Isakhiwo Se-Quinoxalinone Esihlukile Se-Kinase Inhibitors, Ama-HDAC Modulators, kanye Nemithi Eqondiswe ku-ALDH: I-Methyl 3-Oxo-3,4-dihydro-6-quinoxalinecarboxylate CAS# 357637-38-8

I-Methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate (CAS# 357637-38-8), eyaziwa nangokuthi i-methyl 3-oxo-3,4-dihydroquinoxaline-6-carboxylate, i-3,4-dihydro-3-oxo-6-quinoxalinecarboxylic acid methyl ester, noma i-methyl 3-oxo-4H-quinoxaline-6-carboxylate, iyi-heterobicyclic quinoxalinone ester enefomula yamangqamuzana i-C₁₀H₈N₂O₃ kanye nesisindo samangqamuzana esingu-204.18 g/mol. Isakhiwo sayo samangqamuzana sinesistimu yendandatho ye-benzene–pyrazine (quinoxaline) ehlanganisiwe eneqembu le-carbonyl le-3-oxo endandathweni ye-pyrazine kanye ne-6-carboxylate methyl ester endandathweni ye-benzene. Leli phethini elithile lokushintsha—ingqikithi ye-quinoxalinone enesibambo se-methyl ester endaweni yesi-6—inikeza inhlanganisela eyingqayizivele yezakhiwo ze-physicochemical kanye nokusetshenziswa kwe-synthetic okuhlukanisa kwezinye izinto eziseduze nayo zesakhiwo, okuyenza ibe yisisekelo esibalulekile kukhemistri yesimanje yemithi kanye nokuthuthukiswa kwemithi.

I-compound ithatha indawo ehlukile ye-physicochemical maqondana nezinto ezifanayo ngokwesakhiwo. Nge-LogP ebaliwe engu-1.13, icishe ibe ngamayunithi angu-0.5 e-log e-lipophilic kune-free carboxylic acid ehambisanayo (LogP ~0.62) futhi incane kancane e-lipophilic kune-non-oxo methyl quinoxaline-6-carboxylate (LogP ~1.27). Ukuba khona kwe-3-oxo carbonyl kwethula i-hydrogen-bonding pharmacophore eyengeziwe engekho ku-non-oxo analog, kuyilapho i-methyl ester ivumela i-chemoselective N-functionalization ngaphandle kokudinga izinyathelo zokuvikela ezengeziwe. Le nhlanganisela eyingqayizivele ye-lipophilicity elinganiselayo, i-dual carbonyl functionality, kanye ne-hydrogen-bond donor eyodwa (N–H) ibeka i-methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate njenge-intermediate eguquguqukayo yokwakha imitapo yolwazi yamakhompiyutha eqondiswe ku-kinase, evimbela i-HDAC, kanye ne-ALDH-modulating, njengoba kufakazelwa ukucashunwa kwayo okuthile emindenini yamalungelo obunikazi okwelapha eminingi.

I-compound ngokuvamile ivela njengeqiniso elikhazimulayo eline-density engu-1.4 ± 0.1 g/cm³ kanye ne-refractive index engu-1.63. Iyancibilika kuma-organic solvents ane-polarity elinganiselayo njenge-ethyl acetate ne-chloroform, kodwa inokuncibilika okulinganiselwe emanzini. I-compound ngokuvamile ihlinzekwa nge-purity engu-≥95% kuya ku-≥98% (HPLC) futhi kufanele igcinwe endaweni epholile, eyomile evikelwe ekukhanyeni nasezintweni ezinomswakama. Ngaphansi kwe-GHS, ayihlukaniswa njengezinto eziyingozi ngezinjongo zokuthutha, futhi ihloselwe ukusetshenziswa ocwaningweni nasekuthuthukisweni kuphela.

Isidingo semakethe se-methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate (CAS# 357637-38-8) sigxile emikhakheni emithathu eyinhloko: ucwaningo nokuthuthukiswa kwemithi nokutholakala kwezidakamizwa (cishe u-55–60% wokusetshenziswa komhlaba wonke), i-medicinal chemistry nokuthuthukiswa kwe-chemical probe (cishe u-25–30%), kanye ne-specialty chemical synthesis nesayensi yezinto (cishe u-10–15%). Isakhiwo sayo se-quinoxalinone esihlukile kanye nokusebenza kwayo okuguquguqukayo kwe-dual-carbonyl kuyizinto eziyinhloko ezishukumisa ukukhula kwesidingo okuqhubekayo.

Ekuhloleni nasekutholakaleni imithi, i-methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate iyisakhi esibalulekile sokwakhiwa kwemithi yokwelapha eqondiswe ezinhlobonhlobo zezifo. Le nhlanganisela isetshenzisiwe ngqo njenge-intermediate yokwenziwa noma ingxenye ye-scaffold emindenini yamalungelo obunikazi okungenani emithathu ehlukene eqondiswe kumaprotheni okwelapha angahlobene, okuhlanganisa nezinhlanganisela ze-heterocyclic njengezivimbeli ze-aldehyde dehydrogenase (ALDH) zomdlavuza, isifo sikashukela sohlobo 2, nomfutho wegazi ophakeme wemithambo yamaphaphu. I-scaffold ye-quinoxalinone iyisakhiwo esibalulekile kukhemistri yemithi, futhi izinto eziphuma kuyo zikhombisile amanani e-antiproliferative IC₅₀ angu-0.126 μM kumaseli e-HeLa, okugcizelela amandla e-scaffold ekutholakaleni kwemithi yomdlavuza. Ukusebenza kabili kwe-carbonyl kanye nendawo eyodwa yokunikela nge-hydrogen bond kuyenza ibe yi-intermediate eguquguqukayo yokwakha imitapo yezinhlanganisela eqondiswe ku-kinase, evimbela i-HDAC, kanye ne-ALDH-modulating. Umnyombo we-quinoxalinone uye waphenywa njenge-scaffold entsha yezivimbeli ze-EGFR (L858R/T790M/C797S) tyrosine kinase, izivimbeli ze-VEGFR-2 kinase, kanye nezivimbeli ze-JAK2/3, okukhombisa amanani e-IC₅₀ asezingeni eliphansi le-nanomolar ku-JAK2 (13.00 ± 1.31 nM) kanye ne-JAK3 (14.86 ± 1.29 nM). I-methyl ester endaweni yesi-6 yenza kube nokwenzeka ukwenziwa kwe-N-functionalization ngokukhetha i-chemoselective ngaphandle kwezinyathelo ezengeziwe zokuvikela, okuyinzuzo ebalulekile ekwenziweni kwe-analog ngendlela efanele kanye nezifundo zobudlelwano besakhiwo nomsebenzi (SAR).

Kwi-chemistry yemithi kanye nokuthuthukiswa kwezinto zokuhlola zamakhemikhali, i-methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate isebenza njengesisekelo se-quinoxalinone esihlukile sokwakha amalabhulali agxile ezinhlakeni eziphilayo ezinomsebenzi. Isimo salo muthi esiyingqayizivele somzimba—i-lipophilicity elinganiselayo (LogP 1.13) kanye ne-hydrogen-bond donor eyodwa—isekela ukuhlolwa kwezici ezifana nemithi, okwenza kube yigugu ekuthuthukisweni kwe-lead kanye nokubikezelwa kwe-pharmacokinetic. Uhlelo lwendandatho ye-quinoxaline lwaziwa ngemisebenzi yalo ehlukahlukene yezinto eziphilayo, okuhlanganisa izinto ezilwa namagciwane, ezilwa namagciwane ezingamagciwane, ezilwa nomdlavuza, kanye nezilwa nokuvuvukala, okwenza le nhlanganisela ibe yisiqalo esiguquguqukayo sokuthuthukisa imithi yokwelapha umdlavuza, isifo sofuba, kanye ne-malaria. Le nhlanganisela isetshenziswa njengento yokuhlola ye-biochemical ukufunda izindlela zezinto eziphilayo ezihlobene ne-quinoxalinone, futhi umgogodla wayo oqinile we-bicyclic unikeza ukuhlangana okuhle kakhulu kokubopha okuqondiwe kanye nezici ze-pharmacokinetic.

Kuma-specialty chemical synthesis kanye nesayensi yezinto ezibonakalayo, i-methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate isetshenziswa njenge-intermediate ebalulekile yokwenziwa kwezinto ezisebenzayo. Umongo we-quinoxaline wale nhlanganisela unikeza uhlelo lwe-aromatic oluhlangene olungasetshenziswa ukwenza izinto eziphilayo ezinempawu ze-optoelectronic, okwenza kube yigugu ekuthuthukiseni izinto ezintsha ezisebenzayo ze-organic electronics kanye nezinhlelo zokusebenza ze-sensor. Isibambi se-methyl ester sivumela ukuqhubeka nokuguqulwa nge-hydrolysis kuya ku-carboxylic acid ehambisanayo, engabe isetshenziselwa ukwakha izinhlanganisela eziyinkimbinkimbi eziqukethe i-quinoxaline.

I-Methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate (CAS# 357637-38-8) iyi-quinoxalinone ester ehlukile enenani elisuselwa ekusabeleni okuhlukile kwe-3-oxo carbonyl, i-6-methyl ester, kanye ne-N–H functionalities.

Amapharamitha abalulekile e-physicochemical afaka:

I-mvelo yokwenza kwale nhlanganisela ichazwa izibambo zayo ezintathu ezimile ngendlela ehlukene: iqembu le-3-oxo carbonyl elisesiyingini se-pyrazine livumela ukuhlanganiswa kwe-nucleophilic, ukujiyiswa, kanye nokwenza umjikelezo; iqembu le-6-methyl ester livumela ukuhlakazwa emanzini libe i-carboxylic acid ehambisanayo, ukushintshaniswa kwe-ester, kanye nokwenziwa kwe-amide; kanti iqembu le-N–H elisesikhundleni sesi-4 livumela i-N-alkylation, i-N-acylation, kanye ne-N-functionalization. Iqembu le-3-oxo lethula i-pharmacophore eyengeziwe yokuxhumana nge-hydrogen bond esiza ukusebenzisana nezinhloso zebhayoloji, kuyilapho i-methyl ester ithuthukisa ukuncibilika nokwenza izinto ukuze kwenziwe okunye ukuguqulwa. Le nhlanganisela ingenza izinhlobo ezahlukene zokwenza kwamakhemikhali ezihlanganisa i-oxidation, i-reduction (yeqembu le-keto ukuze kutholakale izinto ezisuselwa kwi-alcohol kusetshenziswa i-sodium borohydride), kanye nokushintshwa kwe-electrophilic ezindaweni ezahlukene esiyingini se-quinoxaline.

Ukuhlanganiswa kwe-methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate kungenziwa ngezindlela eziningana zokuhlanganisa. Indlela evamile ihilela ukusabela kwe-o-phenylenediamine ne-diethyl oxalate noma amanye ama-reagents afanayo ukwakha iringi ye-quinoxaline, kulandele ukusabela okulandelayo ukwethula iqembu le-keto endaweni yesi-3 kanye neqembu le-carboxylate endaweni yesi-6. Ezinye izindlela zihlanganisa i-hydrazinolysis ye-ethyl 4-methyl-3-oxo-3,4-dihydroquinoxaline-2-carboxylate ukukhiqiza i-4-methyl-3-oxo-3,4-dihydroquinoxaline-2-carbohydrazide njenge-intermediate, kulandele ukuhlanganiswa nama-methyl esters noma ama-aldehydes ukwethula iqembu le-6-carboxylate. Izimo zokusabela ezijwayelekile zihlanganisa i-reflux kuma-solvents afana ne-ethanol noma i-acetic acid, nama-catalysts afana ne-sulfuric acid asetshenziselwa ukusiza i-cyclization.

Uhlelo lokuhlinzeka lomhlaba wonke lwe-methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate (CAS# 357637-38-8) lunephethini elithi “abakhiqizi bezakhiwo eziyingqayizivele ze-heterocyclic, abasabalalisi bamakhemikhali ocwaningo bamazwe ngamazwe, kanye nabakhiqizi baseShayina abasebenza ezigabeni ezihlukene zemakethe.” Njengoba iyisisekelo se-quinoxalinone esikhethekile hhayi impahla yobuningi, imakethe ibonakala ngenani elilinganiselwe labahlinzeki abasebenza ocwaningweni lwezidakamizwa, i-medicinal chemistry, kanye nocwaningo lwezemfundo.

Ezingxenyeni zocwaningo lomhlaba wonke kanye nezinga lokuhlanzeka okuphezulu, abahlinzeki abakhulu bamazwe ngamazwe bahlanganisa i-AK Scientific (AKSci), enikeza le nhlanganisela ngezinga lokuhlanzeka elingu-95% ngaphansi kwekhodi yomkhiqizo engu-8913DT, enokugcinwa isikhathi eside endaweni epholile neyomile, ukuhlukaniswa kwe-DOT/IATA njengempahla engenabungozi, futhi yonke imikhiqizo igcinwa futhi ithunyelwa isuka e-SF Bay Area, California, e-USA. I-ChemScene inikeza le nhlanganisela ngezinga lokuhlanzeka elingu-≥98% ngaphansi kwenombolo yekhathalogi engu-CS-0620904. I-BenchChem inikeza le nhlanganisela ngaphansi kwenombolo yekhathalogi engu-B13113600 ngezilinganiso ezijwayelekile zokupakisha ezingama-10 mg, 50 mg, 100 mg, kanye nokupakisha okukhulu ngokwezifiso, ngokutholakala okukhona kanye nokwenziwa ngokwezifiso okutholakalayo uma kuceliwe. I-EvitaChem inikeza le nhlanganisela ngaphansi kwenombolo yekhathalogi engu-EVT-13247924 yokusetshenziswa ocwaningweni olungelona olwabantu kuphela. I-VulcanChem inikeza le nhlanganisela ngaphansi kwenombolo yekhathalogi engu-VC17572026. I-CalpacLab inikeza le nhlanganisela ngezinga lokuhlanzeka elingu-95% ngaphansi kwe-CAS 357637-38-8 nokupakisha okungama-250 mg. I-CymitQuimica inikeza le nhlanganisela ngaphansi kwe-CAS 357637-38-8. Laba bahlinzeki bakhonza imiphakathi yezemithi, i-biotechnology, kanye nocwaningo lwezemfundo ngemikhiqizo ehlangabezana nezimfuneko eziqinile zekhwalithi.

Ezingxenyeni zezimboni nasekukhiqizeni okukhulu, i-XinChem ingumkhiqizi nomhlinzeki othembekile we-methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate yekhwalithi ephezulu evela e-China, enikeza le nhlanganisela ngamazinga ekhwalithi aqinile ukuze isetshenziswe ocwaningweni nasekuthuthukisweni kwemithi, ekutholakaleni kwe-kinase inhibitor, nasekusetshenzisweni kwekhemistri yemithi. I-XinChem inikeza le nhlanganisela ngemibhalo yekhwalithi ephelele, izitifiketi zokuhlaziya (COA) eziqondene neqoqo ngalinye, ukupakishwa okungashintshwa, kanye nokukhiqizwa okuhambisana ne-REACH, ISO 9001, kanye ne-GMP emhlabeni wonke. Inkampani igcizelela ukuthi i-methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate iyisakhi esibalulekile ekuhlanganiseni kwamakhemikhali emithi futhi iyinto eluhliziwe ebalulekile yokwakha izinto ezisuselwa ku-quinoxaline ezinomsebenzi webhayoloji ongaba khona, okubaluleke kakhulu ekuthuthukisweni kwemithi emisha yokwelapha izifo ezithile. I-XinChem inikeza le nhlanganisela ngamazinga ahlukene okuhlanzeka (ngokuvamile 95–99%) kanye nezinketho zokupakisha—kusuka ku-100 mg kuya kumanani amaningi amagremu—isebenzela izimakethe zasekhaya nezokuthumela kwelinye izwe.

Imakethe yomhlaba wonke ye-methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate ibonisa izici zesifunda ezihlukile, ngokukhiqiza okugxile e-Asia-Pacific (ikakhulukazi eShayina) nokusetshenziswa okusatshalaliswa eNyakatho Melika, eYurophu, nasezifundeni zase-Asia-Pacific, kuhambisana nezimboni zezidakamizwa, i-biotechnology, kanye nocwaningo lwezemfundo kulezi zifunda.

Isifunda sase-Asia-Pacific sesivele saba yisizinda esibalulekile sokukhiqiza i-methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate, kanti i-China inabakhiqizi nabahlinzeki abaningi abafaka phakathi i-XinChem. Izinzuzo zokuncintisana zalesi sifunda zifaka izindleko eziphansi zokukhiqiza, ingqalasizinda yamakhemikhali eseyakhiwe, kanye nokuba seduze nezimboni zomuthi ne-biotechnology ezikhula ngokushesha. I-XinChem ihlinzeka ngalesi sakhi ngamazinga ahlukene okuhlanzeka (ngokuvamile angu-95–99%) kanye nezinketho zokupakisha, isebenzela izimakethe zasekhaya nezokuthumela kwamanye amazwe. Imikhakha ekhulayo yocwaningo nokuthuthukiswa kwemithi, ukutholakala kwama-kinase inhibitor, kanye nekhemistri yemithi e-China, e-India, e-Japan nase-South Korea iyaqhubeka nokuqhuba ukukhula kokusetshenziswa kwesifunda. Lesi sakhi sihlukaniswa njenge-pharmaceutical intermediate kanye ne-organic synthesis intermediate emakethe yaseChina, kanti abahlinzeki abaningi banikela ngomkhiqizo ngosayizi wokupakisha osukela ku-100 mg kuya ku-5 g.

INorth America ihlala iyimakethe ebalulekile ye-high-purity kanye ne-research-grade methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate, eqhutshwa yisidingo esivela embonini yezemithi, izinkampani ze-biotechnology, kanye nezikhungo zocwaningo zemfundo. I-United States inezinhlangano eziningi zocwaningo, izinkampani zezemithi, kanye nezinhlangano zocwaningo ezinkontileka ezidinga ama-quinoxalinone scaffolds ekhwalithi ephezulu okutholakala kwe-kinase inhibitor, ukuthuthukiswa kwe-HDAC modulator, kanye nemithi eqondiswe ku-ALDH. I-AK Scientific, i-BenchChem, i-ChemScene, kanye ne-EvitaChem zisebenzela imakethe yaseNyakatho Melika ngamanethiwekhi okusabalalisa abanzi. Uhlaka lwemithetho olusungulwe kahle lwalesi sifunda, okuhlanganisa nokuqondisa kwe-FDA kucwaningo nokuthuthukiswa kwezemithi, lusekela isidingo samakhemikhali ocwaningo asezingeni eliphezulu kanye nama-pharmaceutical intermediates.

IYurophu ibonakala ngezimfuneko eziqinile zokulawula, kuhlanganise nokubhaliswa kwe-REACH, kanye nokugxila okunamandla ekhwalithini nasekusimameni ocwaningweni lwemithi namakhemikhali. Izinkampani zemithi zaseYurophu, amalabhorethri ekhemistri yemithi, kanye nezikhungo zocwaningo zidinga izingqamuzana ezingqubuzanayo ze-heterocyclic ezinobumsulwa obuphezulu ezinemibhalo ephelele. I-CymitQuimica isebenzela imakethe yaseYurophu ngokutholakala kwesitoko. Le nhlanganisela ihloselwe ukusetshenziswa ocwaningweni nasekuthuthukisweni kuphela, hhayi ukwelashwa noma ukusetshenziswa kwezilwane.

Njenge-heterocyclic ester kanye ne-pharmaceutical intermediate, i-methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate (CAS# 357637-38-8) ingaphansi kokugadwa kwezomthetho emnothweni omkhulu womhlaba. Ukuhambisana nemithetho efanele kubalulekile ukuze kufinyelelwe emakethe nasekuhwebeni.

I-Methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate ayihlukaniswa njengempahla eyingozi ngezinjongo zokuthutha ze-DOT/IATA. Le nhlanganisela ihloselwe ukusetshenziswa ocwaningweni nentuthuko kuphela futhi ayihloselwe ukusetshenziswa kwezokwelapha, ukudla, izimonyo, noma izinto zabathengi ngaphandle uma kushiwo ngokusobala okunye. Izindlela ezijwayelekile zokuphepha zaselabhorethri kufanele zilandelwe ngesikhathi sokuphatha, okuhlanganisa ukusetshenziswa kwezinto ezifanele zokuzivikela komuntu siqu ezifana namagilavu aselabhorethri, izibuko zokuphepha, nejazi laselabhorethri. Imisebenzi kufanele yenziwe endaweni enomoya ohamba kahle.

I-methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate kufanele igcinwe isikhathi eside endaweni epholile, eyomile, ivikelwe ekukhanyeni nasezintweni ezinomswakama. Inhlanganisela izinzile ngaphansi kwezimo zokugcinwa ezinconywayo kodwa kufanele igcinwe kude nezinto eziqhumayo ezinamandla nezisekelo.

E-European Union, i-compound kufanele ihambisane nezidingo zokubhaliswa kwe-REACH zokungeniswa nokusetshenziswa. Abakhiqizi nabahlinzeki kufanele banikeze ama-Safety Data Sheets (SDS) aphelele futhi bagcine imibhalo efanele. E-United States, i-methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate ihloselwe ukusetshenziswa ocwaningweni nentuthuko kuphela futhi ayihloselwe ukwelashwa, ukudla, izimonyo, noma ukusetshenziswa kwabathengi ngaphandle uma kushiwo ngokusobala ngenye indlela. Ezinhlelweni zokusetshenziswa kwe-pharmaceutical intermediate, abakhiqizi kufanele bahambisane nemithetho efanele ye-FDA kanye namazinga ekhwalithi. I-compound ayisona isidakamizwa esilawulwayo.

I-Methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate ayihlukaniswa njengento eyingozi ngezinjongo zokuthutha ze-DOT/IATA. Ukupakishwa okufanele, ukulebula, kanye nemibhalo kusadingeka ukuthumela kwamanye amazwe. Ikhodi ye-HS yale nhlanganisela yi-2933990090 (izinhlanganisela ze-heterocyclic ezinama-nitrogen hetero-atom kuphela).

Umbono wemakethe we-methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate muhle, usekelwa izinto ezimbalwa ezibalulekile zokukhula kuzo zonke izigaba zayo eziyinhloko zokusetshenziswa. Nakuba le nhlanganisela iseyisisekelo se-quinoxalinone esikhethekile, iphrofayili yayo ehlukile ye-physicochemical kanye nendima yayo ebalulekile ekuthuthukisweni kwe-kinase inhibitor, i-HDAC modulator, kanye ne-ALDH-targeted therapeutic kuyibeka ekukhuleni okuqhubekayo eminyakeni ezayo.

Izinto ezibalulekile zokukhula zihlanganisa:

Ukuthuthukiswa okuqhubekayo kwama-kinase inhibitors e-oncology, ukuvuvukala, kanye nezifo ze-autoimmune kuqhubeka nokudala isidingo sama-privileged quinoxalinone scaffolds avumela ukuhlanganiswa okusheshayo kwama-analog kanye nokuhlolwa kwe-SAR. Ukusetshenziswa okubonisiwe kwale nhlanganisela kuma-EGFR, VEGFR-2, kanye nokuthuthukiswa kwe-JAK2/3 inhibitor kusekela isidingo esiqhubekayo esivela ezinhlelweni zokutholakala kwezidakamizwa ze-oncology kanye ne-immunology.

Ukwanda kwesithakazelo kuma-ALDH inhibitors kumdlavuza, isifo sikashukela sohlobo 2, kanye ne-pulmonary arterial hypertension kudala isidingo se-methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate njengesixazululo esibalulekile sama-heterocyclic ALDH inhibitors. Ukucashunwa okukhethekile kwale nhlanganisela emindenini yamalungelo obunikazi e-ALDH inhibitor kuyibeka phambili kule ndawo yezokwelapha esafufusa.

Ukugcizelelwa okukhulayo kwezokwelapha nge-epigenetic kanye nezivimbeli ze-HDAC kuholela ekufunweni kwama-scaffolds asuselwa ku-quinoxalinone angasebenza ngempumelelo ukuze enzelwe ama-HDAC-targeted compound libraries.

Ukuqashelwa okukhulayo kwe-quinoxalinone scaffold njengesakhiwo esibalulekile kumakhemistri yemithi kuholela ekufunweni kwe-methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate njenge-building block ehlukile engenakushintshwa i-free acid noma i-non-oxo analog ngaphandle kokwethula izinto ezingabalekeki ekuqageleni kwe-pharmacokinetic nasekusetshenzisweni kwe-synthetic.

Ukutshalwa kwezimali okukhulayo ekutholakaleni kwezidakamizwa nasekukhiqizweni kwe-API e-China nase-India kusekela isidingo sama-heterocyclic building blocks asezingeni eliphezulu kanye nama-pharmaceutical intermediates.

Izinselelo nokucatshangelwa:

Njenge-scaffold ekhethekile ye-quinoxalinone, imakethe ye-methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate incane kunaleyo yamakhemikhali ajwayelekile.

Imakethe ibhekene nokuncintisana okuvela kwezinye izinto eziphuma ku-quinoxalinone kanye nezingqimba zokwakha ezi-heterocyclic ezinamaphrofayili okusabela afanayo.

Abanye abahlinzeki bafake le nhlanganisela ohlwini lwezinto eziyekiwe, okungase kudale izinselele zochungechunge lokuhlinzeka ezinhlelweni zocwaningo nentuthuko.

Imithetho yezemithi namakhemikhali eqinisa kakhulu ingase idinge ukutshalwa kwezimali okuqhubekayo ezinhlelweni zekhwalithi kanye nemibhalo.

Ukuze baphumelele kule makethe eshintshayo, abahlinzeki kufanele bagxile ekhwalithini yomkhiqizo (ikakhulukazi ukuhlanzeka nokungaguquguquki phakathi kwamaqoqo), ukuthembeka kochungechunge lokuhlinzeka, ukuhambisana nemithetho, kanye nokuhlinzeka ngosebenza ngokushesha. Izinkampani ezinganikela ngemikhiqizo ehlanzekile kakhulu, izinketho zokupakisha eziguquguqukayo, kanye nokwesekwa kwezobuchwepheshe kwezinhlelo zemithi, ikhemistri yemithi, kanye nokutholakala kwezidakamizwa zizoba sesimweni esihle sokuthola isidingo esikhulayo.

I-Shanghai XinChem Co., Ltd. (XinChem) ingumhlinzeki ohamba phambili emhlabeni wamakhemikhali e-organic kanye nezingqamuzana ze-heterocyclic. Inkampani izinikele ekuhlangabezaneni nezidingo ezintsha zezimboni zemithi, i-biotechnology, kanye namakhemikhali acolekile. Ngokusebenzisa ulwazi olubanzi kanye namakhono okukhiqiza athuthukile, i-XinChem ihlinzeka nge-Methyl 3-Oxo-3,4-dihydro-6-quinoxalinecarboxylate (CAS# 357637-38-8) yekhwalithi ephezulu kumakhasimende emhlabeni wonke.

Njengomkhiqizi nomhlinzeki othembekile ozinze eChina, i-XinChem ihlanganisa izintengo eziqhudelanayo, ukuhlinzeka okuthembekile, kanye nesevisi ekhethekile ukuze izimise njengomlingani okhethwayo wezinkampani zemithi, abacwaningi bemithi yamakhemikhali, kanye nezikhungo zokutholakala kwezidakamizwa ezifuna lesi sakhiwo se-quinoxalinone esihlukene futhi esisebenza ngezindlela eziningi.

I-XinChem isebenzisa izikhungo zokukhiqiza ezisezingeni eliphezulu kanye nezinyathelo zokuqapha izinga eliqinile ukuze iqinisekise ukuhlanzeka, ukungaguquguquki, kanye nokuphepha kwemikhiqizo yayo ye-methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate. Inqubo yokukhiqiza ihlanganisa izindlela zokwenziwa ezisunguliwe—okuhlanganisa ukusabela kwe-o-phenylenediamine ne-diethyl oxalate okulandelwa yi-cyclization kanye nokufakwa komsebenzi okulandelayo—okuvumela ukulethwa kwemikhiqizo enokuhlanzeka okungu-≥95% (HPLC) kanye no-≥98% (HPLC) ukuze kuhlangatshezwane nezidingo ezahlukene zokusetshenziswa. Ukulawulwa kwenqubo okuqinile kuqinisekisa izinga lomkhiqizo elingaguquguquki, ukungcola okuncane, kanye nokuphindaphindeka kwe-batch-to-batch, okunikeza amakhasimende ukusebenza okuthembekile ekutholakaleni kwe-kinase inhibitor, ukuthuthukiswa kwe-HDAC modulator, kanye nokuhlanganiswa kokwelashwa okuhlosiwe kwe-ALDH.

Inqubo yokukhiqiza ilandela ngokuqinile izindinganiso zamazwe ngamazwe zekhwalithi, ngokulawulwa kwekhwalithi okuphelele okuhlanganisa ukutholakala kwezinto zokusetshenziswa, ukuqapha phakathi nenqubo, nokuhlolwa komkhiqizo ophelile. I-batch ngayinye ihambisana ne-Certificate of Analysis (COA) enemininingwane ebhala izici zomzimba namakhemikhali, idatha yokuhlanzeka (HPLC), ukuminyana (1.4 g/cm³), inkomba yokukhanya (1.63), i-LogP (1.13), kanye namaphrofayili okungcola. I-XinChem inikeza i-COA eqondene ne-batch, ukupakisha okulungisekayo, kanye nokukhiqiza okuhambisana ne-REACH, ISO 9001, kanye ne-GMP emhlabeni wonke.

I-XinChem inikeza i-methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate enobumsulwa obungu-≥95% (HPLC) kanye no-≥98% (HPLC) obutholakalayo, okuqinisekisa ukusebenza okuphezulu ocwaningweni nokuthuthukiswa kwemithi, ukutholakala kwe-kinase inhibitor, kanye nokusetshenziswa kwekhemistri yemithi. Ukubumsulwa okuphezulu komkhiqizo kunciphisa ingozi yokuphendula okungafuneki nokungcola, okukwenza kufanelekele izinhlelo ezidinga kakhulu ekutholakaleni kwezidakamizwa, izifundo ze-SAR, kanye nokuthuthukiswa kwe-chemical probe. Inhlanganisela inikezwa njenge-crystalline solid enokubukeka okungaguquki kanye nezakhiwo ze-physicochemical ezichaziwe.

Imininingwane ebalulekile ihlanganisa:

I-XinChem inikeza izinhlobonhlobo zezindlela zokupakisha ukuze kuhlangatshezwane nezidingo ezahlukene zamakhasimende, kusukela kumanani esikali saselabhorethri (10 mg, 50 mg, 100 mg, 250 mg) kuya ekupakisheni kwesikali sezimboni (1 g, 5 g, 10 g, 25 g, 100 g) kanye nokuthunyelwa okukhulu. Izixazululo zokupakisha ezenzelwe wena ziyatholakala uma ziceliwe, ziqinisekisa ukuphathwa, ukugcinwa, kanye nokuthuthwa okuphephile ngokuvikelwa okufanele ekukhanyeni nasezintweni ezimanzi.

Njenge-quinoxalinone scaffold ehlukile, i-Methyl 3-Oxo-3,4-dihydro-6-quinoxalinecarboxylate (CAS# 357637-38-8) ibonisa inani elibanzi lokusetshenziswa ezimbonini eziningi:

Ithimba likaXinChem losokhemisi abanolwazi kanye nonjiniyela bezinhlelo luhlinzeka ngosekelo oluphelele lobuchwepheshe kulo lonke uhambo lwamakhasimende—kusukela ekukhetheni imikhiqizo nasekuthuthukiseni imininingwane kuya ekuqondiseni ngokusetshenziswa nasekuxazululeni izinkinga. Kungakhathaliseki ukuthi amakhasimende adinga ukuthuthukiswa kwemizila yokwenziwa kwezinto, ukuqondiswa ngamasu okuguqulwa kwezinto ukuze kutholakale izivimbeli ze-kinase, noma usizo ngezincwadi zokulawula, ochwepheshe bezobuchwepheshe bakwaXinChem bakulungele ukusiza. Ukwenziwa kwezinto ngokwezifiso kanye nokukhiqizwa ngenkontileka ngokukhula okuguquguqukayo kusuka ocwaningweni nasekuthuthukisweni kuya kumanani okuhweba kuyatholakala uma kuceliwe.

Ngezinhlelo zokuhlinzeka ezisunguliwe ezisebenza ezimakethe kulo lonke elaseYurophu, eNyakatho Melika, e-Asia-Pacific, nakwamanye amazwe, i-XinChem iqinisekisa ukulethwa ngesikhathi nokutholakala komkhiqizo okungaguquguquki. Ithimba lezokuthutha lezimpahla lenkampani liphethe zonke izici zokuthunyelwa kwezimpahla emhlabeni wonke, kufaka phakathi ukugunyazwa kwempahla kanye nemibhalo, ngokuvikelwa okufanele ekukhanyeni nasekumswakameni ukuze kugcinwe ukuzinza komkhiqizo.

I-XinChem ihlinzeka ngemibhalo ephelele yokweseka ukuhambisana nemithetho, okuhlanganisa ama-Safety Data Sheets (SDS), ama-Certificates of Analysis (COA), nezinye izitifiketi ezidingekayo. Inkampani ihlala ihambisana nezidingo zemithetho eziguqukayo ezimakethe ezinkulu, okuhlanganisa i-REACH, i-TSCA, neminye imithetho yesifunda, isiza amakhasimende ukuba abhekane nobunkimbinkimbi bokuhweba komhlaba wonke.

Isipiliyoni esibanzi nolwazi olujulile ekuhlanganiseni nasekuhlinzekeni ngezingxenye zokwakha ze-heterocyclic.

Ukulawulwa kwekhwalithi okuqinile, ukuhlanzeka okuphezulu (≥95% kuya ku-≥98%), nokuhambisana nezindinganiso zamazwe ngamazwe.

Ukuhlinzeka okuzinzile, amanani ancintisanayo, nokulethwa ngesikhathi.

Izixazululo ezenzelwe amakhasimende ahlukahlukene, okuhlanganisa ukuhlanganiswa okwenziwe ngokwezifiso nokupakishwa.

Ukusekelwa kobuchwepheshe okusabelayo kanye nemibhalo ephelele ehlanganisa i-COA eqondene neqembu.

Xhumana nathi namuhla ukuze uqale ubudlelwano bakho ne-XinChem!

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