159857-79-1

Basic information

• Product Name: Val-cit-PAB-OH
• Synonyms: Val-cit-PAB-OH;L-Valyl-N5-(aminocarbonyl)-N-[4-(hydroxymethyl)phenyl]-L-ornithinamide;(S)-2-((R)-2-amino-3-methylbutanamido)-N-(4-(hydroxymethyl)phenyl)-5-ureidopentanamide;EOS-61316;(S)-2-((S)-2-amino-3-methylbutanamido)-N-(4-(hydroxymethyl)phenyl)-5-ureidopentanamide;L-Ornithinamide, L-valyl-N5-(aminocarbonyl)-N-[4-(hydroxymethyl)phenyl]-
• CAS NO: 159857-79-1
• Molecular Formula: C₁₈H₂₉N₅O₄
• Molecular Weight: 379.45396
• EINECS: -0
• Product Categories: Linker;ADC LINKER
• Mol File: 159857-79-1.mol
• Article Data: 34

Chemical Properties

• Melting Point: 168 °C(dec.)
• Boiling Point: 715.0±60.0 °C(Predicted)
• Appearance: /
• Density: 1.243±0.06 g/cm3(Predicted)
• Storage Temp.: 2-8°C(protect from light)
• PKA: 13.75±0.46(Predicted)
• CAS DataBase Reference: Val-cit-PAB-OH(CAS DataBase Reference)
• NIST Chemistry Reference: Val-cit-PAB-OH(159857-79-1)
• EPA Substance Registry System: Val-cit-PAB-OH(159857-79-1)

Safety Data

• Hazardous Substances Data: 159857-79-1(Hazardous Substances Data)

Usage

Description

Val-Cit-PAB-OH is a peptide cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). The Val-Cit will specifically be cleaved by Cathepsin B.

Uses

Val-cit-PAB-OH acts as a reagent in the preparation of cell-penetrating peptidic GRP78 ligand for tumor cell-specific prodrug therapy, preparation of monomethylvaline derivative conjugates with ligands and antibodies for cancer treatment.

Synthetic route

(9H-fluorenyl)methyl ((S)-1-(((S)-1-(((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidovalerylamido-2-yl)amino))-3-methylbutyramido-2-yl)-carbamate (159858-22-7) → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1)

Conditions	Yield
With diethylamine In N,N-dimethyl-formamide for 24h;	100%
With diethylamine In N,N-dimethyl-formamide for 2h;	96%
With diethylamine In N,N-dimethyl-formamide for 2h;	96%

(9H-fluoren-9-yl)methyl (S)-(1-((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidopentan-2-yl)carbamate (870487-04-0) + Fmoc-Val-OPfp (86060-87-9) → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1)

Conditions	Yield
Stage #1: (S)-(9H-fluoren-9-yl)methyl (1-((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidopentan-2-yl)carbamate With piperidine In N,N-dimethyl-formamide at 23℃; for 3h; Stage #2: Fmoc-Val-OPfp With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 23℃; for 24h; Stage #3: With piperidine In N,N-dimethyl-formamide at 23℃; for 1h;	93%

Fmoc-Val-OH (68858-20-8) → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl acetamide 2: sodium hydrogencarbonate / water; tetrahydrofuran 3: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl acetamide 4: diethylamine / 1-methyl-pyrrolidin-2-one View Scheme
Multi-step reaction with 3 steps 1.1: dicyclohexyl-carbodiimide; 1-hydroxy-pyrrolidine-2,5-dione / tetrahydrofuran / 16 h / 20 °C 1.2: 16 h / 20 °C 2.1: N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline / dichloromethane; methanol / 36 h / 20 °C 3.1: piperidine / N,N-dimethyl-formamide / 2 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1: dicyclohexyl-carbodiimide / acetonitrile; tetrahydrofuran / 24 h / 0 - 20 °C 2: sodium hydrogencarbonate / tetrahydrofuran; 1,2-dimethoxyethane; water / 24 h / 20 °C 3: N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline / dichloromethane; methanol / 48 h / 20 °C / Darkness 4: diethylamine / 24 h / 20 °C View Scheme

2,5-dioxopyrrolidin-1-yl-N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-valinate (130878-68-1) → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium hydrogencarbonate / water; tetrahydrofuran 2: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl acetamide 3: diethylamine / 1-methyl-pyrrolidin-2-one View Scheme
Multi-step reaction with 2 steps 1: N,N-dimethyl-formamide / 3 h / 20 °C 2: piperidine / N,N-dimethyl-formamide / 1 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: N,N-dimethyl-formamide / 16 h / 20 °C / Inert atmosphere 2: diethylamine / 1-methyl-pyrrolidin-2-one / 16 h / 20 °C / Inert atmosphere View Scheme

(S)-2-((S)-2-((((9H-fluoren-9-yl)-methoxy)carbonyl)amino)-3-methylbutanamido)-5-ureidopentanoic acid (159858-21-6) → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl acetamide 2: diethylamine / 1-methyl-pyrrolidin-2-one View Scheme
Multi-step reaction with 2 steps 1: N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline / dichloromethane; methanol / 36 h / 20 °C / Darkness; Inert atmosphere 2: diethylamine / 1-methyl-pyrrolidin-2-one / 16 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline / dichloromethane; methanol / 36 h / 20 °C 2: piperidine / N,N-dimethyl-formamide / 2 h / 20 °C View Scheme

4-aminobenzenemethanol (623-04-1) → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl acetamide 2: diethylamine / 1-methyl-pyrrolidin-2-one View Scheme
Multi-step reaction with 5 steps 1.1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / dichloromethane / 16 h / 20 °C 2.1: diethylamine / N,N-dimethyl-formamide / 1 h / 20 °C 3.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 1 h / 20 °C 3.2: 16 h / 20 °C 4.1: dichloromethane / 3 h / 20 °C 5.1: sodium hydroxide; water / 1,4-dioxane / 3 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: N-ethyl-N,N-diisopropylamine; HATU / dichloromethane / 16 h / 20 °C 2.1: diethylamine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C 3.1: HATU / N,N-dimethyl-formamide / 1 h / 20 °C 3.2: 16 h / 20 °C 4.1: trifluoroacetic acid / dichloromethane / 3 h / 20 °C 4.2: 3 h / 20 °C View Scheme

(S)-2-amino-N-(4-(hydroxymethyl)phenyl)-5-ureidopentanamide (1037794-22-1) → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: N,N-dimethyl-formamide / 3 h / 20 °C 2: piperidine / N,N-dimethyl-formamide / 1 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 1 h / 20 °C 1.2: 16 h / 20 °C 2.1: dichloromethane / 3 h / 20 °C 3.1: sodium hydroxide; water / 1,4-dioxane / 3 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: HATU / N,N-dimethyl-formamide / 1 h / 20 °C 1.2: 16 h / 20 °C 2.1: trifluoroacetic acid / dichloromethane / 3 h / 20 °C 2.2: 3 h / 20 °C View Scheme

(S)-tert-butyl 1-(4-(hydroxymethyl)phenylamino)-1-oxo-5-ureidopentan-2-ylcarbamate (1037793-80-8) → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrogenchloride / 1,4-dioxane / 2 h / 20 °C 2: N,N-dimethyl-formamide / 3 h / 20 °C 3: piperidine / N,N-dimethyl-formamide / 1 h / 20 °C View Scheme

Citrulline (372-75-8) → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1)

Conditions	Yield
Multi-step reaction with 5 steps 1: potassium carbonate / water; 1,4-dioxane / 2 h / 0 - 20 °C 2: N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline / methanol; dichloromethane / 16 h / 20 °C / Inert atmosphere 3: piperidine / N,N-dimethyl-formamide / 1 h / 20 °C 4: N,N-dimethyl-formamide / 3 h / 20 °C 5: piperidine / N,N-dimethyl-formamide / 1 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: sodium hydrogencarbonate / 1,2-dimethoxyethane; tetrahydrofuran / 16 h / 20 °C / Inert atmosphere 2: N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline / dichloromethane; methanol / 36 h / 20 °C / Darkness; Inert atmosphere 3: diethylamine / 1-methyl-pyrrolidin-2-one / 16 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 5 steps 1: sodium hydrogencarbonate / 1,2-dimethoxyethane; water / 24 h / 20 °C / Inert atmosphere 2: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 30 h / 20 °C / Darkness; Inert atmosphere 3: piperidine / N,N-dimethyl-formamide / 4 h / 20 °C / Inert atmosphere 4: N,N-dimethyl-formamide / 16 h / 20 °C / Inert atmosphere 5: diethylamine / 1-methyl-pyrrolidin-2-one / 16 h / 20 °C / Inert atmosphere View Scheme

(S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-5-ureidopentanoic acid → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline / methanol; dichloromethane / 16 h / 20 °C / Inert atmosphere 2: piperidine / N,N-dimethyl-formamide / 1 h / 20 °C 3: N,N-dimethyl-formamide / 3 h / 20 °C 4: piperidine / N,N-dimethyl-formamide / 1 h / 20 °C View Scheme
Multi-step reaction with 5 steps 1.1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / dichloromethane / 16 h / 20 °C 2.1: diethylamine / N,N-dimethyl-formamide / 1 h / 20 °C 3.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 1 h / 20 °C 3.2: 16 h / 20 °C 4.1: dichloromethane / 3 h / 20 °C 5.1: sodium hydroxide; water / 1,4-dioxane / 3 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: N-ethyl-N,N-diisopropylamine; HATU / dichloromethane / 16 h / 20 °C 2.1: diethylamine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C 3.1: HATU / N,N-dimethyl-formamide / 1 h / 20 °C 3.2: 16 h / 20 °C 4.1: trifluoroacetic acid / dichloromethane / 3 h / 20 °C 4.2: 3 h / 20 °C View Scheme

(9H-fluoren-9-yl)methyl (S)-(1-((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidopentan-2-yl)carbamate (870487-04-0) → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: piperidine / N,N-dimethyl-formamide / 1 h / 20 °C 2: N,N-dimethyl-formamide / 3 h / 20 °C 3: piperidine / N,N-dimethyl-formamide / 1 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: diethylamine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C 2.1: HATU / N,N-dimethyl-formamide / 1 h / 20 °C 2.2: 16 h / 20 °C 3.1: trifluoroacetic acid / dichloromethane / 3 h / 20 °C 3.2: 3 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: piperidine / N,N-dimethyl-formamide / 4 h / 20 °C / Inert atmosphere 2: N,N-dimethyl-formamide / 16 h / 20 °C / Inert atmosphere 3: diethylamine / 1-methyl-pyrrolidin-2-one / 16 h / 20 °C / Inert atmosphere View Scheme

4-((S)-2-((S)-2-amino-3-methylbutanamido)-5-ureidopentanamido)benzyl 2,2,2-trifluoroacetate → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1)

Conditions	Yield
With water; sodium hydroxide In 1,4-dioxane at 20℃; for 3h;

(S)-(9H-fluoren-9-yl)methyl(1-((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidopentan-2-yl)carbamate → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: diethylamine / N,N-dimethyl-formamide / 1 h / 20 °C 2.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 1 h / 20 °C 2.2: 16 h / 20 °C 3.1: dichloromethane / 3 h / 20 °C 4.1: sodium hydroxide; water / 1,4-dioxane / 3 h / 20 °C View Scheme

tert-butyl ((S)-1-(((S)-1-((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidopentane-2-yl)amino)-3-methyl-1-oxobutane-2-yl)carbamate (870487-09-5) → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: dichloromethane / 3 h / 20 °C 2: sodium hydroxide; water / 1,4-dioxane / 3 h / 20 °C View Scheme
Stage #1: tert-butyl ((S)-1-(((S)-1-((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidopentane-2-yl)amino)-3-methyl-1-oxobutane-2-yl)carbamate With trifluoroacetic acid In dichloromethane at 20℃; for 3h; Stage #2: With water; sodium hydroxide In 1,4-dioxane at 20℃; for 3h;
Stage #1: tert-butyl ((S)-1-(((S)-1-((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidopentane-2-yl)amino)-3-methyl-1-oxobutane-2-yl)carbamate With trifluoroacetic acid In dichloromethane at 20℃; for 3h; Stage #2: With water; sodium hydroxide In 1,4-dioxane at 20℃; for 3h;

tert-butyl ((S)-1-(((S)-1-((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidopentane-2-yl)amino)-3-methyl-1-oxobutane-2-yl)carbamate (870487-09-5) + trifluoroacetic acid (76-05-1) → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + 4-((S)-2-((S)-2-amino-3-methylbutanamido)-5-ureidopentanamido)benzyl 2,2,2-trifluoroacetate

Conditions	Yield
In dichloromethane at 20℃; for 3h;
In dichloromethane at 20℃; for 3h;

(S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-5-ureidopentanoic acid → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + 4-((S)-2-((S)-2-amino-3-methylbutanamido)-5-ureidopentanamido)benzyl 2,2,2-trifluoroacetate

Conditions	Yield
Multi-step reaction with 4 steps 1.1: N-ethyl-N,N-diisopropylamine; HATU / dichloromethane / 16 h / 20 °C 2.1: diethylamine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C 3.1: HATU / N,N-dimethyl-formamide / 1 h / 20 °C 3.2: 16 h / 20 °C 4.1: dichloromethane / 3 h / 20 °C View Scheme

4-aminobenzenemethanol (623-04-1) → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + 4-((S)-2-((S)-2-amino-3-methylbutanamido)-5-ureidopentanamido)benzyl 2,2,2-trifluoroacetate

Conditions	Yield
Multi-step reaction with 4 steps 1.1: N-ethyl-N,N-diisopropylamine; HATU / dichloromethane / 16 h / 20 °C 2.1: diethylamine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C 3.1: HATU / N,N-dimethyl-formamide / 1 h / 20 °C 3.2: 16 h / 20 °C 4.1: dichloromethane / 3 h / 20 °C View Scheme

(9H-fluoren-9-yl)methyl (S)-(1-((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidopentan-2-yl)carbamate (870487-04-0) → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + 4-((S)-2-((S)-2-amino-3-methylbutanamido)-5-ureidopentanamido)benzyl 2,2,2-trifluoroacetate

Conditions	Yield
Multi-step reaction with 3 steps 1.1: diethylamine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C 2.1: HATU / N,N-dimethyl-formamide / 1 h / 20 °C 2.2: 16 h / 20 °C 3.1: dichloromethane / 3 h / 20 °C View Scheme

(S)-2-amino-N-(4-(hydroxymethyl)phenyl)-5-ureidopentanamide (1037794-22-1) → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + 4-((S)-2-((S)-2-amino-3-methylbutanamido)-5-ureidopentanamido)benzyl 2,2,2-trifluoroacetate

Conditions	Yield
Multi-step reaction with 2 steps 1.1: HATU / N,N-dimethyl-formamide / 1 h / 20 °C 1.2: 16 h / 20 °C 2.1: dichloromethane / 3 h / 20 °C View Scheme

C18H28N4O5 → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrogenchloride / 1,4-dioxane / 2 h / 20 °C 2: N,N-dimethyl-formamide / 2 h / 30 °C 3: piperidine / N,N-dimethyl-formamide / 2 h / 30 °C View Scheme

2,5-dioxopyrrolidin-1-yl (2S)-2-(((benzyloxy)carbonyl)amino)-3-methylbutanoate (3496-11-5) → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: N,N-dimethyl-formamide / 5 h / 20 °C 2: hydrogen; palladium 10% on activated carbon / dichloromethane; methanol / 5 h / 20 °C View Scheme

C26H33N5O5 → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline / dichloromethane; methanol / 20 °C / Darkness 2: triethylamine / N,N-dimethyl-formamide / 24 h / 20 °C View Scheme

Nα-benzyloxy-carbonyl-L-citrulline (6692-89-3) → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.25 h / 20 °C 1.2: 48 h / 20 °C / Darkness 2.1: hydrogen; palladium 10% on activated carbon / dichloromethane; methanol / 5 h / 20 °C 3.1: N,N-dimethyl-formamide / 5 h / 20 °C 4.1: hydrogen; palladium 10% on activated carbon / dichloromethane; methanol / 5 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.25 h / 20 °C 1.2: 48 h / 20 °C / Darkness 2.1: hydrogen; palladium 10% on activated carbon / dichloromethane; methanol / 5 h / 20 °C 3.1: piperidine / N,N-dimethyl-formamide / 20 h / 20 °C 4.1: triethylamine / N,N-dimethyl-formamide / 24 h / 20 °C View Scheme

C21H26N4O5 → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrogen; palladium 10% on activated carbon / dichloromethane; methanol / 5 h / 20 °C 2: N,N-dimethyl-formamide / 5 h / 20 °C 3: hydrogen; palladium 10% on activated carbon / dichloromethane; methanol / 5 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: hydrogen; palladium 10% on activated carbon / dichloromethane; methanol / 5 h / 20 °C 2: piperidine / N,N-dimethyl-formamide / 20 h / 20 °C 3: triethylamine / N,N-dimethyl-formamide / 24 h / 20 °C View Scheme

N-Cbz-Val-Cit-4-aminobenzyl alcohol (159858-07-8) → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol; dichloromethane at 20℃; for 5h;

tert-butyl ((S)-1-(((S)-1-((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidopentane-2-yl)amino)-3-methyl-1-oxobutane-2-yl)carbamate (870487-09-5) → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + 4-((S)-2-((S)-2-amino-3-methylbutanamido)-5-ureidopentanamido)benzyl 2,2,2-trifluoroacetate

Conditions	Yield
With trifluoroacetic acid In dichloromethane at 20℃; for 3h;

L-valine (72-18-4) → (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: sodium hydrogencarbonate / water; 1,4-dioxane 1.2: 0 - 20 °C 2.1: dicyclohexyl-carbodiimide / tetrahydrofuran / 0 - 20 °C 3.1: sodium hydrogencarbonate / N,N-dimethyl-formamide; water; tetrahydrofuran / 20 °C 4.1: 1-bromo-2,3,4-tri-O-acetyl-α-D-glucuronic acid methyl ester / dichloromethane; methanol / 48 h / 20 °C / Darkness 5.1: diethylamine / N,N-dimethyl-formamide / 24 h View Scheme

6-maleimidohexanoic acid N-hydroxylsuccinimide ester (55750-63-5) + (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) → 6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-((S)-1-(((S)-1-((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidopentan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)hexanamide (159857-80-4)

Conditions	Yield
In 1-methyl-pyrrolidin-2-one for 24h; Heating;	100%
In 1-methyl-pyrrolidin-2-one at 20℃; for 24h;	100%
In N,N-dimethyl-formamide at 20 - 30℃;	97%

(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + 2-(2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethoxy)ethyl (4- nitrophenyl) carbonate → C27H38N6O9

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0℃; for 2h;	100%

(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + Phth-PEG4-OSu (1415328-95-8) → C37H52N6O12 (1415328-97-0)

Conditions	Yield
In N,N-dimethyl-formamide at 20℃;	98%
In N,N-dimethyl-formamide at 20℃;	98%
In N,N-dimethyl-formamide at 20℃;	98%

(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + C18H18N2O7 (1415328-88-9) → C32H42N6O8 (1415328-89-0)

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 24h;	98%

(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + C23H28N2O10 → C37H52N6O12 (1415328-97-0)

Conditions	Yield
In N,N-dimethyl-formamide at 20℃;	98%

(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + N-succinimidyl-6-maleimidohexanoate → 6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-((S)-1-(((S)-1-((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidopentan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)hexanamide (159857-80-4)

Conditions	Yield
In 1-methyl-pyrrolidin-2-one at 20℃; for 16h; Inert atmosphere;	98%

(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + N2-acetyl-N6-(tert-butyloxycarbonyl)-L-lysine (23500-04-1) → N2-acetyl-N6-(tert-butoxycarbonyl)-L-lysyl-L-valyl-N5-carbamoyl-N-[4-(hydroxymethyl)phenyl]-L-ornithinamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 0.5h;	97%
Stage #1: N2-acetyl-N6-(tert-butyloxycarbonyl)-L-lysine With HATU In N,N-dimethyl-formamide for 0.5h; Inert atmosphere; Cooling with ice; Stage #2: (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 2h; Inert atmosphere; Cooling with ice;	44%

(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + N2-acetyl-N6-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-lysine (148101-51-3) → N2-acetyl-N6-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-lysyl-L-valyl-N5-carbamoyl-N-[4-(hydroxymethyl)phenyl]-L-ornithinamide (1609108-48-6)

Conditions	Yield
With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 0 - 20℃; for 2h; Inert atmosphere;	95.6%

4-nitrophenyl 2-(2-(pyridin-2-yl)disulfanyl)ethyl carbonate (874302-76-8) + (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) → 2-(2-pyridyldisulfanyl)ethyl N-[(1S)-1-[[(1S)-1-[[4-(hydroxymethyl)phenyl]carbamoyl]-4-ureidobutyl]carbamoyl]-2-methylpropyl]carbamate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 16h; Inert atmosphere;	95.4%

(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + pentafluorophenyl 6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoate (692739-25-6) → 6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-((S)-1-(((S)-1-((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidopentan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)hexanamide (159857-80-4)

Conditions	Yield
In N,N-dimethyl-formamide at 20℃;	95%

N-Boc-6-aminohexanoic acid N-hydroxysuccinimide ester (51513-80-5) + (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) → Boc-Ahx-Val-Cit-PAB-OH

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;	94%

(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + 4-azidobutanoic acid (54447-68-6) → C22H34N8O5

Conditions	Yield
With N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline In N,N-dimethyl-formamide at 20℃; for 5h;	91%

(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + (1R,8S,9ξ)-bicyclo[6.1.0]non-4-yn-9-ylmethyl (4-nitrophenyl) carbonate → C29H41N5O6

Conditions	Yield
With 4-methyl-morpholine In N,N-dimethyl-formamide at 23℃; for 24h;	90%

(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + 4-(N-maleimidomethyl)cyclohexane-1-carboxylic acid N-succinimidyl ester (64987-85-5) → C30H42N6O7

Conditions	Yield
With N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline In N,N-dimethyl-formamide at 20℃;	89%

(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + 8-oxononanoic acid (25542-64-7) → 4-(N-(8-oxononanoyl)-L-valinyl-L-citrullinamido)benzyl alcohol

Conditions	Yield
Stage #1: 8-oxononanoic acid With 4-methyl-morpholine; isobutyl chloroformate In dichloromethane at 20℃; for 0.666667h; Cooling with ice; Stage #2: (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide In methanol; dichloromethane at 20℃;	88%

(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + C22H26N2O8 → C34H50N6O9

Conditions	Yield
With triethylamine for 18h;	88%

(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + 6-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}hexanoic acid (88574-06-5) → N-(6-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}hexanoyl)-L-valyl-N-5-carbamoyl-N-[4-(hydroxymethyl)phenyl]-L-ornithinamide (929259-98-3)

Conditions	Yield
Stage #1: 6-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}hexanoic acid With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 0.166667h; Stage #2: (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide In N,N-dimethyl-formamide for 15h;	82%
Stage #1: 6-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}hexanoic acid With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 0.166667h; Inert atmosphere; Stage #2: (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide In N,N-dimethyl-formamide at 20℃; for 15h; Inert atmosphere;

(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + 11-azido-3,6,9-trioxaundecanoic acid (172531-37-2) → C26H42N8O8

Conditions	Yield
With N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline In N,N-dimethyl-formamide at 20℃; Inert atmosphere;	82%

(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + N-acetyl-O-[1-(9H-fluoren-9-yl)-3-oxo-2,7,10,13,16,19-hexaoxa-4-azahenicosan-21-yl]-L-serine → N-acetyl-O-[1-(9H-fluoren-9-yl)-3-oxo-2,7,10,13,16,19-hexaoxa-4-azahenicosan-21-yl]-L-serylvalyl-N5-carbamoyl-N-[4-(hydroxymethyl)phenyl]-L-ornithinamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 2h; Cooling with ice;	80%

(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + 2,5-dioxopyrrolidin-1-yl 2,5,8,11,14,17,20,23,26,29,32,35,38,41,44,47,50,53,56,59,62,65,68,71-tetracosaoxatetraheptacontan-74-oate → C68H127N5O29

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 16h;	77%

(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + bis-(p-nitrophenyl) carbonate (5070-13-3) + C34H39N5O17S → C72H93N15O27S

Conditions	Yield
Stage #1: (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide; C34H39N5O17S With triethylamine In N,N-dimethyl-formamide for 3.5h; Stage #2: bis-(p-nitrophenyl) carbonate With triethylamine In N,N-dimethyl-formamide for 1.25h;	70%

(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + but-3-yn-1-yl (4-nitrophenyl) carbonate → but-3-yn-1-yl ((S)-1-(((S)-1-((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidopentan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)carbamate

Conditions	Yield
With 4-methyl-morpholine In N,N-dimethyl-formamide at 23℃; for 16h;	66%

(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + N2-benzoyl-N6-(tert-butoxycarbonyl)-L-lysine → N2-benzoyl-N6-(tert-butoxycarbonyl)-L-lysyl-L-valyl-N5-carbamoyl-N-[4-(hydroxymethyl)phenyl]-L-ornithinamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 16h;	63%

(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + C30H29NO8S2 → C48H56N6O11S2

Conditions	Yield
Stage #1: C30H29NO8S2 With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 0.333333h; Inert atmosphere; Stage #2: (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide In N,N-dimethyl-formamide at 20℃; Inert atmosphere;	62.2%

(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + 3,6,9,12,15-pentaoxaoctadec-17-ynoic acid (1429934-37-1) → C31H49N5O10

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 12h;	62%

(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + 2,5-dioxopyrrolidin-1-yl 4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzoate (64191-06-6) → C29H34N6O7

Conditions	Yield
With N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline In N,N-dimethyl-formamide at 20℃;	62%

(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide (159857-79-1) + 1-(4-{2-azatricyclo[10.4.0.04,9]hexadeca-1(12),4(9),5,7,13,15-hexane-10-yn-2-yl}-4-oxobutanamido)-3,6,9,12-tetraoxapentadecan-15-oic acid → 1-(4-{2-azatricyclo[10.4.0.04,9]hexadeca1(12),4(9),5,7,13,15-hexaen-10-yn-2-yl}-4-oxobutanamido)-N-[(1S)-1-{[(1S)-4-(carbamoylamino)-1-{[4-(hydroxymethyl)phenyl]carbamoyl}butyl]carbamoyl}-2-methylpropyl]-3,6,9,12-tetraoxapentadecan-15-amide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 3h;	60%
Stage #1: 1-(4-{2-azatricyclo[10.4.0.04,9]hexadeca-1(12),4(9),5,7,13,15-hexane-10-yn-2-yl}-4-oxobutanamido)-3,6,9,12-tetraoxapentadecan-15-oic 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 0.25h; Stage #2: (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide In N,N-dimethyl-formamide at 20℃; for 3h;	60%
Stage #1: 1-(4-{2-azatricyclo[10.4.0.04,9]hexadeca-1(12),4(9),5,7,13,15-hexane-10-yn-2-yl}-4-oxobutanamido)-3,6,9,12-tetraoxapentadecan-15-oic 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 0.25h; Stage #2: (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide In N,N-dimethyl-formamide at 20℃; for 3h;	60%
Stage #1: 1-(4-{2-azatricyclo[10.4.0.04,9]hexadeca-1(12),4(9),5,7,13,15-hexane-10-yn-2-yl}-4-oxobutanamido)-3,6,9,12-tetraoxapentadecan-15-oic 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 0.25h; Stage #2: (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-5-ureidopentanamide In N,N-dimethyl-formamide at 20℃; for 3h;	60%

Upstream product

• 72-18-4 L-valine 
• 870487-09-5 tert-butyl ((S)-1-(((S)-1-((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidopentane-2-yl)amino)-3-methyl-1-oxobutane-2-yl)carbamate 
• 870487-04-0 (S)-(9H-fluoren-9-yl)methyl (1-((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidopentan-2-yl)carbamate 
• 86060-87-9 Fmoc-Val-OPfp 
• 159858-07-8 N-Cbz-Val-Cit-4-aminobenzyl alcohol 
• 6692-89-3 N^α-benzyloxy-carbonyl-L-citrulline 
• 3496-11-5 2,5-dioxopyrrolidin-1-yl (2S)-2-(((benzyloxy)carbonyl)amino)-3-methylbutanoate 
• 1037794-22-1 (S)-2-amino-N-(4-(hydroxymethyl)phenyl)-5-ureidopentanamide 
• 623-04-1 4-aminobenzenemethanol 
• 133174-15-9 (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-5-ureidopentanoic acid 
• 76-05-1 trifluoroacetic acid 
• 372-75-8 Citrulline 
• 1037793-80-8 (S)-tert-butyl 1-(4-(hydroxymethyl)phenylamino)-1-oxo-5-ureidopentan-2-ylcarbamate 
• 159858-21-6 (S)-2-((S)-2-((((9H-fluoren-9-yl)-methoxy)carbonyl)amino)-3-methylbutanamido)-5-ureidopentanoic acid 

Downstream Products

• 1415328-97-0 C₃₇H₅₂N₆O₁₂ 
• 1611498-13-5 C₂₉H₄₂N₆O₁₁S₂ 
• 1611498-14-6 C₃₆H₄₅N₇O₁₅S₂ 
• 646502-53-6 4-((R)-2-((S)-2-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-methylbutanamido)-5-ureidopentanamido)benzyl ((2S)-1-(((2S)-1-(((4S,5S)-1-((S)-2-((1R,2R)-3-(((1S,2R)-1-hydroxy-1-phenylpropan-2-yl)amino)-1-methoxy-2-methyl-3-oxopropyl)pyrrolidin-1-yl)-3-methoxy-5-methyl-1-oxoheptan-4-yl)(methyl)amino)-3-methyl-1-oxobutan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)(methyl)carbamate 
• 1639351-92-0 N-((S)-1-(((S)-1-((4-(chloromethyl)phenyl)amino)-1-oxo-5-ureidopentan- 2-yl)amino)-3-methyl-1-oxobutan-2-yl)-6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamide 
• 159857-80-4 6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-((S)-1-(((S)-1-((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidopentan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)hexanamide 
• 1609108-48-6 N²-acetyl-N⁶-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-lysyl-L-valyl-N⁵-carbamoyl-N-[4-(hydroxymethyl)phenyl]-L-ornithinamide 
• 1609108-32-8 N-(6-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}hexanoyl)-L-valyl-N⁵-carbamoyl-N-(4-{[(tenahydropyridazin-1(2H)-ylcarbonyl)oxy]methyl}phenyl)-L-ornithinamide 
• 1609108-12-4 N-(6-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}hexanoyl)-L-valyl-N⁵-carbamoyl-N-[4-({[(2-methylhydrazinyl)carbonyl]oxy}methyl)phenyl]-L-ornithinamide trifluoroacetate 
• 1609108-10-2 N-(6-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}hexanoyl)-L-valyl-N-{4-[({[2-(tert-butoxycarbonyl)-2-methylhydrazinyl]carbonyl}oxy)methyl]phenyl}-N⁵-carbamoyl-L-ornithinamide 
• 1609108-05-5 N-(6-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}hexanoyl)-L-valyl-N-[4-({[(aminomethyl)carbamoyl]oxy}methyl)phenyl]-N⁵-carbamoyl-L-ornithinamide trifluoroacetate 

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CYCLIC DINUCLEOTIDE STING AGONISTS TETHERED TO A PD-1 OR CTLA-4 ANTIBODIES

Disclosed are antibody-drug conjugates and compositions thereof for the activation or induction of expression of a pattern recognition receptor (e.g., STING, RIG-I, MDA5), and methods of use thereof.

Synthesis, characterization, and targeted chemotherapy of SCT200-linker-monomethyl auristatin E conjugates

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Linker, Antibody-Drug Conjugate Including Same and Use Thereof

Provided are a linker represented by Formula I or I′, an antibody-drug conjugate containing the same, and use of thereof, a pharmaceutical composition comprising the antibody-drug conjugate, and use of the antibody-drug conjugate for treating and/or preventing a disease.