Remikiren - ≥95% , CAS No.126222-34-2

CAS: 126222-34-2 Cat. No.: R1050414 PubChem CID: 6324659

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

Specifiche e purezza

≥95%

Condizioni di conservazione di stoccaggio

Room temperature

Tipo di azione

INHIBITOR

Purezza

≥95%

Nomi e identificatori

Sorrisi canonici

CC(C)(C)S(=O)(=O)CC(CC1=CC=CC=C1)C(=O)NC(CC2=CN=CN2)C(=O)NC(CC3CCCCC3)C(C(C4CC4)O)O

IUPAC Name

(2S)-2-benzyl-3-tert-butylsulfonyl-N-[(2S)-1-[[(2S,3R,4S)-1-cyclohexyl-4-cyclopropyl-3,4-dihydroxybutan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]propanamide

InChIKey

UXIGZRQVLGFTOU-VQXQMPIVSA-N

INCHI

1S/C33H50N4O6S/c1-33(2,3)44(42,43)20-25(16-22-10-6-4-7-11-22)31(40)37-28(18-26-19-34-21-35-26)32(41)36-27(17-23-12-8-5-9-13-23)30(39)29(38)24-14-15-24/h4,6-7,10-11,19,21,23-25,27-30,38-39H,5,8-9,12-18,20H2,1-3H3,(H,34,35)(H,36,41)(H,37,40)/t25-,27+,28+,29+,30-/m1/s1

Isomeri SMILES

CC(C)(C)S(=O)(=O)C[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC2=CN=CN2)C(=O)N[C@@H](CC3CCCCC3)[C@H]([C@H](C4CC4)O)O

CAS alternativo

126222-34-2

PubChem CID

6324659

Termini MeSH

(S)-alpha-((S)-alpha-((t-butylsulfonyl)methyl)hydrocinnamamido)-N-((1S,2R,3S)-1-(cyclohexylmethyl)-3-cyclopropyl-2,3-dihydroxypropyl)imidazole-4-propionamide;remikiren;Ro 42-5892;Ro-42-5892

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic acids and derivatives
    • Classe Carboxylic acids and derivatives
      • Subclass Amino acids, peptides, and analogues
        • Level5 Amino acids and derivatives
          • Level6 Alpha amino acids and derivatives
            • Level7 Histidine and derivatives

• Kingdom: Organic compounds
• Superclass: Organic acids and derivatives
• Classe: Carboxylic acids and derivatives
• Subclass: Amino acids, peptides, and analogues
• Intermediate Tree Nodes: Amino acids and derivatives - Alpha amino acids and derivatives
• Direct Parent: Histidine and derivatives
• Alternative Parents: N-acyl-alpha amino acids and derivatives Alpha amino acid amides Benzene and substituted derivatives Fatty amides Sulfones Imidazoles Heteroaromatic compounds Secondary carboxylic acid amides Secondary alcohols 1,2-diols Azacyclic compounds Carbonyl compounds Hydrocarbon derivatives Organic oxides Organonitrogen compounds Organopnictogen compounds
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Histidine or derivatives - N-acyl-alpha amino acid or derivatives - Alpha-amino acid amide - Monocyclic benzene moiety - Fatty amide - Fatty acyl - Benzenoid - Azole - Imidazole - Heteroaromatic compound - Sulfone - Sulfonyl - 1,2-diol - Carboxamide group - Secondary alcohol - Secondary carboxylic acid amide - Azacycle - Organoheterocyclic compound - Organooxygen compound - Organonitrogen compound - Hydrocarbon derivative - Organic oxide - Alcohol - Carbonyl group - Organopnictogen compound - Organic oxygen compound - Organosulfur compound - Organic nitrogen compound - Aromatic heteromonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as histidine and derivatives. These are compounds containing cysteine or a derivative thereof resulting from reaction of cysteine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Proprietà chimiche e fisiche

• Peso molecolare: 630.800 g/mol
• XLogP3: 4.000
• Hydrogen Bond Donor Count: 5
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 16
• Exact Mass: 630.345 Da
• Monoisotopic Mass: 630.345 Da
• Topological Polar Surface Area: 170.000 Ų
• Heavy Atom Count: 44
• Formal Charge: 0
• Complexity: 1030.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 5
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1

Application Protocols

Validated application details are not provided for this item.

General guidance for biochemical assays (not item-specific)

• Enzyme inhibition assay (fluorometric):
  • Prepare a 10 mM DMSO stock; make serial dilutions in DMSO.
  • Dilute into assay buffer (e.g., 50 mM HEPES, pH 7.0, 150 mM NaCl, 0.01% Tween-20) to achieve a concentration range spanning expected IC50.
  • Preincubate inhibitor with recombinant human renin for 10–30 min at 25–37 °C.
  • Initiate with fluorogenic peptide substrate; monitor initial rates and fit dose–response to determine IC50.
• Orthogonal confirmation: perform LC–MS quantitation of product formation (Ang I peptide) in a parallel assay to rule out fluorescence artifacts.
• Controls: include solvent-only controls, a known orthogonal inhibitor, and substrate-only blanks.

Cell-based studies

• If explored, confirm cell permeability and assess cytotoxicity separately; maintain final DMSO ≤0.1–0.5% v/v when possible.

Note: These are general, literature-style procedures. Optimize all parameters for your system. No claims are made regarding performance in any specific biological model.

Biological Roles

General/biochemistry context (not clinical; literature-based)

• Primary biochemical role: competitive renin inhibitor. Renin is an aspartyl protease that catalyzes the rate-limiting cleavage of angiotensinogen to angiotensin I in the renin–angiotensin system (RAS).
• Mechanism motif: peptidomimetic transition-state analog (hydroxyethylene-type) that occupies the S1/S3 subsites and forms key hydrogen-bonding and hydrophobic contacts within the active site of renin.
• Pathway impact (research context): inhibition of renin reduces downstream formation of Ang I/II in cell-free or cellular models, enabling studies on blood pressure regulation pathways, aldosterone signaling, renal physiology, and feedback mechanisms in RAS without making therapeutic claims.
• Selectivity considerations: designed for high affinity to human renin; off-target profiling against related aspartyl proteases (e.g., pepsin, cathepsin D) is often conducted in the literature to confirm specificity.
• Tool compound use: serves as a positive control in assay development, target validation, and mechanistic studies involving RAS modulation.

Notes for experimentalists

• The presence of serum proteins can bind hydrophobic peptidomimetics; consider protein-free buffers for biochemical assays or determine free fraction if used in cell systems.
• pH sensitivity: renin exhibits activity in mildly acidic conditions; verify that the inhibitor remains stable and soluble in the chosen assay buffer across the working pH range.

Buffer Applications

Not a buffering reagent. This compound is a bioactive inhibitor used within buffered systems rather than as a buffer component.

Practical guidance (general; not item-specific)

• Common assay buffers for renin enzymology include HEPES or MES (pH ~6.0–7.5), supplemented with NaCl, a non-ionic detergent (e.g., 0.01–0.05% Tween-20) to reduce nonspecific binding, and BSA (low %) as needed.
• Maintain final DMSO concentration ≤1–2% v/v to minimize effects on enzyme kinetics.
• If precipitation occurs upon dilution, increase buffer ionic strength, include a small amount of co-solvent, or reduce stock concentration.

For exact buffer recipes and compatibility with your assay format, validate empirically and consult primary literature for renin assay conditions.

Green Alternatives

Context: As a specialized bioactive small molecule, remikiren itself does not have a “green alternative” in the sense of a reagent choice for a chemical transformation. However, you can improve the sustainability profile of the surrounding workflow.

Greener handling strategies (general; not item-specific)

• Solvent reduction: minimize DMSO volumes by preparing higher-concentration master stocks and accurate micro-aliquots to reduce waste.
• Alternative cosolvents: where feasible, use ethanol or isopropanol for intermediate dilutions; verify solubility and assay tolerance first.
• Micro-scale assays: employ microplate formats (384/1536-well) and acoustic dispensing to cut compound and solvent use.
• Energy use: dissolve at ambient temperature with sonication; avoid prolonged heating or repeated evaporation.

Comparison of common stock solvents (general)

• DMSO: excellent solvency and assay compatibility; disposal and worker exposure considerations apply.
• Ethanol/IPA: renewable feedstock options; lower toxicity; may have solubility limits for hydrophobic peptidomimetics.

Packaging and storage considerations

• Use amber, crimp-sealed vials with PTFE-lined caps to reduce evaporative losses and extend stock longevity, minimizing rework and waste.

Note: Selection of a different “compound” is not generally feasible for target-validated biochemical benchmarking; instead, optimize the experimental design to align with green chemistry principles.

Pharmaceutical Uses

Scope of this listing: For research use only. No medical, diagnostic, or therapeutic use is intended or implied.

Formulation/analytical context (general; not item-specific)

• Reference material: employed as a comparator compound in preformulation studies and LC–MS method development targeting renin inhibitors.
• Salt forms: peptidomimetic amines may be handled as free base or as pharmaceutically acceptable salts to improve solubility and stability; verify the form for this specific item on the CoA.
• Excipients for research formulations: aqueous cosolvent systems (e.g., DMSO/PEG400/saline) or cyclodextrin inclusion can be explored in non-clinical settings when solubility enhancement is needed.
• Stability studies: forced-degradation and pH/thermal stress testing can identify degradation pathways (e.g., amide hydrolysis, oxidation at sensitive positions) to inform handling and storage during research.

Regulatory references

• Pharmacopeial monographs are not generally available for legacy discovery compounds of this class. Use internal specifications and validated analytical methods for quality control in research settings.

Physical Properties

Item-specific specifications

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.

General/literature information for peptidomimetic renin inhibitors (not item-specific)

• Physical state: usually isolated as white to off-white solids (literature, representative renin inhibitors).
• Solubility profile: often sparingly soluble in water; typically soluble in polar aprotic organic solvents (e.g., DMSO) and mixed organic/aqueous systems with cosolvent (literature). Exact solubility must be established experimentally for this item.
• pKa: basic centers (tertiary/secondary amines) commonly exhibit pKa in the 7–10 range; amide/urea N–H may be weakly acidic (literature). Actual values depend on substituents.
• LogP/cLogP: renin inhibitors are designed with significant hydrophobic surface for S1/S3 binding; cLogP often in the moderate-to-high range (literature). Actual value is structure-dependent.
• Melting point (MP) / Boiling point (BP): Typically decompose or melt over a range; BP not generally meaningful for complex peptidomimetics (literature). Use DSC/TGA for thermal profiling if needed.
• Refractive index/density: Not typically reported for solid bioactives; determine empirically if required for formulation work.

Practical notes

• Prepare concentrated stock solutions in anhydrous DMSO; dilute into assay buffers immediately prior to use to avoid precipitation.
• Filter sterilization (0.22 µm PTFE) may be used for cell-free biochemical assays if required.

Quality and Grades

Item-specific quality

• Grade/purity: Not specified for this item; refer to CoA/Spec Sheet.
• Stabilizers/additives: Not specified for this item; refer to CoA/Spec Sheet.

Guidance on interpreting grade (general; not item-specific)

• Screening/compound library grade: Remikiren is commonly supplied for discovery biology, target validation, and SAR benchmarking. Such materials prioritize identity (NMR/HRMS), high purity by HPLC/UPLC, and documented potency provenance.
• Analytical reference standard: When used to qualify renin assays or LC–MS methods, reference-standard grade typically includes a high-purity threshold (e.g., ≥98% area by HPLC), residual solvent limits, and water content control. Exact thresholds are item-specific.
• Low-UV/LC grade solvents are recommended for chromatographic analysis of this compound to minimize baseline artifacts.

Documentation and testing

• Recommended characterization: 1H/13C NMR, HRMS or exact mass, HPLC/UPLC purity with peak identity confirmation, and, if relevant, chiral purity (e.g., chiral HPLC) because stereochemistry often influences activity.
• If your application is sensitive to trace metals, peroxides, or specific residual solvents, request the detailed CoA/Spec Sheet; unspecified impurity limits for this item: Not specified for this item; refer to CoA/Spec Sheet.

Note: Always confirm the exact grade, purity assay method, and impurity profile on the lot-specific CoA before use in quantitative studies.

Reaction and Applications

This product is primarily a bioactive tool compound rather than a synthetic reagent. Accordingly, its “applications” are centered on biochemical and discovery research workflows.

Typical research uses (non-clinical; literature guidance)

• Enzymology: reference inhibitor for human renin in biochemical assays to benchmark assay performance, confirm target engagement, or define IC50/Ki windows.
• Chemical biology: probe compound for dissecting renin-dependent signaling in cell-free or cellular models (with appropriate permeability/efflux considerations).
• SAR/comparator: used alongside other renin inhibitors in screening panels to contextualize potency and selectivity.
• Analytical: LC–MS retention-time marker and spectral reference in method development for RAS inhibitor quantitation.

Not typically used as a reagent in organic transformations

• Unlike simple building blocks or catalysts, remikiren is not commonly employed to forge bonds or mediate chemical reactions.

Practical notes

• Prepare concentrated DMSO stocks (e.g., 10 mM) and dilute into assay buffer immediately before use.
• Confirm absence of assay interference (e.g., fluorescence quenching, detergent interaction) when using spectroscopic or high-throughput readouts.
• Include solvent-only and orthogonal control inhibitors to validate target-specific effects.

Reaction Conditions

Not a catalytic or stoichiometric reagent for chemical synthesis; therefore, no standard “reaction conditions” apply in the synthetic sense.

Assay handling conditions (general; not item-specific)

• Stock preparation: dissolve in anhydrous DMSO (e.g., 10–50 mM), vortex and sonicate if needed. Avoid prolonged exposure to air and light.
• Working solutions: dilute into assay buffer to achieve desired concentrations spanning typical IC50 ranges reported for renin inhibitors; keep final DMSO ≤1–2% v/v.
• Temperature: conduct renin enzymatic assays at 25–37 °C depending on the protocol; equilibrate inhibitor and enzyme before substrate addition to ensure steady-state conditions.
• pH: renin activity often profiled near pH 6.0–7.0. Confirm inhibitor stability/solubility in this pH window.
• Incubation time: allow sufficient preincubation (e.g., 10–30 min) for tight-binding inhibitors before initiating the reaction with substrate.

Analytical quality control

• Purity check by HPLC/UPLC prior to critical experiments is recommended; monitor for degradation upon repeated freeze–thaw or long-term storage of solutions.

All numerical concentrations and conditions must be optimized for your specific assay; consult primary literature and validate experimentally.

Safety and Handling

Authoritative safety information must be taken from the item-specific SDS.

Item-specific hazard data

• GHS classification: Not specified for this item; refer to SDS.
• Signal word: Not specified for this item; refer to SDS.
• Hazard statements (H-phrases): Not specified for this item; refer to SDS.
• Pictograms: Not specified for this item; refer to SDS.

General laboratory safety guidance (for small-molecule peptidomimetics; not item-specific)

• PPE: lab coat, safety glasses, and appropriate nitrile gloves. Use a chemical fume hood when weighing solids, preparing stocks, or handling volatile solvents.
• Avoid inhalation of dust and contact with skin/eyes. Wash thoroughly after handling.
• Incompatibilities: strong oxidizing agents; avoid reactive acylating/alkylating reagents that could modify amide/amine functionalities.
• Hygroscopicity: many bioactive amine-containing solids are mildly hygroscopic—minimize atmospheric exposure and reseal promptly with desiccant.
• First aid overview: in case of skin/eye contact, rinse with water for at least 15 minutes; if inhaled, move to fresh air; if ingested, seek medical attention. Always follow SDS instructions.
• Spill response: contain and collect with inert absorbent; clean area with suitable solvent/detergent; dispose according to institutional and local regulations.

Waste disposal

• Collect organic solvent solutions and contaminated disposables in appropriate hazardous waste streams per local regulations and institutional EHS policies.

Solvent Selection

Applicability: Remikiren is a hydrophobic peptidomimetic; solvent selection focuses on preparing stable, clear stock solutions for biochemical assays or analytical workflows.

Item-specific solubility: Not specified for this item; refer to CoA/Spec Sheet.

General/literature guidance (not item-specific)

• Primary stock solvent: DMSO (anhydrous) is commonly used due to excellent solvating power for peptidomimetics and compatibility with biochemical assays at ≤1–2% v/v final.
• Alternative solvents: DMF, NMP, or ethanol can be used for intermediate stocks; final dilutions should be into buffered aqueous systems (e.g., HEPES, Tris, PBS) with attention to precipitation.
• Aqueous compatibility: Expect limited intrinsic water solubility. Use cosolvent strategies or cyclodextrin complexation if aqueous-only delivery is required.
• Filtration: If particulates persist, pass through a 0.22 µm PTFE or PVDF filter. Avoid nylon if the compound contains strongly basic centers that could bind to the membrane.

Quick comparison (general)

• DMSO: highest solvency; low volatility; excellent assay compatibility at low %.
• DMF/NMP: strong solvency; higher boiling point; consider toxicity/handling.
• Ethanol/IPA: greener, but may not fully solubilize at high concentrations.

Tips

• Warm gently (≤40 °C) and vortex/sonicate to assist dissolution. Avoid prolonged heating.
• Prepare aliquots to minimize freeze–thaw and moisture exposure.

Storage and Reconstitution

Item-specific storage/shipping

• Storage conditions: Room temperature (as provided in Product Data). If long-term storage is anticipated, many users prefer 2–8 °C in desiccated, light-protected containers to maximize stability; follow the label for this item.
• Shipped in: Not specified for this item; refer to CoA/Spec Sheet.

Solid handling

• Keep container tightly closed with desiccant. Minimize exposure to ambient humidity and light.
• Allow vial to equilibrate to room temperature before opening to prevent condensation.

Reconstitution (general; not item-specific)

• Recommended stock solvent: anhydrous DMSO.
• Typical stock concentrations: 10–50 mM, depending on solubility; verify clarity and absence of particulates.
• Sterile filtration: if needed for biochemical assays, filter through a 0.22 µm PTFE/PVDF membrane.

Aliquoting and stability

• Prepare single-use aliquots in amber vials or low-bind tubes to avoid repeated freeze–thaw cycles.
• Store DMSO stocks at −20 °C to 4 °C, protected from light. Inspect for precipitation or discoloration before use.

Specifications such as water content, residual solvents, or exact solubility: Not specified for this item; refer to CoA/Spec Sheet.

Research use only: This material is intended exclusively for laboratory research. No medical, diagnostic, or clinical use.

Structure and Identity

Brief overview: Remikiren is a small-molecule, peptidomimetic renin inhibitor frequently used as a biochemical tool compound in RAS (renin–angiotensin system) research.

Item-specific identifiers (from Product Data)

• CAS: 126222-34-2
• SKU: R1050414
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet. (Product Data contained an incomplete placeholder.)
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.

Literature/structure notes (general information; not item-specific)

• Compound type: nonpeptidic/peptidomimetic transition-state (hydroxyethylene-type) renin inhibitor.
• Key functional features: secondary alcohol (transition-state mimic), multiple amide/urea-type linkages, tertiary/secondary amines, and hydrophobic aryl/alkyl moieties designed to occupy S1/S3 pockets of human renin.
• Stereochemistry: multiple defined stereocenters are present in the pharmacophore; correct stereochemistry is essential for renin potency (literature).

2D structural description (conceptual)

• Central hydroxyethylene dipeptide isostere bearing a β-hydroxyl carbon adjacent to a secondary amine, flanked by:
  • A P1 side chain featuring a hydrophobic group (often aryl/alkyl) engaging the S1 pocket.
  • A P2/P3 region incorporating amide/urea-like linkages for hydrogen bonding with the active site.
  • A polar terminus (tertiary amine/amide) that improves solubility and modulates pKa.

Note: For definitive structural strings (SMILES/InChI) and exact formula/MW for this catalog item, please consult the CoA/Spec Sheet.

Synthetic Utility

This compound is not typically used as a building block or reagent in synthetic chemistry. It is the end product of a multistep synthesis aimed at optimizing renin binding, with limited value as a synthon.

General retrosynthetic/medicinal chemistry perspective (not item-specific)

• Pharmacophore: hydroxyethylene dipeptide isostere mimicking the tetrahedral intermediate of peptide bond hydrolysis by aspartyl proteases.
• Core transformations: construction of the secondary alcohol adjacent to an amine (via epoxide opening, asymmetric reduction, or hydroxyl-directed methods), amide/urea couplings, and stereocontrolled installation of hydrophobic side chains.
• Protection strategy: orthogonal N-protecting groups (e.g., Boc, Cbz) and selective activation for stepwise assembly of P1–P3 motifs are common.
• Stereochemical control: multiple chiral centers require enantioselective steps or chiral auxiliary/resolution strategies; chiral HPLC often used for final polishing.

Use in synthesis: As a finished inhibitor, remikiren is more appropriately used as a reference standard or comparator compound rather than as a reagent to facilitate bond-forming reactions.

Target Specificity

Item-specific target data: Not specified for this item; refer to CoA/Spec Sheet or application notes.

General literature context (not item-specific)

• Intended target class: human renin (EC 3.4.23.15), an aspartyl protease in the renin–angiotensin system.
• Mode of action: competitive occupation of the active site with a transition-state-like pharmacophore.
• Off-target assessment: renin inhibitors are commonly profiled against related aspartyl proteases (e.g., pepsin, cathepsin D, BACE1) to assess selectivity; specific Ki/IC50 values are compound- and assay-dependent and should be sourced from primary literature.

Note: For definitive potency/selectivity values for this specific catalog item and lot, consult the CoA or internal validation data.