Delving into the Latest Updates on AZD-5672 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

CCR5

Action

antagonists

Mechanism

CCR5 antagonists(C-C chemokine receptor type 5 antagonists)

Therapeutic Areas

Immune System DiseasesSkin and Musculoskeletal DiseasesUrogenital Diseases

Active Indication-

Inactive Indication

Renal InsufficiencyRheumatoid Arthritis

Originator Organization

AstraZeneca PLC

Active Organization-

Inactive Organization

AstraZeneca PLC

License Organization-

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC31H43F2N3O5S2

InChIKeyQOSMEMHKXNNIGG-SSEXGKCCSA-N

CAS Registry872879-86-2

The stereocontrolled C(sp³)-C(sp³) cross-coupling represents a considerable challenge of great contemporary interest. While this has been achieved through the reactions of boronate complexes with π-allyl iridium complexes, such reactions suffered from a limited substrate scope. We now report that following transmetalation from boronate complexes to organozinc reagents enables previously unreactive substrates to engage in stereocontrolled C(sp³)-C(sp³) cross-coupling. The broader substrate scope has enabled their application to the synthesis of biologically active molecules. The organozinc reagents react through a stereoinvertive coupling pathway with π-allyl iridium complexes, in contrast to reactions with other electrophiles that occur with retention of stereochemistry. The reaction uniquely combines the enantiospecific reactivity of an enantioenriched organometallic nucleophile with the enantioselective engagement of a racemic electrophile, enabling access to all stereoisomers.

09 Nov 2022·Journal of the American Chemical Society

Nickel-Catalyzed Enantioselective Reductive Conjugate Arylation and Heteroarylation via an Elementary Mechanism of 1,4-Addition

Article

Author: Zhao, Mengxin ; Zhang, Luoqiang ; Chen, Caiyou ; Zhou, Jingsong ; Chi, Yonggui Robin ; Ma, Zhaoming ; Pu, Maoping ; Wu, Yun-Dong ; Zhou, Jianrong Steve

A nickel complex of isoquinox promoted enantioselective conjugate arylation and heteroarylation of enones using aryl and heteroaryl halides directly. The reaction was successfully applied to stereoselective syntheses of ar-turmerone, chiral fragments of (+)-tolterodine and AZD5672. Mechanistically, experiments and calculations supported that an arylnickel(I) complex inserted to enones via an elementary 1,4-addition.

01 Jun 2018·Journal of Pharmacokinetics and PharmacodynamicsQ3 · MEDICINE

Assessing QT/QTc interval prolongation with concentration-QT modeling for Phase I studies: impact of computational platforms, model structures and confidence interval calculation methods

Q3 · MEDICINE

Article

Author: Lu, Jingtao ; Al-Huniti, Nidal ; Helmlinger, Gabriel ; Li, Jianguo

Modeling the relationship between drug concentrations and heart rate corrected QT interval (QTc) change from baseline (C-∆QTc), based on Phase I single ascending dose (SAD) or multiple ascending dose (MAD) studies, has been proposed as an alternative to thorough QT studies (TQT), in assessing drug-induced QT prolongation risk. The present analysis used clinical SAD, MAD and TQT study data of an experimental compound, AZD5672, to evaluate the performance of: (i) three computational platforms (linear mixed-effects modeling implemented via PROC MIXED in SAS, as well as in R using LME4 package and linear quantile mixed models (LQMM) implemented via LQMM package; (ii) different model structures with and without treatment- or time-specific intercepts; and (iii) three methods for calculating the confidence interval (CI) of QTc prolongation (analytical and bootstrap methods with fixed or varied geometric mean concentrations). We show that treatment- and time-specific intercepts may need to be included into C-∆QTc modeling through PROC MIXED or LME4, regardless of their statistical significance. With the intersection union test (IUT) in the TQT study as a reference for comparison, inclusion of these intercepts increased the feasibility for C-∆QTc modelling of SAD or MAD to reach the same conclusion as the IUT analysis based on TQT study. Compared to PROC MIXED or LME4, the LQMM method is less dependent on inclusion of treatment- or time-specific intercepts, and the bootstrap CI calculation methods provided higher likelihood for C-∆QTc modeling of SAD and MAD studies to reach the same conclusion as the IUT based on the TQT study.

100 Deals associated with AZD-5672

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11804

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Rheumatoid Arthritis	Phase 2	Italy	AstraZeneca PLC	01 Jul 2008
Rheumatoid Arthritis	Phase 2	Serbia	AstraZeneca PLC	01 Jul 2008
Rheumatoid Arthritis	Phase 2	Czechia	AstraZeneca PLC	01 Jul 2008
Rheumatoid Arthritis	Phase 2	Russia	AstraZeneca PLC	01 Jul 2008
Rheumatoid Arthritis	Phase 2	Slovakia	AstraZeneca PLC	01 Jul 2008
Rheumatoid Arthritis	Phase 2	South Africa	AstraZeneca PLC	01 Jul 2008
Rheumatoid Arthritis	Phase 2	Latvia	AstraZeneca PLC	01 Jul 2008
Rheumatoid Arthritis	Phase 2	Poland	AstraZeneca PLC	01 Jul 2008
Rheumatoid Arthritis	Phase 2	Ukraine	AstraZeneca PLC	01 Jul 2008
Rheumatoid Arthritis	Phase 2	Bulgaria	AstraZeneca PLC	01 Jul 2008

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00713544 (ESCAPE, CTgov)	Phase 2	Rheumatoid Arthritis	373	AZD5672 (AZD5672 20 mg)	vyyakxuufa(ipattmubbk) = qxdduhfwio upheelfvid (fvnfcmofob, vypmypeedi - yaqupewrdy) View more	-	03 Oct 2011
				AZD5672 (AZD5672 50 mg)	vyyakxuufa(ipattmubbk) = bziajvgsoe upheelfvid (fvnfcmofob, hirdcrpjii - bzedpbxrre) View more