ABT-199

Base Information

• Chemical Name: ABT-199
• CAS No.: 1257044-40-8
• Molecular Formula: C45H50ClN7O7S
• Molecular Weight: 868.454
• Mol file: 1257044-40-8.mol

Synonyms:Venetoclax

Chemical Property of ABT-199

Chemical Property:

• PKA: 4.09±0.10(Predicted)
• PSA: 183.09000
• Density: 1.340±0.06 g/cm3(Predicted)
• LogP: 10.73070
• Storage Temp.: -20°C Freezer
• Solubility.: DMSO (Slightly)

Purity/Quality:

>95% ^*data from raw suppliers

ABT199(Venetoclax) ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: ABT-199, also known as venetoclax, is a small, oral chemical molecule used for the treatment of chronic lymphocytic leukemia (CLL) associated with a specific chromosomal abnormality. As a second line treatment drug of CLL, ABT-199 take effects through acting as a BH3-mimetic and inhibitor of Bcl-2 (the anti-apoptotic B-cell lymphoma-2protein), further inducing apoptosis of CLL cells but not platelets. It also has the potential for the treatment of ER-positive breast cancer. Venetoclax, codeveloped by AbbVie (previously Abbott Laboratories) and Genentech/ Roche, was approved in the US for treatment of patients with chronic lymphocytic leukemia (CLL). To meet qualifications for venetoclax treatment, patients must have received prior therapy and possess the 17p deletion genetic mutation, as determined by USFDA testing. Venetoclax functions as a selective inhibitor of B cell lymphoma subtype 2 (BCL-2), which is often overexpressed on malignant cells and thus leads to impairment of the apoptotic pathway. Along these lines, the orally dosed small molecule drug restores the ability of malignant cells to undergo apoptosis as its mechanism of action.90 Although other BCL-2 inhibitors are known, development of similar agents such as navitoclox have been pursued and halted due to undesired inhibition of BCL-XL, leading to significant thrombocytopenia and demonstrating the need for more selective inhibitors. Venetoclax is also currently being considered for approval in Europe and Canada for similar indications and is in various stages of development for the treatment of non-Hodgkin lymphomas (NHL), acute myeloid leukemia (AML), multiple myeloma (MM), and several other disorders, either as a combination therapy or a stand-alone treatment.
• Uses: ABT 199 (>99%) is a potent and selective BCL-2 inhibitor that achieves potent antitumour activity while sparing platelets. It’s practical application is to treat chronic lymphocytic leukaemic cells and estrogen receptor-positive breast cancer.
• Clinical Use: Selective inhibitor of B-cell lymphoma protein: Treatment of chronic lymphocytic leukaemia
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: concentration possibly increased by ciprofloxacin, clarithromycin and erythromycin - reduce venetoclax dose; avoid with rifampicin. Anticoagulants: avoid with dabigatran; concentration of warfarin increased. Antidepressants: avoid with St John’s wort. Antiepileptics: concentration possibly reduced by carbamazepine, fosphenytoin and phenytoin - avoid. Antifungals: concentration possibly increased by fluconazole, itraconazole, ketoconazole, posaconazole and voriconazole - reduce venetoclax dose. Antipsychotics: increased risk of agranulocytosis with clozapine - avoid. Antivirals: concentration possibly reduced by efavirenz and etravirine - avoid; concentration possibly increased by ritonavir - reduce venetoclax dose. Bosentan: concentration of venetoclax possibly reduced by bosentan - avoid. Calcium channel blockers: concentration possibly increased by diltiazem and verapamil - reduce venetoclax dose. Cardiac glycosides: avoid with digoxin. Cytotoxics: avoid with everolimus. Grapefruit juice: avoid concomitant use. Modafinil: concentration of venetoclax possibly reduced - avoid. Sirolimus: avoid concomitant use. Vaccines: avoid with live vaccines.

Technology Process of ABT-199

There total 68 articles about ABT-199 which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 92.0%

C51H53ClN8O11S2 → 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide (1257044-40-8)

Guidance literature:

With caesium carbonate; In isopropyl alcohol; at 20 - 80 ℃;

Reference yield: 91.4%

3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)benzenesulfonamide (1228779-96-1) + [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) → 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide (1257044-40-8)

Guidance literature:

With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 20 ℃; for 3h; Reagent/catalyst; Temperature;

Reference yield: 90.0%

C52H56ClN7O9S2 → 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide (1257044-40-8)

Guidance literature:

With lithium hydroxide; In methanol; at 20 - 68 ℃;

upstream raw materials:

3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)benzenesulfonamide

[2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid]

4-tetrahydropyranmethylamine

4-fluoro-3-nitrobenzenesulfonamide

Downstream raw materials:

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide sulfate

Refernces

• 1、 -. "Anti-apoptosis protein Bcl - 2 inhibitor as well as preparation method and application thereof". Paragraph 0101-0102; 0106; 0110. . Retrieved 2021/09/29.
• 2、 -. "PROCESS FOR THE PREPARATION OF 4-(4-{[2-(4-CHLOROPHENYL)-4,4-DIMETHYLCYCLOHEX-1-EN-1- YL]METHYL}PIPERAZIN-1-YL)-N-({3-NITRO-4-[(TETRAHYDRO-2H-PYRAN-4-YLMETHYL)AMINO] PHENYL}SULFONYL)-2-(1H-PYRROLO[2,3-B]PYRIDIN-5-YLOXY)BENZAMIDE)". Page/Page column 32; 38. . Retrieved 2020/03/29.