公开(公告)号：DE4041188A1

公开(公告)日：1992-06-25

申请号：DE4041188

申请日：1990-12-21

Applicant: BASF AG

Inventor： BOEHM HANS-JOACHIM DR ,  DAUM LOTHAR DR ,  HAUPT ANDREAS DR ,  PETTIG DAGMAR DR ,  WALKER NIGEL DR ,  MAENNEL DANIELA DR ,  FRANK REINER DR ,  STIEHNER RAINER DR

IPC: A61K38/00 ,  C07K14/525

Abstract: Peptides of formula X-Leu-A-B-Asn- E-Leu-F-K-Pro-L-Y (I), derived from tumour necrosis factor (TNF), and their salts with physiologically tolerable acids are new: (where A = Arg, Glu, Thr, Lys or Ser; B = Asp or Asn; E = Gln or Ser; F = Val, Leu or NH-CHT-CO; T = HS(CH2)b, NH2(CH2)b or HOOC(CH2)b; b = 1-6; K = Val or Ile; L = Ser, Ala or Thr; X = G, GNH-CHM-CO or GNH-CHM-COW-; Y = Z, NH-CHQ-COZ, -V-NH-CHQ-COZ; NH-CHQ-CO-V-Z or V-NH-CHQ-CO-V-Z; G = H or amino-protecting gp.; Z = OH, NH2 or carboxy-protecting gp.; or G and Z are together a covalent bond or CO-(CH2)a-NH; a = 1-12; U, V and W = peptide chain with 1-4 naturally occurring amino acids; M and Q = H, CHMe2, CHMe-Et, phenyl, CHOH-Me, (3-indolyl)methyl, (imidazolyl-4-yl)methyl or (CH2)bT; b = 1-6; T = H, OH, MeO, MeS, Me2CH, phenyl (opt. 4-OH substd.), HS, NH2, COOH, CONH2 or guanidino; or M and Q or M and T are together a (CH2)c-S-S-(CH2)d-, (CH2)e-CONH-(CH2)f or (CH2)e-NHCO(CH2)gNH bridge; c and d = 1-4; e and f = 1-6; g = 1-12). (I) are obtd. by standard (chemical or enzymatic) peptide synthesis, initially as linear peptides, opt. followed by appropriate cyclisation reaction under very dilute conditions. USE/ADVANTAGE - Some (I) are TNF agonists, others are TNF antagonists (these have high affinity for cellular receptors but no activity). They are used for treating neoplastic and autoimmune diseases, and for treating or preventing infections, inflammation and transplant rejection. They have significantly lower mol. wt. than TNF.

公开(公告)号：DE4203548A1

公开(公告)日：1993-08-12

申请号：DE4203548

申请日：1992-02-07

Applicant: BASF AG

Inventor： PETTIG DAGMAR DR

IPC: C07F9/12 ,  C07K7/06 ,  C07K7/08

Abstract: Fmoc-phosphotyrosine Fmoc-Tyr(PO(OH)2)OH (I) is new. USE/ADVANTAGE - (I) is used for the prodn. (claimed) of O-phosphotyrosine-contg. peptides which are model substrates for tyrosine kinase and phosphatase determinations. (I) gives better selectivity, purity and yields of O-phosphotyrosine-contg. peptides by avoiding the introduction of a protected phosphate gp. as required in prior art methods. In an example, a soln. of Fmoc-OSu (II) (0.95 mmol) in acetone (5ml) was added to phosphotyrosine (III) (1 mmol) in 10% Na2CO3 soln. (4-5ml) at room temp. and the mixt. was stirred for 24 hrs., acidified (HCl) to pH 2 and evaporated. The residue in H2O was extracted and gave, after drying, evapn. and recrystallisation (ethyl acetate-hexane), Fmoc-phosphotyrosine (I) (0.55mol; 55% yield).

公开(公告)号：DE4041189A1

公开(公告)日：1992-06-25

申请号：DE4041189

申请日：1990-12-21

Applicant: BASF AG

Inventor： BOEHM HANS-JOACHIM DR ,  DAUM LOTHAR DR ,  HAUPT ANDREAS DR ,  PETTIG DAGMAR DR ,  WALKER NIGEL DR ,  MAENNEL DANIELA DR ,  FRANK REINER DR ,  STIEHNER RAINER DR

IPC: A61K38/00 ,  C07K14/525

Abstract: Peptides of formula X-Ala-A-B-E-Y (I), derived from tumour necrosis factor (TNF), and their salts with physiologically tolerable acids are new. A is Leu or Phe; B is Leu or Met; X is GNH-CHM-CO, GNH-CHM-CO-W, G-RNH-CHM-CO or G-R-NH-CHM-CO-W; Y is Z, NH-CHQ-COZ, V-NH-CHQ-COZ, NH-CHQ-CO-U-Z or V-NH-CHQ-U-Z; G is H or amino protecting gp.; Z is OH, NH2 or carboxy-protecting gp.; or G and Z together are a covalent bond or CO(CH2)aNH; a is 1-12; R,U,V and W are each peptide chains of 1-4 naturally occurring amino acids; M and Q = H, CHMe2, CHMe-Et, phenyl, CHOH-Me, 3-indolylmethyl, (imidazol-4-yl)methyl or (CH2)bT; b is 1-6; T is H, OH, MeO, MeS, Me2CH, phenyl (opt. 4-OH substd.), SH, NH2, COOH, CONH2, or guanidino; M and Q can together be (CH2)c-S-S-(CH2)-d, (CH2)e-CONH-(CH2)f, or (CH2)e-NH.CO-(-CH2-)-g-NH.CO-(CH2)-f; c and d = 1-4; e and f = 1-6; g = 1-22. (I) are made by standard (chemical or enzymatic) methods of peptide synthesis, initially as linear peptides, opt. followed by an appropriate cyclisation reaction under very dil. conditions. USE/ADVANTAGE - Some (I) are TNF agonists, others are TNF antagonists (these have high affinity for cellular receptors but no activity). Useful for treating neoplastic and autoimmune disorders, and for treating or preventing infections, inflammation and transplant rejection. (I) have a significantly smaller mol. wt. than TNF.

公开(公告)号：DE4041187A1

公开(公告)日：1992-06-25

申请号：DE4041187

申请日：1990-12-21

Applicant: BASF AG

Inventor： BOEHM HANS-JOACHIM DR ,  DAUM LOTHAR DR ,  HAUPT ANDREAS DR ,  PETTIG DAGMAR DR ,  WALKER NIGEL DR ,  MAENNEL DANIELA DR ,  FRANK REINER DR ,  STIEHNER RAINER DR

IPC: A61K38/00 ,  C07K14/525

Abstract: The description relates to peptides of formula (I), in which A, B, D, E, F, J, T, X, Y and Z have the significances given in the specification, and their production. The novel peptides are suitable for the treatment of diseases.