37793-53-6

Usage

Uses

Used in Pharmaceutical Industry:
N10-(TRIFLUOROACETYL)PTEROIC ACID is used as a reagent for the synthesis of target ligands like Folic acid, which is crucial for the development of chemotherapeutic agents. The application reason is that these ligands can specifically target and deliver chemotherapeutic agents to cancer cells, enhancing the effectiveness of cancer treatment and reducing side effects on healthy cells.
Used in Cancer Research:
In the field of cancer research, N10-(TRIFLUOROACETYL)PTEROIC ACID is used as a key component in the creation of targeted therapies. The application reason is its ability to facilitate the synthesis of ligands that can selectively bind to cancer cells, allowing for more precise and effective treatment strategies.
Used in Drug Development:
N10-(TRIFLUOROACETYL)PTEROIC ACID is also used in drug development as a starting material for the synthesis of novel compounds with potential anticancer properties. The application reason is its unique chemical structure, which can be modified and optimized to create new drugs that can target specific cancer cell pathways or mechanisms.
Overall, N10-(TRIFLUOROACETYL)PTEROIC ACID is a versatile compound with significant applications in the pharmaceutical industry, cancer research, and drug development, primarily due to its role in the synthesis of target ligands for cancer treatment.

InChI:InChI=1/C16H11F3N6O4/c17-16(18,19)14(29)25(9-3-1-7(2-4-9)13(27)28)6-8-5-21-11-10(22-8)12(26)24-15(20)23-11/h1-5H,6H2,(H,27,28)(H3,20,21,23,24,26)

Synthetic route

N10-(trifluoroacetyl)pyrofolic acid (223378-68-5) → N10-trifluoroacetylpteroic acid (37793-53-6) + 2-{4-[(2-Amino-4-oxo-3,4-dihydro-pteridin-6-ylmethyl)-(2,2,2-trifluoro-acetyl)-amino]-benzoylamino}-pentanedioic acid

Conditions	Yield
With hydrogenchloride Hydrolysis;	A 56% B 33%

folic acid (59-30-3) → N10-trifluoroacetylpteroic acid (37793-53-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: tetrahydrofuran / 10.5 h / 0 - 25 °C 1.2: 123 g / ice / tetrahydrofuran / 3 h / 25 °C 2.1: 56 percent / aq. HCl View Scheme

pteroyl azide (197151-79-4) → N10-trifluoroacetylpteroic acid (37793-53-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 67 percent / tetramethylguanidine / dimethylsulfoxide / 9 h / 25 °C 2.1: tetrahydrofuran / 10.5 h / 0 - 25 °C 2.2: 123 g / ice / tetrahydrofuran / 3 h / 25 °C 3.1: 56 percent / aq. HCl View Scheme

pteroic acid (119-24-4) + trifluoroacetic anhydride (407-25-0) → N10-trifluoroacetylpteroic acid (37793-53-6)

Conditions	Yield
Stage #1: pteroic acid; trifluoroacetic anhydride at 20℃; for 96h; Stage #2: With trifluoroacetic acid In water for 48.3333h;
at 20℃; for 24h; Inert atmosphere; Darkness;
With trifluoroacetic acid
at 20℃; for 24h; Inert atmosphere; Darkness;

pteroic acid (119-24-4) + trifluoroacetic acid (76-05-1) + trifluoroacetic anhydride (407-25-0) → N10-trifluoroacetylpteroic acid (37793-53-6)

Conditions	Yield
Stage #1: pteroic acid; trifluoroacetic anhydride at 20℃; for 96h; Sealed tube; Inert atmosphere; Stage #2: trifluoroacetic acid at 20℃; for 48h; Sealed tube; Inert atmosphere;

N10-trifluoroacetylpteroic acid (37793-53-6) + 2-aminopentanedicarboxylic acid 5-tert-butyl ester 1-methyl ester → C26H28F3N7O7

Conditions	Yield
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 3h;	100%

N10-trifluoroacetylpteroic acid (37793-53-6) + L-glutamic acid 5-tert-butyl 1-methyl ester hydrochloride (6234-01-1) → (S)-5-tert-butyl 1-methyl 2-(4-{N-[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]-2,2,2-trifluoroacetamido}benzamido)pentanedioate

Conditions	Yield
Stage #1: N10-trifluoroacetylpteroic acid; L-glutamic acid 5-tert-butyl 1-methyl ester hydrochloride With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 23℃; for 0.25h; Inert atmosphere; Stage #2: With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate In dimethyl sulfoxide at 23℃; for 24h; Inert atmosphere;	100%
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 23℃; Inert atmosphere;

N10-trifluoroacetylpteroic acid (37793-53-6) + C17H33N3O7 → (S)-methyl 18-(4-(N-((2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl)-2,2,2-trifluoroacetamido)benzamido)-2,2-dimethyl-4,15-dioxo-3,8,11-trioxa-5,14-diazanonadecan-19-oate

Conditions	Yield
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0 - 20℃; for 2.5h; Inert atmosphere;	100%
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0 - 20℃; for 2.5h; Inert atmosphere;	4.06 g
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0 - 20℃; for 2.5h; Inert atmosphere;	4.06 g

N10-trifluoroacetylpteroic acid (37793-53-6) + 2-amino-3-(4-tert-butoxy-phenyl)-propionic acid tert-butyl ester (17083-23-7) → C33H36F3N7O6

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 23℃; for 2.16667h; Inert atmosphere;	96.7%

N10-trifluoroacetylpteroic acid (37793-53-6) + (S)-tert-butyl 2-amino-5-((3-azidopropyl)amino)-5-oxopentanoate (1375540-44-5) → (S)-tert-butyl 2-(4-(N-((2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl)-2,2,2-trifluoroacetamido)benzamido)-5-((3-azidopropyl)amino)-5-oxopentanoate (1375540-45-6)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 0 - 20℃; for 48h;	52%

1-hydroxy-pyrrolidine-2,5-dione (6066-82-6) + N10-trifluoroacetylpteroic acid (37793-53-6) → 2,5-dioxopyrrolidin-1-yl 4-(N-((2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl)-2,2,2-trifluoroacetamido)benzoate

Conditions	Yield
With dicyclohexyl-carbodiimide at 20℃; for 14h;	51%
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dimethyl sulfoxide at 20℃; for 24h;

N10-trifluoroacetylpteroic acid (37793-53-6) + C39H57N3O11 → C40H56F3N9O12

Conditions	Yield
Stage #1: C39H57N3O11 With diethylamine In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: N10-trifluoroacetylpteroic acid With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 1h;	50%

N10-trifluoroacetylpteroic acid (37793-53-6) + C39H57N3O11 → C40H56F3N9O12

Conditions	Yield
Stage #1: C39H57N3O11 With diethylamine In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: N10-trifluoroacetylpteroic acid With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 1h;	50%

α,γ-bis(L-glutamoyl)-D-glutamic acid tetra{2-[3,4-di(hexyloxy)phenyl]ethyl} ester + N10-trifluoroacetylpteroic acid (37793-53-6) → α,γ-bis(L-glutamoyl)-N-[N10-(trifluoroacetyl)pteroyl]-D-glutamic acid tetra{2-[3,4-di(hexyloxy)phenyl]ethyl} ester

Conditions	Yield
Stage #1: N10-trifluoroacetylpteroic acid With triethylamine; isobutyl chloroformate In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: α,γ-bis(L-glutamoyl)-D-glutamic acid tetra{2-[3,4-di(hexyloxy)phenyl]ethyl} ester In tetrahydrofuran; N,N-dimethyl-formamide at 40℃; for 72h;	47%

α,γ-bis(D-glutamoyl)-D-glutamic acid tetra{2-[3,4-di(hexyloxy)phenyl]ethyl} ester + N10-trifluoroacetylpteroic acid (37793-53-6) → α,γ-bis(D-glutamoyl)-N-[N10-(trifluoroacetyl)pteroyl]-D-glutamic acid tetra{2-[3,4-di(hexyloxy)phenyl]ethyl} ester

Conditions	Yield
Stage #1: N10-trifluoroacetylpteroic acid With triethylamine; isobutyl chloroformate In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: α,γ-bis(D-glutamoyl)-D-glutamic acid tetra{2-[3,4-di(hexyloxy)phenyl]ethyl} ester In tetrahydrofuran; N,N-dimethyl-formamide at 40℃; for 72h;	42%

N10-trifluoroacetylpteroic acid (37793-53-6) + methyl γ-aminobutyrate hydrochloride (13031-60-2) → C21H20F3N7O5

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 20℃; for 3h; Inert atmosphere;	40%

α,γ-bis(L-glutamoyl)-L-glutamic acid tetra{2-[3,4-di(hexyloxy)phenyl]ethyl} ester + N10-trifluoroacetylpteroic acid (37793-53-6) → α,γ-bis(L-glutamoyl)-N-[N10-(trifluoroacetyl)pteroyl]-L-glutamic acid tetra{2-[3,4-di(hexyloxy)phenyl]ethyl} ester

Conditions	Yield
Stage #1: N10-trifluoroacetylpteroic acid With triethylamine; isobutyl chloroformate In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: α,γ-bis(L-glutamoyl)-L-glutamic acid tetra{2-[3,4-di(hexyloxy)phenyl]ethyl} ester In tetrahydrofuran; N,N-dimethyl-formamide at 40℃; for 72h;	39%

N10-trifluoroacetylpteroic acid (37793-53-6) + C21H23N2O3Pol + Fmoc-Glu(OtBu)-OH (71989-18-9) → Lys-Glu-N10-(trifluoroacetyl)pteroic acid

Conditions

Yield

Stage #1: C21H23N2O3Pol With piperidine In N,N-dimethyl-formamide for 0.166667h; not specified; Stage #2: Fmoc-Glu(OtBu)-OH With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 1h; Inert atmosphere; Stage #3: N10-trifluoroacetylpteroic acid With chlorotriisopropylsilane; trifluoroacetic acid In water for 0.5h; Inert atmosphere;

39%

N10-trifluoroacetylpteroic acid (37793-53-6) + methyl DL-2-amino-4-(methylsulfonyl)butanoate hydrochloride (139974-52-0) → 2-{4-[(2-Amino-4-oxo-3,4-dihydro-pteridin-6-ylmethyl)-amino]-benzoylamino}-4-methanesulfonyl-butyric acid (115510-52-6)

Conditions	Yield
With triethylamine; isobutyl chloroformate 1.) DMSO, RT, 45 min, 2.) 30-35 deg C, 24 h; Yield given. Multistep reaction;

N10-trifluoroacetylpteroic acid (37793-53-6) + methyl DL-2-amino-4-butanoate dihydrochloride (139895-37-7) → pteroyl-S-methylhomocysteine sulfoximine (115453-76-4)

Conditions	Yield
With triethylamine; isobutyl chloroformate 1.) DMSO, RT, 45 min, 2.) 30-35 deg C, 24 h; Yield given. Multistep reaction;

N10-trifluoroacetylpteroic acid (37793-53-6) + methyl DL-2-amino-4-butanoate dihydrochloride (139895-38-8) → pteroyl-S-ethylhomocysteine sulfoximine (115453-77-5)

Conditions	Yield
With triethylamine; isobutyl chloroformate 1.) DMSO, RT, 45 min, 2.) 30-35 deg C, 24 h; Yield given. Multistep reaction;

N10-trifluoroacetylpteroic acid (37793-53-6) + methyl DL-2-amino-4-butanoate dihydrochloride (139895-39-9) → pteroyl-S-propylhomocysteine sulfoximine (115453-78-6)

Conditions	Yield
With triethylamine; isobutyl chloroformate 1.) DMSO, RT, 45 min, 2.) 30-35 deg C, 24 h; Yield given. Multistep reaction;

N10-trifluoroacetylpteroic acid (37793-53-6) + methyl DL-2-amino-4-butanoate dihydrochloride (139895-40-2) → pteroyl-S-1-butylhomocysteine sulfoximine (115453-79-7)

Conditions	Yield
With triethylamine; isobutyl chloroformate 1.) DMSO, RT, 45 min, 2.) 30-35 deg C, 24 h; Yield given. Multistep reaction;

N10-trifluoroacetylpteroic acid (37793-53-6) + (2S,4S)-4-fluoroglutamic acid α,γ-di-tert-butyl ester (173315-21-4) → (2S,4S)-2-{4-[(2-Amino-4-oxo-3,4-dihydro-pteridin-6-ylmethyl)-(2,2,2-trifluoro-acetyl)-amino]-benzoylamino}-4-fluoro-pentanedioic acid di-tert-butyl ester (1025903-77-8)

Conditions	Yield
With benzotriazol-1-ol; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide for 68h; Ambient temperature;

N10-trifluoroacetylpteroic acid (37793-53-6) + DL-3,3-difluoroglutamic acid α,γ-di-tert-butyl ester (139112-62-2) → 2-{4-[(2-Amino-4-oxo-3,4-dihydro-pteridin-6-ylmethyl)-(2,2,2-trifluoro-acetyl)-amino]-benzoylamino}-3,3-difluoro-pentanedioic acid di-tert-butyl ester

Conditions	Yield
With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In N,N-dimethyl-formamide for 72h; Ambient temperature;

N10-trifluoroacetylpteroic acid (37793-53-6) + isobutyl chloroformate (543-27-1) → C21H19F3N6O6 (115255-07-7)

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 20℃; for 1h;
With triethylamine In N,N-dimethyl-formamide at 0℃; for 1h;
With triethylamine In N,N-dimethyl-formamide at 20℃; for 0.75h; Inert atmosphere;

N10-trifluoroacetylpteroic acid (37793-53-6) + isobutyl chloroformate (543-27-1) → 4-[(2-Amino-4-oxo-3,4-dihydro-pteridin-6-ylmethyl)-(2,2,2-trifluoro-acetyl)-amino]-benzoic acid isobutyl ester

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 20℃; for 1h; Esterification;

N10-trifluoroacetylpteroic acid (37793-53-6) + Fmoc-Glu-OtBu (84793-07-7) + Fmoc-(tBu)Asp-OH (71989-14-5) + Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine + H2N-Ser(p-methoxytrityl)-O-Wang resin → C42H50F3N15O18S

Conditions	Yield
Multistep reaction;

(S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)-amino)-3-((1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl)amino)propanoic acid + N10-trifluoroacetylpteroic acid (37793-53-6) + Fmoc-Glu-OtBu (84793-07-7) + Fmoc-(tBu)Asp-OH (71989-14-5) + S-Fm-3-thiopropionic acid + H-Cys(4-methoxytrityl)-2-chlorotrityl resin → C54H59N13O18S2 (926623-18-9)

Conditions	Yield
Multistep reaction.;	450 mg

N10-trifluoroacetylpteroic acid (37793-53-6) → bis{2-[3,4-bis(hexyloxy)phenyl]ethyl} N-[N10-(trifluoroacetyl)pteroyl]-L-glutamate

Conditions	Yield
Multi-step reaction with 2 steps 1: Et3N / dimethylformamide / 1 h / 20 °C 2: dimethylformamide; tetrahydrofuran / 72 h / 40 °C View Scheme
Multi-step reaction with 2 steps 1: Et3N / dimethylformamide / 1 h / 20 °C 2: dimethylformamide; tetrahydrofuran / 40 °C View Scheme

N10-trifluoroacetylpteroic acid (37793-53-6) → (5-nitro-2-furyl)methyl Nε-(pteroyllysyl)-N,N-bis(2-chloroethyl)phosphorodiamidate

Conditions	Yield
Multi-step reaction with 3 steps 1: Et3N / dimethylformamide / 1 h / 0 °C 2: dimethylformamide / 2 h / 0 °C 3: aq. K2CO3 / methanol; tetrahydrofuran / 144 h / 20 °C View Scheme

N10-trifluoroacetylpteroic acid (37793-53-6) → (5-nitro-2-furyl)methyl Nε-(pteroyllysyl)-N,N-bis(2-bromoethyl)phosphorodiamidate

Conditions	Yield
Multi-step reaction with 3 steps 1: Et3N / dimethylformamide / 1 h / 0 °C 2: dimethylformamide / 2 h / 0 °C 3: 89 percent / aq. K2CO3 / methanol; tetrahydrofuran / 144 h / 20 °C View Scheme

N10-trifluoroacetylpteroic acid (37793-53-6) → (5-nitro-2-furyl)methyl Nε-(N10-(trifluoroacetyl)pteroyllysyl)-N,N-bis(2-chloroethyl)phosphorodiamidate (324770-56-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: Et3N / dimethylformamide / 1 h / 0 °C 2: dimethylformamide / 2 h / 0 °C View Scheme

Upstream product

• 119-24-4 pteroic acid 
• 407-25-0 trifluoroacetic anhydride 
• 76-05-1 trifluoroacetic acid 
• 119-24-4 Pteroic acid 
• 59-30-3 folate 
• 59-30-3 folic acid 
• 197151-79-4 pteroyl azide 
• 223378-68-5 N¹⁰-(trifluoroacetyl)pyrofolic acid 

Downstream Products

• 115510-52-6 2-{4-[(2-Amino-4-oxo-3,4-dihydro-pteridin-6-ylmethyl)-amino]-benzoylamino}-4-methanesulfonyl-butyric acid 
• 115453-76-4 pteroyl-S-methylhomocysteine sulfoximine 
• 115453-77-5 pteroyl-S-ethylhomocysteine sulfoximine 
• 115453-78-6 pteroyl-S-propylhomocysteine sulfoximine 
• 115453-79-7 pteroyl-S-1-butylhomocysteine sulfoximine 
• 115255-07-7 C₂₁H₁₉F₃N₆O₆ 
• 926623-14-5 folate-α-Asp-Arg-Asp-Asp-Cys 
• 742091-99-2 pteroyl-γ-Glu-Asp-Arg-Asp-Asp-Cys 
• 926623-13-4 folate-γ-Asp-Asp-Asp-(β-NH2-Ala)-Cys 
• 250143-83-0 Cys-Glu-N₁₀ (trifluoroacetyl)-Pteroic acid 

Relevant academic research and scientific papers

Chemical generation of small molecule-based bispecific antibody-drug conjugates for broadening the target scope

Antibody-drug conjugates (ADCs) hold great therapeutic promise for cancer indications; however, treating tumors with intratumor heterogeneity remains challenging. We hypothesized that ADCs that can simultaneously target two different cancer antigens could

Synthesis and anti-cancer evaluation of folic acid-peptide- paclitaxel conjugates for addressing drug resistance

The drug resistance and the poor water solubility are major limitations of paclitaxel (PTX) of based chemotherapy. To conquer the two problems, targeting folate (FA) receptor PTX-lytic peptides conjugates were synthesized and evaluated. Compared with PTX, FA-P3-PTX and FA-P7-PTX displayed significantly enhanced cell toxicity in many cancer cells, particularly drug resistant cancer cells MCF-7/PTX. FA-P7-PTX possessed stronger effect on cell toxicity (IC50 = 2.92 ± 0.2 μM), membrane disrupting activity and pro-apoptosis in MCF-7/PTX cells than FA-P3-PTX. Further investigation displayed that the anti-cancer mechanisms of FA-P3-PTX and FA-P7-PTX might be a mitochondrial impairment and caspase-3-dependent apoptotic cell death. Furthermore, the in vivo antitumor efficacy study confirmed that FA-P7-PTX performed more stronger potency in inhibition of tumors growth than PTX. The study demonstrated that conjugate FA-P7-PTX with superior properties for antineoplastic activity, which makes it a promising potential candidate for drug-resistant cancer therapy.

USES OF ANTI-CD3 ANTIBODY FOLATE BIOCONJUGATES

Described herein are anti-CD3 antibody folate bioconjugates and uses thereof in the treatment of diseases, conditions, and cancers.

Preparation method of N10-trifluoroacetyl pteroic acid

The invention provides a preparation method of N10-trifluoroacetyl pteroic acid. The preparation method comprises the following step: reacting a compound trifluoroacetic acid or trifluoroacetic anhydride or a mixed solution of the trifluoroacetic acid and the trifluoroacetic anhydride with instant pteroic acid or a mixture of the instant pteroic acid and anhydrous pteroic acid in a DMSO or DMF solvent to obtain the N10-trifluoroacetyl pteroic acid. The method is simple in process, trifluoroacetic anhydride is prevented from being used as a solvent, the reaction time is greatly shortened, and industrial production is facilitated.

ANTI-CD3 ANTIBODY FOLATE BIOCONJUGATES AND THEIR USES

Described herein are novel anti-CD3 Folate antibodies and uses thereof in the treatment of diseases or conditions that would benefit from such.

FOLATE DERIVATIVES, USEFUL IN PARTICULAR IN THE CONTEXT OF THE FOLATE ASSAY

Use of a folate derivative to assay in vitro the folate in a sample such as a biological sample.

Riboflavin-targeted polymer conjugates for breast tumor delivery

Purpose: In breast cancer, a significant decrease in riboflavin (RF) serum levels and increase in RF carrier protein occurs, indicating a potential role of RF in disease progression. To evaluate RF's ability to serve as a targeting agent, mitomycin C (MMC)-conjugated N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers were synthesized and targeted to the RF internalization pathway in human breast cancer cells. Methods: Competitive uptake studies were used to determine specificity of RF-targeted conjugates, and an MTT assay established the IC50 for the conjugates. Endocytic mechanisms were investigated by confocal microscopy. Results: Studies revealed a high-affinity endocytic mechanism for RF-specific internalization of fluorescently-labeled conjugates in both MCF-7 and SKBR-3 cells, whereas folic acid-mediated endocytosis showed high specificity only in SKBR-3 cells. MMC internalization was significantly higher following nontargeted and RF-targeted MMC-conjugate administration compared to that of free MMC. Cytotoxic analysis illustrated potent IC 50 values for RF-targeted MMC conjugates similar to free MMC. Maximum nuclear accumulation of MMC resulted from lysosomal release from RF-targeted and nontargeted MMC-conjugates following 6 h incubations, unlike that of free MMC seen within 10 min. Conclusion: Targeting polymer-MMC conjugates to the RF internalization pathway in breast cancer cells enabled an increase in MMC uptake and nuclear localization, resulting in potent cytotoxic activity.

PROCESSES FOR MAKING EPOTHILONE COMPOUNDS AND ANALOGS

The present invention relates to processes for making epothilone compounds and analogs thereof, such as epi-epothilone A or epi-epothilone B, and aziridinyl-epothilone analogs.

POSITRON EMISSION TOMOGRAPHY IMAGING METHOD

Described herein are compositions and methods for diagnosing and/or monitoring pathogenic disease states using positron emission tomography, wherein the pathogenic cells uniquely express, preferentially express, or overexpress vitamin receptors. Also described herein are 18F conjugates of vitamins and vitamin receptor- binding analogs and derivatives.

AZIRIDINYL-EPOTHILONE COMPOUNDS

The present invention is directed to aziridinyl epothilone compounds as further described herein, and/or pharmaceutically-acceptable salts and/or solvates thereof having the following Formula: wherein K is —O—, —S—, or —NR7—; A is —(CR8R9)—(CH2)m-Z- wherein Z is —(CHR10)—, —C(═O)—, —C(═O)—C(═O)—, —OC(═O)—, —N(R11)C(═O)—, —SO2—, or —N(R11)SO2—; B1 is hydroxyl or cyano and R1 is hydrogen or B1 and R1 are taken together to form a double bond; R2, R3, and R5 are, independently, hydrogen, alkyl, substituted alkyl, aryl or substituted aryl; or R2 and R3 may be taken together with the carbon to which they are attached to form an optionally substituted cycloalkyl; R4 is hydrogen, alkyl, alkenyl, substituted alkyl, substituted alkenyl, aryl, or substituted aryl; R6 is hydrogen, alkyl or substituted alkyl; R7, R8, R9, R10, R11 and R12 are independently hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heterocycloalkyl, substituted heterocycloalkyl, heteroaryl, or substituted heteroaryl; and R13 is aryl, substituted aryl, heteroaryl or substituted heteroaryl.