发明名称 SUBSTITUTED BICYCLIC DIHYDROPYRIMIDINONES AND THEIR USE AS INHIBITORS OF NEUTROPHIL ELASTASE ACTIVITY
摘要 This invention relates to substituted bicyclic dihydropyrimidinones of formula 1;;and their use as inhibitors of neutrophil elastase activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of pulmonary, gastrointestinal and genitourinary diseases, inflammatory diseases of the skin and the eye and other autoimmune and allergic disorders, allograft rejection, and oncological diseases.
申请公布号 US2014221335(A1) 申请公布日期 2014.08.07
申请号 US201414166146 申请日期 2014.01.28
申请人 GNAMM Christian;OOST Thorsten;PETERS Stefan 发明人 GNAMM Christian;OOST Thorsten;PETERS Stefan
分类号 C07D487/04;C07D403/06;C07D409/12;C07D405/12;C07D413/12;C07D239/70;C07D401/06 主分类号 C07D487/04
代理机构 代理人
主权项 1. A compound of formula 1 wherein R1 is phenyl or a five- or six-membered heteroaryl, wherein one, two or three elements are replaced by an element independently selected from the group consisting of N, O or S; each ring optionally substituted with one, two or three substituents independently selected from the group consisting of halogen, O2N—, NC—, H2N—, HO—, R1.1, R1.1O—, R1.2, R1.3S—, R1.3(O)S— and R1.3(O)2S—; R1.1 is independently selected from the group consisting of C1-6-alkyl-, C3-6-cycloalkyl-, C1-6-haloalkyl- and C3-6-halocycloalkyl;R1.2 is HO—C1-6-alkyl- or R1.1—O—C1-6-alkyl-;R1.3 is independently selected from the group consisting of H, HO—, R1.1 and R1.2; R2 is phenyl or a five- or six-membered heteroaryl, wherein one or two elements are replaced by an element independently selected from the group consisting of N, O or S; each ring optionally substituted with a substituent independently selected from the group consisting of halogen, C1-4-alkyl-, C1-4-haloalkyl- and C1-4-alkyl-O—; R3 is a residue independently selected from the group consisting of R3.1—;R3.2(O)C—;R3.2O(O)C—;R3.2O(O)C-A-;R3.2S—; R3.2(O)S—; R3.2(O)2S—;(R3.2)2N(O)C and(R3.2)2N(O)C-A-;R3.1 is independently selected from the group consisting of H, R3.3, R3.4, C1-6-alkyl-C3-6-cycloalkyl- and C3-6-cycloalkyl-C1-6-alkyl-, each optionally substituted with one or two substituents independently selected from R3.1.1—; R3.1.1 is selected from the group consisting of HO—, halogen, NC—, R3.3O—, R3.5, R3.6 and R3.7 orR3.1.1 denotes a ring independently selected from phenyl and a four-membered heterocyclic ring containing one element independently selected from among N, O, S, S(O) and S(O)2;R3.1.1 denotes a five- or six-membered heterocyclic or heteroaryl ring containing one, two or three elements independently selected from among N, O, S, S(O) and S(O)2; each of the rings optionally substituted with one or two substituents independently selected from among HO—, O═, halogen, NC—, R3.3, R3.3O—, R3.3—(O)C—, R3.4, R3.5, R3.6 and R3.7 or two substituents are together R3.8;R3.2 is independently selected from among R3.1, phenyl and a five- or six-membered heterocyclic or heteroaryl ring containing one, two or three elements independently selected from among N, O, S, S(O) and S(O)2; each ring optionally substituted with one or two substituents independently selected from among HO—, O═, NC—, halogen, R3.3, R3.3O—, R3.3—(O)C—, R3.4, R3.5, R3.6 and R3.7 or two substituents are together R3.8; or two R3.2 are together a three-, four-, five- or six-membered monocyclic or a six-, seven-, eight-, nine- or ten-membered bicyclic heterocyclic or heteroaryl ring optionally containing additional to the nitrogen one or two elements independently selected from among N, O, S, S(O) and S(O)2; optionally substituted with one or two substituents, independently selected from among HO—, F, O═, NC—, R3.3, R3.3O—, R3.3—(O)C—, R3.4, R3.5, R3.6, R3.7, phenyl and a five- or six-membered heterocyclic or heteroaryl ring containing one, two or three elements independently selected from among N, O, S, S(O) and S(O)2; or two substituents are together R3.8;R3.3 is independently selected from the group consisting of C1-6-alkyl-, C3-6-cycloalkyl-, C1-6-haloalkyl- and C3-6-halocycloalkyl;R3.4 is HO—C1-6-alkyl- or R3.3—O—C1-6-alkyl-;R3.5 is independently selected from the group consisting of H2N—, R3.3—HN—, (R3.3)2N—, R3.3—(O)C—HN— and R3.3—(O)C—(R3.3)N—;R3.6 is independently selected from the group consisting of R3.3—(O)S—, R3.3—(O)2S—, R3.3(HN)S—, R3.3(HN)(O)S—, R3.3(R3.3N)S—, R3.3(R3.3N)(O)S—, R3.3(R3.4N)S—, R3.3(R3.4N)(O)S—; R3.3(NC—N)S and R3.3(NC—N)(O)S—;R3.7 is independently selected from the group consisting of HO(O)C—, H2N(O)C—, R3.3—O—(O)C—, R3.3—NH—(O)C— and (R3.3)2N—(O)C—;R3.8 is independently selected from the group consisting of C1-6-alkylene and C1-6-haloalkylene, wherein optionally one or two CH2-groups are replaced by —HN—, —(R3.3)N—, —(R3.4)N—, —(R3.3(O)C—)N—, —(R3.4(O)C—)N—, —O—, —S—, —S(O)— or —S(O)2—;A is —CH2—, —CH2—CH2— or —CH2—CH2—CH2—; optionally substituted with one or two substituents independently selected from the group consisting of halogen, R3.3, R3.3O— and R3.4 or two substituents together are R3.8; R4 is independently selected from the group consisting of halogen, C1-6-alkyl-, C3-6-cycloalkyl-, C1-6-haloalkyl- and C3-6-halocycloalkyl; or two R4 are together C1-6-alkylene or C1-6-haloalkylene; m is 0, 1 or 2; or a salt thereof.
地址 Biberach an der Riss DE