CALCULATE + USERELATIONSHIP: Evaluation behaves differently when split into to measures

If those filters with related are coming from other dimensions and the relationship between Sales and the Dimension is Many (Sales) to One (Dimension) then you shouldnt need RELATED. As you mention RELATED needs a row context but you could just simply apply a filter on the dimension, something like this:

CALCULATE(
    DISTINCTCOUNTNOBLANK( InternetSales[ProductKey] ),
    InternetSales[StoreKey] = 306 ,
    InternetSales[Net Price] > 8 ,
    'Product'[Brand] = "Contoso",
    OR(
        'Product'[Color] = "Blue",
        'Product'[Color] = "Red"
    ),
    USERELATIONSHIP( InternetSales[Delivery Date], TablaFecha[Fecha] )
)

In your case if im not mistaken it would be:

CALCULATE(
    DISTINCTCOUNTNOBLANK( Sales[Item ID] ),
    Sales[Vertriebsart] = "Handel" ,
    Sales[Typ] = "N" ,
    Produktgruppe[Key] = "M",
    OR( 
        Kunden[Gruppe] <> "Intercompany", 
        Kunden[Gruppe] = "Intercompany" && Sales[Mandant] = "50"
    ),
    Sales[Rechnungsnummer] <> BLANK() ,
    'AP'[P_Text]  <> "Dublette" 
)

Again, this will work if best practices of data modeling are followed, that is mainly implementing a Star Schema
https://www.sqlbi.com/articles/power-bi-star-schema-or-single-table/