃ -C ₁₀ cyclo alkyl, C ₃ -C ₁₀ cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl, each alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl and heterocyclyl moiety is oxo , Halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azide, —NR ⁷ SO ₂ R ⁸ , —SO ₂ NR ⁹ R ⁷ , —C (O) R ⁹ , —C (O) OR ^9, -OC (O) R ^{, -NR 7 C (O) OR} 8, -NR 7 C (OCR 9, -C (O) NR 7 R 9, -NR 7 R 9, -NR 10 C (O) NR 7 R 9, -NR 10 5 independently selected from C (NCN) NR ⁷ R ⁹ , —OR ⁹ , —S (O) R ¹³ , —SO ₂ R ¹³ , aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl. Optionally substituted with up to groups, R ⁷ , R ⁸ , R ⁹ , R ¹⁰ and R ¹³ are the same as R ⁷ , R ⁸ , R ⁹ , R ¹⁰ and R ¹³ as defined above. ,
A is represented by the following formula (II):

T _is, C 1 _{-C 10 alkyl,} C 2 _{-C 10 alkenyl,} C 2 _{-C 10 alkynyl,} C 3 _{-C 10 cycloalkyl,} C 3 _{-C 10} cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroaryl Represents arylalkyl, heterocyclyl or heterocyclylalkyl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl and heterocyclyl moiety is oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azide, ^{_{-NR 7 SO 2 R 8, -SO}} 2 NR 9 R 7, -C (O) R 9, -C (O) OR 9, -OC (O) R 9, -NR 7 C (O) OR 8, ^{-NR 7 C (O) R 9} , -C (O) NR 7 R 9, -NR 7 R 9 , —NR ¹⁰ C (O) NR ⁷ R ⁹ , —NR ¹⁰ C (NCN) NR ⁷ R ⁹ , —OR ⁹ , —S (O) R ¹³ , —SO ₂ R ¹³ , aryl, arylalkyl, heteroaryl Optionally substituted with up to 5 groups independently selected from: heteroarylalkyl, heterocyclyl and heterocyclylalkyl, wherein R ⁷ , R ⁸ , R ⁹ , R ¹⁰ and R ¹³ are R ^{7 as} defined above. , R ⁸ , R ⁹ , R ¹⁰ and R ¹³ , T may optionally contain one or more heteroatoms, which may be further substituted or oxidized, m is an integer of 0 to 1,
L is a nitrogen atom or CR ⁴ group, and R ⁴ is hydrogen, trifluoromethyl, difluoromethyl, trifluoromethoxy, C ₁ -C ₁₀ alkyl, C ₂ -C ₁₀ alkenyl, C ₂ -C ₁₀ alkynyl, C ₃ -C _{10 cycloalkyl,} C 3 _{-C 10} cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, represents heterocyclyl or heterocyclylalkyl, each alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl And the heterocyclyl moiety may be oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azide, —NR ⁷ SO ₂ R ⁸ , —SO ₂ NR ⁹ R ⁷ , —C (O) R ⁹ , -C ^(O) OR 9, -OC ^{O) R 9, -NR 7 C} (O) OR 8, -NR 7 C (OCR 9, -C (O) NR 7 R 9, -NR 7 R 9, -NR 10 C (O) NR 7 R 9 ^{, -NR 10 C (NCN) NR} 7 R 9, -OR 9, -S (O) R 13, -SO 2 R 13, aryl, arylalkyl, heteroaryl, heteroarylalkyl, independently from heterocyclyl and heterocyclylalkyl Optionally substituted with up to 5 groups selected, R ⁷ , R ⁸ , R ⁹ , R ¹⁰ and R ¹³ are R ⁷ , R ⁸ , R ⁹ , R ¹⁰ and R ^{13 as} defined above. Is the same as
Q is selected from CR ³ R ¹¹ R ¹² or NR ¹¹ R ¹² , R ³ is the same as R ² defined above, and R ¹¹ and R ¹² are independently hydrogen, trifluoromethyl, difluoro , _{trifluoromethoxy,} C 1 _{-C 10 alkyl,} C 2 _{-C 10 alkenyl,} C 2 _{-C 10 alkynyl,} C 3 _{-C 10 cycloalkyl,} C 3 _{-C 10} cycloalkylalkyl, aryl, arylalkyl, heteroaryl Aryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, —NR ⁷ SO ₂ R ⁸ , —SO ₂ NR ⁹ R ⁷ , —C (O) R ⁹ , —C (O) OR ⁹ , —OC (O) R ^{9 , -NR 7 C (O) OR} 8, -NR 7 C (O) R 9, -C (O) NR 7 R 9, -NR 7 R 9, -NR 10 C (O) ^{R 7 R 9, -OR 9,} -S (O) represents ^{R 13} or _SO 2 ^{R 13,} each _C 1 _{-C 10 alkyl,} C 2 _{-C 10 alkenyl,} C 2 _{-C 10 alkynyl,} C 3 -C ₁₀ cycloalkyl, C ₃ -C ₁₀ cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl moieties are oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy , Azide, —NR ⁷ SO ₂ R ⁸ , —SO ₂ NR ⁹ R ⁷ , —C (O) R ⁹ , —C (O) OR ⁹ , —OC (O) R ⁹ , —NR ⁷ C (O) ^{OR 8, -NR 7 C (O} ) R 9, -C (O) NR 7 R 9, -NR 7 R 9, -NR 10 C (O) NR 7 R 9, - Independently selected from NR ¹⁰ C (NCN) NR ⁷ R ⁹ , —OR ⁹ , —S (O) R ¹³ , —SO ₂ R ¹³ , aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl Optionally substituted with up to 5 groups, R ⁷ , R ⁸ , R ⁹ , R ¹⁰ and R ¹³ are R ⁷ , R ⁸ , R ⁹ , R ¹⁰ and R ^{13 as} defined above. Except that (i) when Q is CR ³ R ¹¹ R ¹² , no more than one group of R ³ , R ¹¹ or R ¹² is simultaneously bonded to C via a heteroatom. (Ii) when Q is CR ³ R ¹¹ R ¹² , R ³ is not cyano and halogen, and (iii) when Q is NR ¹¹ R ¹² , between R ¹¹ and R ¹² 1 or more Groups may be bonded to the N through a hetero atom, (iv) when L is CR ^4, Q is ^NR 11 ^{R 12,}
D is hydrogen, trifluoromethyl, _{difluoromethyl,} C 1 _{-C 10 alkyl,} C 2 _{-C 10 alkenyl,} C 2 _{-C 10 alkynyl,} C 3 _{-C 10 cycloalkyl,} C 3 _{-C 10} cycloalkylalkyl, Aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, —SO ₂ NR ⁹ R ⁷ , —C (O) R ⁹ , —C (O) OR ⁹ , —OC (O) R ⁹ or C (O) NR ⁷ R ⁹ , each alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl and heterocyclyl moiety is oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azide, ^{_{-NR 7 SO 2 R 8, -SO}} 2 NR 9 R 7, ^{C (O) R 9, -C} (O) OR 9, -OC (O) R 9, -NR 7 C (O) OR 8, -NR 7 C (O) R 9, -C (O) NR 7 ^{R 9, -NR 7 R 9,} -NR 10 C (O) NR 7 R 9, -NR 10 C (NCN) NR 7 R 9, -OR 9, -S (O) R 13, -SO 2 R 13 , Aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl, optionally substituted with up to 5 groups independently selected from R ⁷ , R ⁸ , R ⁹ , R ¹⁰ and R ^13. Is the same as R ⁷ , R ⁸ , R ⁹ , R ¹⁰ and R ¹³ defined above, provided that when L is N, (i) D is hydrogen, L is a carbon atom or S _{(O) i} group (i is an integer of 1-2) to bind to It is selected, if the (ii) m = 1, T is either L is (are j, an integer from 1 to 2) carbon atom or S _{(O) j} group is selected to bind to, Q and D together includes 0 to 3 heteroatoms in addition to the nitrogen atom that is part of the cyanoguanidine or cyanoamidine group, and N and S (O) _k (k is an integer of 1 to 2 A 5- to 11-membered ring that is not directly bonded between any two heteroatoms except for a bond between (the present) and carbon atoms of the ring are oxo, halogen, cyano, nitro, trifluoromethyl, difluoro methoxy, trifluoromethoxy, azido, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, alkyl, alkenyl, alkynyl, ^cycloalkyl, -NR 7 _SO 2 ^{R 8} , —SO ₂ NR ⁹ R ⁷ , —C (O) R ⁹ , —C (O) OR ⁹ , —OC (O) R ⁹ , —NR ⁷ C (O) OR ⁸ , —NR ⁷ C (O) ^{R 9, -C (O) NR} 7 R 9, -NR 7 R 9, -NR 10 C (O) NR 7 R 9, -NR 10 C (NCN) NR 7 R 9, -OR 9, -S ( ^{O) R 13,} and _SO 2 when a group from ^{R 13} to 2 substituents selected is optionally substituted ^{with, R 7, R 8, R} 9, R 10 and ^{R 13, R} 7 as defined above, is the same as R ^{8, R 9, R 10} and ^{R 13,} each nitrogen atom of the ring may be substituted by optionally and independently ^{R 4} group, ^{R 4} is ^{R 4} as defined above Is the same].