37793-53-6

Basic information

• Product Name: N10-(TRIFLUOROACETYL)PTEROIC ACID
• Synonyms: N10-(TRIFLUOROACETYL)PTEROIC ACID;TRIFLUOROACETYLPTEROIC ACID;N(sup 10)-(trifluoroacetyl)pteroic acid;4-(N-((2-Amino-4-oxo-3,4-dihydropteridin-6-yl)-methyl)-2,2,2-trifluoroacetamido)benzoic acid;4-[[(2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl](trifluoroacetyl)amino]benzoic acid;Benzoic acid,4-[[(2-aMino-3,4-dihydro-4-oxo-6-pteridinyl)Methyl](2,2,2-trifluoroacetyl)aMino]-;N10-(Trifluoroacetyl)pteroic acid 95%;4-[[(2-amino-3,4-dihydro-4-oxo-6-pteridinyl)methyl](2,2,2-trifluoroacetyl)amino]-Benzoic acid
• CAS NO: 37793-53-6
• Molecular Formula: C₁₆H₁₁F₃N₆O₄
• Molecular Weight: 408.29
• Product Categories: Building Blocks;Heterocyclic Building Blocks;Quinazolines
• Mol File: 37793-53-6.mol
• Article Data: 12

Chemical Properties

• Melting Point: 270 °C (dec.)(lit.)
• Boiling Point: 650.2°Cat760mmHg
• Flash Point: 347.1°C
• Appearance: /
• Density: 1.74g/cm³
• Vapor Pressure: 8.54E-18mmHg at 25°C
• Refractive Index: 1.697
• Storage Temp.: 2-8°C
• Solubility: DMF (Slightly), DMSO (Slightly)
• PKA: 4.11±0.10(Predicted)
• Stability: Hygroscopic
• CAS DataBase Reference: N10-(TRIFLUOROACETYL)PTEROIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: N10-(TRIFLUOROACETYL)PTEROIC ACID(37793-53-6)
• EPA Substance Registry System: N10-(TRIFLUOROACETYL)PTEROIC ACID(37793-53-6)

Safety Data

• Hazard Codes: T
• Statements: 45-20/21/22-36/37/38
• Safety Statements: 53-22-26-36/37/39-45
• RIDADR: UN 2811 6.1/PG 3
• WGK Germany: 3
• Hazardous Substances Data: 37793-53-6(Hazardous Substances Data)

Usage

Chemical Properties

white Solid

Uses

N10-Trifluoroacetylpteroic acid is a derivative of Pteroic acid (P840110), both of which are used as reagents to synthesize target ligands, like Folic acid (F680300), that have the ability to deliver chemotherapeutic agents specifically to cancer cells.

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

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

Downstream Products

• 63948-16-3 α-tert-butyl N¹⁰-(trifluoroacetyl)pteroyltriglutamate 
• 115255-07-7 C₂₁H₁₉F₃N₆O₆ 
• 910661-26-6 C₃₂H₄₀F₃N₉O₈ 
• 1431696-61-5 C₁₆H₁₈N₈O₂ 
• 742091-99-2 pteroyl-γ-Glu-Asp-Arg-Asp-Asp-Cys 
• 926623-13-4 folate-γ-Asp-Asp-Asp-(β-NH2-Ala)-Cys 
• 926623-14-5 folate-α-Asp-Arg-Asp-Asp-Cys 
• 124153-32-8 α-tert-butyl N¹⁰-(trifluoroacetyl)pteroyltetraglutamate 

Relevant articles and documents

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.

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.