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：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：JPH1099088A

公开(公告)日：1998-04-21

申请号：JP25044397

申请日：1997-09-16

Applicant: HOECHST AG

Inventor： UHLMANN EUGEN DR ,  BREIPOHL GERHARD DR ,  BRENNER STEVEN A PROF DR ,  LUTZ MICHAEL

IPC: C12N15/09 ,  C12N9/12 ,  C12Q1/68 ,  C12Q1/6844

Abstract: PROBLEM TO BE SOLVED: To advantageously amplify a nucleic acid by using a polyamide-nucleic acid derivative/DNA primer having a nucleoside unit having 3'-hydroxyl group at one terminal, a thermostable polymerase enzyme and a usually required component. SOLUTION: One or more polyamide-nucleic acid derivatives (PNA)/DNA primers having at least one nucleoside unit having 3'-hydroxyl group at one terminal, a DNA polymerase derived from a microorganism such as the genus Thermus, Thermococcus or Pyrococcus as a thermostable DNA polymerase and a usually required component are used and reacted according to a method similar to a well-known amplifying method such as a polymerase chain reaction(PCR) and a ligase chain reaction (LCR) to thereby advantageously amplify the nucleic acid according to the method usable in diagnosis of viral infection or diseases or cancer diagnosis, etc.

公开(公告)号：EP0739898A3

公开(公告)日：1998-09-16

申请号：EP96103533

申请日：1996-03-07

Applicant: HOECHST AG

Inventor： PEYMAN ANUSCHIRWAN DR ,  UHLMANN EUGEN DR ,  BREIPOHL GERHARD DR ,  WALLMEIER HOLGER DR

IPC: A61K31/66 ,  A01N43/04 ,  A61K31/7088 ,  A61P31/16 ,  A61P31/18 ,  A61P35/00 ,  A61P43/00 ,  C07F9/38 ,  C07F9/40 ,  C07H19/00 ,  C07H21/00 ,  C07H21/02 ,  C07K14/00 ,  C12Q1/68 ,  C12Q1/70 ,  A61K31/70

CPC classification number: C07H21/00 ,  C07F9/4006 ,  C07F9/4087 ,  C07K14/003

Abstract: Es werden neue Oligonucleotidanaloga der Formel (I) beschrieben, worin A, B, D, G, L, P, Q, Q', R
5 , R
6 , X, Y, Z und n wie in der Beschreibung definiert sind, die wertvolle physikalische, biologische und pharmakologische Eigenschaften haben sowie ein Verfahren zu deren Herstellung. Ihre Anwendung bezieht sich auf die Verwendung als Inhibitoren der Genexpression (Antisense Oligonucleotide, Ribozyme, Sense Oligonucleotide und Triplex Forming Oligonucleotide), als Sonden zum Nachweis von Nucleinsäuren und als Hilfsmittel in der Molekularbiologie.

公开(公告)号：DK0836853T3

公开(公告)日：2003-04-14

申请号：DK97117540

申请日：1997-10-10

Applicant: HOECHST AG

Inventor： BREIPOHL GERHARD DR ,  WIRTH KLAUS DR ,  HEITSCH HOLGER DR ,  HENKE STEPHAN DR ,  KNOLLE JOCHEN 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：BR9706387A

公开(公告)日：2000-03-14

申请号：BR9706387

申请日：1997-12-17

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: Purine derivatives of formula (I) and (Ia), and their salts, are new. One of R', R" = (CR1R2)nA-(CR1R2)m(CR1R3)i-(CR1R2)qR4 and the other = (CR1R2)rA'-(CR1R2)s(CR1R3)k-(CR1R2)tDE; X = H, NH2, OH, NHCOR6; A, A' = bond, CONR5, NR5CO, C(O), NR5, O, S, SO, SO2, Ar, 2-4C alkynylene, 2-4C alkenylene, or a 3-7 membered ring (optionally containing 1-2 Het and optionally substituted by =O, =S or R3); Ar = 5-14C arylene optionally with 1-5 C replaced by heteroatoms; R1, R2 = H, F, Cl, CN, nitro, 1-10C alkyl, 3-14C cycloalkyl, (3-12C cycloalkyl)(1-8C alkyl), 5-14C aryl, (5-14C aryl)(1-8C alkyl), R7-O-R6, R7-S(O)p-R6 or R7N-R6R61; R3 = H, F, Cl, CN, nitro, 1-14C alkyl, 3-14C cycloalkyl, (3-14C cycloalkyl)(1-8C alkyl), 5-14C aryl, (5-14C aryl)(1-8C alkyl), R7-O-R6, R7-S(O)p-R6, R7N-R6R61, R7OCOR6, R7COR6, R7COOR6, R7OCONR5R6, R7NR5S(O)pR6, R7NR5COOR6, R7NR5COR6, R7NR5CONR5R6, R7NR5S(O)pNR5R6, R7S(O)pR6, R7NS(O)pNR5R6, R7NR6COSR6, R7COR6 or R7CONR5R6, (where alkyl is optionally substituted, and alkyl (sic) and aryl are all optionally substituted, by one or more of F, Cl, Br, CN, NO2, R7NR5R6, R7NR6R61, R7COOR6, R7COR6, ; R7CONR5R6, R7S(O)pNR5R6, R6 or R7OR6); R4 = COR8, CSR8, S(O)pR8, POR8R81, a D- or L-aminoacid or a 4-8-membered saturated or unsaturated heterocycle containing 1-4 Het; R5 = H, 1-10C alkyl, 3-14C cycloalkyl, (3-14C cycloalkyl)-1-8C alkyl, 5-14C aryl or (5-14C aryl)-1-8C alkyl; R6, R61 = H, 1-8C alkyl, 3-14C cycloalkyl, 1-8C alkyl (substituted by 3-14C cycloalkyl or ArH) or ArH; or R6+R61 complete a ring system which may contain Het; R7 = a bond or 1-4C alkylene; R8, R81 = OH, 1-8C alkoxy, (5-14C aryl)(1-8C alkoxy), 5-14C aryloxy, (1-8C alkylcarbonyloxy)(1-4C alkoxy), (5-14C aryl)(1-8C alkyl)carbonyloxy(1-6C alkoxy), NR6R61, 1-8C dialkylaminocarbonylmethyloxy, (5-14C aryl)(1-8C dialkyl)aminocarbonylmethyloxy, 5-14C arylamino or an L or D amino acid; B = bond, O, S, NR5, NR5CO, CONR5, or a 3-7 membered ring (optionally containing 1-2 heteroatoms and optionally substituted by one or two =O, =S or R3); D = bond, NR6, CONR6, NR6CO, SO2NR6, NR6CONR6, NR6CSNR6, NR6S(O)uNR6, NR6COO, NR6N=CR6, NR6S(O)u, (5-14C aryl)CO, (5-14C aryl)S(O)u, N=CR6, CR6=N or CR6=N-NR6; E = H, NR6C(R6)=NR6, C(=NR6)NR6R61, NR6C(=NR6)NR6R61, or a 4-11 membered monocyclic or polycyclic aromatic or non-aromatic ring system (optionally containing 1-4 Het and optionally mono- to tri- substituted by R3, R5, =O, =S or C(=NR6)NR6R61); Het = N, O, S; n, m, s, t = 0-5; i, k = 0 or 1; p, q = 0-2; r = 0-6; u = 1 or 2.

公开(公告)号：DK0672701T3

公开(公告)日：2000-01-03

申请号：DK95103319

申请日：1995-03-08

Applicant: HOECHST AG

Inventor： UHLMANN EUGEN DR ,  KNOLLE JOCHEN DR ,  BREIPOHL GERHARD DR

IPC: C07C231/02 ,  C07C233/36 ,  C07C233/47 ,  C07C237/12 ,  C07D239/46 ,  C07D239/54 ,  C07D473/18 ,  C07D473/34 ,  C07K1/00 ,  C07K1/04 ,  C07K1/113 ,  C07K5/04 ,  C07K14/00 ,  C07K14/485 ,  C07K14/52 ,  C08G69/06 ,  C08G69/10

Abstract: A process is claimed for preparing peptide nucleic acid (PNA) oligomers of formula (I). Ro=H, 1-18C alkanoyl, 2-19C alkoxycarbonyl, 3-8C cycloalkanoyl (sic), 7-15C aroyl, 3-13C heteroaroyl or a gp. which enhances the intracellular uptake of the oligomer or interacts with a target nucleic acid during hybridisation; A and Q=amino acid residues; k and m=0-20; B=a nucleotide base, opt. in prodrug form; Qo=OH, NH2 or NHR''; R''=1-18C alkyl, 2-18C aminoalkyl or 2-18C hydroxyalkyl; n=1-50. The process comprises: (a) opt. coupling amino acids (Q') to a support of formula L-(Polymer) by solid-phase synthesis to give (Q')m-L-(Polymer), where L=a linking gp. contg. Qo in latent form and Q'=Q with optional side-chain protection; (b) coupling a cpd. of formula (II) to L-(Polymer) or (Q')m-L-(Polymer), where PG=a base-labile protecting gp. and B'=a nucleotide base with a protected exocyclic amino gp.; (c) removing PG; (d) repeating steps (b) and (c) n-1 times; (e) opt. coupling amino acids (A') to the prod. by solid-phase synthesis, where A'=A with optional side-chain protection, and introducing Ro if Ro is other than H; and (f) cleaving the PNA oligomer from the prod. of formula (III) and simultaneously or subsequently deprotecting B', A' and Q'. Also claimed are cpds. (II) and a process for preparing them.

公开(公告)号：CZ284783B6

公开(公告)日：1999-03-17

申请号：CS397990

申请日：1990-08-13

Applicant: HOECHST AG

Inventor： HENKE STEPHAN DR ,  BREIPOHL GERHARD DR ,  KNOLLE JOCHEN DR ,  SCHOLKENS BERNWARD PROF DR ,  GERHARDS HERMANN DR

IPC: A61K38/00 ,  A61K38/08 ,  A61P43/00 ,  C07K1/06 ,  C07K7/06 ,  C07K7/08 ,  C07K7/18

Abstract: Peptides of the formula I A-B-C-E-F-K-(D)-Phe-G-M-F'-I (1> in which A is hydrogen, alkyl, alkanoyl, alkoxycarbonyl, alkylsulphonyl, cycloalkyl, aryl, aryloyl, arylsulphonyl, heteroaryl or an amino acid, each of which can optionally be substituted, B is a basic amino acid, C is a di- or tripeptide, E is the residue of an aromatic amino acid, F is, independently of one another, an amino acid which is optionally substituted in the side chain or is a direct bond, G is an amino acid, F' is defined as F or can be -NH-(CH2)2-8 or optionally a direct bond, I is -OH, -NH2 or -NHC2H5, and K is a radical -NH-(CH2)1-4-CO- or is a direct bond, act as bradykinin antagonists. Their therapeutic uses comprise all pathological states promoted, induced or assisted by bradykinin and bradykinin-related peptides. The peptides of the formula I are prepared by known methods of peptide synthesis.

公开(公告)号：ES2119837T3

公开(公告)日：1998-10-16

申请号：ES93110754

申请日：1993-07-06

Applicant: HOECHST AG

Inventor： ZOLLER GERHARD DR ,  JABLONKA BERND DR ,  JUST MELITTA DR ,  KLINGLER OTMAR DR ,  BREIPOHL GERHARD DR ,  KNOLLE JOCHEN DR

IPC: A61K31/415 ,  A61K31/4166 ,  A61K38/00 ,  A61K38/04 ,  A61K38/05 ,  A61P7/02 ,  A61P19/10 ,  A61P35/00 ,  A61P35/04 ,  A61P43/00 ,  C07D233/40 ,  C07D233/42 ,  C07D233/72 ,  C07D233/76 ,  C07D233/78 ,  C07D233/80 ,  C07D233/86 ,  C07K5/06 ,  C07K5/072 ,  C07K5/08 ,  C07K5/10 ,  C07K5/117

Abstract: Phenylimidazolidine derivatives of the general formula I in which, for example, Y is -CH2-CH2-CO- r is 0 to 3 Z is oxygen W is hydroxyl R is -NH-C(=NH)-NH2 R, R , R are hydrogen R is -CO-NHR where -NH-R is an alpha -amino acid residue, have valuable pharmacological properties.

公开(公告)号：DE19653646A1

公开(公告)日：1998-06-25

申请号：DE19653646

申请日：1996-12-20

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: Purine derivatives of formula (I) and (Ia), and their salts, are new. One of R', R" = (CR1R2)nA-(CR1R2)m(CR1R3)i-(CR1R2)qR4 and the other = (CR1R2)rA'-(CR1R2)s(CR1R3)k-(CR1R2)tDE; X = H, NH2, OH, NHCOR6; A, A' = bond, CONR5, NR5CO, C(O), NR5, O, S, SO, SO2, Ar, 2-4C alkynylene, 2-4C alkenylene, or a 3-7 membered ring (optionally containing 1-2 Het and optionally substituted by =O, =S or R3); Ar = 5-14C arylene optionally with 1-5 C replaced by heteroatoms; R1, R2 = H, F, Cl, CN, nitro, 1-10C alkyl, 3-14C cycloalkyl, (3-12C cycloalkyl)(1-8C alkyl), 5-14C aryl, (5-14C aryl)(1-8C alkyl), R7-O-R6, R7-S(O)p-R6 or R7N-R6R61; R3 = H, F, Cl, CN, nitro, 1-14C alkyl, 3-14C cycloalkyl, (3-14C cycloalkyl)(1-8C alkyl), 5-14C aryl, (5-14C aryl)(1-8C alkyl), R7-O-R6, R7-S(O)p-R6, R7N-R6R61, R7OCOR6, R7COR6, R7COOR6, R7OCONR5R6, R7NR5S(O)pR6, R7NR5COOR6, R7NR5COR6, R7NR5CONR5R6, R7NR5S(O)pNR5R6, R7S(O)pR6, R7NS(O)pNR5R6, R7NR6COSR6, R7COR6 or R7CONR5R6, (where alkyl is optionally substituted, and alkyl (sic) and aryl are all optionally substituted, by one or more of F, Cl, Br, CN, NO2, R7NR5R6, R7NR6R61, R7COOR6, R7COR6, ; R7CONR5R6, R7S(O)pNR5R6, R6 or R7OR6); R4 = COR8, CSR8, S(O)pR8, POR8R81, a D- or L-aminoacid or a 4-8-membered saturated or unsaturated heterocycle containing 1-4 Het; R5 = H, 1-10C alkyl, 3-14C cycloalkyl, (3-14C cycloalkyl)-1-8C alkyl, 5-14C aryl or (5-14C aryl)-1-8C alkyl; R6, R61 = H, 1-8C alkyl, 3-14C cycloalkyl, 1-8C alkyl (substituted by 3-14C cycloalkyl or ArH) or ArH; or R6+R61 complete a ring system which may contain Het; R7 = a bond or 1-4C alkylene; R8, R81 = OH, 1-8C alkoxy, (5-14C aryl)(1-8C alkoxy), 5-14C aryloxy, (1-8C alkylcarbonyloxy)(1-4C alkoxy), (5-14C aryl)(1-8C alkyl)carbonyloxy(1-6C alkoxy), NR6R61, 1-8C dialkylaminocarbonylmethyloxy, (5-14C aryl)(1-8C dialkyl)aminocarbonylmethyloxy, 5-14C arylamino or an L or D amino acid; B = bond, O, S, NR5, NR5CO, CONR5, or a 3-7 membered ring (optionally containing 1-2 heteroatoms and optionally substituted by one or two =O, =S or R3); D = bond, NR6, CONR6, NR6CO, SO2NR6, NR6CONR6, NR6CSNR6, NR6S(O)uNR6, NR6COO, NR6N=CR6, NR6S(O)u, (5-14C aryl)CO, (5-14C aryl)S(O)u, N=CR6, CR6=N or CR6=N-NR6; E = H, NR6C(R6)=NR6, C(=NR6)NR6R61, NR6C(=NR6)NR6R61, or a 4-11 membered monocyclic or polycyclic aromatic or non-aromatic ring system (optionally containing 1-4 Het and optionally mono- to tri- substituted by R3, R5, =O, =S or C(=NR6)NR6R61); Het = N, O, S; n, m, s, t = 0-5; i, k = 0 or 1; p, q = 0-2; r = 0-6; u = 1 or 2.