http://rdf.ncbi.nlm.nih.gov/pubchem/patent/AR-078446-A1
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_24d41624f4c12622605b7048517fe8f7 |
| classificationCPCAdditional | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K38-00 |
| classificationCPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07K7-02 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07K7-06 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P27-02 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P27-06 |
| filingDate | 2010-09-24-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationDate | 2011-11-09-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | AR-078446-A1 |
| titleOfInvention | NPR-B AGONISTS. USE. |
| abstract | Compounds that have agonist activity of NPR-B. Preferred compounds are linear peptides containing 8-13 conventional or unconventional L or D amino acid residues connected to each other via peptide bonds. Claim 1: Use of a composition comprising a therapeutically effective amount of a compound consisting of the amino acid sequence of the formula (1), B-Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9- Xaa10-Z where: B is selected from the group consisting of H, Rb1-, Rb2-C (O) -, Rb2-S (O) 2-, Rb3-Baa-; Baa is a conventional alpha-amino acid, an unconventional alpha-amino acid or a beta-amino acid; Rb1 is selected from C1-12 alkyl optionally substituted with NRb4Rb5, OH, ORb6, C3-8 cyclic alkyl, aryl, heteroaryl, or heterocyclyl; C1-12 alkenyl optionally substituted with NRb4Rb5, OH, Orb6, C3-8 cyclic alkyl, aryl, heteroaryl, or heterocyclyl; C1-12 aryl alkyl optionally substituted with NRb4Rb5, OH, or ORb6; C1-12 alkynyl optionally substituted with NRb4Rb5, OH, ORb6, C3-8 cyclic alkyl, aryl, heteroaryl, or heterocyclyl; aryl C1-12 alkyl optionally substituted with NRb4Rb5, OH, ORb6, C3-C8 cyclic alkyl, aryl, heteroaryl, or heterocyclyl; C1-12 alkyl C3-8 cyclic alkyl optionally substituted with NRb4Rb5, OH, ORb6, aryl, heteroaryl, or heterocyclyl; C3-6 cyclic alkyl C1-12 alkyl optionally substituted with NRb4Rb5, OH, ORb6, aryl, heteroaryl, or heterocyclyl; C 1-10 alkylthio C2-10 alkyl optionally substituted with NRb4Rb5, OH, ORb6, C3-8 cyclic alkyl, aryl, heteroaryl, or heterocyclyl; C1-9 alkylsulfonyl C1-4 alkyl optionally substituted with NRb4Rb5, OH, ORb6, C3-8 cyclic alkyl, aryl, heteroaryl, or heterocyclyl; C1-9 alkylsulfoxyl C1-10 alkyl optionally substituted with NRb4Rb5, OH, ORb6, C3-8 cyclic alkyl, aryl, heteroaryl, or heterocyclyl; CH3- (CH2) qb-O- [CH2- (CH2) nbO] mb-CH2- (CH2) pb-, 2-thiazolo optionally substituted with C1-8 alkyl; qb = 0-3; nb = 1-3; mb = 1-3; pb = 1-3; Rb2 is selected from C1-12 alkyl optionally substituted with NRb4Rb5, OH, ORb6, C3-8 cyclic alkyl, aryl, heteroaryl or heterocyclyl; C1-12 alkenyl optionally substituted with NRb4Rb5, OH, ORb6 C3-8 cyclic alkyl, aryl, heteroaryl, or heterocyclyl; aryl C1-12 alkyl optionally substituted with NRb4Rb5, OH, ORb6, C3-8 cyclic alkyl, aryl, heteroaryl, or heterocyclyl; C1-12 alkynyl optionally substituted with NRb4Rb5, OH, ORb6 C3-8 cyclic alkyl, aryl, heteroaryl, or heterocyclyl; C1-12 aryl alkyl optionally substituted with NRb4Rb5, OH, or ORb6; C1-12 alkyl C3-8 cyclic alkyl optionally substituted with NRb4Rb5, OH, ORb6, C3-8 cyclic alkyl, aryl, heteroaryl, or heterocyclyl; C3-6 cyclic alkyl C1-12 alkyl optionally substituted with NRb4Rb5, OH, ORb6 C3-8 cyclic alkyl, aryl, heteroaryl, or heterocyclyl; C1-9 alkylthio C1-10 alkyl optionally substituted with NRb4Rb5, OH, ORb6, C3-8 cyclic alkyl, aryl, heteroaryl, or heterocyclyl; C1-9 alkylsulfonyl C1-10 alkyl optionally substituted with NRb4Rb5, OH, ORb6, C3-8 cyclic alkyl, aryl, heteroaryl, or heterocyclyl; C1-9 alkylsulfoxyl C1-4 alkyl optionally substituted with NRb4Rb5, OH, ORb6, C3-8 cyclic alkyl, aryl, heteroaryl, or heterocyclyl, CH3- (CH2) qb-O - [- CH2- (CH2) nbO] mb- CH2 (CH2) bp; qb = 0-3; nb = 1-3; mb = 1-3; pb = 0-3; Rb3 is selected from H, Rb1-, Rb2-C (O) -, or Rb2-S (O2) -; Rb4, Rb5 and Rb6 are independently selected, consisting of H or C1-4 alkyl and Xaa1 is selected from the group consisting of a direct bond, a conventional alpha-amino acid; an unconventional alpha-amino acid; a beta-amino acid; a gamma-amino acid, or a residue of the formula (2 a-y); R1a is selected from H, C1-6 alkyl; R1b is selected from H, C1-6 alkyl optionally substituted with OH, hydroxy C1-6 alkyl optionally substituted with OH; R1c is selected from H, C1-C6 alkyl; R1d is selected from H, C1-6 alkyl; R1a and R1b together can form a heterocyclic ring; n1 is 0 to 3; Xaa2 is an amino acid residue of the formula (3 a-g) where: R2a is selected from the group consisting of H, methyl, ethyl, propyl, isopropyl, C1-2 alkyl C3-7 cycloalkyl and aryl C1-2 alkyl; R2b and R2c are independently selected from the group consisting of H, methyl, ethyl, propyl and isopropyl, with the proviso that at least one of R2b and R2c is H; R2d represents 0 to 3 substituents, where each substituent, independently, is selected from the group consisting of H, CI, F, Br, NO2, NH2, CN, CF3, OH, OR2 and C1-4 alkyl; R2a and R2b or R2a and R2c together can form a heterocyclic ring; R2e is selected from the group consisting of methyl, ethyl, propyl and isopropyl; or Xaa1 and Xaa2 together can be selected from an amino acid residue of the formula (4 a-b); Xaa3 is selected from the group consisting of Gly, Ala, a conventional D-alpha-amino acid, an unconventional D-alpha-amino acid, and an amino acid residue of the formula (5a) where R3a is selected from the group consisting of H or C1-4 alkyl; R3b is selected from the group consisting of H, - (CH2) n3a-X3a; n3a is 1 to 5; X3a is selected from the group consisting of H, NR3cR3d; R3c and R3d are independently selected from the group consisting of H, C1-8 alkyl, - (C = N) -NH2 and - (CH2) n3bX3b; n3b is 1 to 4; X3b is selected from the group consisting of NR3eR3f, C5-6 heteroaryl, C4-7 heterocyclyl, -NHC (= N) NH2; R3e and R3f are independently selected from the group consisting of H, C1-8 alkyl; where R3e and R3f can form a cyclic structure; R3a and R3b can be ligated in order to form a cyclic structure; or R3a and R3b can be ligated with a heteroatom selected from the group consisting of N, O and S, in order to form a heterocyclic structure; or Xaa2 and Xaa3 together can be selected from an amino acid residue of the formula (5b) where R3g represents 0 to 3 substituents, where each substituent is independently selected from the group consisting of H, CI, F, Br, NO2, NH2, CN; CF3, OH, OR3h and C1-4 alkyl; R3h is selected from the group consisting of C1-4 alkyl, Xaa4 is an amino acid residue of the formula (6 ah) where R4a is selected from the group consisting of H, C1-8 alkyl which may be substituted with a portion selected from the group consisting of OH, CO2R4c, C (= O) -NH2, a 5-6 membered heteroaryl, C1-10 alkyl, C5-8 cycloalkyl C1-10 alkyl and C5-8 cycloalkyl, - (CH2) n4a-X4a ; n4a is 1 or 2; R4b is selected from the group consisting of H and methyl; R4c is selected from the group consisting of H and C1-3 alkyl; and X4a is OH, CO2R4d, NR4eR4f, SR4g, 4-imidazoyl, 4-hydroxyphenyl; R4d, R4e and R4f are independently selected from the group consisting of H and C1-3 alkyl; R4g is selected from the group consisting of C1-3 alkyl; m4a and m4b are independently selected from 0 or 1; R4h is C2-6 alkyl; or Xaa3 and Xaa4 together can be selected from an amino acid residue of the formula (6 b-h); Xaa5 is an amino acid residue of the formula (7) where R5a is (CH2) n5a-X5a; n5a is 1 to 6; X5a is selected from the group consisting of H, NH2, and an aliphatic heterocyclic ring containing C4-7 amine; R5b is selected from the group consisting of H and methyl; R5c is selected from the group consisting of H and methyl; and where R5c and R5a can be combined to form a four to six membered heterocyclic ring, or they can be ligated with a heteroatom selected from the group consisting of N, O and S, so as to form a heterocyclic monocyclic or bicyclic structure; wherein said heterocyclic ring may have 0 to 3 substituents, where each substituent, independently, is selected from the group consisting of OH, OR5d, F, C1-4alkyl, -NHC (= NH) NH2, aryl and NR5eR5f; R5d is selected from C1-4 alkyl, C1-4 alkylaryl; R5e is selected from the group consisting of H, C1-4 alkyl, -C (= O) (CH2) n5b-X5b, -CH2 (CH2) n5c-X5b; R5f is selected from the group consisting of H, C1-4 alkyl, -CH2 (CH2) n5d-X5c; n5b is selected from the group consisting of 1, 2, 3 and 4; n5c and n5d are independently selected from the group consisting of 2, 3 and 4; X5b and X5c are independently selected from the group consisting of H, NR5gR5h; R5g and R5h are independently selected from the group consisting of H, C1-4 alkyl; Xaa6 is an amino acid residue of the formula (8 ad) where R6a is selected from the group consisting of C1-8 alkyl, aryl C1-4 alkyl, C4-7 cycloalkyl C1-4 alkyl, C1-4 S alkyl (C1 alkyl -4) and C4-7 cycloalkyl, wherein said C1-8 alkyl and C4-7 cycloalkyl may be substituted with a portion selected from the group consisting of OH, O (C1-4 alkyl), S (C1-4 alkyl) and NR6dR6e; R6b is H; R6c is selected from the group consisting of H and C1-4 alkyl; R6d and R6e are independently selected from the group consisting of H and C1-4 alkyl; where R6a and R6c may form a cyclic structure, which may be substituted with a portion selected from the group consisting of OH, C1-4 alkyl, NH2 and F; or R6a and R6c may be linked with a heteroatom selected from the group consisting of N, O and S, in order to form a heterocyclic structure; or Xaa5 and Xaa6 together can be an amino acid residue of the formula (8e); Xaa7 is an amino acid residue of the formula (9 a-b); wherein R7a is selected from the group consisting of C1-4 alkyl, C3-7 cycloalkyl, 2-thienyl, (CH2) n7a-X7a and C1-4 alkyl substituted with OH; R7b is H and 2-thienyl; R7c is selected from a group consisting of H and methyl; R7d is C1-4 alkyl; n7a is selected from the group consisting of 1 and 2; X7a is selected from the group consisting of 2-thienyl, C (= O) OR7e, C (= O) NH2, S (= O) 2OH, OS (= O) 2OH, B (OH) 2, P (= O ) (OH) 2 and OP (= O) (OH) 2; where R7e is selected from the group consisting of H and C1-4 alkyl; Xaa8 is an amino acid residue of the formula (10 a-g); where R8a is selected from the group consisting of (CH2) m8a-X8a and a het ring |
| priorityDate | 2009-12-18-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
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Total number of triples: 30.