November 2022 | Page 3 of 3 | Heterocyclic Building Blocks-Tetrahydroisoquinoline

Zhang, Yingjie’s team published research in Journal of Medicinal Chemistry in 54 | CAS: 142335-42-0

Journal of Medicinal Chemistry published new progress about 142335-42-0. 142335-42-0 belongs to tetrahydroisoquinoline, auxiliary class Tetrahydroisoquinoline,Chiral,Carboxylic acid,Amide,Alcohol, name is (S)-2-(tert-Butoxycarbonyl)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, and the molecular formula is C9H6FNO2, Formula: C15H19NO5.

Zhang, Yingjie published the artcileDiscovery of a Tetrahydroisoquinoline-Based Hydroxamic Acid Derivative (ZYJ-34c) as Histone Deacetylase Inhibitor with Potent Oral Antitumor Activities, Formula: C15H19NO5, the publication is Journal of Medicinal Chemistry (2011), 54(15), 5532-5539, database is CAplus and MEDLINE.

Histone deacetylase (HDAC) has emerged as an attractive target for the development of antitumor agents during the past decade. Previously tetrahydroisoquinoline-bearing hydroxamic acid analog, ZYJ-25e (1), was identified and validated as a potent histone deacetylase inhibitor (HDACi) with marked in vitro and in vivo antitumor potency. In the present study, further modification of 1 led to another more potent, orally active HDACi, ZYJ-34c (4). Compared to FDA-approved drug suberoylanilide hydroxamic acid (SAHA), compound 4 exhibited higher in vivo antitumor potency in a human breast carcinoma (MDA-MB-231) xenograft model and in a mouse hepatoma-22 (H22) pulmonary metastasis model and similar in vivo antitumor potency in a human colon tumor (HCT116) xenograft model.

Referemce:
https://en.wikipedia.org/wiki/Tetrahydroisoquinoline,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

Perez, Heidi L.’s team published research in Journal of Medicinal Chemistry in 58 | CAS: 142335-42-0

Perez, Heidi L. published the artcileDiscovery of Potent Heterodimeric Antagonists of Inhibitor of Apoptosis Proteins (IAPs) with Sustained Antitumor Activity, Application of (S)-2-(tert-Butoxycarbonyl)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, the publication is Journal of Medicinal Chemistry (2015), 58(3), 1556-1562, database is CAplus and MEDLINE.

The prominent role of IAPs in controlling cell death and their overexpression in a variety of cancers has prompted the development of IAP antagonists as potential antitumor therapies. The authors describe the identification of a series of heterodimeric antagonists with highly potent antiproliferative activities in cIAP- and XIAP-dependent cell lines. Compounds I (L = none) and I (L = NH) further demonstrate curative efficacy in human melanoma and lung cancer xenograft models and are promising candidates for advanced studies.

Referemce:
https://en.wikipedia.org/wiki/Tetrahydroisoquinoline,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

Li, Yangmei’s team published research in Journal of Medicinal Chemistry in 59 | CAS: 142335-42-0

Li, Yangmei published the artcilePotent μ-opioid receptor agonists from cyclic peptides Tyr-c[D-Lys-Xxx-Tyr-Gly]: Synthesis, biological, and structural evaluation, COA of Formula: C15H19NO5, the publication is Journal of Medicinal Chemistry (2016), 59(3), 1239-1245, database is CAplus and MEDLINE.

To optimize the structure of a μ-opioid receptor ligand, analogs H-Tyr-c[D-Lys-Xxx-Tyr-Gly] were synthesized and their biol. activity was tested. The analog containing a Phe³ was identified as not only exhibiting binding affinity 14-fold higher than the original hit but also producing agonist activity 3-fold more potent than morphine. NMR study suggested that a trans conformation at D-Lys²-Xxx³ is crucial for these cyclic peptides to maintain high affinity, selectivity, and functional activity toward the μ-opioid receptor.

Referemce:
https://en.wikipedia.org/wiki/Tetrahydroisoquinoline,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

Thomas, James B.’s team published research in Journal of Medicinal Chemistry in 46 | CAS: 142335-42-0

Thomas, James B. published the artcileIdentification of (3R)-7-Hydroxy-N-((1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)- 3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl)-1,2,3,4-tetrahydro- 3-isoquinolinecarboxamide as a Novel Potent and Selective Opioid κ Receptor Antagonist, Name: (S)-2-(tert-Butoxycarbonyl)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, the publication is Journal of Medicinal Chemistry (2003), 46(14), 3127-3137, database is CAplus and MEDLINE.

(3R)-7-Hydroxy-N-((1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide (JDTic) was identified as a potent and selective κ opioid receptor antagonist. Structure-activity relation (SAR) studies on JDTic analogs revealed that the 3R,4R stereochem. of the 3,4-dimethyl-4-(3-hydroxyphenyl)piperidine core structure, the 3R attachment of the 7-hydroxy-1,2,3,4-tetrahydroisoquinoline group, and the 1S configuration of the 2-methylpropyl (isopropyl) group were all important to its κ potency and selectivity. The results suggest that, like other κ opioid antagonists such as nor-BNI and GNTI, JDTic requires a second basic amino group to express potent and selective κ antagonist activity in the [³⁵S]GTPγS functional assay. However, unlike previously reported κ antagonists, JDTic also requires a second phenol group in rigid proximity to this second basic amino group. The potent and selective κ antagonist properties of JDTic can be rationalized using the “message-address” concept wherein the (3R,4R)-3,4-dimethyl-4-(hydroxyphenyl)piperidinyl group represents the message, and the basic amino and phenol group in the N substituent constitutes the address. It is interesting to note the structural commonality (an amino and phenol groups) in both the message and address components of JDTic. The unique structural features of JDTic will make this compound highly useful in further characterization of the κ receptor.

Referemce:
https://en.wikipedia.org/wiki/Tetrahydroisoquinoline,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem