Month: November 2022

Ogata, Masaru published the artcilePyridazines. II. 4-Methylpyridazine N-oxides, Recommanded Product: (6-Methoxypyridazin-3-yl)methanol, the publication is Chem. Pharm. Bull. (Tokyo) (1963), 35-9, database is CAplus.

4-Methylpyridazine as above gave 4-methylpyridazine 1-oxide (XVI), m. 83-4°, λ (EtOH) 266, 314 mμ (log ε 4.05, 3.61) and 2-oxide (XVII), b₄ 135° (no m.p. given), λ (EtOH) 265, 305 mμ (log ε 4.01, 3.52). 6-Chloro-4methyl-3(2H)-pyridazinone (2 g.), 50 cc. MeOH, 5 cc. 28% NH₄OH, 0.5 g. 10% Pd-C and H gave 1.2 g. 4-methyl-3(2H)pyridazinone (XVIII), m. 165-6° (EtOAc); similarly, 4 g. 6-chloro-5-methyl-3(2H)-pyridazinone gave 2.95 g. 5-methyl-3(2H)-pyridazinone (XIX), m. 160-1°. XVIII and POCl₃ as above gave 3-chloro-4-methylpyridazine (XX), m. 46-7° and XIX gave 6-chloro-4-methylpyridazine (XXI), m. 33°; XX and XXI with BzO₂H in CHCl₃ at room temperature gave the corresponding 1-oxides, m. 148-9° (XXII) and 127-8° (XXIII), resp. XXII (250 mg.), 10 cc. MeOH, 1 cc. MeOH-NH₃, 0.1 g. 10% Pd-C and H gave XVI; XXIII similarly gave XVII. The following were prepared by procedures described in the first part: 4-methyl-5-nitropyridazine 2-oxide, m. 144-5°; 4-methyl-5-aminopyridazine, m. 137-8°; 3-amino-5-methylpyridazine, m. 183-4°; and 4-amino-4-methylpyridazine, m. 200° (decomposition).

Chem. Pharm. Bull. (Tokyo) published new progress about 89532-79-6. 89532-79-6 belongs to pyridazine, auxiliary class Pyridazine,Alcohol,Ether, name is (6-Methoxypyridazin-3-yl)methanol, and the molecular formula is C6H8N2O2, Recommanded Product: (6-Methoxypyridazin-3-yl)methanol.

Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem

Ogata, Masaru published the artcilePyridazines. I. 3-Methylpyridazine N-oxides, HPLC of Formula: 89532-79-6, the publication is Chemical & Pharmaceutical Bulletin (1963), 29-35, database is CAplus and MEDLINE.

3-Methylpyridazine (I) (2.4 g.), 15 cc. glacial AcOH, and 7 cc. 30% H₂O₂ heated 3 h. at 70°, 7 cc. 30% H₂O₂ added, the whole heated 3 h. at 70°, 15 mL. H₂O added, the AcOH evaporated in vacuo, the residue neutralized with Na₂CO₃, extracted with CHCl₃, and the CHCl₃ solution passed over 27 g. alumina and eluted with C₆H₆ gave 630 mg. I 2-oxide (II), m. 83-4° (C₆H₆); elution with CHCl₃ gave 230 mg. I 1-oxide (III), m. 68.5-9.5° (C₆H₆). Under similar conditions, 1 g. 3-methyl-6-chloropyridazine gave 0.7 g. 2-oxide (IV), m. 163-4° (C₆H₆). IV (0.7 g.), 10 cc. MeOH, 1 cc. 28% NH₄OH, 0.1 g. 10 Pd-C, and H gave II. To 500 mg. II in 2 cc. concentrated H₂SO₄ with cooling was added slowly 0.5 cc. fuming HNO₃; the whole heated 6 h. at 100° and poured on ice gave with CHCl₃ extraction 610 mg. 3-methyl-5-nitropyridazine 2-oxide (IVa), m. 118-19° (C₆H₆). To MeONa (from 100 mg. Na and 10 cc. MeOH) was added 200 mg. IVa, the whole refluxed 1 h., evaporated to dryness, the residue treated with saturated NaCl, gave with CHCl₃ extraction 70 mg. 3-methyl-5-methoxypyridazine 2-oxide (V), m. 103-4° (C₆H₆). To 500 mg. IVa was added 5 cc. AcCl slowly, with cooling, the whole kept 2 h. at room temperature, evaporated to dryness and the residue treated with MeOH to give 150 mg. VI (C₅H₄N₃O₂Cl), m. 220° (decomposition) (MeOH); the structure of VI was not determined The MeOH filtrate from VI chromatographed on alumina gave 50 mg. 3-methyl-5-chloropyridazine 2-oxide (VII), m. 166-7° (C₆H₆). IVa (100 mg.) and 1 cc. concentrated HCl heated 2 h. at 100° and poured on H₂O gave, with CHCl₃ extraction, 50 mg. VII. To MeONa (from 10 mg. Na and 5 cc. MeOH) was added 60 mg. VII and the whole refluxed 1 h. to give with C₆H₆ extraction 20 mg. V; IV similarly gave 3-methyl-6-methoxypyridazine 2-oxide (VIII), m. 95-6°. 3-Methyl-6-methoxypyridazine (3 g.), 18 cc. glacial AcOH, and 6 cc. 30% H₂O₂ (added repetitively as above) gave 2.5 g. VIII. IV (500 mg.), 2 cc. concentrated H₂SO₄, and 0.5 cc. fuming HNO₃ as above gave 210 mg. 5-nitro derivative (IX), m. 103-3.5° (C₆H₆); similarly was obtained 5-nitro derivative (X) of VIII, m. 101-1.5° (MeOH). IX and X (500 mg.) treated as above with MeONa in MeOH gave 3-methyl-5,6-dimethoxypyridazine 2-oxide, m. 150-1° (C₆H₆). X (500 mg.), 10 cc. Ac₂O, and 500 mg. 10% Pd-C absorbed 4 mol H; the residue after filtration and evaporation of the filtrate was heated 10 min. at 100° with 5 cc. 6N HCl, the whole neutralized, saturated with HCl and extracted with CHCl₃ to give 180 mg. 3-methyl-5-amino-6-methoxypyridazine (Xa), m. 159-60° (EtOAc). Xa (150 mg.) and 2 cc. concentrated HI refluxed 3 h. and the whole cooled and neutralized with NaHCO₃ gave 4-amino-6-methyl-3(2H)-pyridazinone (XI), m. 260-1° (H₂O). To 1.7 g. 6-methyl-3(2H)-pyridazinone-4-carboxamide in 30 cc. 5% NaOH at 0° was added 10 g. 13.4% NaOCl dropwise and the whole added to 10 cc. boiling H₂O, the whole kept 20 min., cooled, neutralized with HCl and an excess of NH₄OH added gave 1.0 g. XI. IVa (300 mg.), 20 cc. MeOH, and 0.2 g. 10% Pd-C absorbed 3 mol H to give 150 mg. 3-methyl-5-aminopyridazine 2-oxide, m. 258° (MeOH); IX under similar conditions gave 3-methyl-5-aminopyridazine (XII), m. 162-3°, and XII was also obtained from X. VIII (1 g.) 10 cc. CHCl₃, and 2 g. POCl₃ refluxed 0.5 h., the whole concentrated, the residue neutralized with K₂CO₃, extracted with CHCl₃, the CHCl₃ distilled, and the residue in C₆H₆ passed over alumina and the eluate concentrated gave 650 g. 3-methyl-5-chloro-6-methoxypyridazine (XIII), m. 121-2° (petr. ether). IX (500 mg.) and 5 cc. AcCl as above gave a MeOH-insoluble unidentified C₆H₆N₃O₃Cl, m. 206-7° (decomposition); from the MeOH after chromatog. on alumina and elution with CHCl₃ was obtained 70 mg. 3-methyl-5-chloro-6-methoxypyridazine (XIV), m. 138-9°; alternately, 200 mg. VIII and 2 cc. concentrated HCl heated 2 h. at 100 gave 90 mg. XIV. To cold 400 mg. XIV in 10 cc. CHCl₃ was added 900 mg. PCl₃, the whole kept 24 h., poured on ice, neutralized, and chromatographed as above, gave 150 mg. XIII. VII (2 g.) and 10 cc. Ac₂O refluxed 2 h. and evaporated to dryness gave 1.1 g. 6-methoxy-3-pyridazinemethanol acetate (XV), m. 59-60° (cyclohexane); 500 mg. XV and 10 cc. 3N HCl heated 0.5 h. at 100°, neutralized with Na₂CO₃, the whole evaporated to dryness, and the residue extracted with EtOH gave 150 mg. 6-methoxy-3-pyridazinemethanol, m. 53-4° (C₆H₆). XV (1.4 g.) and 20 cc. 3N HCl heated 0.5 h. at 100°, the whole neutralized with Na₂CO₃, evaporated to dryness, the residue extracted with EtOH, the EtOH extract concentrated to dryness and the residue with 5 cc. concentrated H₂SO₄ and 2 g. K₂Cr₂O₇ heated 3 h. at 50° and then poured on ice gave 150 mg. 6-oxo-1,6-dihydro-3-pyridazinecarboxylic acid, m. 260° (H₂O). II. 4-Methylpyridazine N-oxides. Ibid. 35-9. 4-Methylpyridazine as above gave 4-methylpyridazine 1-oxide (XVI), m. 83-4°, λ (EtOH) 266, 314 mμ (log ε 4.05, 3.61) and 2-oxide (XVII), b₄ 135° (no m.p. given), λ (EtOH) 265, 305 mμ (log ε 4.01, 3.52). 6-Chloro-4methyl-3(2H)-pyridazinone (2 g.), 50 cc. MeOH, 5 cc. 28% NH₄OH, 0.5 g. 10% Pd-C and H gave 1.2 g. 4-methyl-3(2H)pyridazinone (XVIII), m. 165-6° (EtOAc); similarly, 4 g. 6-chloro-5-methyl-3(2H)-pyridazinone gave 2.95 g. 5-methyl-3(2H)-pyridazinone (XIX), m. 160-1°. XVIII and POCl₃ as above gave 3-chloro-4-methylpyridazine (XX), m. 46-7° and XIX gave 6-chloro-4-methylpyridazine (XXI), m. 33°; XX and XXI with BzO₂H in CHCl₃ at room temperature gave the corresponding 1-oxides, m. 148-9° (XXII) and 127-8° (XXIII), resp. XXII (250 mg.), 10 cc. MeOH, 1 cc. MeOH-NH₃, 0.1 g. 10% Pd-C and H gave XVI; XXIII similarly gave XVII. The following were prepared by procedures described in the first part: 4-methyl-5-nitropyridazine 2-oxide, m. 144-5°; 4-methyl-5-aminopyridazine, m. 137-8°; 3-amino-5-methylpyridazine, m. 183-4°; and 4-amino-4-methylpyridazine, m. 200° (decomposition).

Chemical & Pharmaceutical Bulletin published new progress about 89532-79-6. 89532-79-6 belongs to pyridazine, auxiliary class Pyridazine,Alcohol,Ether, name is (6-Methoxypyridazin-3-yl)methanol, and the molecular formula is C6H8N2O2, HPLC of Formula: 89532-79-6.

Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem

Westphal, Matthias V. published the artcileWater-compatible cycloadditions of oligonucleotide-conjugated strained allenes for DNA-encoded library synthesis, COA of Formula: C5H4N2O, the publication is Journal of the American Chemical Society (2020), 142(17), 7776-7782, database is CAplus and MEDLINE.

DNA-encoded libraries of small mols. are being explored extensively for the identification of binders in early drug-discovery efforts. Combinatorial syntheses of such libraries require water- and DNA-compatible reactions, and the paucity of these reactions currently limit the chem. features of resulting barcoded products. The present work introduces strain-promoted cycloadditions of cyclic allenes under mild conditions to DNA-encoded library synthesis. Owing to distinct cycloaddition modes of these reactive intermediates with activated olefins, 1,3-dipoles, and dienes, the process generates diverse mol. architectures from a single precursor. The resulting DNA-barcoded compounds exhibit unprecedented ring and topog. features, related to elements found to be powerful in phenotypic screening. DNA-encoded libraries of small mols. are being explored extensively for the identification of binders in early drug-discovery efforts. Combinatorial syntheses of such libraries require water- and DNA-compatible reactions, and the paucity of these reactions currently limit the chem. features of resulting barcoded products. The present work introduces strain-promoted cycloadditions of cyclic allenes under mild conditions to DNA-encoded library synthesis. Owing to distinct cycloaddition modes of these reactive intermediates with activated olefins, 1,3-dipoles and dienes, the process generates diverse mol. architectures from a single precursor. The resulting DNA-barcoded compounds exhibit unprecedented ring and topog. features-related to elements found to be powerful in phenotypic screening.

Journal of the American Chemical Society published new progress about 50901-42-3. 50901-42-3 belongs to pyridazine, auxiliary class Pyridazine,Aldehyde, name is Pyridazine-4-carbaldehyde, and the molecular formula is C8H6BrF3S, COA of Formula: C5H4N2O.

Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem

Haider, Norbert published the artcilePyridazines. LIX. Synthesis of c-annelated pyridazines from 3-amino-4-pyridazinecarbonitrile, Synthetic Route of 119581-52-1, the publication is Journal of Heterocyclic Chemistry (1991), 28(5), 1441-4, database is CAplus.

Annelated pyridazines I, II (R = Ph, R¹R² = O, X = NH; R = H, R¹ = H, R² = Ph, 3-pyridyl, X = O), and III were prepared from 3-amino-4-pyridazinecarbonitrile (IV). Thus, condensation of IV with hydrazine and treatment with Ac₂O gave I in 45% yield.

Journal of Heterocyclic Chemistry published new progress about 119581-52-1. 119581-52-1 belongs to pyridazine, auxiliary class Pyridazine,Nitrile,Amine, name is 3-Aminopyridazine-4-carbonitrile, and the molecular formula is C5H4N4, Synthetic Route of 119581-52-1.

Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem

Haider, Norbert published the artcilePyridazines. XXXV. Preparation of some novel pyrimido[4,5-c]pyridazine derivatives from 3-(alkylamino)- and 3-(arylamino)-4-pyridazinecarboxamides, COA of Formula: C5H4N4, the publication is Journal of Heterocyclic Chemistry (1988), 25(1), 119-24, database is CAplus.

Pyrimido[4,5-c]pyridazinediones I (R = Ph, PhCH₂; R¹R² = O), pyrimido[4,5-c]pyridazinones II (R = Ph, PhCH₂; R³ = H, Me, Et), and dihydropyrimido[4,5-c]pyridazinones I (R = Ph, PhCH₂, Me₂CH; R¹ = H, R² = Ph, 3-pyridyl) were prepared from 3-chloro-4-pyridazinecarbonitrile III (R⁴ = Cl) via amino carbonitriles III (R⁴ = NHR) and amino carboxamides. In addition, III (R⁴ = NH₂) was prepared from III (R⁴ = Cl), via the tetrazolo[1,5-b]pyridazine IV as the key intermediate.

Journal of Heterocyclic Chemistry published new progress about 119581-52-1. 119581-52-1 belongs to pyridazine, auxiliary class Pyridazine,Nitrile,Amine, name is 3-Aminopyridazine-4-carbonitrile, and the molecular formula is C5H4N4, COA of Formula: C5H4N4.

Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem

Dostal, Wolfgang published the artcilePyridazines. LI. On the reactivity of pyridazinecarboxaldehydes towards selected active-hydrogen compounds, Recommanded Product: Pyridazine-4-carbaldehyde, the publication is Journal of Heterocyclic Chemistry (1990), 27(5), 1313-21, database is CAplus.

Reactions of 3-pyridazinecarboxaldehyde (I) and 4-pyridazinecarboxaldehyde (II) with various active methylene carbanions were studied. The products obtained in Knoevenagel reactions, Horner-Emmons reactions, and Hantzsch-type reactions are presented. Thus, II was treated with CH₂(CN)₂ in refluxing EtOH to give 80% pyridazinylmethylenemalononitrile III. Further, I and MeCOCH₂CO₂Me were refluxed in EtOH and then treated with H₂NCMe:CHCO₂Et to give 52% the pyridazinyldihydropyridinedicarboxylate IV.

Journal of Heterocyclic Chemistry published new progress about 50901-42-3. 50901-42-3 belongs to pyridazine, auxiliary class Pyridazine,Aldehyde, name is Pyridazine-4-carbaldehyde, and the molecular formula is C5H4N2O, Recommanded Product: Pyridazine-4-carbaldehyde.

Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem

Waechter, Gerald A. published the artcileTetrahydronaphthalenes: Influence of Heterocyclic Substituents on Inhibition of Steroidogenic Enzymes P450 arom and P450 17, Category: pyridazine, the publication is Journal of Medicinal Chemistry (1996), 39(4), 834-41, database is CAplus and MEDLINE.

In search of new leads for selective inhibition of estrogen and androgen biosynthesis, resp., heterocyclic substituted 2-(arylmethylene)-1-tetralones (1-4, 9-17), 2-(arylhydroxymethyl)-1-tetralones (5-8), exo-1a,2,3,7b-tetrahydro-1H-cyclopropa[a]naphthalenes (18-24), and 3-alkyl substituted 4,5-dihydronaphtho[1,2-c]pyrazoles (25-27) were synthesized and tested for inhibitory activity toward four steroidogenic enzymes, P 450 arom, P 450 17, P 450 18, and P 450 scc, as well as another P 450 enzyme, thromboxane A₂ (TXA₂) synthase. The test compounds inhibited human placental P 450 arom, showing a wide range of inhibitory potencies. (Z)-4-Imidazolyl compound 17 was the most potent inhibitor, with a relative potency (rp) of 110 [rp of aminoglutethimide (AG) = 1, rp of fadrozole = 359]. A competitive type of inhibition was shown by the (E)-4-imidazolyl compound 16 (rp = 71). On the other hand some of these compounds inhibited rat testicular P 450 17. Maximum activity was shown by the 3-pyridyl compound 20 (rp = 10, rp of ketoconazole = 1). Compound 20 was the only compound which exhibited a marked inhibition of TXA₂ synthase (IC₅₀ = 14.5 μM; IC₅₀ of dazoxiben = 1.1 μM). Regarding selectivity toward the steroidogenic enzymes, compound 16 was relatively selective toward P 450 arom, whereas compound 20 was relatively selective toward P 450 17 (P 450 arom: K_m testosterone = 42 nM, K_i 16 = 33 nM, K_i 20 = 3 μM; P 450 17: K_m progesterone = 7 μM, K_i 16 = 9 μM, K_i 20 = 80 nM). Compounds 17 and 24 were not selective since they showed strong inhibition of P 450 arom (K_i 17 = 26 nM, K_i 24 = 0.12 μM) and P 450 17 (K_i 17 = 0.7 μM, K_i 24 = 0.11 μM).

Journal of Medicinal Chemistry published new progress about 50901-42-3. 50901-42-3 belongs to pyridazine, auxiliary class Pyridazine,Aldehyde, name is Pyridazine-4-carbaldehyde, and the molecular formula is C11H12O4, Category: pyridazine.

Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem

Jacobs, Jon published the artcileDiscovery, Synthesis, And Structure-Based Optimization of a Series of N-(tert-Butyl)-2-(N-arylamido)-2-(pyridin-3-yl) Acetamides (ML188) as Potent Noncovalent Small Molecule Inhibitors of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) 3CL Protease, COA of Formula: C5H4N2O, the publication is Journal of Medicinal Chemistry (2013), 56(2), 534-546, database is CAplus and MEDLINE.

A high-throughput screen of the NIH mol. libraries sample collection and subsequent optimization of a lead dipeptide-like series of severe acute respiratory syndrome (SARS) main protease (3CLpro) inhibitors led to the identification of probe compound ML188 (I), [(R)-N-(4-(tert-butyl)phenyl)-N-(2-(tert-butylamino)-2-oxo-1-(pyridin-3-yl)ethyl)furan-2-carboxamide, Pubchem CID: 46897844]. Unlike the majority of reported coronavirus 3CLpro inhibitors that act via covalent modification of the enzyme, I is a noncovalent SARS-CoV 3CLpro inhibitor with moderate MW and good enzyme and antiviral inhibitory activity. A multicomponent Ugi reaction was utilized to rapidly explore structure-activity relationships within S_1′, S₁, and S₂ enzyme binding pockets. The X-ray structure of SARS-CoV 3CLpro bound with I was instrumental in guiding subsequent rounds of chem. optimization. I provides an excellent starting point for the further design and refinement of 3CLpro inhibitors that act by a noncovalent mechanism of action.

Journal of Medicinal Chemistry published new progress about 50901-42-3. 50901-42-3 belongs to pyridazine, auxiliary class Pyridazine,Aldehyde, name is Pyridazine-4-carbaldehyde, and the molecular formula is C5H4N2O, COA of Formula: C5H4N2O.

Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem

Tosh, Dilip K. published the artcileIn Vivo Phenotypic Screening for Treating Chronic Neuropathic Pain: Modification of C2-Arylethynyl Group of Conformationally Constrained A₃ Adenosine Receptor Agonists, Product Details of C6H4N2, the publication is Journal of Medicinal Chemistry (2014), 57(23), 9901-9914, database is CAplus and MEDLINE.

(N)-Methanocarba adenosine 5′-methyluronamides containing 2-arylethynyl groups were synthesized as A₃ adenosine receptor (AR) agonists and screened in vivo (po) for reduction of neuropathic pain. A small N⁶-Me group maintained binding affinity, with human > mouse A₃AR and MW < 500 and other favorable physicochem. properties. E_max (maximal efficacy in a mouse chronic constriction injury pain model) of previously characterized A₃AR agonist, 2-(3,4-difluorophenylethynyl)-N⁶-(3-chlorobenzyl) derivative 6a, MRS5698, was surpassed. More efficacious analogs (in vivo) contained the following C2-arylethynyl groups: pyrazin-2-yl 23 (binding K_i, hA₃AR, nM 1.8), fur-2-yl 27 (0.6), thien-2-yl 32 (0.6) and its 5-chloro 33, MRS5980 (0.7) and 5-bromo 34 (0.4) equivalent, and physiol. unstable ferrocene 36, MRS5979 (2.7). 33 and 36 displayed particularly long in vivo duration (>3 h). Selected analogs were docked to an A₃AR homol. model to explore the environment of receptor-bound C2 and N⁶ groups. Various analogs bound with μM affinity at off-target biogenic amine (M₂, 5HT_2A, β₃, 5HT_2B, 5HT_2C, and α_2C) or other receptors. Thus, we have expanded the structural range of orally active A₃AR agonists for chronic pain treatment.

Journal of Medicinal Chemistry published new progress about 1017793-08-6. 1017793-08-6 belongs to pyridazine, auxiliary class Pyridazine,Alkynyl, name is 3-Ethynylpyridazine, and the molecular formula is C11H21BO2Si, Product Details of C6H4N2.

Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem

Velaparthi, Upender published the artcileDiscovery of BMS-986260, a Potent, Selective, and Orally Bioavailable TGFβR1 Inhibitor as an Immuno-oncology Agent, SDS of cas: 2001559-19-7, the publication is ACS Medicinal Chemistry Letters (2020), 11(2), 172-178, database is CAplus and MEDLINE.

Novel imidazole-based TGFβR1 inhibitors were identified and optimized for potency, selectivity, and pharmacokinetic and physicochem. characteristics. Herein, we report the discovery, optimization, and evaluation of a potent, selective, and orally bioavailable TGFβR1 inhibitor, 10 (BMS-986260). This compound demonstrated functional activity in multiple TGFβ-dependent cellular assays, excellent kinome selectivity, favorable pharmacokinetic properties, and curative in vivo efficacy in combination with anti-PD-1 antibody in murine colorectal cancer (CRC) models. Since daily dosing of TGFβR1 inhibitors is known to cause class-based cardiovascular (CV) toxicities in preclin. species, a dosing holiday schedule in the anti-PD-1 combination efficacy studies was explored. An intermittent dosing regimen of 3 days on and 4 days off allowed mitigation of CV toxicities in one month dog and rat toxicol. studies and also provided similar efficacy as once daily dosing.

ACS Medicinal Chemistry Letters published new progress about 2001559-19-7. 2001559-19-7 belongs to pyridazine, auxiliary class TGF-beta/Smad,TGF-beta Receptor, name is 6-(4-(3-Chloro-4-fluorophenyl)-1-(2-hydroxyethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile, and the molecular formula is C9H21NO3, SDS of cas: 2001559-19-7.

Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem