368426-78-2

Usage

Uses

3-Amino-1,2-benzisoxazole-6-methanamine is used in the preparation of MASP-2 inhibitors.

InChI:InChI=1/C8H9N3O/c9-4-5-1-2-6-7(3-5)12-11-8(6)10/h1-3H,4,9H2,(H2,10,11)

Upstream product

• 229623-53-4 6-cyano-3-amino-1,2-benzisoxazole 
• 1897-53-6 2-fluoroterephthalonitrile 
• 105942-08-3 4-bromo-6-fluorobenzonitrile 
• 229623-55-6 4-(tert-butoxycarbonylaminomethyl)-2-fluorobenzonitrile 
• 368426-77-1 tert-butyl ((3-aminobenzo[d]isoxazol-6-yl)methyl)carbamate 

Downstream Products

• 308834-73-3 C₂₄H₂₄ClN₇O₃ 

Relevant academic research and scientific papers

FACTOR XIIa INHIBITORS

This invention relates to compounds of formula (I). The compounds of formula (I) are modulators of Factor XII, specifically Factor XIIa. The compounds are inhibitors of Factor XIIa and may be useful as anticoagulants. The compounds of formula (I) may be used in methods of treatment (or prevention) of blood disorders related to bleeding or coagulation.

Improving the Selectivity of PACE4 Inhibitors through Modifications of the P1 Residue

Paired basic amino acid cleaving enzyme 4 (PACE4), a serine endoprotease of the proprotein convertases family, has been recognized as a promising target for prostate cancer. We previously reported a selective and potent peptide-based inhibitor for PACE4, named the multi-Leu peptide (Ac-LLLLRVKR-NH2 sequence), which was then modified into a more potent and stable compound named C23 with the following structure: Ac-dLeu-LLLRVK-Amba (Amba: 4-amidinobenzylamide). Despite improvements in both in vitro and in vivo profiles of C23, its selectivity for PACE4 over furin was significantly reduced. We examined other Arg-mimetics instead of Amba to regain the lost selectivity. Our results indicated that the replacement of Amba with 5-(aminomethyl)picolinimidamide increased affinity for PACE4 and restored selectivity. Our results also provide a better insight on how structural differences between S1 pockets of PACE4 and furin could be employed in the rational design of selective inhibitors.

Design, synthesis, and biological evaluation of pyrazinones containing novel P1 needles as inhibitors of TF/VIIa

Herein is described the design, synthesis, and enzymatic activity of a series of substituted pyrazinones as inhibitors of the TF/VIIa complex. These inhibitors were designed to explore replacement and variation of the P1 amidine described previously [J. Med. Chem. 2003, 46, 4050]. The P1 needle replacements were selected based upon their reduced basicity compared to the parent phenyl amidine (pKa ～ 12). A contributing factor towards the oral bioavailability of a compound is the ionization state of the compound in the intestinal tract. The desired outcome of the study was to identify an orally bioavailable TF-VIIa inhibitor.

Non-covalent thrombin inhibitors featuring P3-heterocycles with P1-bicyclic arginine surrogates

Novel, potent, and highly selective classes of thrombin inhibitors were identified, which resulted from judicious combination of P4-aromatics and P2-P3-heterocyclic dipeptide surrogates with weakly basic (calcd pKa ～non-basic - 8.6) bicyclic P1-arginine mimics. The design, synthesis, and biological activity of achiral, non-covalent, orally bioavailable inhibitors NC1-NC44 featuring P1-indazoles, benzimidazoles, indoles, benzotriazoles, and aminobenzisoxazoles is disclosed.

THROMBIN INHIBITORS

Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: or a pharmaceutically acceptable salt thereof, wherein b is N Y 1 or O; c is CY 2 or N; d is CY 2; e is CY 1 or N; f is CY 1 or N; g is CY 1 or N; Y 1 is hydrogen, C 1-4 alkyl, or halogen; Y 2 is hydrogen, C 1-4 alkyl, C 3-7 cycloalkyl, halogen, NH 2, OH or C 1-4 alkoxy;A is and W, X, Z, R 3, R 4 and R 5 are defined in the specification.