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：JPH10182645A

公开(公告)日：1998-07-07

申请号：JP36553097

申请日：1997-12-22

Applicant: HOECHST AG ,  GENENTECH INC

Inventor： PEYMAN ANUSCHIRWAN DR ,  KNOLLE JOCHEN DR ,  WEHNER VOLKMAR DR ,  BREIPOHL GERHARD DR ,  GOURVEST JEAN-FRANCOIS DR ,  CARNIATO DENIS DR ,  GADEK THOMAS RICHARD DR

IPC: C07D473/00 ,  A61K31/52 ,  A61P3/00 ,  A61P9/00 ,  A61P13/12 ,  A61P19/00 ,  A61P19/10 ,  A61P29/00 ,  A61P35/00 ,  A61P43/00 ,  C07D233/00 ,  C07D239/00 ,  C07D401/12 ,  C07D403/12 ,  C07D473/02 ,  C07D473/26 ,  C07D473/34 ,  C07D473/40

Abstract: PROBLEM TO BE SOLVED: To obtain a new substituted purine derivative exhibiting the activity to inhibit bone resorption by osteoclasts, thus useful for mitigating, avoiding or treating osteoporosis, hypercalcemia and osteoopathy induced by e.g. lack in sexual hormone. SOLUTION: This new derivative is shown by formula I X is H, F, etc.; Y is F, cyano, etc.; G is a group of formula II [A is a direct bond, O, etc.; R and R are each H, F, etc.; R is H, F, etc.; R is a group of the formula C(O)R (R is OH, a 1-8C alkoxy, etc.), etc.; (m) and (n) are each 0-5; (i) is 0 or 1; (q) is 0-2]; W is a group of formula III [A' is the same as A; B is a direct bond, O, etc.; D is a direct bond, group of the formula NR (R is a ring formed with bound atom), etc.; E is H, a group of the formula R -C(=NR )-NR , etc.; (s) and (t) are each the same as (m); (k) is the same as (i); (r) is 0-6]} or group IV (G is a group of formula V; W is a group of formula VI), e.g. N -[1-(5- guanidinopentyl)]-N - 3-[2S-(benzuyloxycarbonylamino)propionic acid]}-adenine.

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：JPH10182617A

公开(公告)日：1998-07-07

申请号：JP36552897

申请日：1997-12-22

Applicant: HOECHST AG ,  GENENTECH INC

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

IPC: C07D295/18 ,  A61K31/33 ,  A61K31/415 ,  A61K31/4184 ,  A61K31/495 ,  A61K31/496 ,  A61K31/535 ,  A61K31/5355 ,  A61K31/536 ,  A61K31/5375 ,  A61K31/55 ,  A61K31/66 ,  A61P9/00 ,  A61P19/10 ,  A61P27/02 ,  A61P29/00 ,  A61P35/00 ,  A61P43/00 ,  C07D235/30 ,  C07D239/84 ,  C07D243/06 ,  C07D243/24 ,  C07D253/06 ,  C07D253/08 ,  C07D263/52 ,  C07D265/12 ,  C07D265/18 ,  C07D267/08 ,  C07D277/60 ,  C07D279/00 ,  C07D471/04 ,  C07D521/00 ,  C07F9/6561

Abstract: PROBLEM TO BE SOLVED: To obtain a new compound useful for bone diseases such as osteoporosis and chronic arthrorheumatism, capable of suppressing bone absorption by osteoclast. SOLUTION: This new compound is shown by the formula A-B-D-E-F-G A is a group of formula I (Y is an NR , O, etc.; R is H, a 1-10C alkyl, etc.; (q) is 0 or 1; a group of formula II is a five- to tenmembered cyclic base; B is a direct bond, a 1-8C alkanediyl, etc.; D and F are each a direct bond, a 1-8C alkanediyl, etc.; E is a template selected from fibrinogen receptor antagonists; G is a group of formula III [R to R are each H, F, OH, etc.; R is C(O)R (R is OH, a 1-8C alkoxy, etc.), C(S)R , etc.]} such as a human vitronectin receptor. The compound of the formula is obtained by condensing a compound of the formula A-B-D-E-M (M is hydroxycarbonyl, etc.) with a compound of the formula HNR k-G. For example, in the case of A-B is a ground of formula IV, a compound of formula V is reacted with a sulfonic acid of the formula Q-S(O)n -D-E-F-G or its derivative to give the objective compound.

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：MY119617A

公开(公告)日：2005-06-30

申请号：MYPI9705419

申请日：1997-11-13

Applicant: HOECHST AG

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

IPC: C07D233/00 ,  A61K31/415 ,  C07K5/023 ,  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 ,  C07K5/078 ,  C07K5/08 ,  C07K5/097 ,  C07K5/10 ,  C07K5/117 ,  C07K7/06 ,  C07K14/78

Abstract: 5-MEMBERED RING HETEROCYCLES AS INHIBITORS OF LEUCOCYTE ADHESION AND AS VLA-4 ANTAGONISTS COMPOUNDS OF THE FORMULA I(FORMULA 1)IN WHICH B, D, E, R, W, Y, Z, b, c, d, e, f, g AND h HAVE THE MEANINGS INDICATED IN THE CLAIMS, ARE INHIBITORS OF THE ADHESION AND MIGRATION OF LEUCOCYTES AND/OR ANTAGONISTS OF THE ADHESION RECEPTOR VLA-4 WHICH BELONGS TO THE GROUP OF INTEGRINS. THE INVENTION RELATES TO THE USE OF COMPOUNDS OF THE FORMULA I AND OF PHARMACEUTICAL PREPARATIONS WHICH CONTAIN SUCH COMPOUNDS FOR THE TREATMENT AND PROPHYLAXIS OF DISEASES WHICH ARE CAUSED BY AN UNDESIRED EXTENT OF LEUCOCYTE ADHESION AND/OR LEUCOCYTE MIGRATION OR WHICH ARE ASSOCIATED THEREWITH OR IN WHICH CELL-CELL OR CELL-MATRIX INTERACTIONS WHICH ARE BASED ON INTERACTION OF VLA-4 RECEPTORS WITH THEIR LIGANDS PLAY A PART, FOR EXAMPLE OF INFLAMMATORY PROCESSES, OF RHEUMATOID ARTHRITIS OR OF ALLERGIC DISORDERS, AND IT ALSO RELATES TO THE USE OF COMPOUNDS OF THE FORMULA I FOR THE PRODUCTION OF PHARMACEUTICALS FOR USE IN SUCH DISEASES. IT FURTHER RELATES TO NOVEL COMPOUNDS OF THE FORMULA I.

公开(公告)号：BR9706385A

公开(公告)日：1999-07-20

申请号：BR9706385

申请日：1997-12-17

Applicant: HOECHST AG

Inventor： WEHNER VOLKMAR 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 ,  C07D233/50 ,  C07D235/30 ,  C07D239/26 ,  C07D239/42 ,  C07D239/74

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.