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：JPH10130163A

公开(公告)日：1998-05-19

申请号：JP27830197

申请日：1997-10-13

Applicant: HOECHST AG

Inventor： HEITSCH HOLGER DR ,  HENKE STEPHAN DR ,  BREIPOHL GERHARD DR ,  KNOLLE JOCHEN DR ,  WIRTH KLAUS DR ,  WIEMER GABRIELE

IPC: A61K38/00 ,  A61K38/04 ,  A61K38/22 ,  A61K45/00 ,  A61P25/28 ,  A61P43/00 ,  C07K7/06 ,  C07K7/18

Abstract: PROBLEM TO BE SOLVED: To obtain an agent useful for the treatment and prevention of Alzheimer's disease by using a bradykinin antagonistic agent (or its physiologically permissible salt) as an active component,. SOLUTION: A bradykinin antagonistic agent (or its physiologically permissible salt) consisting of e.g. a peptide of the formula H-D-Arg-Arg-Pro-Hyp-Gly- Thi-Ser-D-Tic-Oic-Arg-OH (HOE 140) [the abbreviations of the amino acids correspond to conventional 3-letter codes of peptide chemistry described in Europ.J.Biochem.138,9(1984) and the others are Oic: cis, endo-octahydroindole-2- carbonyl; Thi: 2-thienylalanyl; Tic: 1,2,3,4-tetrahydroisoquinolin-3-ylcarbonyl] is used as an agent for the treatment and prevention of Alzheimer's disease. It can be administered by oral, parenteral, nasal, transrectal or respiratory administration in the form suitable for the administration method.

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：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：ES2194842T3

公开(公告)日：2003-12-01

申请号：ES93105575

申请日：1993-04-03

Applicant: HOECHST AG

Inventor： ZOLLER GERHARD DR ,  JUST MELITTA DR ,  JABLONKA BERND DR ,  KONIG WOLFGANG DR ,  KNOLLE JOCHEN DR

IPC: A61K31/415 ,  A61K31/4166 ,  A61K31/42 ,  A61K31/425 ,  A61K38/00 ,  A61K38/04 ,  A61K38/06 ,  A61P7/02 ,  A61P19/10 ,  A61P35/00 ,  A61P43/00 ,  C07D233/72 ,  C07D233/76 ,  C07D233/80 ,  C07D233/96 ,  C07D403/12 ,  C07K5/08 ,  C07K5/10 ,  C07K5/117 ,  C08K5/08

Abstract: The present invention relates to 2,4-dioxoimidazolidine derivatives of the general formula I in which R to R and Y are defined as indicated in the description, processes for their preparation and their use as inhibitors of platelet aggregation, the metastasis of carcinoma cells and osteoclast binding to the bone surfaces.

公开(公告)号：SI0836853T1

公开(公告)日：2003-06-30

申请号：SI9730497

申请日：1997-10-10

Applicant: HOECHST AG

Inventor： HEITSCH HOLGER DR ,  HENKE STEPHAN DR ,  BREIPOHL GERHARD DR ,  KNOLLE JOCHEN DR ,  WIRTH KLAUS DR ,  WIEMER GABRIELE PROF DR

IPC: A61K38/00 ,  A61K38/04 ,  A61K38/22 ,  A61K45/00 ,  A61P25/28 ,  A61P43/00 ,  C07K7/06 ,  C07K7/18

Abstract: Use of bradykinin antagonists, or their salts, to treat or prevent Alzheimer's disease, is new

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：GR3031543T3

公开(公告)日：2000-01-31

申请号：GR990402630

申请日：1999-10-15

Applicant: HOECHST AG

Inventor： BREIPOHL GERHARD DR ,  HENKE STEPHAN DR ,  KNOLLE JOCHEN DR ,  SCHOELKENS BERNWARD PROF DR ,  ALPERMANN HANS-GEORG DR ,  GERHARDS HERMANN DR ,  WIRTH KLAUS DR

IPC: A61K38/00 ,  A61K38/04 ,  A61K38/08 ,  A61P43/00 ,  C07K7/06 ,  C07K7/18

Abstract: Peptides of the formula I Z - P - A - B - C - E - F - K - (D)Q - G- M- F' - I (I), in which Z is optionally substituted (cyclo)alk(ano)yl(sulphonyl), (C1-C8)-alkoxycarbonyl, (hetero)ar(o)yl(sulphonyl), carbamoyl, P is a direct linkage or a radical II -NR -(U)-CO- (II> in which R is H, methyl or a urethane protective group, U is (cyclo)(aryl)alkylidene, (hetero)arylidene or (CHR )n, R is hydrogen, (cyclo)alkyl, (hetero)aryl, or in which R and R form, together with the atoms carrying them, a ring system; A is defined as P; B is a basic amino acid in the L or D configuration, C is a compound of the formula IIIa or IIIb G'-G'-Gly (IIIa> G'-NH-(CH2)p-CO (IIIb> in which p is 2 to 8 and G' are, independently of one another, a radical of the formula IV -NR -CHR -CO- (IV> in which R and R form, together with the atoms carrying them, a heterocyclic ring system; E is the residue of a neutral, acid or basic, aliphatic or alicyclic-aliphatic amino acid; F are, independently of one another, the radical of a neutral, acid or basic, aliphatic or aromatic amino acid, or a direct linkage; (D)Q is D-Tic, D-Phe, D-Dic, D-Thi or D-Nal, or a radical of the formula (V) in which X is O, S or a direct linkage, and R is H, (cyclo)alkyl or aryl(alkyl), G is defined as G' above or is a direct linkage; F' is defined as F, is a radical -NH-(CH2)q- with q = 2 to 8 or, if G is not a direct linkage, can be a direct linkage, and I is -OH, -NH2 or NHC2H5; K is the radical -NH-(CH2)x-CO- with x = 1-4 or is a direct linkage, and M is defined as F and their physiologically tolerated salts are described. They have excellent bradykinin-antagonistic action. They are obtained by reacting a fragment with a C-terminal free carboxyl group or its activated derivative with an appropriate fragment with an N-terminal free amino group, or by assembling the peptide stepwise, eliminating one or more protective groups temporarily introduced where appropriate to protect other functionalities in the compound obtained in this way, and converting the compounds of the formula I obtained in this way where appropriate into their physiologically tolerated salt.