203866-14-2

Usage

Uses

Used in Pharmaceutical Industry:
BOC-TRANS-4-FLUORO-L-PROLINE is used as a synthetic intermediate for the development of various pharmaceutical compounds. It plays a crucial role in the preparation of:
1. Dipeptidyl Peptidase IV Inhibitors:
BOC-TRANS-4-FLUORO-L-PROLINE is used as a key component in the synthesis of potent 3or 4-substituted-2-cyanopyrrolidine dipeptidyl peptidase IV inhibitors. These inhibitors are essential for the treatment of type 2 diabetes and related metabolic disorders, as they help regulate blood glucose levels by increasing insulin secretion and decreasing glucagon release.
2. Pan-Aurora Kinase Inhibitors and Anti-Tumor Agents:
BOC-TRANS-4-FLUORO-L-PROLINE is also utilized in the synthesis of pyrrolotriazines derivatives, which act as pan-Aurora kinase inhibitors. These inhibitors are vital in the development of anti-tumor agents, as they target Aurora kinases, a family of serine/threonine protein kinases that play a significant role in cell cycle regulation and are often overexpressed in various cancers. By inhibiting Aurora kinases, these agents can help control tumor growth and progression, offering potential therapeutic benefits in cancer treatment.

InChI:InChI=1/C10H16FNO4/c1-10(2,3)16-9(15)12-5-6(11)4-7(12)8(13)14/h6-7H,4-5H2,1-3H3,(H,13,14)/t6-,7+/m1/s1

Upstream product

• 74844-91-0 (2S,4S)-N-tert-butoxycarbonyl-4-hydroxyproline methyl ester 
• 74844-91-0 1-tert-butyl 2-methyl (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylate 
• 121147-94-2 1-tert-butyl 2-methyl (2S,4S)-4-((benzoyl)oxy)-1,2-pyrrolidinedicarboxylate 
• 129430-93-9 (2S,4S)-methyl 4-hydroxy-1-tritylpyrrolidine-2-carboxylate 
• 129430-93-9 methyl (2S,4R)-4-hydroxy-1-tritylpyrrolidine-2-carboxylate 
• 40216-83-9 L-4-hydroxyproline methyl ester hydrochloride 
• 89813-47-8 N-(tert-butoxycarbonyl)-(2S,4R)-4-hydroxyproline benzyl ester 
• 87691-27-8 N-tert-butoxycarbonyl-L-cis-4-hydroxyproline 
• 132622-90-3 (2S,4S)-2-benzyl 1-tert-butyl 4-hydroxypyrrolidine-1,2-dicarboxylate 
• 587887-98-7 2-benzyl 1-(tert-butyl) (2S,4R)-4-fluoropyrrolidine-1,2-dicarboxylate 
• 203866-18-6 methyl (2S,4R)-N-(tert-butyloxy)carbonyl-4-fluoropyrrolidine-2-carboxylate 

Downstream Products

• 2438-57-5 (2S,4R)-4-fluoropyrrolidine-2-carboxylic acid 
• 1299466-03-7 (2S,4R)-2-{[4-bromo-2-(4-methoxy-phenoxy)-phenylamino]-methyl}-4-fluoro-pyrrolidine-1-carboxylic acid tert-butyl ester 
• 1299466-04-8 (2S,4R)-2-{[4-(5-cyano-pyridin-3-yl)-2-(4-methoxy-phenoxy)-phenylamino]-methyl}-4-fluoro-pyrrolidine-1-carboxylic acid tert-butyl ester 
• 1384246-34-7 C₂₇H₂₉FN₄O₅ 
• 1384246-36-9 C₂₃H₂₇FN₄O₅ 
• 1410975-64-2 (2S,4R)-tert-butyl 2-((N-(tert-butoxycarbonyl)-2-nitrophenylsulfonamido)methyl)-4-fluoropyrrolidine-1-carboxylate 
• 1410975-65-3 N-(((2S,4R)-4-fluoropyrrolidine-2-yl)methyl)-2-nitrobenzenesulfonamide 

Relevant academic research and scientific papers

COMBINATION OF CHIMERIC ANTIGEN RECEPTOR THERAPY AND AMINO PYRIMIDINE DERIVATIVES

The invention provides compositions and methods for treating diseases associated with expression of CD19, e.g., by administering a recombinant T cell comprising the CD19 CAR as described herein, in combination with a BTK inhibitor, e.g., an amino pyrimidi

NOVEL AMINO PYRIMIDINE DERIVATIVES

The present invention describes new amino pyrimidine derivatives and pharmaceutically acceptable salts thereof which appear to interact with Bruton's tyrosine kinase (Btk). Accordingly, the novel amino pyrimidines may be effective in the treatment of autoimmune disorders, inflammatory diseases, allergic diseases, airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD), transplant rejection, cancers e.g. of hematopoietic origin or solid tumors.

NOVEL AMINO PYRIMIDINE DERIVATIVES

The present invention describes new amino pyrimidine derivatives of formula (I) and pharmaceutically acceptable salts thereof which appear to interact with Bruton's tyrosine kinase (Btk). Accordingly, the novel amino pyrimidines may be effective in the treatment of autoimmune disorders, inflammatory diseases, allergic diseases, airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD), transplant rejection, cancers e.g. of hematopoietic origin or solid tumors.

N-FORMYL HYDROZYAMINE COMPOUNDS

Novel N-formyl hydroxylamine compounds and their derivatives are disclosed. These N-formyl hydroxylamine compounds inhibit peptidyl deformylase (PDF), an enzyme present in prokaryotes. The compounds are useful as antimicrobials and antibiotics. The compou

Incorporation of fluoroprolines to proctolin: Study on the effect of a fluorine atom toward peptidic conformation

In spite of quite small steric perturbation, substitution of proline (Pro) in the target pentapeptide proctolin (Arg-Tyr-Leu-Pro-Thr) for (4R)- as well as (4S)-4-fluoroproline led to apparent alteration of the pyrrolidine ring structure which eventually r

Synthesis, biological evaluation, and pharmacokinetic study of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives as VLA-4 antagonists

A series of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives were synthesized and evaluated for their activity as VLA-4 antagonists. Of 22 compounds synthesized, 19 compounds showed potent activity with low nanomolar IC50 values. In addition, the representative compounds 11o and 11p with a hydroxy group in the pyrrolidine ring showed moderate plasma clearance in rats (11o, 30 ml/min/kg and 11p, 21 ml/min/kg) and in dogs (11o, 12 ml/min/kg and 11p, 9 ml/min/kg).

Stereoelectronic and steric effects in the collagen triple helix: Toward a code for strand association

Collagen is the most abundant protein in animals. The protein consists of a helix of three strands, each with sequence X-Y-Gly. Natural collagen is most stable when X is (2S)-proline (Pro) and Y is (2S,4R)-4-hydroxyproline (4R-Hyp). We had shown previously that triple helices in which X is (2S,4S)-4- fluoroproline (4S-Flp) or Y is (2S,4R)-4-fluoroproline (4R-Flp) display hyperstability. This hyperstability arises from stereoelectronic effects that preorganize the main-chain dihedral angles in the conformation found in the triple helix. Here, we report the synthesis of strands containing both 4S-Flp in the X-position and 4R-Flp in the Y-position. We find that these strands do not form a stable triple helix, presumably because of an unfavorable steric interaction between fluoro groups on adjacent strands. Density functional theory calculations indicate that (2S,3S)-3-fluoroproline (3S-Flp), like 4S-Flp, should preorganize the main chain properly for triple-helix formation but without a steric conflict. Synthetic strands containing 3S-Flp in the X-position and 4R-Flp in the Y-position do form a triple helix. This helix is, however, less stable than one with Pro in the X-position, presumably because of an unfavorable inductive effect that diminishes the strength of the interstrand 3S-FlpC=O...H-NGly hydrogen bond. Thus, other forces can counter the benefits derived from the proper preorganization. Although (Pro-Pro-Gly) 7 and (4S-Flp-4R-Flp-Gly)7 do not form stable homotrimeric helices, mixtures of these two peptides form stable heterotrimeric helices containing one (Pro-Pro-Gly)7 strand and two (4S-Flp-4R-Flp-Gly) 7 strands. This stoichiometry can be understood by considering the cross sections of the two possible heterotrimeric helices. This unexpected finding portends the development of a "code" for the self-assembly of determinate triple helices from two or three strands.

CYANOPYRROLIDINE DERIVATIVES

A cyanopyrrolidine derivative represented by Formula (1): [wherein R1 is a halogen atom, a hydroxyl group, an alkoxy group having 1 to 5 carbon atoms or an alkyl group having 1 to 5 carbon atoms, R2 is a hydrogen atom, a halogen atom, a hydroxyl group, an alkoxy group having 1 to 5 carbon atoms or an alkyl group having 1 to 5 carbon atoms, or R1 and R2 together form an oxo, a hydroxyimino group, an alkoxyimino group having 1 to 5 carbon atoms or an alkylidene group having 1 to 5 carbon atoms, ???R3 and R4 are each a hydrogen atom, a halogen atom, a hydroxyl group, an alkoxy group having 1 to 5 carbon atoms or an alkyl group having 1 to 5 carbon atoms, or R3 and R4 together form an oxo, a hydroxyimino group, an alkoxyimino group having 1 to 5 carbon atoms or an alkylidene group having 1 to 5 carbon atoms, ???X is an oxygen atom or a sulfur atom, ???Y is -CR5R6- (wherein R5 and R6 are the same or different, and are each a hydrogen atom, a halogen atom, an optionally substituted alkyl group having 1 to 10 carbon atoms or an optionally substituted alkenyl group having 2 to 10 carbon atoms), or -CR7R8-CR9R10- (wherein R7, R8, R9 and R10 are the same or different, and each a hydrogen atom, a halogen atom or an optionally substituted alkyl group having 1 to 10 carbon atoms, or R7 and R9 together with the carbon atom to which they are attached form an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an optionally substituted cycloalkenyl group having 4 to 8 carbon atoms, an optionally substituted bicycloalkyl group having 5 to 10 carbon atoms, or an optionally substituted bicycloalkenyl group having 5 to 10 carbon atoms) and ???Z is a hydrogen atom or an optionally substituted alkyl group having 1 to 10 carbon atoms, or Y and Z together with the nitrogen atom to which they are attached form an optionally substituted cyclic amino group having 2 to 10 carbon atoms], or a pharmaceutically acceptable salt thereof.

Stereoelectronic effects on collagen stability: The dichotomy of 4-fluoroproline diastereomers

Collagen is the most abundant protein in animals. Natural collagen consists of a triple helix of (Xaa-Yaa-Gly)n chains, in which the Xaa and Yaa residues are often l-proline. Here, a (2S,4S)-4-fluoroproline (flp) residue is shown to be greatly stabilizing in the Xaa position (but destabilizing in the Yaa position). In contrast, a (2S,4R)-4-fluoroproline (Flp) residue is shown to be greatly destabilizing in the Xaa position (but stabilizing in the Yaa position). The dichotomous effect of the diastereomers appears to arise from a gauche effect, which alters pyrrolidine ring pucker and hence properly (or improperly) preorganizes main-chain dihedral angles. Thus, the rational use of stereoelectronic effects can enhance the conformational stability of a protein. Copyright

Practical synthesis of Boc and Fmoc protected 4-fluoro and 4-difluoroprolines from trans-4-hydroxyproline

Boc-cis-4-fluoro-L-proline and 4-difluoro-L-proline, usable in classical peptide synthesis, were obtained in respectively 71% (3 steps) and 65% (4 steps) overall yields from the readily available trans-4-hydroxy-L-proline methyl ester. The corresponding fluorinated trans-isomer was isolated in 24% yield (5 steps). Transformation of Boc-protected compounds to their Fmoc-equivalents was performed in high yields.