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Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

(S)-N-(5-(1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-4,6-dioxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)acetamide

+ [1]

Target

PDE4

Mechanism

PDE4 inhibitors(Phosphodieterase 4 inhibitors)

Therapeutic Areas

Immune System DiseasesCardiovascular DiseasesCongenital Disorders+ [7]

Active Indication

Plaque psoriasisBehcet SyndromeDermatitis, Atopic+ [4]

Inactive Indication-

Originator Organization

Tianjin Hemei Biological Technology Co.,Ltd.

Active Organization

Ganzhou Hemei Pharmaceutical Co Ltd

Hainan Hailing Chemipharma Corp. Ltd.

Inactive Organization

Tianjin Hemei Biological Technology Co.,Ltd.

Drug Highest PhaseNDA/BLA

First Approval Date-

RegulationSpecial Review Project (CN), Orphan Drug (US)

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Structure

Molecular FormulaC20H22N2O7S2

InChIKeyPRSNGWLHNWGOKD-CQSZACIVSA-N

CAS Registry1255909-03-5

Several pyrrole derivatives exhibit insecticidal activity and can be effective as grain protectants. In the present study, we evaluate the insecticidal efficacy of six novel pyrrole derivatives, namely methyl 3-(methylthio)-4,6-dioxo-5-phenyl-1,3a,4,5,6,6a-hexahydropyrrolo[3,4-c]pyrrole-1 carboxylate (compound syn) (2a-syn), methyl 3-(methylthio)-4,6-dioxo-5-phenyl-1,3a,4,5,6,6a-hexahydropyrrolo[3,4-c]pyrrole-1-carboxylate (compound anti) (2a-anti), methyl 3-(benzylthio)-4,6-dioxo-5-phenyl-1,3a,4,5,6,6a-hexahydropyrrolo[3,4-c]pyrrole-1-carboxylate (compound syn) (2f-syn), methyl 3-(benzylthio)-4,6-dioxo-5-phenyl-1,3a,4,5,6,6a-hexahydropyrrolo[3,4-c]pyrrole-1-carboxylate (compound anti) (2f-anti), methyl 3-(butylthio)-4,6-dioxo-5-phenyl-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrrole-1-carboxylate (3e), and methyl 2-benzyl-3-(methylthio)-4,6-dioxo-5-phenyl-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrrole-1-carboxylate (0665), against four important species infesting stored products, the rice weevil, Sitophilus oryzae (Coleoptera: Curculionidae), the lesser grain borer, Rhyzopertha dominica (Coleoptera: Bostrychidae), the confused flour beetle, Tribolium confusum (Coleoptera: Tenebrionidae), and the Mediterranean flour moth, Ephestia kuehniella (Lepidoptera: Pyralidae). The six pyrrole derivatives were evaluated on wheat at different doses (0.1, 1, and 10 ppm) and exposure intervals (7, 14, and 21 days). For S. oryzae adults, the highest mortality was recorded at 10 ppm of 2a-syn (36.7%) followed by 2f-syn (32.2%) and 2f-anti (27.8%) after 21 days of exposure. Regarding progeny production, the application of the six pyrrole derivatives significantly reduced offspring emergence if compared with the controls. After 21 days, mortality of R. dominica reached 50% testing 10 ppm of 2f-syn, followed by 2a-syn (46.7%), 2f-anti (41.1%), and 2a-anti (33.3%), while for 3e and 0665, mortality remained low, not exceeding 17.8%. Mortality of T. confusum adults was very low, ranging from 0 to 16.7% after 21 days of exposure. Progeny production was low (< 1.7 individuals per vial) for all doses of the tested pyrrole derivatives, including control vials. For 2a-syn, 2a-anti, 2f-anti, and 0665, no progeny production was recorded testing 1 and 10 ppm, while for 2f-syn and 3e, no offspring emergence was noted testing 10 ppm. For T. confusum larvae, after 21 days of exposure, mortality reached 62.2% testing 10 ppm of 3e followed by 0665 (55.6%) and 2a-anti (42.2%). For E. kuehniella larvae, mortality reached 57.8% at 10 ppm of 2a-syn, followed by the pyrrole derivative 2f-anti (43.3%) after 21 days of exposure. Overall, these results show that the efficacy of pyrrole derivatives strongly varied according to the exposure interval, tested dose, treated insect species and developmental instar. The tested pyrrole derivatives, with special reference to 2a-syn, 2a-anti, 2f-syn, 2f-anti and 0665, are slow-acting compounds exerting relevant toxicity on key stored-product pests over time. They can be considered further for assays with selected blends aiming to develop novel control tools against stored-product pests in real-world conditions.

01 Jun 2018·BioanalysisQ4 · MEDICINE

Determination of a PDE4 Inhibitor Hemay005 in Human Plasma and Urine by UPLC–MS/MS and its Application to a PK Study

Q4 · MEDICINE

Article

Author: Wang, Hongyun ; Hu, Pei ; Zeng, Guanghuai ; Jiang, Ji ; Liu, Xiuping ; Gao, Ying ; Chen, Rui ; Liu, Xuemei ; Zhang, Donglei

Aim: Hemay005 is a novel small-molecule inhibitor of phosphodiesterase-4 developed for the treatment of psoriasis. Measurement of Hemay005 in biological samples is critical for evaluation of its pharmacokinetics in clinical studies. Methodology & results: Plasma and urine samples were extracted and then chromatographed on an Acquity UPLC HSS T3 column with a gradient elution. Detection was performed on a Xevo TQ-S tandem mass spectrometer using negative ESI. Conclusion: For the first time, a sensitive and robust ultra-high performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was established and validated for the quantitative determination of Hemay005 in human plasma and urine, and it was successfully applied to evaluate the pharmacokinetics of Hemay005 in healthy subjects in a first-in-human study.

100 Deals associated with Mufemilast

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Plaque psoriasis	NDA/BLA	CN	Ganzhou Hemei Pharmaceutical Co Ltd	24 Apr 2024
Behcet Syndrome	Phase 3	CN	Ganzhou Hemei Pharmaceutical Co Ltd	16 Oct 2023
Dermatitis, Atopic	Phase 2	CN	Ganzhou Hemei Pharmaceutical Co Ltd	24 Nov 2022
Ulcerative colitis, active severe	Phase 2	CN	Ganzhou Hemei Pharmaceutical Co Ltd	08 Nov 2022
Ankylosing Spondylitis	Phase 2	CN	Ganzhou Hemei Pharmaceutical Co Ltd	05 Aug 2022
Psoriasis	Phase 1	-	Ganzhou Hemei Pharmaceutical Co Ltd	11 Oct 2024
Pulmonary Disease, Chronic Obstructive	IND Approval	CN	Ganzhou Hemei Pharmaceutical Co Ltd	30 Jun 2022

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


Phase II Clinical Study (ACR2023)	Phase 2	-	90	Hemay005 60 mg BID	(wpwfqrxmfp) = gxbchxggmm zgnewppxfw (tpdbjjgceu )	Positive	14 Nov 2023
ACR2023	Not Applicable	Plaque psoriasis	-	Hemay005	(cukybcuzno) = ocdgejxjbr nrmnbdyusb (dxhcbvfxfk )	-	13 Nov 2023
ACR2023	Not Applicable	Plaque psoriasis	-	Placebo	(cukybcuzno) = ukfwcmsziw nrmnbdyusb (dxhcbvfxfk )	-	13 Nov 2023