公开(公告)号：JPH10114751A

公开(公告)日：1998-05-06

申请号：JP19715597

申请日：1997-07-23

Applicant: HOECHST AG ,  GENENTECH INC

Inventor： WEHNER VOLKMAR DR ,  KNOLLE JOCHEN DR ,  STILZ HANS ULRICH DR ,  GOURVEST JEAN-FRANCOIS DR ,  CARNIATO DENIS DR ,  GADEK THOMAS RICHARD DR ,  MAC DOWELL ROBERT DR ,  PITTI ROBERT MAURICE ,  BODARY SARAH CATHERINE DR

IPC: C07C229/04 ,  A61K31/19 ,  A61K31/197 ,  A61K31/415 ,  A61K31/445 ,  A61P3/00 ,  A61P9/00 ,  A61P13/02 ,  A61P15/00 ,  A61P19/08 ,  A61P27/02 ,  A61P29/00 ,  A61P35/00 ,  A61P43/00 ,  C07C251/02 ,  C07D211/18 ,  C07D233/52 ,  C07D233/54 ,  C07D233/66 ,  C07D257/04

Abstract: PROBLEM TO BE SOLVED: To obtain the subject novel compound which is useful as an inhibitor of bone resorption by osteoclast cells, a tumor growth and metastasis inhibitor, an antiinflammatory agent, a vitronectin receptor antagonist and the like. SOLUTION: This novel compound is one of stereisomers or their mixture represented by the formula; R -Y-A-B-D-E-F-G [A is a single bond, a 1-8C alkanediyl, a 5-14C arylene; B is a single bond, a 1-8C alkanediyl; D is a single bond, a 1-8C alkanediyl, -O-, -OC(O)-; E is a 6-membered aromatic ring which may contains 1-4N atoms; F is same as D; G is a group of formula II (R -R are independently H, F, OH or the like; R is a 4-8-membered heterocyclic ring; p and q are independently 0, 1); Y is a single bond and the like; R is a 4-10-membered monocyclic or polycyclic aromatic group]. Typically, the compound of the formula is cited.

公开(公告)号：JPH1143476A

公开(公告)日：1999-02-16

申请号：JP19715497

申请日：1997-07-23

Applicant: HOECHST AG ,  GENENTECH INC

Inventor： WEHNER VOLKMAR DR ,  KNOLLE JOCHEN DR ,  STILZ HANS ULRICH DR ,  GOURVEST JEAN-FRANCOIS DR ,  CARNIATO DENIS ,  GADEK THOMAS RICHARD DR ,  MCDOWELL ROBERT DR ,  PITTI ROBERT MAURICE ,  BODARY SARAH CARHERINE DR

IPC: C07C229/04 ,  A61K31/155 ,  A61K31/197 ,  A61K31/27 ,  A61K31/415 ,  A61K31/445 ,  A61K31/505 ,  A61P9/00 ,  A61P13/02 ,  A61P15/00 ,  A61P19/00 ,  A61P19/08 ,  A61P19/10 ,  A61P27/02 ,  A61P29/00 ,  A61P35/00 ,  A61P43/00 ,  C07C251/02 ,  C07C279/20 ,  C07C333/00 ,  C07D233/48 ,  C07D233/54 ,  C07D239/16 ,  C07D239/72 ,  C07D239/84

Abstract: PROBLEM TO BE SOLVED: To obtain the subject new compound inhibiting the bone absorption of osteoclast and useful for bone diseases such as osteoporosis and hypercalcemia. SOLUTION: A compound of the formula: R -Y-A-B-D-E-F-G R is a (substituted) four to ten-membered ring, etc.; A is CO2 , etc.; B is a single direct bond, etc.; D, F are each O, etc.; E is a (substituted) aromatic ring system; G is a group of formula I [R is a 10-18C cycloalkyl, etc.; R is H, etc.; R is pyrazolyl, etc.; (q) is 0, 1]; Y is NR (R is H, etc.}. For example, a compound of formula II. The objective compound of the formula wherein F is C(O)NR is obtained e.g. by condensing a compound of the formula: R -Y-A-B-D-E-M (M is hydroxycarbonyl, etc.), with a compound of the formula: HNR -G. When orally administered as a medicine, the objective compound is preferably administered at a daily dose of 0.01-50 mg/kg.

公开(公告)号：JPH1059948A

公开(公告)日：1998-03-03

申请号：JP14561797

申请日：1997-06-03

Applicant: HOECHST AG

Inventor： STILZ HANS ULRICH DR ,  BECK GERHARD DR ,  RADAU MANFRED DR

IPC: C07D233/78 ,  A61K31/415 ,  A61K31/416 ,  A61K31/4164 ,  A61K31/4166 ,  A61P7/02 ,  A61P9/00 ,  A61P9/10 ,  A61P9/14 ,  A61P35/00 ,  A61P35/04 ,  C07D233/72 ,  C07D233/74 ,  C07D233/76

Abstract: PROBLEM TO BE SOLVED: To obtain the subject compound useful as a medicine in a non- hygroscopic form by including a specific ethyl ester and maleic acid in a form of a salt. SOLUTION: This 3-(2-(4-(4-(amino-imino-methyl)-phenyl)-4-methyl-2,5-dioxo- imidazolidin-1-yl)-acetylamino)-3-phenyl-propionic acid ethyl ester salt is represented by formula I (HB is maleic acid). The salt is obtained by carrying out anion exchange between maleic acid and a maleic acid salt by using a compound of formula II (HV is an arbitrary inorganic or organic acid different from maleic acid). The compound of formula I is useful as a platelet aggregation inhibitor, a medicine for preventing thrombosis, an inhibitor of metastasis of cancer cell and a medicine for treating and preventing coronary vessel-based or cerebral blood vessel-based diseases.

公开(公告)号：JPH10158298A

公开(公告)日：1998-06-16

申请号：JP32970397

申请日：1997-11-14

Applicant: HOECHST AG

Inventor： STILZ HANS ULRICH DR ,  WEHNER VOLKMAR DR ,  HUELS CHRISTOPH DR ,  SEIFFGE DIRK DR

IPC: C07D277/20 ,  A61K38/00 ,  A61K38/05 ,  A61K38/06 ,  A61K38/07 ,  A61P3/08 ,  A61P9/00 ,  A61P9/10 ,  A61P11/00 ,  A61P11/06 ,  A61P19/02 ,  A61P29/00 ,  A61P33/02 ,  A61P35/00 ,  A61P37/00 ,  A61P37/08 ,  A61P43/00 ,  C07D233/54 ,  C07D233/72 ,  C07D277/34 ,  C07K5/06 ,  C07K5/078 ,  C07K5/097 ,  C07K5/107 ,  C07K5/11 ,  C07K5/117

Abstract: PROBLEM TO BE SOLVED: To obtain a new heterocyclic compound comprising a specific heterocyclic compound, having activities as a VLA-4 antagonist, and used for treatment and prevention of inflammatory progression, rheumatic arthritis, allergic disease, etc., as an inhibitor, etc., against adhesion of leukocyte. SOLUTION: This new heterocyclic compound is represented by formula I W is R -A-C(R ) [R is SR (R is H, a 1-8C alkyl, a 6-14C aryl, etc.), SOR , etc.; A is a 1-6C alkylene, phenylene, a direct bond, etc.; R is H, a 1-6C alkyl, a (substituted) 6-14C aryl, etc.], etc.; Y is CO, CS or methylene; Z is O, S, methylene, etc.; B is a 1-6C alkylene, phenylene, etc. ; D is CR R [R is H, a 1-8C alkyl, a (substituted) 6-14C aryl; R is H, a 1-8C alkyl, a 2-8C alkenyl, etc.], etc.; R is H, a 1-8C alkyl, an aryl, etc.; E is tetrazolyl, etc.; (b), (c), (d) and (f) are each 0 or 1; (e), (g) and (h) are each 0-6}. The compound is obtained by reacting a compound of formula II (G is hydroxycarbonyl, etc.) with amines of formula III.

公开(公告)号：JPH11147867A

公开(公告)日：1999-06-02

申请号：JP36552997

申请日：1997-12-22

Applicant: HOECHST AG ,  GENENTECH INC

Inventor： WEHNER VOLKMAR DR ,  STILZ HANS ULRICH DR ,  PEYMAN ANUSCHIRWAN ,  KNOLLE JOCHEN DR ,  RUXER JEAN-MARIE DR ,  CARNIATO DENIS DR ,  LEFRANCOIS JEAN-MICHEL ,  GADEK THOMAS RICHARD DR ,  MCDOWELL ROBERT DR

IPC: C07D239/00 ,  A61K31/155 ,  A61K31/16 ,  A61K31/18 ,  A61K31/33 ,  A61K31/395 ,  A61K31/415 ,  A61K31/4184 ,  A61K31/47 ,  A61K31/472 ,  A61K31/55 ,  A61K38/04 ,  A61P9/00 ,  A61P19/08 ,  A61P19/10 ,  A61P25/00 ,  A61P27/02 ,  A61P29/00 ,  A61P35/00 ,  A61P43/00 ,  C07C279/20 ,  C07C279/24 ,  C07C311/64 ,  C07C313/30 ,  C07C327/00 ,  C07D217/24 ,  C07D233/04 ,  C07D235/16 ,  C07D243/06 ,  C07D253/06 ,  C07D253/08 ,  C07D263/52 ,  C07D267/08 ,  C07D277/60 ,  C07D471/02 ,  C07D471/04 ,  C07D487/04 ,  C07K5/04

Abstract: PROBLEM TO BE SOLVED: To obtain a new compound useful as a vitronectin receptor antagonist used as an agent for inhibiting the bone resorption by osteoclasts, an agent for inhibiting the growth or metastasis of tumors or an anti-inflammatory agent and further used for treating and preventing cardiovascular diseases, neuropathy, retinopathy or the like. SOLUTION: The compound of the formula: A-B-D-E-F-G [G is A1 or the like; A1 is R R N-C(=NR )NR C(O) or the like; B is a direct bond or the like; D and F are each a direct bond or the like; E is a template selected from a series of fibrinogen receptor antagonists; G is a group of the formula; R and R are each H or the like; R to R are each H or the like; R is C(O)R or the like; R is OH or the like; (q) and (p) are each 0 or 1], The wherein F is C(O)NR , is obtained, for example, by condensing a compound of the formula: A-B-D-E-M (M is a hydroxycarbonyl or the like) with a compound of the formula: HNR -G.

公开(公告)号：JPH10147574A

公开(公告)日：1998-06-02

申请号：JP32970197

申请日：1997-11-14

Applicant: HOECHST AG

Inventor： STILZ HANS ULRICH DR ,  WEHNER VOLKMAR DR ,  HUELS CHRISTOPH DR ,  SEIFFGE DIRK DR

IPC: C07D233/76 ,  A61K31/415 ,  A61K31/4166 ,  A61K38/00 ,  A61K38/05 ,  A61K38/06 ,  A61K38/07 ,  A61P3/08 ,  A61P9/00 ,  A61P9/10 ,  A61P11/00 ,  A61P19/02 ,  A61P29/00 ,  A61P33/02 ,  A61P35/00 ,  A61P37/00 ,  A61P37/08 ,  A61P43/00 ,  C07D233/54 ,  C07D233/72 ,  C07K5/02 ,  C07K5/023 ,  C07K5/06 ,  C07K5/08 ,  C07K5/10 ,  C07K5/117

Abstract: PROBLEM TO BE SOLVED: To obtain a new compound useful as a medicine for inhibiting the adhesion and movement of leukocytes and as an adhesion receptor VLA-4 antagonist belonging to the group of integrins. SOLUTION: A compound of formula I [W is R -A-C(R ) (R is H, a 1-10C alkyl, etc.; A is a 1-6C alkylene, etc.; R is H, a 1-6C alkyl, etc.), etc.; Y is (thio)carbonyl, etc.; Z is N(R ) (R is H, a 1-8C alkyl, etc.), etc.; B is a 1-6C alkylene, etc.; D is C(R )(R ) (R ) is H, a 1-8C alkyl, etc.; R is H, a 1-8C alkyl, etc.), etc.; E is tetrazolyl, etc.; R is H, a 1-8C alkyl, etc.; (b), (c), (d), (f) are each 0, 1, but simultaneously not 0; (e), (g), (h) are each 0-6], e.g. ((R, S)-4-(4-(aminocarbonylphenyl)-3-benzyl-4-methyl-2,5-dioxoimidazolidine -2,5- dioxoimidozolin-1-yl)acetyl-L-aspartyl-L-phenylglycine. The compound of formula I is obtained by the fragment condensation of a compound of formula II (G is hydroxycarbonyl, etc.) with a compound of formula III.

公开(公告)号：JPH10147573A

公开(公告)日：1998-06-02

申请号：JP32970297

申请日：1997-11-14

Applicant: HOECHST AG

Inventor： STILZ HANS ULRICH DR ,  WEHNER VOLKMAR DR ,  KNOLLE JOCHEN DR ,  BARTNIK ECKART DR ,  HUELS CHRISTOPH DR

IPC: C07D233/00 ,  A61K31/415 ,  A61K31/4166 ,  A61K31/4178 ,  A61K31/421 ,  A61K31/426 ,  A61K38/00 ,  A61K38/06 ,  A61K38/07 ,  A61K38/39 ,  A61P3/08 ,  A61P9/00 ,  A61P9/10 ,  A61P11/00 ,  A61P19/02 ,  A61P29/00 ,  A61P33/02 ,  A61P35/00 ,  A61P37/00 ,  A61P37/08 ,  A61P43/00 ,  C07D233/32 ,  C07D233/72 ,  C07D233/74 ,  C07D233/76 ,  C07D233/86 ,  C07D257/00 ,  C07D403/12 ,  C07D405/12 ,  C07K5/02 ,  C07K5/023 ,  C07K5/078 ,  C07K5/08 ,  C07K5/097 ,  C07K5/10 ,  C07K5/117 ,  C07K7/06 ,  C07K14/78

Abstract: PROBLEM TO BE SOLVED: To obtain a new compound useful as a medicine for inhibiting the adhesion and movement of leukocytes and as an adhesion receptor VLA-4 antagonist belonging to the group of integrins. SOLUTION: A compound of formula I W is R -A-C(R ) [R is X-NH-C (=NH)-(CH2 )p [(p) is 0-3; X is H, a 1-6C alkyl, etc.], etc.; R is H, a 1-6C alkyl, etc.], etc.; Y is (thio)carbonyl, etc.; Z is N(R ) (R is H, a 1-8c alkyl, etc.], O, S, etc.; B is a 1-6C alkylene, etc.; D is a C(R )(R ) (R is H, a 1-8C alkyl, etc.; R is H, a 1-8C alkyl, etc.), etc.; E is tetrazolyl, etc.; (b), (c), (d), (f) are each 0, 1, but simultaneously not 0; (e), (g), (h) are each 0-6}, e.g. ((R,S)-4-(4-(amino- imino-methyl)phenyl)-4-methyl-2,5-dioxoimidazolidin-1-yl)acetyl-L-aspa rtyl-l- phenylglycine. The compound of formula I is obtained by the fragment condensation of a compound of formula II with a compound of formula III.

公开(公告)号：DK0842943T3

公开(公告)日：2003-06-02

申请号：DK97119638

申请日：1997-11-10

Applicant: HOECHST AG

Inventor： BARTNIK ECKART DR ,  HUELS CHRISTOPH DR ,  WEHNER VOLKMAR DR ,  STILZ HANS ULRICH DR ,  KNOLLE JOCHEN DR

IPC: C07D233/00 ,  A61K31/415 ,  A61K31/4166 ,  A61K31/4178 ,  A61K31/421 ,  A61K31/426 ,  A61K38/00 ,  A61K38/06 ,  A61K38/07 ,  A61K38/39 ,  A61P3/08 ,  A61P9/00 ,  A61P9/10 ,  A61P11/00 ,  A61P19/02 ,  A61P29/00 ,  A61P33/02 ,  A61P35/00 ,  A61P37/00 ,  A61P37/08 ,  A61P43/00 ,  C07D233/32 ,  C07D233/72 ,  C07D233/74 ,  C07D233/76 ,  C07D233/86 ,  C07D257/00 ,  C07D403/12 ,  C07D405/12 ,  C07K5/02 ,  C07K5/023 ,  C07K5/078 ,  C07K5/08 ,  C07K5/097 ,  C07K5/10 ,  C07K5/117 ,  C07K7/06 ,  C07K14/78

Abstract: Use of N-substituted pyrrolidone, imidazolidinone, oxazolidinone or thiazolidinone derivatives of formula (I), in all stereoisomer (or mixture) forms, or their salts for inhibiting the adhesion and/or migration of leukocytes or inhibiting VLA-4 receptors is new. W = R1-A-CR13 or R1A-CH=C; Y = CO, CS or CH2; Z = O, S or CH2 etc.; A = 1-6C alkylene, 3-7C cycloalkylene, (1-6C) alkylene-phenylene, or the divalent residue of a 5- or 6-membered ring containing 1 or 2 N (optionally substituted); B = 1-6C alkylene (optionally substituted), 2-6C alkenylene, phenylene, phenylene-(1-3C) alkyl or (1-3C) alkylene-phenylene; D = CR2R3, NR3 or CH=CR3; E = tetrazolyl, SO3H etc.; R = H, alkyl, 3-8C cycloalkyl, Ar or Ar-alkyl ; R1 = X-NH-C(=NH)-(CH2)p or X1-NH-(CH2)p; p = 0-3; X = H, 1-6C alkyl, (1-6C) alkylcarbonyl, Ar-(1-6C) alkoxycarbonyl, CN, OH, etc.; X1 = X etc.; R2 = H, alkyl, Ar, Ar-alkyl or 3-8C cycloalkyl; R3 = H, alkyl, Ar, alkenyl, alkynyl, pyridyl etc.; R13 = H, 1-6C alkyl, Ar-alkyl or 3-8C cycloalkyl; b, c, d, f = 0 or 1, but not all 0; e, g, h= 0-6; Ar = optionally substituted 6-14C aryl; unless specified otherwise alkyl moieties have 1-8C, alkenyl or alkynyl moieties 2-8C, cycloalkyl moieties 3-12C and bi- or tri-cycloalkyl moieties 6-12C.

公开(公告)号：AT232881T

公开(公告)日：2003-03-15

申请号：AT97119636

申请日：1997-11-10

Applicant: HOECHST AG

Inventor： STILZ HANS ULRICH DR ,  WEHNER VOLKMAR DR ,  HUELS CHRISTOPH DR ,  SEIFFGE DIRK DR

IPC: C07D277/20 ,  A61K38/00 ,  A61K38/05 ,  A61K38/06 ,  A61K38/07 ,  A61P3/08 ,  A61P9/00 ,  A61P9/10 ,  A61P11/00 ,  A61P11/06 ,  A61P19/02 ,  A61P29/00 ,  A61P33/02 ,  A61P35/00 ,  A61P37/00 ,  A61P37/08 ,  A61P43/00 ,  C07D233/54 ,  C07D233/72 ,  C07D277/34 ,  C07K5/06 ,  C07K5/078 ,  C07K5/097 ,  C07K5/107 ,  C07K5/11 ,  C07K5/117

Abstract: Use of N-substituted pyrrolidone, imidazolidinone, oxazolidinone or thiazolidinone derivatives of formula (I), in all stereoisomer or mixture forms, or their salts as medicaments is new. W = R1-A-CR13 or R1A-CH=C; Y = CO, CS or CH2; Z = O, S or CH2 etc.; A = direct bond, 3-12C cycloalkylene, (1-6C) alkylene-(3-12C) cycloalkylene, phenylene, or the divalent residue of a 5- or 6-membered ring containing 1 or 2 N (optionally mono- or disubstituted) etc.; B = 1-6C alkylene (optionally substituted), 2-6C alkenylene, phenylene, phenylene-(1-3C) alkyl or (1-3C) alkylene-phenylene; D = CR2R3, NR3 or CH=CR3; E = tetrazolyl, SO3H etc.; R = H, alkyl, cycloalkyl, cycloalkylalkyl, Ar, Ar-alkyl, Het' or Het '-alkyl (where alkyl residues are optionally substituted by one or more F); R1 = SR21, SSR21, SOR22, SO2R22, S-OR21, SO-OR21, SO2-OR21, SCOR21, SCOOR22, SCSSR22, OCOR21, OCSR21, OCOOR22, OSO2R22, OSO-R22, OP(O)(OR21)2, P(O)(OR21)2, P(O)(R22)OR21, CN, halo etc.; R2 = H, alkyl, Ar, Ar-alkyl or 3-8C cycloalkyl; R3 = H, alkyl, Ar, Ar-alkyl, 3-8C cycloalkyl, alkenyl, alkynyl, alkenylcarbonyl, alkynylcarbonyl, pyridyl etc.; R13 = H, 1-6C alkyl, Ar, Ar-alkyl, 3-8C cycloalkyl or (3-8C) cycloalkylalkyl; R21 = H, alkyl, hydroxyalkyl, alkenyl, cycloalkyl, cycloalkylalkyl, Ar, Ar-alkyl, Het' or Het'-alkyl (where alkyl residues are optionally substituted by one or more F); b, c, d, f = 0 or 1 provided not all are 0; e, g,h = 0-6; Ar = optionally substituted 6-14C aryl; Het' = optionally substituted heteroaryl; unless specified otherwise alkyl moieties have 1-8C, alkenyl or alkynyl moieties 2-8C, cycloalkyl moieties 3-12C and bi- or tri-cycloalkyl moieties 6-12C.

公开(公告)号：CZ411397A3

公开(公告)日：1998-07-15

申请号：CZ411397

申请日：1997-12-18

Applicant: HOECHST AG ,  GENENTECH INC

Inventor： WEHNER VOLKMAR DR ,  STILZ HANS ULRICH DR ,  PEYMAN ANUSCHIRWAN DR ,  KNOLLE JOCHEN DR ,  RUXER JEAN-MARIE DR ,  CARNIATO DENIS DR ,  LEFRANCOIS JEAN-MICHEL ,  GADEK THOMAS RICHARD DR ,  MCDOWELL ROBERT DR

IPC: C07D239/00 ,  A61K31/155 ,  A61K31/16 ,  A61K31/18 ,  A61K31/33 ,  A61K31/395 ,  A61K31/415 ,  A61K31/4184 ,  A61K31/47 ,  A61K31/472 ,  A61K31/55 ,  A61K38/04 ,  A61P9/00 ,  A61P19/08 ,  A61P19/10 ,  A61P25/00 ,  A61P27/02 ,  A61P29/00 ,  A61P35/00 ,  A61P43/00 ,  C07C279/20 ,  C07C279/24 ,  C07C311/64 ,  C07C313/30 ,  C07C327/00 ,  C07D217/24 ,  C07D233/04 ,  C07D235/16 ,  C07D243/06 ,  C07D253/06 ,  C07D253/08 ,  C07D263/52 ,  C07D267/08 ,  C07D277/60 ,  C07D471/02 ,  C07D471/04 ,  C07D487/04 ,  C07K5/04

Abstract: Guanidine and cycloguanidine derivatives of formula A-B-D-E-F-G (I) and their salts are new. A = R R N-C(=NR )NR Z- or a group of formula (a) or (b); Z = C(Q) or S(O)n; Q = O or S; n = 1 or 2; R = 5-10 membered mono- or polycyclic, aromatic or non-aromatic ring (optionally containing 1-4 N, O and/or S and optionally substituted by 1 or more of R -R ); B = direct bond; or alkyl, -CR =CR -, 5-10C aryl, 3-8C cycloalkyl or -C IDENTICAL C- (all optionally mono- or disubstituted by 1-8C alkyl), e.g. Me-Ph-Me or Et-CH=CH-; D, F = direct bond or alkyl, 5-10C aryl, -Q-; -NR -, -CO-NR -, -NR -CO-, -NR -C(Q)-NR -, -O-C(O)-,-C(O)-O-, -C(Q)-, -S(O)n, -S(O)n-NR , -NR -S(O)n, -CR =CR -, -C IDENTICAL C-, -NR -N=CR -, -N=CR -, -R C=N- or -CH(OH)- (all optionally mono- or disubstituted by alkyl, -CR -CR - or 5-6C aryl), e.g. Me-Ph-CH=CH- or Et-O-, and D is optionally linked to B via one of these substituents; E = template of a fibrinogen receptor antagonist; G = -CR R -(CR R )p-(CH2)p-R ; R , R = H; 1-10C alkyl (optionally substituted by 1 or more F); cycloalkyl; cycloalkyl-alkyl; aryl; aryl-alkyl; R OC(O)R ; R R NC(O)R ; or R C(O)R ; R -R = H; F; OH; alkyl; cycloalkyl; cycloalkyl-alkyl; R QR ; R CO2R ; R OC(O)R ; R -5-14C aryl-R ; R N(R )R ; R R NR ; R N(R )CO(O)R ; R S(O)n-N(R )R ; R QC(O)N(R )R ; R C(O)N(R )R ; R N(R )C(O)N(R )R ; R N(R )S(O)N(R )R ; R S(O)nR ; R C(O)R ; R N(R )C(O)R ; or R N(R )S(O)nR ; R = H; Alk; cycloalkyl; cycloalkyl-Alk; aryl; or aryl-Alk; Alk = alkyl (optionally substituted by 1 or more F); R = direct bond or alkyl; R = C(Q)R ; S(O)n-NR ; P(O)nR ; or a 4-8 membered saturated or unsaturated heterocycle containing 1-4 N, O and/or S, e.g. tetrazolyl, imidazolyl, pyrazolyl, oxazolyl or thiadiazolyl; R = OH; alkoxy; aryl-alkoxy; aryloxy; alkylcarbonyloxy-(1-4C) alkoxy; aryl-alkylcarbonyloxy-(1-6C) alkoxy; NH2; NH(alkyl); N(alkyl)2; aryl-alkylamino; dialkylaminocarbonylmethoxy; aryl- dialkylaminocarbonylmethoxy; arylamino; or a L- or D-aminoacid; R -R = H; 1-10C alkyl (optionally substituted by one or more F); 3-12C cycloalkyl; 3-12C cycloalkyl-alkyl; aryl; aryl-alkyl; NH2; R ONR ; R OR ; R OC(O)R ; R R NR ; R -aryl-R ; HO-alkyl-N(R )R ; R N(R )C(O)R ; R C(O)N(R )R ; R C(O)R ; R R N-C(=NR )-NR ; R R N-C(=NR ); or Q; or two adjacent R R substituents form -O-(CH2)n-O- or -OC(CH3)2O-; p, q = 0 or 1; alkyl moieties have 1-8C, cycloalkyl moieties 3-14C and aryl moieties 5-14C unless specified otherwise; compounds where E is a 6-membered aromatic ring (optionally containing 1-4 N and/or 1-4 substituents ) and the compound 4-methyl-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine are excluded.