公开(公告)号：JPH1053531A

公开(公告)日：1998-02-24

申请号：JP12050297

申请日：1997-05-12

Applicant: HOECHST AG

Inventor： TOEPFER ALEXANDER DR ,  KRETZSCHMAR GERHARD DR ,  SCHMIDT WOLFGANG DR ,  BARTNIK ECKART DR ,  HUELS CHRISTOPH DR ,  SEIFFGE DIRK DR

IPC: A61K31/78 ,  A61P9/00 ,  A61P29/00 ,  A61P43/00 ,  C08F20/04

Abstract: PROBLEM TO BE SOLVED: To provide a method useful for treatment and prevention of diseases accompanying excess cell adhesion derived by selectin receptor by using a polymer of acryclic acid or methacrylic acid. SOLUTION: Polyacrylic acids and polymers of methacrylic acid or their salts, preferably polyacrylic acids having molecular weight of 900-63,000g/mol, are effective for treatment and prevention of diseases relating to selectin receptor-induced excess cell adhesion at tissues affected with a disease, particularly diseases of cardiac and vascular system or rheumatic diseases. This medicine is possible to administrate intravenously, orally or nonorally, or as pieces of transplantation and through rectum. The polyacrylic acids and polymethacrylic acids with high molecular weights are extremely strong and specific p-selectin antagonists.

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：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：CZ360197A3

公开(公告)日：1998-06-17

申请号：CZ360197

申请日：1997-11-13

Applicant: HOECHST AG

Inventor： STILZ HANS ULRICH DR ,  WEHNER VOLKMAR DR ,  HULS 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 ,  C07K5/08 ,  C07D207/00 ,  C07D213/00

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：DE19647382A1

公开(公告)日：1998-05-20

申请号：DE19647382

申请日：1996-11-15

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 ,  C07D239/20

Abstract: Use of N-substituted pyrrolidone, imidazolidinone, oxazolidinone or thiazolidinone derivatives of formula (I), in all stereoisomer or mixture forms, or their salts is 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, 3-12C cycloalkylene, (1-6C), phenylene-(1-6C)alkyl, 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-phenyl; 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); R1 = H, 1-10C alkyl (optionally fluorinated), cycloalkyl, cycloalkylalkyl, O or S 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-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; 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：DE19619238A1

公开(公告)日：1997-11-20

申请号：DE19619238

申请日：1996-05-13

Applicant: HOECHST AG

Inventor： TOEPFER ALEXANDER DR ,  KRETZSCHMAR GERHARD DR ,  SCHMIDT WOLFGANG DR ,  BARTNIK ECKART DR ,  HUELS CHRISTOPH DR ,  SEIFFGE DIRK DR

IPC: A61K31/78 ,  A61P9/00 ,  A61P29/00 ,  A61P43/00 ,  C08F20/04

公开(公告)号：DE19602355A1

公开(公告)日：1997-07-31

申请号：DE19602355

申请日：1996-01-24

Applicant: HOECHST AG

Inventor： TOEPFER ALEXANDER DR ,  KRETZSCHMAR GERHARD DR ,  BARTNIK ECKART DR ,  HUELS CHRISTOPH DR ,  SEIFFGE DIRK DR

IPC: C07H15/04 ,  A61K31/70 ,  A61K31/7028 ,  A61K31/715 ,  A61K49/00 ,  A61P9/00 ,  A61P9/08 ,  A61P11/00 ,  A61P17/00 ,  A61P29/00 ,  A61P37/06 ,  A61P43/00 ,  C07C55/02 ,  C07C55/22 ,  C07C55/24 ,  C07C55/26 ,  C07C59/235 ,  C07C217/08 ,  C07C219/06 ,  C07C229/24 ,  C07H3/04 ,  C07H3/06 ,  C08B37/00 ,  C07H1/00

Abstract: Multiple fucosylated carboxylic acid derivatives of formula (I) and their salts are new. R , R = H, OH, COOH, NH2, NHAc, O(CH2)cX , (CH2)cX , CH2O(CH2)cX or Z; A, B, D, E, G = O, S, NH, NHC(O), C(O)NH, OC(O), NHC(O)O, OC(O)NH, NHC(O)NH, SC(O), C(S)O, OC(S)S, SC(S)O, NHC(S)S, SC(S)NH, CH2, OCH2, CH2O, CH2NH, or NHCH2; V , V = C or N, provided that R or R is absent if V or V = N; Q, Y = (CX , X )b, (CX , R )b, CR , R )b or CH2(CX , X )b; an optionally saturated 5 or 7 membered carbo- or hetero-cycle or a combination of these and (CX , X )b, (CX , R )b, (CR , R )b; R , R = H, OH, COOH, NH2, NHC(O)CH3, O(CH2)dX or CH2O(CH2)dX ; X -X = H, NH2, COOH, OH, CH2OH, CH2NH2, 1-20C alkyl or 6-10C aryl; K, L = HCGZ or CH2; R -R = H, OH or GZ; Z = pyranoside, C6 bonded pyranoside residue, C6 bonded alkylpyranoside, furanoside, C5 bonded alkylfuranoside, or a polyalcohol having one or more hydroxyl groups substituted by R or R bonded via G; a-d, l-n, p, q, t, v-y, = 0-20; and r, z = 0 or 1, provided that when r = 0, then q and t = 0 and R and R are absent.

公开(公告)号：CZ9602940A3

公开(公告)日：1997-04-16

申请号：CZ294096

申请日：1996-10-07

Applicant: HOECHST AG

Inventor： TOEPFER ALEXANDER DR ,  KRETZSCHMAR GERHARD DR ,  SCHOLKENS BERNWARD PROF DR ,  KLEMM PETER DR ,  HULS CHRISTOPH DR ,  SEIFFGE DIRK DR

IPC: C07D295/20 ,  A61K31/215 ,  A61K31/33 ,  A61K31/40 ,  A61K31/435 ,  A61K31/445 ,  A61K31/495 ,  A61K31/70 ,  A61K31/7028 ,  A61K31/7034 ,  A61P3/08 ,  A61P9/00 ,  A61P9/08 ,  A61P9/10 ,  A61P11/00 ,  A61P17/00 ,  A61P29/00 ,  A61P35/00 ,  A61P37/06 ,  A61P37/08 ,  A61P43/00 ,  C07D207/08 ,  C07D207/16 ,  C07D211/34 ,  C07D211/62 ,  C07D405/00 ,  C07H15/203 ,  C07H15/207 ,  C07H17/00 ,  C07H19/04

CPC classification number: C07H15/207

公开(公告)号：DK0442348T3

公开(公告)日：1996-11-11

申请号：DK91101497

申请日：1991-02-05

Applicant: HOECHST AG

Inventor： GRAEVE ROLF DR ,  OKYAYUZ-BAKLOUTI ISMAHAN DR ,  SEIFFGE DIRK DR

IPC: A61K31/415 ,  A61K31/445 ,  A61K31/495 ,  A61K31/535 ,  A61P7/02 ,  A61P9/00 ,  A61P9/10 ,  C07D233/84 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12 ,  C07D417/12 ,  C07D491/10 ,  C07D491/113

Abstract: Imidazole derivs. of formula (I) and their salts are new. R1 = 1-6C alkyl. R2, R3 = independently H, F, Cl, Br, I or 1-3C alkyl. X = OH or -NR4R5. R4 = H or 1-7(1-4)C alkyl, opt. substd. by CN, NH2 or CO2H. R5 = 1-8 (1-5)C alkyl, opt. interrupted by phenyl and opt. substd. by not less than 1 OH, 1-3C alkoxy, (un)substd. phenyl, CO2H, CO2-(1-3C alkyl), -CONH2, CN, 2-5C alkynyl, NH2, NHR6, N(R6)2, N+(R6)3, NH-CO-(1-6C alkyl), a gp. of formula (i), a monocyclic 5-7 membered (un)saturated opt. substd. heterocycle with one N heteroatom, and opt. an extra N, O or S heteroatom, where the S atom can be oxidised to SO or SO2. Alternatively, R4 and R5 together form a 5-7 membered opt. substd. heterocycle which may contain, in addn. to the amide N atom, a further N, O or S heteroatom. The heterocycle is not morpholine. R6 = independently 1-4C alkyl, 2-6C alkoxyalkyl or phenyl-(1-3C alkyl). N-(2-morpholinoethyl)-1-methyl -2-imidazolsulphonic acid amide and N-(2-morpholinopropyl) -1-methyl-4-imidazolsulphonic acid amide are specifically claimed. Also claimed.are methods for preparing (I), e.g. by sulphonation of the corresponding mono-, di- or trisubstituted imidazole cpd.

公开(公告)号：GR3020570T3

公开(公告)日：1996-10-31

申请号：GR960401776

申请日：1996-07-18

Applicant: HOECHST AG

Inventor： GRAEVE ROLF DR ,  OKYAYUZ-BAKLOUTI ISMAHAN DR ,  SEIFFGE DIRK DR

IPC: A61K31/415 ,  A61K31/445 ,  A61K31/495 ,  A61K31/535 ,  A61P7/02 ,  A61P9/00 ,  A61P9/10 ,  C07D233/84 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12 ,  C07D417/12 ,  C07D491/10 ,  C07D491/113

Abstract: Imidazole derivs. of formula (I) and their salts are new. R1 = 1-6C alkyl. R2, R3 = independently H, F, Cl, Br, I or 1-3C alkyl. X = OH or -NR4R5. R4 = H or 1-7(1-4)C alkyl, opt. substd. by CN, NH2 or CO2H. R5 = 1-8 (1-5)C alkyl, opt. interrupted by phenyl and opt. substd. by not less than 1 OH, 1-3C alkoxy, (un)substd. phenyl, CO2H, CO2-(1-3C alkyl), -CONH2, CN, 2-5C alkynyl, NH2, NHR6, N(R6)2, N+(R6)3, NH-CO-(1-6C alkyl), a gp. of formula (i), a monocyclic 5-7 membered (un)saturated opt. substd. heterocycle with one N heteroatom, and opt. an extra N, O or S heteroatom, where the S atom can be oxidised to SO or SO2. Alternatively, R4 and R5 together form a 5-7 membered opt. substd. heterocycle which may contain, in addn. to the amide N atom, a further N, O or S heteroatom. The heterocycle is not morpholine. R6 = independently 1-4C alkyl, 2-6C alkoxyalkyl or phenyl-(1-3C alkyl). N-(2-morpholinoethyl)-1-methyl -2-imidazolsulphonic acid amide and N-(2-morpholinopropyl) -1-methyl-4-imidazolsulphonic acid amide are specifically claimed. Also claimed.are methods for preparing (I), e.g. by sulphonation of the corresponding mono-, di- or trisubstituted imidazole cpd.