Patent ID: 6436999
Filing Date: 2002-08-20
Classification: A61P,C07C,C07D

Abstract:
A diacyl-substituted guanidine of the formula I in which:X(1) and X(2) are T1 is zero, 1, 2, 3 or 4, R(A) and R(B) are, independently, â€ƒhydrogen, F, Cl, Br, I, CN, OR(106), (C1-C8)-alkyl, (C3-C8)-cycloalkyl, Ozk(CH2)zlCzmF2zm, NR(107)R(108), phenyl or benzyl, where the aromatic radicals are not substituted or are substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR(109)R(110), R(109) and R(110) being â€ƒhydrogen, (C1-C4)-alkyl or (C1-C4)-perfluoroalkyl, â€ƒzl is zero, 1, 2, 3 or 4, â€ƒzk is zero or 1, â€ƒzm is 1, 2, 3, 4, 5, 6, 7 or 8, â€ƒR(106) is hydrogen, (C1-C8)-alkyl, (C1-C8)-perfluoroalkyl, (C3-C8)-alkenyl, (C3-C8)-cycloalkyl, phenyl or benzyl, â€ƒwhere the aromatic radicals are not substituted or are substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR(111)R(112), â€ƒR(111) and R(112) being hydrogen, (C1-C4)-alkyl or (C1-C4)-perfluoroalkyl, â€ƒR(107) and R(108) are, independently of each other, defined as R(106), â€ƒor â€ƒR(107) and R(108) are together 4 or 5 methylene groups of which one CH2 group can be replaced by oxygen, S, NH, Nâ€”CH3 or N-benzyl, or X(1) and X(2) are â€ƒT2a and T2b are, independently of each other, zero, 1 or 2, where the double bond can have the E or Z configuration; or X(1) and X(2) are T3 is zero, 1 or 2, U, YY and Z are, independently of each other, â€ƒC or N, â€ƒwhere U, YY and Z can carry the following number of substituents: Bonded to a doubleNumber of permittedU, YY or Zbond in the ringsubstituentsCyes1Cno2Nyes0Nno1R(D) is hydrogen, (C1-C8)-alkyl or (C1-C8)-perfluoroalkyl, R(U1), R(U2), R(Y1), R(Y2), R(Z1) and R(Z2) are, independently of each other, â€ƒhydrogen, F, Cl, Br, I, CN, OR(114), (C1-C8)-alkyl, (C3-C8)-cycloalkyl, Ozka(CH2)zlaCzmaF2zma+1, NR(115)R(116), phenyl or benzyl, where the aromatic radicals are not substituted or are substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR(117)R(118), â€ƒR(117) and R(118) being hydrogen, (C1-C4)-alkyl or (C1-C4)-perfluoroalkyl, zka is zero or 1, zla is zero, 1, 2, 3 or 4, zma is 1, 2, 3, 4, 5, 6, 7 or 8, R(114) is hydrogen, (C1-C8)-alkyl, (C1-C8)-perfluoroalkyl, (C3-C8)-alkenyl, (C3-C8)-cycloalkyl, phenyl or benzyl, â€ƒwhere the aromatic radicals are not substituted or are substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR(119)R(120), â€ƒR(119) and R(120) being hydrogen, (C1-C4)-alkyl or (C1-C4)-perfluoroalkyl, R(115) and R(116) are, independently of each other, defined as R(114), or R(115) and R(116) â€ƒare together 4 or 5 methylene groups of which one CH2 group can be replaced by oxygen, S, NH, Nâ€”CH3 or N-benzyl, â€ƒwhere, however, the constitution U is nitrogen (N), YY is nitrogen (N) and Z is carbon (C) is excepted, R(101), R(102), R(103), R(104) and R(105) are, independently of each other, â€ƒhydrogen, F, Cl, Br, I, â€”Câ‰¡N, Xzoaâ€”(CH2)zpaâ€”(CzqaF2zqa+1), R(110a)â€”SOzbm, R(110b)R(110c)Nâ€”CO, R(111a)â€”COâ€” or R(112a)R(113a)Nâ€”SO2â€”, where the perfluoroalkyl group is straight-chain or branched, â€ƒX is hydrogen, S or NR(114a), â€ƒzoa is zero or 1, â€ƒR(114a) being H or (C1-C3)-alkyl, â€ƒzbm is zero, 1 or 2, â€ƒzpa is zero, 1, 2, 3 or 4, â€ƒzqa is 1, 2, 3, 4, 5, 6, 7 or 8, â€ƒR(110a), R(110b), R(111a) and R(112a) are, independently, (C1-C8)-alkyl, (C3-C8)-alkenyl, â€”CznH2znâ€”R(115a) or (C1-C8)-perfluoroalkyl, zn is zero, 1, 2, 3 or 4, â€ƒR(115a) is (C3-C8)-cycloalkyl, phenyl, biphenylyl or naphthyl, â€ƒwhere the aromatic radicals are not substituted or are substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR(116a)R(117a), â€ƒR(116a) and R(117a) being hydrogen, (C1-C4)-perfluoroalkyl or (C1-C4)-alkyl, â€ƒor â€ƒR(110b), R(111a) and R(112a) are also hydrogen, R(110c) and R(113a) are, independently, hydrogen, (C1-C4)-perfluoroalkyl or (C1-C4)-alkyl, â€ƒor â€ƒR(110b) and R(110c) and also R(112a) and R(113a) are together 4 or 5 methylene groups of which one CH2 group can be replaced by oxygen, sulfur, NH, Nâ€”CH3 or N-benzyl, or R(101), R(102), R(103), R(104) and R(105) are, independently of each other, â€ƒ(C1-C8)-alkyl, â€”CzalH2zalR(118a) or (C3-C8)-alkenyl, zal is zero, 1, 2, 3 or 4, â€ƒR(118a) is (C3-C8)-cycloalkyl, phenyl, biphenylyl or naphthyl, â€ƒwhere the aromatic radicals are not substituted or are substituted by 1-3 substituents from the group consisting of F, Cl, CF3, methyl, methoxy or NR(119a)R(119b), â€ƒR(119a) and R(119b) being hydrogen, (C1-C4)-alkyl or (C1-C4)-perfluoroalkyl, or R(101), R(102), R(103), R(104) and R(105) are, independently of each other, â€ƒ(C1-C9)-heteroaryl which is linked via C or N and which is unsubstituted or is substituted by 1-3 substituents from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxyl, amino, methylamino and dimethylamino, or R(101), R(102), R(103), R(104) and R(105) are, independently of each other, â€ƒâ€”Câ‰¡Câ€”R(193), â€ƒR(193) is phenyl which is not substituted or is substituted by 1-3 substituents from the group consisting of F, Cl, CF3, methyl, methoxy or NR(194)R(195), R(194) and R(195) being hydrogen or CH3, or R(101), R(102), R(103), R(104) and R(105) are, independently of each other, â€ƒâ€”Y-para-C6H4â€”(CO)zhâ€”(CHOH)ziâ€”(CH2)zjâ€”(CHOH)zkâ€”R(123), â€”Y-meta-C6H4â€”(CO)zadâ€”(CHOH)zaeâ€”(CH2)zafâ€”(CHOH)zagâ€”R(124) â€ƒor â€ƒâ€”Y-ortho-C6H4â€”(CO)zahâ€”(CHOH)zaoâ€”(CH2)zapâ€”(CHOH)zakâ€”R(125), â€ƒY is oxygen, â€”Sâ€” or â€”NR(122d)â€”, â€ƒzh, zad and zah are, independently, zero or 1, â€ƒzi, zj, zk, zae, zaf, zag, zao, zap and zak are, independently, zero, 1, 2, 3 or 4, â€ƒwhere, however, in each case, zh, zi and zk are not simultaneously zero, zad, zae and zag are not simultaneously zero, zah, zao and zak are not simultaneously zero, â€ƒR(123), R(124), R(125) and R(122d) are, independently, hydrogen or (C1-C3)-alkyl, or R(101), R(102), R(103), R(104) and R(105) are, independently of each other, â€ƒSR(129), â€”OR(130), â€”NR(131)R(132) or â€”CR(133)R(134)R(135), â€ƒR(129), R(130), R(131) and R(133), are, independently, â€”CzabH2zabâ€”(C1-C9)-heteroaryl which is unsubstituted or is substituted by 1-3 substituents from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxyl, amino, methylamino and dimethylamino, zab is zero, 1 or 2, â€ƒR(132), R(134) and R(135) are, independently of each other, defined as R(129), or hydrogen, (C1-C4)-alkyl or (C1-C4)-perfluoroalkyl, or R(101), R(102), R(103), R(104) and R(105) are, independently of each other, â€ƒâ€”W-para-(C6H4)â€”R(196), â€”W-meta-(C6H4)â€”R(197) or â€”W-ortho-(C6H4)â€”R(198), â€ƒR(196), R(197) and R(198) are, independently, (C1-C9)-heteroaryl which is linked via C or N and which is unsubstituted or is substituted by 1 to 3 substituents from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxyl, amino, methylamino, dimethylamino and benzyl, â€ƒW is oxygen, S or NR(136)â€”, R(136) being hydrogen or (C1-C4)-alkyl, or R(101), R(102), R(103), R(104) and R(105) are, independently of each other, â€ƒR(146)X(1a)â€”, â€ƒX(1a) is oxygen, S, NR(147), (D&boxH;O)Aâ€” or NR(148)C&boxH;MN(*)R(149)â€”, M is oxygen or sulfur, A is oxygen or NR(150), and D is C or SO, â€ƒR(146) is (C1-C8)-alkyl, (C3-C8)-alkenyl, (CH2)zbzâ€”CzdzF2zdz+1 or â€”CzxaH2zxaâ€”R(151), zbz is zero or 1, zdz is 1, 2, 3, 4, 5, 6 or 7, zxa is zero, 1, 2, 3 or 4, R(151) is â€ƒ(C3-C8)-cycloalkyl, phenyl, biphenylyl or naphthyl, â€ƒwhere the aromatic radicals are not substituted or are substituted by 1-3 substituents from the group consisting of F, Cl, CF3, methyl, methoxy and NR(152)R(153), â€ƒR(152) and R(153) being hydrogen, (C1-C4)-alkyl or (C1-C4)-perfluoroalkyl, R(147), R(148) and R(150) are, independently, hydrogen, (C1-C4)-alkyl or (C1-C4)-perfluoroalkyl, R(149) is defined as R(146), â€ƒor â€ƒR(146) and R(147), or R(146) and R(148), respectively, are together 4 or 5 methylene groups of which one CH2 group can be replaced by oxygen, sulfur, NH, Nâ€”CH3 or N-benzyl, where A and N(*) are bonded to the phenyl nucleus of the alkanoyl parent substance, or R(101), R(102), R(103), R(104) and R(105) are, independently of each other, â€ƒâ€”SR(164), â€”OR(165), â€”NHR(166), â€”NR(167)R(168), â€”CHR(169)R(170), â€”CR(154)R(155)OH, â€”C=CR(156), â€”CR(158)&boxH;CR(157) or â€”[CR(159)R(160)]zuâ€”(C&boxH;O)â€”[CR(161)R(162)]zvâ€”R(163), â€ƒR(164), R(165), R(166), R(167) and R(169) are identical or different and are â€ƒâ€”(CH2)zyâ€”(CHOH)zzâ€”(CH2)zaaâ€”(CHOH)ztâ€”R(171) or â€ƒâ€”(CH2)zabâ€”Oâ€”(CH2-CH2O)zacâ€”R(172), R(171) and R(172) being hydrogen or methyl, zu is 1, 2, 3 or 4, zv is zero, 1, 2, 3 or 4, â€ƒzy, zz, zaa, zab and zac are identical or different and are zero, 1, 2, 3 or 4, â€ƒzt is 1, 2, 3 or 4, R(168), R(170), R(154) and R(155) are identical or different and are â€ƒhydrogen or (C1-C6)-alkyl, or R(169) and R(170), or R(154) and R(155), respectively, are, together with the carbon atom carrying them, a (C3-C8)-cycloalkyl, R(163) â€ƒis hydrogen, (C1-C6)-alkyl, (C3-C8)-cycloalkyl or â€”CzebH2zebâ€”R(173), â€ƒzeb is zero, 1, 2, 3 or 4, R(156), R(157) and R(173) are, independently, â€ƒphenyl which is unsubstituted or is substituted by 1-3 substituents from the group consisting of F, Cl, CF3, methyl, methoxy and NR(174)R(175), â€ƒR(174) and R(175) being hydrogen or (C1-C4)-alkyl, or R(156), R(157) and R(173) are, independently, â€ƒ(C1-C9)-heteroaryl which is unsubstituted or is substituted as phenyl, R(158), R(159), R(160), R(161) and R(162) are hydrogen or methyl, or R(101), R(102), R(103), R(104) and R(105) are, independently of each other, â€ƒR(176)â€”NHâ€”SO2â€”, â€ƒR(176) is R(177)R(178)Nâ€”(C&boxH;Yâ€²)â€”, Yâ€² is oxygen, S or Nâ€”R(179), R(177) and R(178) are identical or different and are â€ƒhydrogen, (C1-C8)-alkyl, (C3-C6)-alkenyl or â€”CzfaH2zfaâ€”R(180), â€ƒzfa is zero, 1, 2, 3 or 4, â€ƒR(180) is (C5-C7)-cycloalkyl or phenyl which is unsubstituted or substituted by 1-3 substituents from the group consisting of F, Cl, CF3, methoxy or (C1-C4)-alkyl, or R(177) and R(178) â€ƒare together 4 or 5 methylene groups of which one CH2 group can be replaced by oxygen, sulfur, NH, Nâ€”CH3 or N-benzyl, R(179) is defined as R(177) or is amidine, or R(101), R(102), R(103), R(104) and R(105) are, independently of each other, â€ƒOR(184b), SR(184c) or â€”CznxH2znxâ€”R(184d), â€ƒznx is zero, 1, 2, 3 or 4, â€ƒR(184d) is (C3-C7)-cycloalkyl or phenyl which is not substituted or is substituted by 1-3 substituents from the group consisting of F, Cl, CF3, methyl, methoxy and NR(116k)R(117k), â€ƒR(116k) and R(117k) being hydrogen or (C1-C4)-alkyl, â€ƒR(184a), R(184b), R(184c) and R(185) are, independently of each other, hydrogen, (C1-C8)-alkyl, (C1-C8)-perfluoroalkyl or (CH2)zaoâ€”R(184g), zao is zero, 1, 2, 3 or 4, 184g is (C3-C7)-cycloalkyl or phenyl which is not substituted or is substituted by 1-3 substituents from the group consisting of F, Cl, CF3, methyl, methoxy and NR(184u)R(184v), â€ƒR(184u) and R(184v) being hydrogen or (C1-C4)-alkyl, â€ƒor â€ƒR(184a) and R(185) are together 4 or 5 methylene groups of which one CH2 group can be replaced by oxygen, sulfur, NH, Nâ€”CH3 or N-benzyl, and also pharmaceutically tolerated salts thereof, here, however, the following compounds are excepted: and where, additionally, the compounds are excepted in which the radicals R(1) to R(5) are combined as follows: R(101)R(102)R(103)R(104)R(105)[X(1)][X(1)][X(1)][X(1)][X(1)]HClClHHHHNH2HHHHHHHClHHHHHHClHHHHCH3HHHHNH2HHHHClHHHHCH3HHR(105)R(104)R(103)R(102)R(101)[X(2)][X(2)][X(2)][X(2)][X(2)]HHClClHHHNH2HHHHHHHHHHHClHHClHHHHCH3HHHHHHHHHHHHHHHHH.